1. A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%. CXR is shown below:
What are the radiological characteristics of PCP? CXR: diffuse, bilateral, interstitial infiltrates. Unusual radiographic patterns include lobar infiltrates, solitary or multiple nodules which may become cavitary; pneumatoceles up to pneumothorax. PErihilar pattern sparing the periphery. High-resolution CT: ground-glass opacities or cystic lesions
How sensitive CXR in the diagnosis of PCP? Findings on chest radiography may be normal (in 10-39% of patients), or radiographic changes may lag behind clinical symptoms.
Management :
Investigations:CBC ,sputum culture ,BAL for PCP BCR,respiratory panel,CMV PCR
CXR ,HRCT,BAL
Treatment:
Trimethoprim/sulfamethoxazole
in case of contraindications:Pyrimethamine/trimethoprim ,Atovaquine,Pentamidine
Radiological characteristics of PCP:
Perihilar infiltrations with subpleural sparing
Bilateral interstitial infiltrations
Honey comb appearance
reticulations
Cysts
Management: -CBC, CRP with titer, sputum bio fire, culture and sensitivity, blood culture and sensitivity, CMV PCR quantitative analysis. Treatment -TMP-SMX is the drug of choice , with pentamidine , primaquine and dapsone as secondary lines .
A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%. CXR done revealed bilateral interstitial infiltrates. Issues/ concerns – fever, dry cough, oxygen saturation 89% – 4 months post cadaveric transplantation – CMV serostatus D-/ R+ – CXR shows bilateral interstitial infiltrates What is your differential diagnosis? Chest x-ray showing interstitial infiltrates perihilar with sparing of periphery. – Bacterial: either typical or atypical organism in such immunocompromised patient – Viral pneumonia: (Cytomegalovirus (CMV), SARSCOV2) -fungal: like Pneumocystis jiroveci How will you manage this case? –Respiratory panel screening (gene expert) showed be obtained as early as possible. –Multidisciplinary approach including infectious disease, microbiologists, nephrologist, pulmonologists. -Based on high clinical suspicious IV co-trimoxazole can be started especially if the patient wasn’t on prophylactic treatment 4months post-transplant. -BAL should be arranged by chest team with screening for CMV, PCP, TB in BAL.
-According to clinical presentation with life threatening infection all immunosuppression should be stopped and stress dose of IV steroids should be started with proper counselling of the patient or his relatives about risks and benefits of holding immunosuppression 4months post-transplant. IF PCP proven based on PCR duration of antibiotics should be ~21days followed by PCP prophylaxis for at least 6-12 months or even extended courses can be used. References 1. Martin SI, Fishman JA. Pneumocystis pneumonia in solid organ transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Mar;13 Suppl 4:272-9. PubMed PMID: 23465020. Epub 2013/03/08. eng. 2. Grover SA, Coupal L, Suissa S, Szentveri T, Falutz J, Tsoukas C, et al. The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. Clinical and investigative medicine Medecine clinique et experimentale. 1992 Aug;15(4):309-17. PubMed PMID: 1516288. Epub 1992/08/01. eng. 3. Fauchier T, Hasseine L, Gari-Toussaint M, Casanova V, Marty PM, Pomares C. Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients. Journal of clinical microbiology. 2016 Jun;54(6):1487-95. PubMed PMID: 27008872. Pubmed Central PMCID: PMC4879311. Epub 2016/03/25. eng. 4. Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. The Journal of antimicrobial chemotherapy. 2016 Sep;71(9):2386-96. PubMed PMID: 27550991. Epub 2016/08/24. eng. 5. LaRocque RC, Katz JT, Perruzzi P, Baden LR. The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2003 Nov 15;37(10):1380-3. PubMed PMID: 14583873. Epub 2003/10/30. eng. 6. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2007 Feb;13(1):1-7. PubMed PMID: 17334722. Epub 2007/03/06. eng.
The probable differential diagnosis is mainly PCP vs CMV pneumonia or ARDS.
PCP main characteristic is being early post-transplant especially after heavy induction and high doses of immunosuppression initially, and the presence of dry cough signifies this.
Confirmation of diagnosis is done by negative CMV serology, BAL is positive for PCP as well as tissue biopsy.
Management of this case primarily needs reduction of immunosuppression, oxygen supply by mechanical ventilation on need, treatment by TMP using to renally adjusted doses.
Fever and dry cough after 4 month cadaveric transplant in older recipient with CXR shows bilateral central perihilar infiltrates sparing the periphery consists mostly with PCP but other differential diagnosis include:
☆ CMV pneumonia
☆ Bacterial pneumoniae
☆ Fungal pneumoniae
☆ TB
☆ Other pneumoniae as covid 19
☆ Mycoplasma infection
● How do you manage this case?
Laboratory evaluation
CBC,CRP, ABG, TST, IGRA, PCR for CMV , PCJ, and covid 19 , liver tests and renal function.
Chest CT scan
Supportive management as hydration and oxygen.
In PCP pneumonia:
TMP-SMX IV with high doses in case of PCP and pentamide in case of no response to TMP-SMX
Steroid can be useful in severe hypoxia
What is your differential diagnosis? · In view of dry cough and hypoxia, PJP comes on the top of the list · DD: · Viral: Influenza, parainfluenza , cytomegalovirus(Unlikely with D-/R+ Sero status) · Fungal: PCP · Bacterial: community acquired bacteria and Mycobacteria · Parasites
How would you manage this case? · MDT approach involving pulmonologist, ICU and Nephrologist · ITU admission and ventilatory support · Detailed history and full physical examination · Supportive treatment with IV fluids and Nutritional support · Initial investigations including FBC,ESR, CRP, RFTs. LFTs, and blood culture including TB cultures. Check for Tacrolinus trough level transplant graft US. · Viral throat swab to diagnose viral infections including COVID 19, Influenza and para-influenza and Mycoplasma pneumonia · Urine sample for Legionella urinary antigen · CMV-DNA by PCR test(D-/R+).Unlikely positive with such sero-status · Bronchoscopy & BAL ( including CMV PCR on the BAL) · Immunosuppression modification: stop anti-metabolites and continue on CNIs and steroids. · Broad spectrum antibiotics including cover for atypical pneumonia · Definitive treatment: · In case of CMV: IV gancycolvir 5mg/kg BD for 5 days followed by oral valgancyclovir 900 mg od until 2 X PCR are negative.If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV IVIG. · In case of PJP: TMP-SMT given initially IV at a high dose of 15 to 20 mg/kg IV then switching to oral treatment after clinical improvement. Second-line therapy is pentamide 4 mg/kg IV OD with comparable efficacy but worse safety profile Primaquine plus Clindamycin for severe cases. Increasing steroid dose can be useful in severe hypoxia(Sat <70%) · In case of CMV: IV gancycolvir 5mg/kg BD for 5 days followed by oral valgancyclovir 900 mg OD until 2 X PCR are negative.If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV IVIG. · Monitor graft function during treatment Radiological features of PJP: · No pathognomonic radiologic features for Pneumocystis infection. · 90% of chest X rays are abnormal but 10-15% have normal chest radiographs · Features highly suggestive of PCP include: · Bilateral, diffuse, interstitial or alveolar infiltrates sparing sub-pleural region · It is predominantly peri-hilar in distribution · Patients receiving aerosolized pentamidine classically presents largely or solely in the upper lobes on chest X rays
· HRCT: · More sensitive and specific compared to X ray. · Features on CT include nodular or patchy ground glass appearance.
References: 1. Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13545. 2. Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587.
3. Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58.
Diagnosis-The diagnosis of PCP should be considered in patients with risk factors for PCP who present with pneumonia and suggestive radiographic findings. Microbiologic identification of the organism when possible . Detection of the organism in respiratory specimens is most commonly achieved by microscopy with staining of an induced sputum specimen or BAL fluid .The serum beta-D-glucan assay can be used as an adjunct to the diagnosis of PCP.
Treatment–
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract. For renal dose adjustment recommendations, refer to TMP-SMX drug information.
Differential Diagnosis:
The most likely cause of the patient’s symptoms, including dry cough, 4 months post-cadaveric transplantation, CMV positivity, and oxygen saturation of 89%, is Pneumocystis pneumonia. Chest X-ray shows a perihilar ground glass appearance, with sparing of the subpleuritic region. Other possible differential diagnoses include viral pneumonia (such as CMV pneumonia or COVID pneumonia), fungal pneumonia (such as Aspergillus pneumonia), bacterial pneumonia (including TB, Legionella, or Mycoplasma), sarcoidosis, and ARDS.
Management:
The patient should be admitted to the intensive care unit for close observation, in case escalation of ventilatory support is required. Currently, respiratory support can be provided through a nasal oxygen cannula. Investigations that should be conducted include CBC, LDH, β-D-Glucan (BDG), ABG, serum creatinine, BUN, urine analysis, ALT, AST, blood culture, induced sputum culture, CMV PCR test, and monitoring of immunosuppressives such as CNI trough levels. BAL with Pneumocystitis quantitative PCR from respiratory fluid, stained samples, or metagenomic next-generation sequencing can also be performed. Pulmonary function tests should be conducted, and the severity of the illness can be determined based on the alveolar-arterial gradient and room air partial pressure of oxygen.
Treatment:
Prompt initiation of treatment is crucial, and the first-line agent is cotrimoxazole, which can be administered orally or intravenously in 3-4 daily doses for a minimum of 3-4 weeks. It is important to consider any potential interaction with cyclosporine, another medication the patient is receiving. Second-line treatment options include pentamidine, dapsone (often used in combination with pyrimethamine), or atovaquone.
What is your differential diagnosis?
The differential diagnosis is of Viral associated Pneumonia (CMV pneumonia, COVID-19, ARDS)
How do you manage this case?
Tests for CBC, ABG, Sputum test, BAL, HRCT of chest, Bronchoscopy and lung biopsy
Management with IV ganciclovir in case of CMV pneumonia, Prednisolone or steroids
Q1: ΔΔ: 1. Pneumocystic jirovani pneumonia 2. CMV pneumonitis, fungal, bacterial, or parasitic pneumonia 3. Covid-19 pneumonia 4. Other types of atypical pneumonia
Q2: management includes: 1. ICU admission 2. Oxygen supplementation 3. Cotrimoxazole (15-20 mg/kg/day) TMP divided Q6-8 hours preferably IV oral doses with two double-strength tablets Q8h in mild cases. 4. Alternatives pentamedine(4 mg/kg/day), atovaquone (750 mg ), clindamycine (600-900mg/Q8h) with primaquine dapsone and TMP 5. Lab test: PCR test for CMV, covid, and other viruses, BAL specimen test for cytology, gram stain, acid-fast bacilli, and PCR for PCP, CMV, and other respiratory viruses. 6. If influenza positive: oseltamivir 7. Wide-spectrum empirical antibiotics 8. Reduction of immunosuppression. Stop MMF adjust CNI
– Chest CT: for a better evaluation of the alterations present on the chest X-ray, with a view to excluding any of the suspected infectious pulmonary conditions.
– Boncoscopy with bronchoalveolar lavage: CT scan of the chest would not exclude all etiologies, so a bronchoscopy with bronchoalveolar lavage would also be necessary with collection of:
What is your differential diagnosis?
1-Typical and atypical pneumonia .
2-Fungal infection ;
Pneumocyst carinii
Spergellous
3-Viral infection ;
CMV ,EBV , adenovirus ,Covid .
2-How do you manage this case?
1-The diagnostic approach ;
A-None invasive approach;
a-Blood ,sputum .
b-Serum antibodies against EBV ,CMV ,Ligionella and mycoplasma .
c-Galactomannan test( GM test), and Interferon-γ release assays (T-SPOT).
B-The invasive approach ;
The guidelines recommend fiberoptic bronchoscopy with BAL in patient with negative findings .
2-The therapeutic approach ;
1-The empirical antimicrobial therapy included;
A- For early onset pneumonia (the presented case );
moxifloxacin, ganciclovir, and trimethoprim-sulfamethoxazole (TMP-SMX) .
B-For late onset pneumonia ;
moxifloxacin plus ganciclovir .
C- The guidelines recommend antifungal therapy in cases of suspicion or confirmed fungal infection.
D-The dosages of all the drugs should be adjusted based on the allograft function.
E- The antimicrobial should adjusted within 24 h after the results of the microbiological cultures and serum tests became available.
F-Reduction immunosuppressant ;
1-None ICU admission;
Withdrawn of anti proliferative agent ,continue CNI and steroids .
2-ICU admission;
In critically ill patients. all the immunosuppressants should be withdrawn on admission to the ICU, methylprednisolone (1 mg/kg every 12 h) can be initiated, followed by gradual tapering . Calcineurin inhibitors can be resumed at a low dose when the intravenous methylprednisolone dose was reduced to 1.0 mg/kg/d.
G-The management of other aspects of care, such as blood glucose control, nutritional support, thromboembolic prophylaxis, sedation, and analgesia, was performed according to the current guidelines .
References:
1- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358588/Int J Clin Exp Med. 2015; 8(1): 1324–1332. Published online 2015 Jan 15. Early- and late-onset severe pneumonia after renal transplantation .
2https://ukkidney.org/sites/renal.org/files/Coronavirus%20transplant%20information%2021%20October%202020.pdf
The patient has fever, dry cough. No expectations and desaturation
DD include
1. Viral infections including respiratory virusrs, CMV and other herpes viruses
2. Bacterial infections less possibility
3. Fungal as PCP, histoplasmosis, cryptococcosis
And even parasites
In such patient with CMV positive recipient, desaturation, dry cough and fever most probably PCP
Management include
1 complete history and clinical examination including immunosuppression protocols and induction history
2. Lab tests including routine tests, inflammatory markers, virology, cultures, and immunosuppression trough levels
3. Imaging after CXR we should perform HRCT
4. In case of sputum we shall perform cytology and culture even BAL with virology markers
5. Being CMV positive recipient so risk of reactivation is high and CMV PCR
Regarding treatment
ICU administration owing to hypoxia
Empirical antibiotics should be started including beta lactame antibiotics
Pcp empirical treatment including Trimethoprin sulphamethoxazole
If confirmed continue for 3 weeks if allergic or CI give pentamidine
If negative stop the drug
If CMV manage for CMV treatment
Regarding immunosuppression
Stop MMF and adjust CNI according to trough level
Plus continue supportive care
In the above case, likely diagnosis is PCP because of history of fever, dry cough ,hypoxia and X-ray Chest showing bilateral perihilar shadowing with bilateral infiltrates. Though x-ray chest has only 5-30% sensitivity. Other differentials which should be considered include: viral pneumonia like CMV, COVID infection, bacterial and fungal pneumonias
Patient should be admitted and oxygen therapy should be started immediately along with broad spectrum antibiotics .Intensivist and pulmonologist should be taken on board and assessment for noninvasive ventilation i.e., CPAP or BiPAP should be done by them. Immunosuppression should be modified i.e., antimetabolites stopped and CNIs reduced . Investigations should be done to confirm the diagnosis which include: CBC, serum LDH, B-glucan, PCR for CMV DNA and PCP , CT scan chest (sub pleural sparing , honeycombing, reticular shadowing with ground glass haze, spontaneous pneumothorax)and then BAL or sputum samples for microbiological diagnosis with special staining. Metagenomic next-generation sequencing is the new diagnostic test which will help in detecting rare pathogens easily. First line treatment for PCP is Trimethoprim-Sulfamethoxazole (TMP-SMX)in a dose of 15mg/kg -20mg/kg in 3-4 divided doses for a duration of 14-21 days. After that prophylaxis is continued for 6-12 mths. Second line options include Intravenous pentamidine, Atovaquone, clindamycin-primaquine, or dapsone-TMP. Steroids in a dose of 40–60 mg of prednisone /day with tapering in 1–2 weeks is recommended in those patients with PaO2 <70 mmHg on room air, A-a oxygen gradient ≥35 mmHg,or SpO2 <92%.
REFERENCES:
1-Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587
What is your differential diagnosis? 4 months post-transplant, cadaveric donor, CMV (D-/R+), presented with fever, non-productive cough and hypoxia (PaO2 89%). CXR shows diffuse reticulo-nodular opacity. differential diagnosis:
· Viral pneumonia: Influenza, parainfluenza, CMV
· Fungal: Pneumocystis jirovecii (PJP), Aspergillus, histoplasma, Cryptococcus
· Tuberculosis
· Bacterial pneumonitis (atypical)
In view of hypoxia and non-productive cough, probability of PCP is high. In view of CMV status D-/R+, CMV pneumonia possibility is less (it may present with patchy ground glass opacities, small nodules, or consolidation). Bacterial etiology of the clinical picture is unlikely (no expectoration). How do you manage this case? 1. detailed history – Induction therapy and agent; immunosuppressive regime being used; examination – resp rate, saO2, chest auscultation for crepitations, look for pneumothorax 2. Laboratory testing – CBC, RFT, LFT, CRP, Tac C0 drug level 3. HRCT chest Viral assays – CMV DNA PCR, influenza testing, H1N1 (swine flu) testing Serum beta D Glucan, Serum LDH 3. Induced sputum examination – cytology, gram stain, AFB and culture. If no sputum – may need BAL – fluid test for CMV and PJP 4.Treatment: – Admission and monitoring in HDU / ICU – oxygen therapy in view of hypoxia. May need non-invasive ventilation (CPAP or BiPAP) or ventilatory support if worsen – Bronchoscopy with bronchoalveolar lavage (BAL) with or without transbronchial lung biopsy – PCR for respiratory viruses, CMV, pneumocystis etc, and histopathological analysis. – Start empiric treatment: 1) Influenza season: Antiviral against influenza (Oseltamivir) till the results for respiratory virus panel is available. 2) Empirical antibiotics: Co-amoxy-clav / Azithromycin 3) PCP treatment – considering the clinical scenario, co-trimoxazole double strength (TMP 160 +SMX 800) 2tab PO tid should be started, pending the investigation results. – Steroids to be added if hypoxemia PaO2 <70% on room air develops. – Anti-PCP treatment can be stopped once investigations for pneumocystis are negative. 4) Immunosuppression reduction: Antimetabolites to be stopped, CNI doses to be minimal adjusted as per trough levels. Further management as per the laboratory reports: Ø If Sputum / BAL fluid / biopsy shows PCP:TMP-SMX. Treatment should be given for 3 weeks, followed by secondary prophylaxis with low dose of TMP-SMX for 6-12months. – If TMP=SMX is contraindicated (patient is allergic) or not effective – then second line drugs Pentamidine, Atovaquone, Dapsone, Primaquine + clindamycin can be used. Ø If BAL shows CMV: Treatment with Valgancyclovir 900mg PO bid or Inj Ganciclovir (5mg/kg IV 12 hourly) adjusted to creatinine clearance – To be continued for 2 weeks until resolution of clinical symptoms and radiological findings with clearance of CMV in blood. – Complete blood count and serum creatinine should be monitored weekly during the treatment. – If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG). – Secondary prophylaxis with oral Valganciclovir post-treatment can be given for 3-6 months in patients with high-risk of relapse. References:
Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9): e13545. doi: 10.1111/ctr.13545. Epub 2019 Apr 23. PMID: 30900275; PMCID: PMC7162188.
Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616.
Kang EY, Patz EF Jr, Müller NL. Cytomegalovirus pneumonia in transplant patients: CT findings. J Comput Assist Tomogr. 1996 Mar-Apr;20(2):295-9. doi: 10.1097/00004728-199603000-00024. PMID: 8606241.
Moon JH, Kim EA, Lee KS, Kim TS, Jung KJ, Song JH. Cytomegalovirus pneumonia: high-resolution CT findings in ten non-AIDS immunocompromised patients. Korean J Radiol. 2000 Apr-Jun;1(2):73-8. doi: 10.3348/kjr.2000.1.2.73. PMID: 11752933; PMCID: PMC2718167.
Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9): e13512. doi: 10.1111/ctr.13512. Epub 2019 Mar 28. PMID: 30817026.
As the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest the differential could be,
1. PCP, can present with parihylar infiltrates and sphering of peripheral lungs, with hypoxemia.
2. CMV pneumonitis,
3. Bacterial infection,
4. Influenza, other viral pneumonia,
5. Other fungal infection,
6. COVID-19
7. Tuberculosis.
How do you manage this case?
As the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Further high resolution CT chest,
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, genexpert, blood C/S, procalcitonine, CRP.
General management;
Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange CPAP.
Empirical broad spectrum antibiotic.
If persistently hypoxemic start corticosteroids.
Specific management;
. The next treatment will be according to labs evidence, and
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day,
If responsive or allergic to sulfa group switch to second line agent, depson, pentamidine 4mg IV od, atorviquine 750mg bd, primaquine 30mg tid.
*Differential diagnosis include
PCP pneumonia or CMV pneumonia
*CXR show bilateral perhailer infiltrate with sparing of the peripheral lung tissue which goes mostly with PCP
treatment with high dose septrin
This is a 65 year patient S/P cadaveric transplantation before 4 months presented with fever , dry couph .and hypoxemia , on CXR perihilar shadows and Diffuse bilateral interstitial infiltration. so our differential diagnosis : 1- PCP on the top of differential
2- other fungal infection
3- Viral infection mainly CMV
4- TB
5- Bacterial infection
6- COVID 19 infection
How do you manage this case?
1- More detailed history especially about the induction therapy , maintenance immunosupression , CMV and PCP prophylaxis , viral status for both donor and recipient before transplantation
2- This patient needs to be admitted to ICU with MDT including ( Nephrologist , Infectious and ICU specialist )
3- supportive management with IV fluid , O2 supplement , antipathetic
4- laboratory test : CBC , KFT , LFT , CRP , ESR , urine analysis , blood urine and sputum Cx , LDH ( high in PCP ) , Tac level ,β-D-Glucan (BDG), ABG 5- Consider HRCT : more informative than CXR 6- BAL with transbronchial biopsy and staining is a highly sensitive method of identifying pulmonary disease. looking for PCP , CMV , TB and other common infection .
7- Broad spectrum antibiotics until the results of cultures and BAL ,
8- First-line treatment is with TMP-SMX 15 to 20 mg/kg for 21 days. Treatment of severe disease should include adjunctive steroids as for HIV-infected persons with PJP (60 mg/day initially, then taper).
9- Second-line agents include intravenous pentamidine (4 mg/kg/day), dapsone-trimethoprim (100 mg dapsone daily with trimethoprim 100 mg twice daily), or clindamycin plus primaquine (600 mg 4 times daily clindamycin with 30 mg base daily primaquine).
10- Look carefully for the adverse effects of trimethoprim which include nephrotoxicity, pancreatitis, and bone marrow suppression. Dapsone is associated with hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.
Mild-to-moderate PJP can be treated with atovaquone (750 mg orally twice daily for 21 days) in patients allergic to TMP-SMX.
11- continue Prophylactic agents,for 6 months .
References :
1) Hand book of Kidney Transplantation 6th edition
2) Prof Gamal Saadi lecture Pneumocystis Pneumonia in SOT
Differential diagnosis in this patient…The patient is a recent post transplant case (4 months ago), CMV negative donor to CMV positive recipient…. 4 months post transplant the patient has presented with fever, non productive cough and desaturation….The clinical diagnosis is suggestive of pneumonia for which the following possibilities are possible
Viral – COVID 19, RSV, Influenza and para influenzas viruses, pneumovirus and metapneumo virus, CMV pneumonitis (in the given setting of CMV +recipient from CMV negative donor the risk is lower)
Fungal – Histoplasma, cryptococcus and PCP
By order of preference the first diagnosis will be PCP in view of fever, non productive cough and hypoxia
Management of the patient includes investigations and treatment… Patient needs to be admitted….Detailed history regarding the use of immunosuppressives post transplant needs to be elicited out…Laboratory testing includes CBC, RFT, Liver function test, LDH..I would always keep bacterial sepsis in mind and send procalcitonin and Blood cultures and start on empirical antibiotics…
Patient needs CNI trough level to be monitored at baseline….CT chest will give better understanding of the opacities and introduce us to any cavities which cannot be seen in CXR…Sputum examination is not possible in the case due to non productive cough and induced sputum examination with 3% saline, may help in few cases…Sputum to be stained for gram stain, culture, AFB stain, PCP stain including giemsa or toulidine blue….CMV PCR testing should be done although it is unlikely in this scenario…..
Patient needs NIV like CPAP or high flow oxygen to maintain the oxygen saturation…
Antimetabolites needs to be stopped…CNI dose should be adjusted as per the trough levels….
Treatment with empirical antibiotics like Piperaccilin tazobactum should be considered…Oseltamivir should be started if there is an outbreak of influenza and the results can be stopped later… PCP treatment should be started with high dose Trimethoprim/sulfamethaoxazole 160/800 mg IV twice daily for 3 weeks, followed by secondary prophylaxis with low dose TMP-SMX for 6 months atleast.. Potassium levels need to be monitored while on TMP-SMX…In PCP steroids have to be added for hypoxia ..The dose being higher than the regular maintenance dosage…Second line agents like dapsone, atovoquone, primaquine with clindamycin can be used in patients who develop allergic reactions to TMP-SMX….
Radiological characteristics of PCP are perihilar shadowing, reticulonodular opacities with sparing of sub pleural stages at an early stage…These findings are not specific for PCP…CXR is not sensitive in the diagnosis of PCP and it can be normal also
. According to history the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest the differential could be,
1. PCP, can present with parihylar infiltrates and sphering of peripheral lungs, with hypoxemia.
2. CMV pneumonitis,
3. Bacterial infection,
4. Influenza, other viral pneumonia,
5. Other fungal infection,
6. COVID-19
7. Tuberculosis.
How do you manage this case?
. According to history the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Further high resolution CT chest,
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, genexpert, blood C/S, procalcitonine, CRP.
General management;
. Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange CPAP.
Empirical broad spectrum antibiotic.
If persistently hypoxemic start corticosteroids.
Specific management;
. The next treatment will be according to labs evidence, and
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day,
If responsive or allergic to sulfa group switch to second line agent, depson, pentamidine 4mg IV od, atorviquine 750mg bd, primaquine 30mg tid.
this patient with history of respiratory symptoms in nearly post-transplant period the condition most probably caused by opurtunistic infection .
Q 1- differntial diagnosis include :
Ø Pneumocystic jirvocii pneumonia
Ø COVID 19
Ø CMV
Ø TB
Ø Others EBV, HSV …
Q 2- How do you manage this case?
This patient is critical state needs
1- Admition to ICU.
2- Monitoring of the vital signs , O2 saturation .
3- O2 therapy – o2 supply by mask or nasal prang , non-invasive o2 support , invasive mechanical ventilation .
4- IV hydration .
5- WORK UP to prove the most probable diagnosis (PCP ) .
5-1 Chest x RAY – radiographic feature include
May be normal or there is bilateral, symmetric, diffuse, reticular, or granular opacities ,( although are non-specific). It is perihilar in mild presentations or diffuse in severe presentations . Typically, reticular and poorly defined ground-glass opacities progress to alveolar consolidation in 3–4 days .
5-2 High-resolution computed-tomography scans (HRCT) are more sensitive than chest radiography at detecting PCP. With a sensitivity and specificity of 100% and 89%, respectively, a normal HRCT may allow exclusion of PCP. Pulmonary cysts occur in 3%–6% of PCP .
5-3 Microbiological diagnosis: type of sputum sensitivity for diagnosis
Routine sputum Poor
Induced sputum 30–55%
Bronchoalveolar lavage 80–95%
Bronchoalveolar lavage and transbronchial biopsy, Open-lung biopsy >95%
Note: Pneumocystis remains a non-cultivable microorganism.
5-4 – Polymerase Chain Reaction:
PCR is a highly effective at diagnosing . the negative predictive value of this method, close to 100%, allows PCP to be excluded .
5-5- Plasmatic Markers
– the level of serum LDH is elevated (>300 IU) in most patients with PCP .
– serum levels of β-d-glucan (BDG), a polysaccharide present in the Pneumocystis cyst wall, as a noninvasive diagnostic test for PCP. with sensitivities ranging from 90% to 100% and specificities of 88%–96% .
6- WORK UP to exclude other possible cause .
1- SPUTUM for covid 19 PCR and chest ct scan .
2- CMV PCR.
3- T B – sputum for AFB, IgRA , Gen Expert .
4- PCR for EBV , SHV ..
TREATMENT :
Trimethoprim-Sulfamethoxazole (TMP-SMX) TMP-SMX is the first-line agent for the treatment of mild to severe PCP . The recommended daily dose is TMP 15–20 mg/kg plus SMX 75–100 mg/kg, preferably by IV administration for severe PCP. Recommended duration of treatment is 21 days.
Intravenous pentamidine is about as effective as TMP-SMX and it is the best second-line agent after TMP-SMX for SOT recipients .
second-line treatment
Atovaquone, clindamycin-primaquine, or dapsone-TMP have only been evaluated in mild to moderate PCP. The clindamycin-primaquine combination seems to be the most effective regimen, particularly in cases where TMP-SMX has failed .
patients with moderate-to-severe PCP, the use of adjunctive glucocorticoids remains questionable and is highly controversial. KDIGO and the American Society of Transplantation guidelines recommend treatment with adjunctive corticosteroids for SOT recipients with moderate to severe PCP (as defined by PaO2 <70 mmHg in room air). American Society of Transplantation guidelines suggest that 40–60 mg of prednisone is administered per os twice daily and tapered after 5–7 days over a period of 1–2 weeks
references : Jay A, etal: Pneumocystis Jirovecii in solid organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9
1.oxygen supply.
2.reduction of immunosuppression.
3.TMP-SMX its a first choice line treatment in PCP, upto to 20 mg/kg IV, switching to oral after clinical improvement.
Second line (sulfa allergies): Atovaquone, dapsone, or aerosolized pentamidine
TMP-SMX also reduces the incidence of Toxoplasma gondii, Listeria monocytogenes, and Nocardia asteroides and reduces the incidence of UTI in kidney transplant recipients. Check glucose-6-phosphate dehydrogenase before initiation of dapsone
65-year-old man transplanted
patient was admitted with a fever (38 °C) dry cough and Oxygen saturation on air was
reported at 89%.
CXR was done showing fine
bilateral interstitial infiltrates with ground-glass opacities more central sparing subpleural space.
Dry cough with hypoxia early on presentation With the x ray findings
in transplant recipient suggests PCP infection.
*Differential diagnosis
PCP.
CMV.
COVID- 19.
Bacterial pneumonia.
TB
*Investigation
-Cbc,CRP
-ABG
-Kidney function test
– Tuberculin skin test (TST) and
Interferon-gamma release assay.
-PCR tests for SARS-CoV-2.
-PCR for PCP,CMV,EBV.
-sputum and blood cultures
-Chest CT scan.
*Management
-oxygen supply to increase saturation .
-adjust immunosuppression.
– In case of PCP, treatment with TMP-SMX is the first-line therapy with 15 to 20 mg/kg IV, switching to oral after clinical improvement.
-Second-line therapy for
severe cases would be pentamide 4 mg/kg IV o.d., though with comparable
efficacy but worse safety profile .
– Primaquine plus Clindamycin for severe cases.
-Atovaquone or Dapsone/TMP for mild to moderate cases are
third-line options that can be considered for patients who do not tolerate the
above treatments or show no clinical improvement.
– Prednisone if oxygen saturation
declined to < 70 mmhg on room air.
*Reference
Dominykas Varnas and Augustina Jankauskienė.Pneumocystis
Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after
Transplantation: A Case Report and Literature Review.Acta Med Litu. 2021;
28(1): 136–144.
Approach to diagnosis: · It should include microbiologic identification of the PCP when possible (ie, when a sample such as an induced sputum or bronchoalveolar lavage [BAL] fluid can be obtained safely). In situations in which a respiratory specimen cannot be obtained safely, treatment can be initiated based upon the patient’s risk, clinical presentation, and use of serum diagnostic assays such as beta-D-glucan testing as the basis for presumptive diagnosis. · CRP,ESR, PCT · CMV PCR and Covid test · HRCT scan. · Respiratory culture · AFB smear and culture
Most important differential is PCP in this setting as occurred within 6 months post-transplant and clinical manifestations include fever, dry cough and low oxygen saturation.
Tuberculosis
Aspergillosis
Viral infections: CMV, EBV, HSV, Covid-19.
Management:
It is essential to confirm the diagnosis before specific treatment. Multi disciplinary approach needed.
General management:
– To correct hypoxia: Oxygen inhalation, non-invasive / invasive ventilation according to demand. – Anti-pyretic for fever. – I/V fluid if necessary.
Investigation:
– CBC, CRP – Blood culture, urine culture, sputum culture – PCR for CMV, PCP – Serum beta D-glucan: is non-specific but if positive it supports diagnosis of fungal infection. – LDH for the assessment of severity of PCP and prognosis – BAL should be checked for gram stains, silver stain or IF for PCJ, ZN stain, and sent for microbial cultures including fungus. – CT scan of Chest – Sputum for GeneXpert TB test
Specific management:
– Following confirm diagnosis, treatment of PCP drug of choice is TMP SMX we need to give at least for 3 weeks at a dose of 15-20 mg/ kg IV of TMP – Close monitoring for side effects of drugs is important as may need to decrease the dose. – Alternative agents are less effective such as IV pentamidine, Dapsone with Pyrimethamine plus Leucovorin, aerosolized Pentamidine and Atovaquone. – Modification of immunosuppressive medications: Hold MMF or Azathioprine. Reduce the dose of CNIs, aiming at lower target level. Increase the dose of steroid – Secondary prophylaxis for life.
Patient should be on secondary prophylaxis for 12 months and some authors recommend prophylaxis for life.
If proved that there is concomitant CMV we need to give antiviral therapy.
References: (i) UpTodate (ii) Jay A, etal: Pneumocystis Jirovecii in solid organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9 (iii) Sunsane B, etal: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
65 yr old man.
4/12 post transplant.
CMV D-VE/R+VE.
Fever 38 degrees. dry cough,SPO2 89%
CXR- Heterogenous opacification.
DX ;PCP
DDX;
CMV
Covid 19.
Atypical pneumonia- TB,LIP
PE
Bacterial pneumonia.
MGT.
MDT -Transplant nephrologist, chest physician.
Admit in ICU,
Inv ;LDH >220iu/l in PCR, Higher cases associated with more lung injury. PCP PCR on sputum post induction or via BAL, Beta D glucan though not specific for PCP, Pulmonary function tests; decreased DLCO of <75% more linked to PCP,BGA to assess severity of respiratory acidosis, Sputum for staining with methenamine silver or toluidine blue, this has sensitivity of 50-90% and specificity of 99-100% for PCP.
Start tx ;
Supplement oxygen to keep MAP > 90%
Assess severity using alveolar arteriolar gradient; mild <35mmHG,Moderate/severe 35-45/>45mmHG.
For severe dx, we add steroids – PDL 40mg BD x 5/7,then 40mg OD X 5/7,then 20mg OD X 11/7.
Prophylaxis post treatment ;x1 double strength septrin daily for 6-12/12 or dapsone 100mg OD or dapsone 50mg + pyrimethamine 50mg +leucovorin 25mg OD or Atovaquone 1500mg OD.
Consider RIS if pt deteriorates and condition becomes life threatening with close monitoring of graft function.
REFERENCES.
Uptodate ;Treatment and prevention of PCP in patients without HIV.
Gabriel M et al ; 6th edition handbook of Kidney Transplantation.
Jay et al; PCP in SOT; Guidelines from American Society of Infectious Disease, Clinical Transp, Vol 99,9
Management
Through history and physical examination
Oxygen supplementation to maintain SP02 >92%
Blood works: CBC, UEC, LFT,CRP,ESR, PCT, CNI trough level, Serum LDH levels, Serum β D glucan levels, CMV PCR
BAL- for direct immunofluorescence antibody staining is the diagnostic modality of choice or Gomori methanamine silver stain which stain the wall of the cysts.
Treatment
TMP/SMX is the drug of choice
Steroids should be given for HIV negative patients who are desaturating due to the associated high mortality.
Patients who are allergic to sulpha alternatives include:
Sensitivity of CXR
Accuracy of diagnosing using CXR is approximately 75%.
Maybe normal in 5-30% of patients.
False negative CXR may occur in 35-40% of patients.
Atypical findings may be seen in 5% and may include cysts, pneumothorax, lobar consolidation.
References.
Diagnosis and management of Pneumocystis jirovecii infection P Lewis White, Matthijs Backx, Rosemary A Barnes
Pneumocystis Pneumonia in Solid Organ Transplantation S.I. Martin J.A. Fishman The AST Infectious Diseases Community of Practice
Imaging features of Pneumocystis carinii pneumonia.C A Crans, P M Boiselle
1- This kidney transplant recipient presented with fever , dry cough and desaturation , 4 months after transplantation ( after stopping the prophylaxis against CMV).His X ray show fine perihilar reticulations ,all that are highly suggestive of PJP DD:
-PJ pneumonia
– Viral pneumonia : CMV pneumonia (either alone or associated with PJP)
– Covid-19 pneumionia but tend to affect lung prephery rather than perihilar.
-Drug induced pneumonitis specially m TOR inhibitors.
2- Management
A- Confirm the diagnosis of PJP: bronchoscopy and BAL for PCR , immunofluresent and Gomori silver stain .
– Exclude other concomitant infections with
– Nasal swap and PCR for covid , CMV PCR.
– Withdrawl of m TOR if the patient was receiving them.
– CBC, CRP ,procalcitonin. B- Treatment :
1- ICU admission , o2 therapy and stabilization of the general condition.
2- IS doses :withdraw m TOR , decrease dose of antiproliferative drugs as MMF and increase steroid doses .
3- Specific treatment :
-For PJP: TM-SMX is the initial drug of choice .If the patient is allergic to sulfa use pentamidine or dapsone with primaquine .
– For CMV pneumonia : IV gancyclovir 5 mg /kg for 5 days followed by oral valgancyclovir .
What are the radiological characteristics of PCP? CXR: perihilar infiltrates, central infiltrates sparing the pleura How sensitive CXR in diagnosis of PCP? Chest radiography may be normal in 10-39% of patients.Chest Xray: of PCP patient shows diffuse, often perihilar finely granular, reticular, or ground-glass opacities on chest HRCT perihilar shadowing and septa are there but real time PCR is diagnostic
DDX
1- PJP
2-CMV
3-Covid 19
4-TB
5-Atypical Pneumonia Management
Admission to ICU
O2 supply
Hydration
Complete work up
Start TMP/ SMX at a dose of 15-20/ 75-100 mg/ kg intravenous for 3 weeks then as the patient tolerated moved to oral 480 mg single dose daily , for 6-12 months.
It there is allergy to sulfa or intolerance due to AEs second line treatment can be started as dapson with trimethoprim , pentamidine spray ,
Atovaquone 750 mg/12 h
primaquine plus clindamycin.
If CMV treated by gancyclovir I.v then valgancyclovir 900 mg for 200 days.
Management of her IS by stopping antimetabolites , reduce the dose of Tac by 50% and adjunctive glucocorticoid should be given
if room air pao2 <70 by increasing the dose of steriod to 20-40 mg dialy.
Regular monitoring of RFT and LFT and drug level.
What is your differential diagnosis?
– According to history and chest x-ray most likely PCP
-CMV peumonia
– pulmonary TB
-Covid pneumonia. How do you manage this case?
-ICU admission.
-Detail history and examination.
-CBC ,CRP,ESR, RFT, LFT ,immunosuppression level,CMV and Covid PCR,and screening for TB
– sputum and bronchoscopy with BALF for staining.
-HRCT scan.
-O2 supply .
– If PCP confirm :TMP-SMX 15-20 mg/kg for 21days.
-After improvement :secondary prophylaxis of PCP. Reference:
Danovitch G.M .Handbook of kidney transplantation. sixth edition. Wolters Kluwer .Press:2017.
>What is your differential diagnosis? mostly a case of PCP. Differential diagnosis: 1- COVID pneumonia. 2- CMV pneumonia. 3- TB pneumonia. 4- Bacterial pneumonia.
>How do you manage this case? Investigations: -serum beta D-glucan, serum LDH, CBC, pan cultures, RFTs, LFTs, CRP – sputum examination for PCP, acid fast bacilli. – Respiratory syndromic panel – Nasopharyngeal swapping for COVID 19 – CMV PCR – BAL examination, metagenomic next generation sequencing analysis & lung biopsy may be considered – HRCT chest Treatment: 1- ICU settings for the hypoxia management 2- Supportive management 3- Reduction of immunosuppression: – Hold antimetabolites (MMF) – Keep tacrolimus guided by trough level around 6-8, follow graft function assessment – Consider Increase dose of steroid up to 40-60 mg/d 4- Antibiotics: – Empirical broad spectrum antibiotic coverage till culture results – For PCP: >Start IV TMP/SMX (15-20 mg/kg/d for TMP & 75-100mg/kg/d for SMX) >other options: dapsone, atovaquone, clindamycin plus primaquine & aerosolized pentamidine – if CMV +ve: start IV ganciclovir 5mg/kg/d in 2 divided doses 4- extend prophylaxis with TMP/SMX ds tab 3 times per week for 6-12 months >How sensitive CXR in the diagnosis of PCP? Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings. (Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation)
HRCT is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs. ( Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation)
>What are the radiological characteristics of PCP? Para hilar shadowing with subpleural sparing especially in early disease. ground glass appearance with reticulations & stripes honeycombing pneumatic cyst (Professor Gamal Alsaadi’s lecture)
Management :
Admission to ICU . because this patient has low oxygen saturation and connected to oxygen
Detailed history and examination ,ask if he received prophylaxis after tx like septrin and valganciclovir
Investigations:
To do CBC,CRP,RFT and electrolytes,TB screen .ESR,CMV screen ,Blood culture ,sputum culture ,CT chest ,lung function test ,HIV screen ,lactate dehydrogenase ,B-glucan
Bronch alveolar lavage and PCR
Transbronchial biopsy
Staining by silver and immune fluorescent stained
Microscopic examination of stained sputum and Broncho Alveolar Lavage Fluid (BALF) .
Meta genomic next generation sequencing (mNGS )analysis
Of BALF specimen . Treatment :
TMP:15-20mg/kg
SMX:75-100mg/kg
Iv or oral divided into 3-4 doses daily .or
Pentamidine :
4mg/kg as induction reduced to 2-3 mg/kg /day or
Atovaquone :
75omg per oral bd up to 1500mg bd or Primaquine plus clindamycine . References :
1-Prof Jamal lecture
2-Hand book of kidney tx
Scenario 1
Our 65 year old patient presented with a fever,non-productive (dry) cough 4 months after cadaveric transplantation and Spo2 on air was reported at 89% ,giving hx CMV negative to CMV positive recipient
CXR shows bilateral para hilar infiltration and diffuse interstitial infiltrates all make PJP highly suggestive.
Pneumocystis pneumonia can be life threatening. It can cause respiratory failure that can lead to death. People with this condition need early and effective treatment.
So MDT( nephrologist ,pulmonologist,ICU ,infectious ) is mandatory in management.
Brief history including drug hx and prophylaxis
Physical examination
Routine labs including CBC ,KFT ,LFT,Serum electrolytes,RBS
LDH for prognosis
Urine analysis
Septic work up including blood cx ,urine cx and if available sputum cx
ABG if po2 < 70 to consider high dose steroids
Cxr
HR chest CT
Beta-1,3 glucan level in the blood and/or lavage fluid from bronchoscopy
>>>> Given the lack of specificity of beta-D-glucan testing for PCP, the possibility of other fungal infections should be kept in mind.
BAL with transbronchial biopsy and staining is a highly sensitive method of identifying pulmonary disease
>>> The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens. This is particularly true of the diagnosis of PCP in patients without HIV infection, since the number of organisms is significantly lower than in patients with HIV.
First line treatment is with TMP-SMX 15 to 20 mg/kg for 21 days.
Treatment of severe disease should include adjunctive steroids as for HIV-infected persons with PJP (60 mg/day initially, then taper).
Second line agents include intravenous pentamidine (4 mg/kg/day), dapsone-trimethoprim (100 mg dapsone daily with trimethoprim 100 mg twice daily), or clindamycin plus primaquine (600 mg 4 times daily clindamycin with 30 mg base daily primaquine).
Mild-to-moderate PJP can be treated with atovaquone (750 mg orally twice daily for 21 days) in patients allergic to TMP-SMX.
Prophylactic agents, in order of efficacy, include TMP-SMX (single-strength tablet 3 times weekly), monthly aerosolized pentamidine, daily dapsone, and daily atovaquone.
Prophylaxis against disease should be reinstituted following augmentation of immunosuppression, such as steroid bolus or ATG administration for acute rejection.
Patients reporting sulfa allergies should be questioned regarding the nature of their reaction; desensitization may be possible with mild reactions. For those with severe allergies, dapsone should also be avoided, and PJP prophylaxis provided using atovaquone.
Reference
Uptodate
Treatment and prevention of Pneumocystis pneumonia in patients without HIV
Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV
SIXTH EDITION Handbook of Kidney Transplantation ,Edited by Gabriel M. Danovitch, MD
Medical Director, Kidney and Pancreas Transplant Program Ronald Reagan Medical Center at UCLA John J. Kuiper Chair of Nephrology and Renal Transplantation Distinguished Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles, California
This is an immunocompromised recipient within 6 months of transplantation, has fever, dry cough, hypoxia, CMV viremia, and bilateral lung infiltration, all are risk factors and suggestive of Pneumocystis jirovecii pneumonia.
Laboratory Studies
· LDH is done as a part of the initial workup. It has a high sensitivity (78%-100%), and LDH levels may reflect the degree of lung injury.
· Quantitative PCR for pneumocystis may be useful in distinguishing between colonization and active infection.
· PCR of respiratory fluid, in particular BAL, is increasingly used to make the diagnosis of PCP
· Sputum P jirovecii PCR testing may be a viable alternative to invasive testing.
Chest Radiography
· Can be normal in patients with early mild disease.
· Diffuse bilateral infiltrates extending from the perihilar region are seen in most patients with PJP.
· Less-common findings include patchy asymmetric infiltrates, pneumothorax, and pneumatoceles.
· Pleural effusions and intrathoracic adenopathy are rare
Computed Tomography
· The typical appearance is patchy areas of ground-glass attenuation with a background of interlobular septal thickening.
Pulmonary function tests
· Decreased DLCO of less than 75% predicted has a high sensitivity (89%-100%) but poor specificity (53%).
· PJP is unlikely if DLCO is normal.
Pulse oximetry
· The oxygen saturation should be measured both at rest and with exertion.
· In case of any detected hypoxemia, ABG should be done for the possible need for steroid therapy
Treatment of PJP
· TMP-SMX is the drug of choice and is the preferred initial therapy during pregnancy
· second-line agents including pentamidine, dapsone (often in combination with pyrimethamine), or atovaquone
· For the treatment of infections that are resistant to TMP-SMX, the combination of clindamycin and primaquine is likely to be more effective than intravenous pentamidine.
· Adjunctive steroids are not recommended in patients without HIV infection.
Prevention of PJP
· Smoking cessation. As smokers are at an increased risk of P jiroveci pneumonia (PJP) and have a more complicated treatment course.
· Chemoprophylaxis. TMP-SMX one double-strength tablet (160 mg TMP to 800 mg SMX) daily. One single-strength tablet (80 mg TMP to 400 mg SMX) daily is also effective
65 year man, 4 months post- transplant, with fever and nonproductive cough, D-, R+, with hypoxia and CXR showed: diffuse bilateral interstitial infiltrates with perihilar involvement.
1. What is the differential diagnosis?
PCP is the first DD, occurring within 6 months post-transplant, clinical including age of the patient and CXR are highly suggestive.
Viral pneumonia especially CMV either alone or concomitant with PCP, HSV, EBV AND Covid19
Tuberculosis
Fungal pneumonitis
Bacterial like staph aureus, mycoplasma.
Drug related interstitial involvement as in sirolimus
2. How do you manage this case?
History to explore the other risk factors such as induction therapy and maintenance IS treatment drugs, dosages and levels. We need to know whether received prophylaxis for PCP, CMV, types and duration. History of AR, corticosteroids, CMV infection
MD approach (pulmonologist, infectious disease physician and microbiologist) and admission to the ICU as patient needs respiratory support and may need intravascular volume support.
Check for ABG, CBC, CRP, LFT, RFT, PCR for CMV, PCR for tuberculosis, Blood cultures.
Check for HSV and EBV.
LDH for the assessment of severity of PCP and prognosis.
Sputum or BAL should be checked for gram stains, silver stain or IF for PCJ, ZN stain, and sent for microbial cultures including fung.
Level of beta D- glucan. It is highly sensitive for PCP.
Medications:
Broad spectrum antibiotics pending blood culture and sensitivity result.
For PCP: We need to give empirical treatment waiting for the results of investigations, as early treatment improves the prognosis.
Drug of choice is TMP SMX we need to give at least for 3 weeks at a dose of 15-20 mg/ kg IV of TMP and looking for side effects is important as we may need to decrease the dose.
Lower dose of < 10 mg/kg of TMP is claimed to be effective with less side effects.
Alternative agents are less effective such as IV pentamidine, Dapsone with Pyrimethamine plus Leucovorin, aerosolized Pentamidine and Atovaquon.
Corticosteroids is recommended for HIV patients when PaO2 is < 70 mmHg , it should be used within 72 hours of treatment, it use in non HIV patient is controversial. The American society of Transplantation recommended that 40 60 mg of prednisolone twice daily and tapered after 5-7 days over a period of 1-2 weeks.
We need to reduce the antimetabolite by 50% as in any other opportunistic infections and may need to stop it if infection gets life threatening. We may need to reduce CNI to the lowest accepted level. Important to Monitor for AR.
Patient should be on secondary prophylaxis for 12 months and some authors recommend prophylaxis for life.
If proved that there is concomitant CMV we need to give antiviral therapy.
References
1. Jay A, ETAL: Pneumocystis Jiroveci in solid Organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9
2. Sunsane B, etL: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
3. Xavir, etal: Pneumocystis pneumonia in solid organ trasnplnt receipients, journal of fungi,MDPI,28 SEP, 2018
4. Ji Eun Kim1, Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome, BMC Nephrology (2019) 20:212
65-year-old male, 4 months post-renal-transplant, CMV D/R -ve/+ve, presented with Fever (38), low oxygen saturation at 89% associated with dry cough.
Chest x-ray: bilateral prominent broncho-vascular markings and perihilar infiltrates, few pneumatoceles are seen.
Differential diagnosis includes: 1- Fungal infection like PJP is the first possible DD because of clinical manifestations mainly fever, dry cough and low oxygen saturation associated with minimal chest X-ray finidings. 2- Aspergillosis. 3- Viral infection: CMV, EBV, Covid-19. 4- Bacterial infection. 5- TB pneumonia.
How do you manage this case?
General Non-specific measures: 1- Hypoxia: Oxygen, serial ABG, escalation to non-invasive ventilation (CPAP or BIPAP) 2- Keep ITU in the loop in case of deterioration. 3- Fever: anti-pyretic.
Septic work up: 1- CRP, Blood culture, urine culture, induced sputum culture. 2- CMV PCR, PJP PCR 3- Serum beta D-glucan: is non-specific but if positive it supports diagnosis of fungal infection. 4- Metagenomic next generation sequencing. 5- CT-Chest 6- Bronchoscopy and broncho-alveolar lavage: PJP can be detected using stains like Giemsa, modified Grocott, Weigert-Gram, or methenamic silver.
Modification of immunosuppression medications: 1- Consider stopping MMF or Azathioprine. 2- Monitor level of CNIs, aiming at lower target level. 3- Consider increasing steroids especially if hypoxic.
Specific treatment for PJP: 1- PJP lines of treatment includes TMP/SMX (either IV or orally 15-20mg/Kg/day divided on 12 hours, course for 2-3 weeks), using steroids if ABG shows hypoxaemia PaO2 below 70mmHg. 2- If patient is allergic to TMP/SMX, alternatives include Atovaquone, Dapson, or Primaquine, or IV pentamidine.
Treatment of other pathogens according to results of septic work up.
Detailed history of his presentation, duration, associated weight loss, sweating, desaturation on exertion. History of chest problems before.
Any prophylaxis for PJP, TB and CMV after transplantation, type, any interruption.
Septic workup, including routine lab, CBC differentials, CRP, sputum culture (induced sputum), CMV PCR, sputum for ZN stain, AFB.
Admission to high dependency unit or ICU.
Pulmonology consultation.
Empirical antibiotics to cover bacterial, CMV and PCP infections.
If no improvement within 48hours to start anti PCP with a reduction of immmmonsuppresion. Starting by the antimetabolite.
Anti PCP include cotrimoxazole. If contra indicated, like G6PD deficiency, alternatives are pentamidine, dapsone or primaquine.
References:
Pulmonary Pneumocystis Jiroveci infection
Last revised by Blake Milton on 07 Feb 2023
What is your differential diagnosis? This patient has dry cough, high grade fever and hypoxia. He is 4 month post transplant and CMV – to CMV +. Chest X Ray shows hilar shadowing. Differential will include- PCP pneumonia CMV Pnemonitis Covid 19 Tuberculosis Asperagillosis Bacterial chest infections
How do you manage this case?
This patient will require resuscitation, investigation and treatment accordingly.
He may require admission to ITU / HDU
A multimodality approach involving Nephrologist, respiratory, ID and ITU physician will be required.
· Basic Investigations will include, Full blood counts, Renal and liver functions, CRP, ABGs, Beta D -Glucan.
· HRCT Chest
· CMV PCR
· Covid 19 PCR
· Bronchoscopy and Broncholaveolar lavage- PCP PCR from respiratory specimen
Patient can treated with trimethoprim ( 15-20 mg/kg) and sulphamethoxazole.75-100 mg/kg in divided doses.
Those allergic to sulpha drugs can have -Atavaquone 750 mg, orally twice daily for 21 days , Trimethoprim 15 mg/kg/day by mouth twice daily plus dapsone 100 mg by mouth every day, Primaquine 30 mg daily, plus clindamycin by mouth 450 mg every 6 hours or 600 mg every 8 hours.
White PL, Price JS, Backx M. Therapy and Management of Pneumocystis jirovecii Infection. J Fungi (Basel). 2018 Nov 22;4(4):127.
What is your differential diagnosis?
The etiology of infectious pneumonitis in immunocompromised patients
In one series using invasive diagnostic approaches for pulmonary infiltrates in immunocompromised hosts, a specific diagnosis was obtained in 162 of the 200 cases evaluated (81 percent)
An infectious etiology was found in 125 patients (77 percent) and a noninfectious etiology in 37 (23 percent); 38 (19 percent) remained undiagnosed.
Among infectious causes, bacteria were documented in 24 percent, fungi in 17 percent, and viruses in 10 percent. In 7 percent, the etiology was polymicrobial.
●Conventional bacteria – 37 percent (higher with neutropenia and mucositis and early after lung transplantation) ●Fungi – 14 percent (higher with prolonged neutropenia) ●Viruses – 15 percent (common with T cell suppression) ●P. jirovecii (formerly P. carinii) – 5 to 15 percent (without prophylaxis) ●Nocardia spp – 7 percent (including sulfa-resistant strains) ●Mycobacterium tuberculosis – 1 percent (higher in endemic regions) ●Mixed infections – 20 percent
The spectrum of pulmonary fungal infection includes infection with non-fumigatus Aspergillus spp, Fusarium spp, Scedosporium spp, and the Mucorales in patients with neutropenia and/or in association with graft-versus-host disease (GVHD)
Azole-resistant mold infection may emerge during therapy
Mixed infections with combinations of respiratory viruses, cytomegalovirus (CMV), Aspergillus spp, and/or gram-negative bacilli are common in neutropenic hosts and hematopoietic cell transplant (HCT) recipients
Pneumocystis pneumonia (PCP) is most common in patients receiving glucocorticoids as a part of a chemotherapeutic or maintenance regimen
Invasive CMV disease may be difficult to distinguish from viral shedding (or activation in the setting of severe systemic illness) in the immunocompromised host with pulmonary infiltrates. Confirmation of invasive CMV pneumonitis can be achieved using assays from blood samples (eg, CMV viral load by nucleic acid testing) and/or tissue histology
Noninfectious etiologies for pulmonary infiltrates are common in immunocompromised patients, including pulmonary embolus, tumor, radiation pneumonitis, cancer, fibrosis, atelectasis with pulmonary edema, drug allergy or toxicity, and pulmonary hemorrhage
How do you manage this case?
Diagnostic approach — The initial evaluation for immunocompromised patients with fever with or without pulmonary findings, at a minimum, should include: ●Rapid assessment of vital signs, including oxygen saturation ●Complete blood count with differential ●Electrolytes, blood urea nitrogen, and creatinine ●Blood cultures (minimum of two sets, with at least one peripheral set and one set from any indwelling catheter) ●Urine sediment examination and culture ●Sputum for Gram stain, fungal smears, and cultures ●Imaging of the lungs (chest radiography or, if possible, chest computed tomographic scanning) and imaging of any symptomatic site (eg, abdomen) ●Skin examination, looking for evidence of metastatic infection ●CMV quantitative molecular testing is often valuable; other viral polymerase chain reaction (PCR) assays as appropriate to the individual (adenovirus, parvovirus B19, severe acute respiratory syndrome coronavirus 2) ●Consideration of sample collection for nonculture-based diagnostic tools (eg, specific molecular and antigen tests such as Aspergillus or Pneumocystis PCR, cryptococcal antigen), Aspergillus galactomannan, beta-1,3,-glucan, whole genome sequencing)
Hypoxemia — The presence or absence of hypoxemia can assist in the differential diagnosis of pulmonary infiltrates in immunocompromised patients. Hypoxemia with an elevation in lactic dehydrogenase or beta-1,3-glucan and minimal radiographic findings are common inPneumocystis pneumonia (PCP),
whereas the absence of hypoxemia with pulmonary consolidation is more common in nocardiosis, tuberculosis, and fungal infections until later in the course.
TREATMENT
We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
if the patient has a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis), TMP-SMX should be avoided
For mild disease, options include: •Atovaquone •Clindamycin plus primaquine •TMP plus dapsone
All of these agents can be given orally. Although there are limited data, we prefer oral atovaquone in patients with mild disease.
For severe disease, options include: •Clindamycin plus primaquine •intravenous pentamidine Clindamycin can be given intravenously, but primaquine is available only as an oral formulation. Pentamidine should be given intravenously.
For severe disease, we prefer intravenous clindamycin plus oral primaquine because this regimen is less toxic than IV pentamidine. Patients should receive clindamycin intravenously until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract, at which point they can be switched to oral clindamycin.
Adjunctive glucocorticoids are recommended in patients with HIV and moderate or severe PCP because their use improves clinical outcomes and mortality without increasing the risk of other opportunistic infections.
we suggest the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg, or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent). Patients who worsen clinically and meet criteria for glucocorticoids while receiving anti-Pneumocystis therapy are also candidates for adjunctive glucocorticoids.
The patient is 4 months post-transplant, cadaveric transplant (D-/R+), presented with fever, non-productive cough, and hypoxia. The chest x ray shows diffuse reticulo-nodular pattern.
The differential diagnosis:
viral pneumonitis:
CMV pneumonitis
COVID-19
Mycobacterium tuberculosis: when upper zone cysts are prominent and if tree-in-bud opacities are present.
angioinvasive aspergillosis
Community acquired pneumonia: bacterial pneumonia
Fungal: PCP, histoplasmosis, cryptococcus
hypersensitivity pneumonitis
Kaposi sarcoma
With the clinical scenario and exertional hypoxia, PCP high likely
The management
History about the induction agent will provide useful information
Investigation :Full blood count, renal function tess, liver function test, C reactive protein, blood culture, chest X ray, respiratory viral panel testing , serum beta D Glucan, Serum LDH, IS levels
sputum examination for cytology, gram stain and acid fast bacilli stain, and culture.
HRCT of lungs
CMV QNAT testing: To rule out CMV infection
Bronchoscopy with bronchoalveolar lavage for stain and culture
PCR for respiratory viruses, CMV, pneumocystis etc, and histopathological analysis.
Empirical anti PCP treatment (trimethoprim-sulfamethoxazole, TMP-SMX) should be started without any delay. Steroids should to be added.
Antimetabolites to be stopped, CNI doses to be adjusted as per trough levels.
If confirmed PCP: TMP-SMX continued for 3 weeks, followed by secondary prophylaxis with low dose of TMP-SMX. If patient is allergic toTMP_SMX,, then second line drugs like Pentamidine, Atovaquone, Dapsone, Primaquine with clindamycin can be considered
Huang, L.; Cattamanchi, A.; Davis, J.L.; den Boon, S.; Kovacs, J.; Meshnick, S.; Miller, R.F.; Walzer, P.D.; Worodria, W.; Masur, H. HIV-associated Pneumocystis pneumonia. Proc. Am. Thorac. Soc. 2011, 8, 294–300. [CrossRef] [PubMed] 2. Thomas, C.F., Jr.; Limper, A.H. Pneumocystis pneumonia. N. Engl. J. Med. 2004, 350, 2487–2498.
How do you manage this case?
In this setting, the likely diagnosis is pneumocystis carinii pneumonia. This is supported by fever, prolonged dry cough and hypoxia post renal transplant with the described cheast radiograph.
Arterial blood gas
NIV or intubation
Confirmed the diagnosis by sending sputum for PCP; however in this case, BAL is important as the patient has a non-productive cough. Other BAL specimens should be sent for AFB, mycobacterium culture, BAL for fungal culture and BAL specimen for culture and sensitivity.
While waiting, I will initiate a broad-spectrum antibiotic ie: piperacillin-tazobactam.
Empirical start the patient with Trimethoprim-Sulphamethoxazole 15-20 mg/kg per day in two or three divided doses
Reduction of immunosuppression, especially anti-metabolite
How do you manage this case?
In this setting, the likely diagnosis is pneumocystis carinii pneumonia. This is supported by fever, prolonged dry cough and hypoxia post renal transplant with the described cheast radiograph.
Arterial blood gas
NIV or intubation
Confirmed the diagnosis by sending sputum for PCP; however in this case, BAL is important as the patient has a non-productive cough. Other BAL specimens should be sent for AFB, mycobacterium culture, BAL for fungal culture and BAL specimen for culture and sensitivity.
While waiting, I will initiate a broad-spectrum antibiotic ie: piperacillin-tazobactam.
Empirical start the patient with Trimethoprim-Sulphamethoxazole (TMP-SMX) 15-20 mg/kg/day in three to four divided doses for 14-21 days. This is followed by lifelong prophylaxis.
Second-line treatment with pentamidine or in the setting of the patient has allergic to TMP-SMX. Other alternative treatments are Atovaquone, primaquine and clindamycin, dapsone and trimethoprim.
Corticosteroid in the setting of hypoxemia PaO2 < 70 mmHg (2)
S.I. Martin, J.A. Fishman and the AST Infectious Diseases Community of Practice. Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of Transplantation 2013; 13: 272–279
1. A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%. CXR done revealed bilateral interstitial infiltrates.
– comprehensive history i.e., additional history of progressive exertional dyspnoea, weight loss, chest discomfort/ pain, drenching night sweats, weight loss, treatment for rejection, induction therapy
– admit to HDU/ ICU, initiate on oxygen therapy, IV paracetamol
– adjust his immunosuppression prescription accordingly i.e., reduce the CNI dose to the bare minimum, hold antimetabolite until the patient recovers, maintain on corticosteroids (as adjunctive therapy)
serum LDH – high sensitivity (78-80%) but lower specificity since other disease states can cause elevation in LDH
beta-D-glucan (BDG) is a cell wall component of fungi i.e., candida, aspergillus, pneumocystis (95% sensitivity 85% specificity) – lacks specificity for PCP
induced sputum samples are preferred to the routine sputum smears
quantitative PCR for pneumocystis using respiratory fluid in particular bronchoalveolar lavage (BAL) – unfortunately it cannot differentiate between colonization and disease
sputum PCR is a viable alternative to the invasive BAL PCR but further studies are required
transbronchial biopsy increases the yield of routine BAL
open lung biopsy – considered to be a gold standard, can detect lesions missed on BAL; video assisted thoracoscopic (VATS) biopsies can be considered
screen for routine bacterial, mycobacterial, fungal, CMV and other respiratory viral infections
CNI trough level
– 3 distinct morphologic stages of the organism have been described: –
Trophozoite (trophic form) – often exists in clusters
Sporozoite (precystic form)
Cyst – contains several intracystic bodies (spores)
– diagnostic method of choice is demonstration of the organism in the respiratory tract or secretions using invasive or noninvasive methods
– use of immunofluorescent/ immunoperoxidase monoclonal antibody stains against the organism have greatly improved the diagnosis of PCP (5)
– direct antibody staining of samples binds to both the cyst and trophozoite forms of pneumocystis increasing the sensitivity of detecting the organism
– on the other hand, routine stains like gomori methanamine-silver stains the cyst form only, giemsa and wright’s stain can also stain trophozoites the most common form of the organism in the alveolus
Trimethoprim-sulfamethoxazole (TMP-SMX) – it is the drug of choice (1st line agent), most effective systemic therapy for PCP, can be given in combination with corticosteroids, maintain adequate hydration, monitor cell counts, potassium and creatinine, has been shown to be as effective as IV Pentamidine
TMP-SMX is given at a dose of 1920mg TID for 21 days
– other options if the patient cannot tolerate TMP-SMX
Pentamidine (4mg/kg/day IV) – 2nd line agent after TMP-SMX in severe disease; side effects include hypo/ hyperglycemia, bone marrow suppression, pancreatitis, kidney failure, electrolyte imbalance
Atovaquone (750mg BD) – approved for mild and moderate PCP
Primaquine and clindamycin – long-term clindamycin use predisposes to C. difficile infection
Dapsone (100mg OD) and trimethoprim (320mg TID) – for patients who cannot tolerate sulfa, although dapsone can cause sulfa allergies as well
Pyrimethamine and sulfadiazine – use with folinic acid to reduce bone marrow toxicity
Macrolide and sulfamethoxazole – no recommendations available
Caspofungin and TMP-SMX – echinocandins have activity against pneumocystitis in animal models
– corticosteroids are used as adjunctive initial treatment in patients with severe disease – best given within 72hours of initiating antibiotics in states of hypoxia i.e., pAO2 < 70 mmHg on room air
Prednisone 40mg BD 5days, 20mg BD 5days then 20mg OD 11days
– duration of antibiotics should be ~21days
– preventive measures include chemoprophylaxis, smoking cessation play an important role
– relapse of PCP is uncommon with completion of therapy
– offer CMV prophylaxis
– Indications for PCP prophylaxis: –
high dose immunosuppression in the face of graft rejection
recurrent or chronic active CMV infection
prolonged neutropenia
prolonged corticosteroid use e.g., prednisone >20mg for at least 2weeks
autoimmune disease flares
immediate post-transplant period (the first 6-12 months) due to the high immunosuppression burden
References
1. Martin SI, Fishman JA. Pneumocystis pneumonia in solid organ transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Mar;13 Suppl 4:272-9. PubMed PMID: 23465020. Epub 2013/03/08. eng.
2. Grover SA, Coupal L, Suissa S, Szentveri T, Falutz J, Tsoukas C, et al. The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. Clinical and investigative medicine Medecine clinique et experimentale. 1992 Aug;15(4):309-17. PubMed PMID: 1516288. Epub 1992/08/01. eng.
3. Fauchier T, Hasseine L, Gari-Toussaint M, Casanova V, Marty PM, Pomares C. Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients. Journal of clinical microbiology. 2016 Jun;54(6):1487-95. PubMed PMID: 27008872. Pubmed Central PMCID: PMC4879311. Epub 2016/03/25. eng.
4. Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. The Journal of antimicrobial chemotherapy. 2016 Sep;71(9):2386-96. PubMed PMID: 27550991. Epub 2016/08/24. eng.
5. LaRocque RC, Katz JT, Perruzzi P, Baden LR. The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2003 Nov 15;37(10):1380-3. PubMed PMID: 14583873. Epub 2003/10/30. eng.
6. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2007 Feb;13(1):1-7. PubMed PMID: 17334722. Epub 2007/03/06. eng.
The index patient is a recent (4 months post-transplant), CMV negative to CMV positive cadaveric transplant (D-/R+), who presented with fever, non-productive cough, and hypoxia (89% oxygen saturation on room air). The chest x ray shows diffuse reticulo-nodular shadows.
The clinical symptoms are suggestive of pneumonia. The differential diagnosis in such a scenario would be (1):
3) Bacterial: community acquired like streptococcus, tuberculosis etc.
4) Parasitic
In view of hypoxia and non-productive cough, probability of PCP is high (2).
Bacterial etiology of the clinical picture is unlikely (no expectoration).
In view of D-/R+ CMV status, CMV pneumonia possibility is less (it may present with patchy ground glass opacities, small nodules, or consolidation) (3,4).
How do you manage this case?
The management of the index case involves:
1. A detailed history and clinical examination. History regarding induction therapy use and the immunosuppressive regime being used is especially important.
2. Laboratory testing including complete blood count, renal function tests, liver function tests, C reactive protein, blood culture, chest X ray, influenza testing (if in influenza season) and other respiratory viral testing (biofire), serum beta D Glucan, Serum LDH, Calcineurin inhibitor (CNI) trough levels (if on CNIs).
3. Induced sputum examination for cytology, gram stain and acid fast bacilli stain, and culture.
4. High resolution computed tomogram (HRCT) of chest.
5. CMV PCR testing: To rule out CMV infection (although unlikely in this setting).
6. Admission in intensive care unit (ICU): With oxygen therapy in view of hypoxia. May need non-invasive ventilation (CPAP or BiPAP) or ventilatory support if worsening takes place.
7. Bronchoscopy with bronchoalveolar lavage (BAL) with or without transbronchial lung biopsy (although biopsy usually not required): For stain and culture, as well as PCR for respiratory viruses, CMV, pneumocystis etc, and histopathological analysis.
8. Empiric initial treatment (1):
1) If influenza season: Antiviral against influenza (Oseltamivir) till the results for respiratory virus panel is available.
2) Empirical antibiotics: Beta lactam agent and agent against intracellular organisms should be started.
3) Considering the clinical status, empirical anti PCP treatment in form of co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX) should be started pending the investigation results. Steroids to be added if hypoxemia with oxygen saturation <70% on room air develops. Anti-PCP treatment can be stopped once investigations for pneumocystis are negative.
9. Immunosuppression: Antimetabolites to be stopped, CNI doses to be adjusted as per trough levels.
10. Further management as per the laboratory reports:
1) If BAL or biopsy shows PCP: continue TMP-SMX. Treatment should be given for 3 weeks, followed by secondary prophylaxis with low dose of TMP-SMX. If TMP=SMX is contraindicated, or patient is allergic to it, then second line drugs like Pentamidine, Atovaquone, Dapsone, Primaquine with clindamycin can be used.
2) If BAL shows CMV: Treatment with intravenous ganciclovir (5mg/kg IV 12 hourly, to be adjusted according to creatinine clearance). It should be continued for minimum 2 weeks (can be changed to oral valganciclovir, if improves earlier), and until resolution of clinical symptoms and radiological findings with clearance of CMV in blood, if present (5). Complete blood count and serum creatinine should be monitored weekly during the treatment. If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG) (5). Secondary prophylaxis with oral valganciclovir post-treatment can be given for 1-2 months in patients with high-risk of relapse.
Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13545. doi: 10.1111/ctr.13545. Epub 2019 Apr 23. PMID: 30900275; PMCID: PMC7162188.
Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616.
Kang EY, Patz EF Jr, Müller NL. Cytomegalovirus pneumonia in transplant patients: CT findings. J Comput Assist Tomogr. 1996 Mar-Apr;20(2):295-9. doi: 10.1097/00004728-199603000-00024. PMID: 8606241.
Moon JH, Kim EA, Lee KS, Kim TS, Jung KJ, Song JH. Cytomegalovirus pneumonia: high-resolution CT findings in ten non-AIDS immunocompromised patients. Korean J Radiol. 2000 Apr-Jun;1(2):73-8. doi: 10.3348/kjr.2000.1.2.73. PMID: 11752933; PMCID: PMC2718167.
Razonable RR, Humar A. Cytomegalovirus in solid organ transplant recipients-Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13512. doi: 10.1111/ctr.13512. Epub 2019 Mar 28. PMID: 30817026.
In this patient who is post transplanted kidney presenting with fever ,dry cough and on examination was oxygen desaturation ,
CXR may be normal in around 25% of patients .
The radiological manifestations of pneumocystis jerovecii pneumonia (pcp). Pneumocystis jirovecii pneumonia is an opportunistic and life-threatening fungal infection that is prevalent among immunocompromised hosts is bilateral diffuse,often perihilar rticulo interstitial opacification
And CT findings like
subpleural at the early stage
Honeycombing.
Groundglass appearance.
Other differential diagnosis that mimics the PCP are :
Viral pneumonitis.
Pulmonary edema
CMV
Covid 19
Other opportunistic infections .
How do you manage this case?
First admit this patient in isolated ICU.
Take good history and examination .
Stablish the diagnosis of PCP by :
CT scan which is more sensitive.
LDH
Sputum sample which is 50% sensitive.
Bronchoscopy with BAL which is more than 75% sensitive .
PCR for PJ.
Lung biopsy.
Then to exclude other differential by doing
PCR for covid 19
PCR for CMV.
CBC.RFT.LFT.CRP
MANAGEMENT of PCP firstly Trimethoprim-SulfamethoxazoleTMP-SMX
is the recommended first-line treatment for PCP in mild, moderate, and severe with intravenous therapy generally recommended for inpatients with moderate to severe disease and oral therapy used for outpatients with milder disease
Considering the below mentioned findings in an immunosuppressed kidney transplant recipient: Signs/symptoms: fever, dry cough and reduction in oxygen saturation CXR findings: Bilateral, symmetrical, perihilar, interstitial infiltrates/fine to medium reticular opacities
Diagnosis is highly suggestive of Pneumocystis Pneumonia(PCP) Differential diagnosis may include:
CMV infection
Bacterial Infection
Mycobacterial infection
Invasive mould infection(Like aspergillosis)
How do you manage this case?
Confirmation of diagnosis:
1.HRCT: typically findings includes
Ground glass opacities(GGO) which may be
extensive,
symmetric,
predominant in peri-hilar regions+/- apices or mosaic pattern and
subpleural sparing.
Less common findings may include
consolidation/septal thickening/nodules-centrilobular or random/cavitations
D/D: PJP, ARDS, DPLD, Acute Pulmonary oedema.
Supportive & specific management according to cause( e.g. TMP-SMX for PJP, justify the use of I/V steoid etc..)
differential diagnosis? -Pneumocystis jirovecii. -CMV Pneumonitis. -COVID infection with ARDS -Pulmonary aspergillosis. -Tuberculous pneumonia -Nosocomial Infections -Respiratory syncytial virus, adenoviruses, and human metapneumovirus -Drug-induced interstitial pneumonitis (mTOR) Radiological finding favoring PCP
PCP often manifests as a bilateral interstitial pattern, could be coarsely granular, reticular, or ground-glass opacities in appearance.
High-resolution CT may be useful in the diagnosis of PCP, because of high-resolution leading to higher detection.
Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
How to manage
–High flow O2 (BIPAP CPAP) and maintaining O2 >95% –Multidisciplinary Teams (Nephrology / ICU / Pulmonology / ID).
meanwhile sending the following investigations
CBC CRP, LFTs, LDH, RFTs
-BAL staining for PCP (Gomori methenamine silver (GMS) staining).
also send for respiratory panel (Influenza type A,B, Adenovirus ,covid-19 , etc).
CMV PCR) – As the patient is at high risk for CMV.
-sputum for C/S and AFB.
Treatment of PJP; -Trimethoprim-sulfamethoxazole (TMP-SMZ) -corticosteroids in patients with moderate to severe infections. -In case of allergy or contraindication can be given the following medicines; –Dapsone, Inhaled pentamidine , Atovaquone , Primaquine combined with clindamycin , Combined dapsone and trimethoprim , Pyrimethamine and sulphadiazine. with treatment, survival is good (50-95%), but relapses are common.
Needs long term prophylaxis for minimum of 1 year or even life long.
References; Up To Date; diagnosis of Pneumocystis pneumonia Aug 02, 2022.
PCP often manifests itself as a bilateral interstitial pattern, which may be described as having coarsely granular, reticular, or ground-glass opacities. This is the classic presentation of the disease. High-resolution CT may be useful in the diagnosis of PCP when chest radiographic results are normal or equivocal. This is because high-resolution CT has a higher detection sensitivity than chest radiographs do.
Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS are demonstrated by different radiographic patterns: widespread ground-glass opacities in the former and cystic lesions in the latter.
Hardak, E., Brook, O., & Yigla, M. (2010). Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
CHEST X RAY shows prominent interstitial infiltration and some ground glass appearances
in the setting of transplant and immunosuppression , opportunistic infections are very likely like PCP
in general CXR is not diagnostic of PCP infection , but few findings are specific to PCP , like pneumatocele formation , honey-comb pattern
sensitivity is low at 5-30 % to detect PCP
management
stabilization with nasal O2 ,
SPUTUM OR BAL MICROSCOPY AND CULTURE( NOT FOR PCP BUT FOR OTHER ORGANISM LIKE BACTERIA )
COTRIAMAXAZOLE IN PCP
DIFF DIAGNOSIS
OTHER VIRAL PNEUMONIA LIKE CMV, BACTERIAL PNEUMONIA
FLARE UP OF CHEST TB
Management According to the Amrican society of transplantation (Infectious disease community practice) Updated Guidelines in the prophylaxis, diagnosis, and management of PJP;
PJP prophylaxis is recommended during the first 6-12 month post transplantation, preferably with TMP-SMX.
TMP-SMX is the drug of choice for management of PJP, as follow
The appropriate dose for adequate antimicrobial activity.
Dose optomisation is required to ensure effectiveness, avoid resistance and to avoid side effects.
The recommended dose is 320-640 mg/day every 12 hrs PO for bacterial infection, and 15-20 mg/kg every 6-8 hrs IV then POfor PCP infection.
A high dose of TMP-DMX is recommended for PCP infection (TMP 15-20 mg/kg/D and SMXn75-100 mg/kg/D for 2-3 weeks), with high AEs.
In one randomized trial a high dose TMP-SMX associated with a higher rate of AEs (Rash, GI disturbance, bone marrow suppression,renal impairement, hepatotoxicity, and electrolyte disorders) which necesciate alternative regiment to avoid side effects.
3.In case of drug resistance; the alternative is;
TMP-SMX = 1 DS 3/W.
Dapsone = 50 mg BD or 100 mg 2/W.
Dapsone with 50 mg daily
Pyrimethamine plus 50 mg weekly
Leucovorin 25 mg weekly
Dapsone with 200 mg weekly
Pyrimethamine plus 75 mg weekly
Leucovorin 25 mg weekly
Pentamidine aerosolized 300 mg monthly via a nebulizer system
Atovaquone 1.500 mg dialy
Pyrimethamine plus 25-75 mg qd
Sulfadiazine 0.5 – 2.0 g q6h
Refferences;
Huang, L.; Cattamanchi, A.; Davis, J.L.; den Boon, S.; Kovacs, J.; Meshnick, S.; Miller, R.F.; Walzer, P.D.; Worodria, W.; Masur, H. HIV-associated Pneumocystis pneumonia. Proc. Am. Thorac. Soc. 2011, 8, 294–300. [CrossRef] [PubMed] 2. Thomas, C.F., Jr.; Limper, A.H. Pneumocystis pneumonia. N. Engl. J. Med. 2004, 350, 2487–2498. [CrossRef] [PubMed] 3. Utsunomiya, M.; Dobashi, H.; Odani, T.; Saito, K.; Yokogawa, N.; Nagasaka, K.; Takenaka, K.; Soejima, M.; Sugihara, T.; Hagiyama, H. Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: Results from a non-blinded, randomized controlled trial. Arthirits Res. Ther. 2017, 19, 7.
Carini A. Formas de eschizogonia de Trypanosoma lewisii. Arch Soc Med Ci Sao Paulo 1910;204 2. Chagas C. Nova trypanomiazaea humanan. Über eine neue Trypanomiasis der Menchen. Mem Inst Osvaldo Cruz 1909;1: 159–218 3. Delanoe P, Delanoe M. Sur les supports des kystes Pneumocystis carinii du poumon des rats avec Tryponosoma lewisi. C R Acad Sci (Paris) 1912;155:658–660 4. van der Meer MG, Brug SL. Infection à Pneumocystis chez l’homme et chez les animaux. Am Soc Belge Méd Trop 1942;22:301–309
◇ Management of the case: 1. Generalmanagement–
– ICU admission.
– Non invasive ventilation/ give the patient an oxygen therapy.
– Fluid management
2. Investigations: – Measure ABGs.
– CBCsLFTs and RFTs
– Viral screening ( CMV, HIV). CMV- PCR
– To confirm the diagnosis of PCP: The gold standard method for the diagnosis of PCP mainly relies on microscopic detection for cysts in respiratory specimens (sputum or a sample that is obtained by bronchoalveolar lavage) and PCR (which is sensitive).
3. Treatment [1]: ▪︎ Treatment for a presumed PCP should not be withheld while diagnostic measures are pending.Treatment should be initiated in patients with known risk factors and when clinical suspicion of infections exists.
▪︎IV Sulfamethoxazole and Trimethoprim are the most important drugs and commonly uses treatment for PCP.
▪︎ In patients with a mild allergy to TMP-SMX, desensitization should be attempted as this is the most effective drug of choice. ▪︎In patients with severe allergies to TMP-SMX, desensitization is no longer recommended, and choosing a different drug regimen is more appropriate. Alternative drug regimens for the treatment of PCP in those with sulfa allergies and mild to moderate disease include: pentamidine or dapson with primaquine. ▪︎ Give steroids by increasing the dose or restart it if the patient is steroid free.
▪︎ If the investigatios revealed any other causes then treat accordingly
————————–
–Differential diagnosis
Pneumocystitis pneumonia is most likely due multiple predisposing factors present including dry cough , 4 months after cadaveric transplantation, CMV positive recipient, oxygen saturation 89%.
Chest xray finding of perihilar ground glass appearance sparing subpleuritic region
Other DD
Viral pneumonia as CMV pneumonia,COVID pneumonia
Fungal pneumonia asAspergillus pneumonia
Bacterial pneumonia as TB ,legionella , Mycoplasma
Sarcoidosis
ARDS
–Management
Admission to intensive care to be under close observation in case needed escalation of ventilatory support.
He can need nasal oxygen cannula for respiratory support for now
Investigations :
CBC,LDH, β-D-Glucan (BDG),ABG
serum creatinine , BUN , urine analysis ,ALT ,AST ,blood culture , induced sputum culture
CMV PCR test
Immunosuppresives as CNI trough levels need to be followed
BAL with Pneumocystitis quantitative PCR from respiratory fluid, or stained samples or metagenomic next generation sequencing
Chest xray findings show perihilar interstitial pattern with subpleural sparing
Pulmonary function test
Illness degree is based on the alveolar-arterial gradient: mild (< 35 mm Hg), moderate/severe (35-45 mm Hg), or severe (>45 mm Hg).
Severe disease is also categorised by a room air partial pressure of oxygen lower than 70 mm Hg. Treatment Cotrimoxazole oral or IV in 3-4 daily doses must be started as soon as possible for at least 3-4 weeks.
Interaction with cyclosporine must be considered
second-line agents are pentamidine, dapsone (often in combination with pyrimethamine), or atovaquone.
Reference
-Gilroy SA , Pneumocystis jiroveci Pneumonia (PJP) Overview of Pneumocystis jiroveci Pneumonia.Medscape 2022
-Iriart X, Bouar ML, Kamar N, Berry A. Pneumocystis Pneumonia in Solid-Organ Transplant Recipients. J Fungi (Basel). 2015;1(3):293-331.
DIFFERENTIAL DIAGNOSIS:
The above chest radiograph shows parahilar opacities bilaterally with prominent bronchivascular markings.
This feature in otherwise non transplanted individual is suggestive of a viral pneumonia like COVID 19 which also applies to the patient unde discussion.
But apart from viral pneumonia, the second most common possibility PJP.
MANAGEMENT:
1. Assessment of vitals and hemodynamics to decide whether patient requires ICU care.
2. Immediate vlood gas to decide need of O2 support and/or non-invasive vs invasive ventilation
3. If vitals and hemodynamics compromised then IV fluids and vasopressors
4. Initial baseline investigations with sepsis markers, COVID RT PCR, PJP PCR, beta D glucan
5. Start broad spectrum antibiotics
6. In case PCP positive, then patient will require specific therapy for the same. The first line includes IV TMP-SMX given every 6 hourly.
7. Reduction of immunosupression: Exact guideline not available but would be advisable to taper down B cell inhibitor drug , MMF
A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%.
Transplant recipient with fever, cough desaturation up to 6 months after transplantation and history of. CMV positive
Chest X-ray showed:
Bilateral differ pulmonary infiltration increased susceptibility to PCP especially if patient is not received prophylaxis.
Management.
1- hospital admission ICU (reverse isolation).
2- respiratory support with target SPO2 > 92%.
3- start empirical antibiotics:
1st line:
Trimethoprime-sulphamethoxazole (15-20) mg/kg for 21 intravenous or orally three to four divided doses , patient must continue intravenously until pao2 > 60 or respiratory rate < 25 with functioning gastrointestinal tract so, can shift to oral therapy.
2nd line:
If patient had avsevere allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrosis).
according to disease severity.
>>>>>>Mild disease:
Atovaquine
Clindamycin I.
-primaquine
TMP +dapsone
. >>>moderate disease :
Clindamycin.
-primaquine –
TMP +dapson
sever disease,
clindamycin+ primaquaine – intravenous pentamidine
>>Glucocorticoid:
Inpatients with HIV with moderate to severe PCP.
.Full Lab
CRP CBC FERRTIN
blood culture aerobic
urine culture
PCR CMV
BAL
References
uptodate
handbook of kidney transplant 6th edition (6 edition)
1-What is your differential diagnosis? -Pneumocystis jirovecii (formerly P. carinii) pneumonia) (most likely). -CMV Pneumonitis. -Pulmonary aspergillosis. -Respiratory viruses; Respiratory syncytial virus, adenoviruses, and human metapneumovirus COVID-19 – ARDS. -Idiopathic Pneumonia Syndrome. -Tuberculous pneumonia (M. haemophilum and M. avium complex) -Drug-induced interstitial pneumonitis( mTOR) 2-How do you manage this case? -Maintain the O2 above 94% by giving High flow O2 (BIPAP CPAP) & Request ABG, -Check Vital signs, to evaluate the need for ICU or high dependency unit. -Multidisciplinary Teams (Nephrology / ICU / Pulmonology / ID). -Further Investigations; CBC (search for leukopenia and thrombocytopenia) CRP (often normal) – LDH Liver function tests, and Renal function tests. BAL staining for PCP (Gomori methenamine silver (GMS) staining)& serum beta-D-glucan assay . BAL and send for respiratory panel (Influenza type A,B, Adenovirus ,covid-19 , etc). (CMV PCR) – As the patient is at high risk for CMV. Full septic screen (including sputum C/S). -Management; Treatment of PJP; -Trimethoprim-sulfamethoxazole (TMP-SMZ) given in a high dose, combined with corticosteroids in patients with moderate to severe infections. -If there is allergy or side effects to trimethoprim-sulfamethoxazole, alternative drugs can be used including; –Dapsone, Inhaled pentamidine , Atovaquone , Primaquine combined with clindamycin , Combined dapsone and trimethoprim , Pyrimethamine and sulphadiazine. -Prophylaxis is highly efficacious in preventing PJP in transplant patients. -Overall, with prompt treatment, survival is good (50-95%), relapses are common. Treatment of CMV tissue invasive disease (cmv pneumonitis); -Consider decreasing the IS; (stop the antiproliferative medication, and decrease the CNI by 50%, with monitoring Graft Functions. -IVganciclovir(5 mg/kg every 12 hours) for 2-3 weeks; should be used in place of valganciclovir. (after ID recommendations) -IV ganciclovir can be transitioned to oral valganciclovir once the patient has demonstrated clear clinical improvement, viral loads are down-trending, and the patient can tolerate/absorb oral medications. -While treating with either ganciclovir or valganciclovir, we monitor the serum creatinine at regular intervals in case dose adjustment is needed. -Monitoring on therapy;RFTS / LFTS / Blood cell counts / LDH. -References; Up To Date; diagnosis of Pneumocystis pneumonia in patients without HIV:Aug 02, 2022.
Maintain air way by oxygen (ventori mask)
ABG
CBC, ESR, CRP , Procalcitonin RFT, LFT,
CXR
Monitoring of renal function and drug level of calcinurine inhibitor’s
de novo DSA
PCR of pneumocystis
HRCT scan for chest
Bronchoalveolar lavage
Open lung biopsy
Treatment by trimethoprim/sulfamethoxazole for 3 weeks stop anti metabolites reduce dose of calcinurine inhibitors
Management:
-Futher imaging with CT Thorax, which may show ground glass opacities with sub pleural sparring, reticulations, separations, stripes, honeycombing and pneumatic cysts
-LAbs: ABGs, LDH, CMV serology, Serum 1,3,B D Glucan, Induced Sputum microscopy and PCR or Metagenomic Next Generation Sequencing if available
-Further tests would be Bonchoscopy with BAL and trans-bronchial biopsy, consideration for VATS if necessary.
-Treatment with Cotrimoxazole will be indicated. IV if severe, but this case seems mild, so two tabs DS CTX may be sufficient. Oxygen therapy also necessary. Consider Drug interactions particularly CNIs: Monitor levels, Keep low. Consider reducing MMF as well and keeping on higher steroid doses
Xie D, Xu W, You J, Yuan X, Li M, Bi X, Zhang K, Li H, Xian Y. Clinical descriptive analysis of severe Pneumocystis jirovecii pneumonia in renal transplantation recipients. Bioengineered. 2021 Dec;12(1):1264-1272. doi: 10.1080/21655979.2021.1911203. PMID: 33896387; PMCID: PMC8806328.
DD:
-Pneumocystis pneumonia: most likely.
_CMV pneumonitis or superadded to PCP.
_COVID 19 despite it tends to have subpleural affection ; to be ruled out by PCR & COVID IgM.
_Drug induced interstitial lung disease; with mTOR ;to check drug list.
Management: need ICU for associated mortality of 30%.
-O2 supplementation or non invasive ventilation as CPAP or BIPAP to combat hypoxemia in addition to well hydration.
If PaO2 less than 70 mmHg, steroids are indicated.
– BAL with staining with Gomori silver stain or IF or PCR to confirm diagnosis.
-SMX TMP is the preferred line of treatment.
– Pentamidine or Dapson with primaquine are alternatives.
– IV ganciclovir treatment for 5 days followed by oral vanganciclovir for concomitant CMV.
-Antiproliferative stopping till stabilization and decrease CNI to the lower therapeutic target to reduce immunosuppression; with steroid use as complementary.
-Replacing of sirolimus by MMF, as it is a risk factor of PCP.
-Routine lab follow up.
-Monitoring LDH; usually more than 300 iu/ml
– SMX_TMP as secondary prophylaxis.
CXR may be totally normal in 5-30% of cases or showing classic pattern of perihilar and interstitial ground glass infiltrates. CT scanning is more sensitive to the diffuse interstitial and nodular pattern than CXR.CXR has false negative rate of 35-40%.
What is your differential diagnosis?
KTR with pre-transplant CMV serostatus of D-/R+ which is risky for CMV infection and reactivation.
History of dry cough and low oxygen saturation on air beside non-specific bilateral interstitial lung findings with sparing of subpleural space, all point towards PCP. The likely differential diagnoses are: · PCP · CMV Pneumonitis. · COVID-19 pneumonia. · Miliary TB. · Other viral infection e.g. RSV, HSV. · Bacterial infection. How do you manage this case? 1. To admit the patient in HDU or ICU. 2. Respiratory support with oxygen via N/C, FM or even MV when needed. 3. Laboratory tests: · CBC, RFT,ABG, LFT, CRP, RBG & LDH. · Sputum for C&S(looking for concomitant bacterial infection). · Silver methenamine staining and PCR for PCJ (from sputum, respiratory secretions or BAL). · CMV IgG & IgM beside PCR for CMV may be needed. · Screening for TB. 4. PCP is the most likely diagnosis(dry cough, hypoxia and CXR findings) and specific management for PCP is warranted: · Respiratory support with oxygen supply. · Reduction and adjustment of immunosuppression. · TMP-SMX is the first line of therapy; low to intermediate dose of TMP-SMX is preferred as it is effective and associated with low adverse effects(1).
5. Drug treatment options for PCP(2):
a) The first choice: trimethoprim-sulfam ethoxazoleat a dose of 2tablets DS every 8h or IVTrimethoprim 5 mg/kg with sulfamethoxazole 20 mg/kg every 8 h.
b) Alternatives:
I. Dapsone( 100 mg daily) plus trimethoprim(320 mg every 8 h).
II. Clindamycin(PO 300–450 mg every 6 h) plus primaquine (IV 30 mg daily).
III. Pentamidine IV at 4mg/kg/day.
IV. Atovaquone PO 750 mg BID.
c) Adjunctive therapy: Prednisone in patients with room air pAO2 < 70 mmhg (9.3 kPa)
· 40 mg twice daily for 5 days.
· 40 mg daily; days 6 through 11.
· 20 mg daily, days 12 through 21 while on anti-PCP therapy.
d) Dapsone has not been studied as a single drug and thus should not be used alone for treatment. Dapsone–trimethoprim is effective, however, and probably has potency that is comparable to TMP–SMX. References: 1. Haseeb A, Abourehab MAS, Almalki WA, Almontashri AM, Bajawi SA, Aljoaid AM, Alsahabi BM, Algethamy M, AlQarni A, Iqbal MS, Mutlaq A, Alghamdi S, Elrggal ME, Saleem Z, Radwan RM, Mahrous AJ, Faidah HS. Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review. Int J Environ Res Public Health. 2022 Feb 28;19(5):2833. doi: 10.3390/ijerph19052833. PMID: 35270525; PMCID: PMC8910260. 2. Drug Resistance in Pneumocystis jirovecii Jannik Helweg-Larsen, Thomas Benfield, Joseph Kovacs & Henry Masur.
Admission
O2 to maintain sop2 more than 92%( nasal prong/face mask or noninvasive ventilation) Sputum profile(gram statin /AFB 1,2/Culture) Can be induce sputum- if not possible broncho alveolar lavage Cbc, rft, lft, crp, ABG, blood c/s, urine c/s PJP pcr in sputum Beta D Glucan LDH for prognosis HRCT CHEST
Anti-Pneumocystis Agents: Trimethoprim-Sulfamethoxazole TMP-SMX – (160/800mg) double strength thrice a dayfor 2 to 3 weeks Alternative Pentamidine isethionate
Clindamycin and Primaquine Atovaquone Dapsone Adjuctive Corsticosteroid Stop antimetabolites, decrease the CNI dose
References 1)Lecture :Pneumocystis Pneumonia in SOT, Prof Gamal Saadi
2) Iriart X, Bouar ML, Kamar N, Berry A. Pneumocystis Pneumonia in Solid-Organ Transplant Recipients. J Fungi (Basel). 2015 Sep 28;1(3):293-331. doi: 10.3390/jof1030293. PMID: 29376913; PMCID: PMC57531
PCP CMV PNEMONITIS COVID 19 TB PNEMUMONITIS How do you manage this case?
Admission to HDU or icu according to ABG of the patientDleivering oxygen throgh nasal canula or venturi mask Pulmonology consulatioanSend fbc,full chmistrey panel,esr,crp, procalcitonin, bllod culture , respiartory multiplex,sputu, cluture , qiantiferon test.Ct chest Ask pulmonolgist for brnchosscopy and broncholavelora lavage .In this index case with long standing hoistory of dry cough fever, with this cxr finding mostprobably its is acase of pcp,as the patient is recently transplanted from cadveric donor , using for sure high aggresive immunosuppresion.tretment of pcp is chaleniging most of gude line recomend the following,Bactrim 15/20mg iv/kg divedev q/6, iv for 2-3 weeks if patient recoverd , contiue propylaxis for 3-6 month , some centers prefere to give prophlaxis for life .if allergic to bactrim or seiroius side effects happens ,which is bad sign pentamidine can be given .Hold mmf , target tac is 4-6 , steroids sholud be doubled to till patient recovery.
1.Bil pneumonitis due to Pneumocystis jirovecii (formerly P. carinii), Nocardia asteroides, Cryptococcus neoformans, varicella-zoster virus, community-acquired respiratory viruses (influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2), or Legionella spp.
2 .COVID pneumonia
Management:
1.0xygen as required,
2.sputum for gm stain ,c/s,fungal stain ,and c/s,
3.PCR pneumocystis,ligionella,corona
4.other test:CBC,ABG,BAL,HRCT of chest
5. Treatment: According to organism.
6.Adjustment of immunosuppressive dose
This is a patient who has a possible pneumonia 4 months after transplantation. He is CMV donor -/CMV recipient +.
His CXR is showing increase bronchopulmonary lung markings with sparing of the costophrenic angles – batwing appearance
The differential diagnosis includes:
Pneumocystis jirovecii penumonia – most likely diagnosis
CMV pneumonitis
Fungal pneumonitis
Pulmonary tuberculosis
Atypical pneumonia
Management:
The management will include:
1.Doing a further work up:
Arterial blood gas – to assess the degree of hypoxemia and to assess for CO2 retention
Complete blood count – To check for leucopenia which will point towards a viral cause
ESR
C reactive protein
Lactate Dehydrogenase – will be high in PJP pneumonitis
Bronchoscopy and bronchoalveolar lavage – Send for pneumocytis PCR, silver metheneamine staining, TB gen xpert, microscopy for CMV inclusion bodies
Lung biopsy
2.The treatment will include:
Supportive care – oxygen
Paracetamol – for the fever
Definitive treatment – will depend on the causative organism:
PJP pneumonitis – High dose septrin. If the patient is allergic to septrin, clindamycin and primaquine can be used
CMV pneumonitis – IV gancilcovir for three to five days followed by valganciclovir once the patient is stable
Fungal pneumonitis – Antifungals – caspofungin would be the drug of choice
Radiographic featuresPlain radiograph– up to 90% of chest radiographs are abnormal, appearances are often non-specific.
– Between 10-15% of patients have normal chest radiographs
– close to 30% have non-specific or inconclusive findings 2-4,6,7.
– Features which are highly suggestive in patients with CD4 counts below 200/mm3 include 5:
Pleural effusions are normally not a feature, seen in less than 5% of cases 9.
High-resolution computed tomography
is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs 3.
Features include 2,3,7:
Atypical features, found more frequently in patients treated prophylactically, include 7:
consolidation
nodules (granulomas)
lymphadenopathy
pleural effusions are also more frequently encountered in this group of patients
References
Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation
3. Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation
4. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
5. Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58. Radiographics (abstract) – Pubmed citation
6. Suster B, Akerman M, Orenstein M et-al. Pulmonary manifestations of AIDS: review of 106 episodes. Radiology. 1986;161 (1): 87-93. Radiology (abstract) – Pubmed citation
7. Müller NL, Franquet T, Lee KS et-al. Imaging of pulmonary infections. Lippincott Williams & Wilkins. (2007) ISBN:078177232X. Read it at Google Books – Find it at Amazon
PCR assay of respiratory specimen, either induced sputum +/- BAL for PCP, CMV, AFB
Laboratory test to check FBC, renal function, LFTS and inflammatory markers. Blood culture
Plasma PJP and CMV PCR
COVID- 19 PCR
Beta-D-glucan
Start antibiotcs and given high suspicion of PJP, start IV septrin, adjust dose according to renal function. Alternative if patient is allergic to septrin.
Adjunctive steroid if PaO2 <70 mm Hg in RA or an alveolar gradient of >35 mm Hg.
Might need CT chest
Reduction of immunosuppression. Withhold antimetabolite, check CNI level
Monitor progress and response to treatment, escalate level of care if sever disease needing respiratory support.
Differential diagnosis: differential diagnosisIn the current scenario of transplant patient on immunosuppression with respiratory symptoms of non productive cough with hypoxemia and in view of chest x ray findings of bilateral pulmonary infiltrates with fluffy cotton appearance,most probably indicating PCP (The most significant risk factors for PCP in patients with organ transplantation are glucocorticoid use and defects in cell-mediated immunity).
-For confirmation: Laboratory findings:
– Elevated LDH in the setting of pulmonary infiltrates without another apparent cause. -High Beta-D-glucan in view of clinical suspicion. -Definitive diagnosis of PCP is by microbiological test of an induced sputum or bronchoalveolar lavage [BAL] fluid which can be obtained safely. Radiological findings: diffuse, bilateral, interstitial infiltrates, ground-glass opacities and foci of consolidation.
DD: Physicians have to be vigilant to other diagnoses like: ARDS bacterial pneumonia pulmonary tuberculosis
Managment: Antimicrobial therapy directed against P. jirovecii is the mainstay of treatment for PCP -Patients with mild disease have a PO2 ≥70 mmHg:The treatment of choice is oral trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of (15 to 20 mg/kg/day, for at least21 days.
-Patients with moderate disease with PO2≥60 and <70 mmHg oral trimethoprim-sulfamethoxazole plus adjunctive steroids (Prednisone40 mg orally twice daily for five days, followed by 40 mg orally once daily for five days, followed by 20 mg orally once daily for 11 days).
-Patients with Severe disease with PO2 <60 mmHg: recommend parentral TMP-SMX plus Adjunctive corticosteroids.
Alternative regimens:
-TMP plus dapsone
–Primaquine plus clindamycin –Atovaquone suspension750 mg orally twice daily
-Pentamidine 4 mg/kg IV once daily
Oxygen support to optimize saturation to above 92%
Serum LDH – usually elevated. Helpful in diagnosis and prognostication (when measured serially)
Serum Beta D- glucan – usually elevated.
Induced sputum or Bronchoalveolar lavage sample microscopy for cyst identification.
Nasopharyngeal swab for covid 19
CMV PCR
Treatment – Given for 21 days.
TMP-SMX – 15 to 20mg/kg/day orally or IV in 3 or 4 divided doses
Alternatively, or in cases of allergy to TMP-SMX.
TMP plus dapsone – TMP: 5mg/kg orally 3 times daily and Dapsone, 100mg orally once daily
Primaquine plus clindamycin – Primaquine, 30mg orally daily and clindamycin 900mg daily IV 8 Hourly or 600mg 3 times daily.
Atovaquone 750mg orally twice daily
Pentamidine – 4mg/kg IV once daily
Adjunctive steroids – 40mg twice daily orally for 5 days, then 40mg orally for 5 days, then 20mg once daily for 11 days
Reference
Limper AH, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011.
Hughes WT et al. Treatment of Pneumocystis carinii pneumonitis with Trimethoprim-Sulphamethoxazole Can Med ASssoc J 1975
Chest radiographs– -Chest x-rays are initially normal in up to one-fourth of patients with PCP. -The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates. -Upper lobe infiltrates and pneumothoraces can also be seen.
5 % of patients with SOT have PCP in the absence of prophylaxis
is at the top of our differential diagnosis in the presence of:
fever the incidence is(81 to 87%).
non productive cough(71 to80)
bilateral hilar infiltration (abnormal CXR (92 to 96%).
presence of hypoxia incidence(78-91%)
2-CMV PNEUMONIA EITHER WITH PCP OR WITHOUT
3-COVID 19 INFECTION COMPLICATED PNEUMONIA 4-Atypical pneumonia with an atypical bacterial infection such as legionella. 5- pneumonia due to fungal infection
How do you manage this case?
patient needs ICU admission to maintain his oxygen sat by nasal cannula oxygen or by noninvasive or invasive ventilation
consultation for a pulmonologist to be involved in the plan of management
investigation to confirm the diagnosis and roll out the other differential diagnosis
such BAL with staining silver stain or immunofluorescent or PCR,also role out fungal infection
PCR FOR CMV INFECTION
PCR FOR COVID 19 VIRUS INFECRION
High-resolution CT scan of the chest if the patient is stable
LDH level for the prognosis
LFT, KFT.CBC , drug level
Treatment of PCP
1-TMP-SMX is recommended for all patients, it has a broad spectrum against p jirovecii in addition to toxoplasma Gondi, listeria spp, Nocardia spp, streptococcus pneumonia).given in form of one double-strength tablet daily or three times per week.
if allergic desensitization should be attempted when possible
alternative medication if allergic or SE to TMP-SMX
for mild disease the option include
1- Atovaquone .
2- clindamycin plus primaquine .
3-TMP plus dapsone
for moderate disease
1- clindamycin plus primaquine.
2- TMP plus dapsone
severe disease
clindamycin
primaquine
i.v pentamidine such in our case
duration of therapy is 21 days and secondary prophylaxes for 6 to 12 months or lifelong prophylaxis if he is at high risk of recurrence for this patient
glucocorticoid should be offered for this patient as his oxygen sat low because recommended if ABG po2 less than 70 and oxygen sat less than 92%
reduction of immunosuppression such as MMF and decrease TAC and keep the trough to the lowest acceptable level
monitor patient clinically and laboratory and try to balance between the patient survival and graft survival because the mortality rate is high in PCP/
4 months following cadaveric transplantation, a 65-year-old male with 38 °C temperature and an ineffective (dry) cough, who is CMV negative but CMV positive.
The air’s oxygen saturation level was recorded at 89%. (hypoxic).
Differential diagnoses are;
1-PcP pneumonia
2-Superimposed infection on top of PCP
3-CMV pneumonia
4-Others viral pneumonia like COVID, influenza
5-Aspergillus
Managment
Supportive therapy in the form of oxygen, admit in HDU, evaluate hydration status.
Full investigation including ABGs, Complete blood picture, blood culture and sensitivity, CRP, LDH, D-dimmers and electrolytes, serum 1,3 beta-D-glucan asaay metabolic profile.
Radiological; HRCT, and BAL or bronchial secretion for PCP PCR
After G6PD enzyme activity, we advise commencing with TMP-SMX (15 to 20 mg/kg/day of the trimethoprim component), administered orally or intravenously in three or four divided doses.
Rest of treatment thatv can be ysed for treatment and prevention are;
Atovaquon, TMP plus dapson, clindamycine plus primaquine,
Pneumocystis Pneumonia Charles F. Thomas, Jr., M.D., and Andrew H. Limper, M.D Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice Jay A. Fishman, Hayley Gans, on behalf of the AST Infectious Diseases Community of Practice
4 months post- KT, CMV status D-/ R+, presented with symptoms suggestive for pneumonia ( fever, non-productive cough) with hypoxia 82 % Spo2. CXR showed; diffuse, bilateral, interstitial infiltrates.
The etiology of infectious pneumonitis in immunocompromised patients is diverse. Differential diagnosis is the setting of immunocompromised host:
– PJP pneumonia.
– Viral pneumonia; CMV, HSV, Covid .
– Bacterial pneumonia
– Tuberculosis.
– Fungal infection.
– Drug-induced Interstitial pneumonitis.
*Hypoxemia out of proportion to plain radiographic imaging is highly suggestive for PCP.
-PCP it still remains an important causative pathogen among SOT recipients . However, the survival of non-HIV patients with PCP is worse than those with AIDS and reaches up to 50% even with adequate therapy.
-Incidence of symptomatic CMV infection is 15-20% for D-/R+ patients.
-Several studies have identified CMV as a clear risk factor for PCP in SOT patients, studies shows that 20%–53% of SOT recipients with PCP had a CMV infection compared to 0.6%–24% of those who did not develop PCP. However, it is unclear whether CMV infections simply reflect the degree of immunosuppression or if CMV can directly increase the risk of PCP.
-Presentation of PCP is usually non-specific and insidious, the most common symptoms being dyspnea and/or non-productive cough and hypoxia.
How do you manage this case?
Further history is needed about the induction therapy, current IS regimen and levels, CMV prophylaxis and PJP prophylaxis, any recent contact with
Recent virual load as part of pre-emptive therapy.
Management: General measures:
– HDU / ICU; Stabilized the patient
– ABC; O2 and respiratory support to maintain Spo2 > 94%
– Manage the fever with antipyretic.
– Patient should be managed empirically till we have the results.
– Fluid management.
Work up required: – CBC with differential, CRP, procalcitonin.
– VBG
– RFT, LFT.
– LDH
– Blood culture.
– Respiratory culture, and viral panel.
– COVID PCR
– Viral load; CM PCR, , EBV PCR.
– Sputum for microscopy, staining, CMV, PJP and aspergillus (It may be difficult to obtain a sample as patient has dry cough) hypertonic saline can be used to induce sputum. The sensitivity of induced sputum is only 30%‐55%, compared with 80%‐95% with BAL
– BAL bronchoscopy; staining with Gomori methenamine‐silver stain, PCR( can’t distinguish colonization from infection)
– Immunosuppression level Tacrolimus level.
– serum levels of beta-D-glucan. a high sensitivity (>90%) with lower specificity (<80%)
– CXR; abnormal up to 90 %, No radiographic pattern is pathognomonic for PJP is a diffuse interstitial
– HRCT chest. often demonstrates abnormalities not appreciated on routine chest radiography and should be obtained, especially if CXR is normal with a consistent clinical presentation
Cover for bacterial pneumonitis:
– Generally start broad spectrum antibiotics then guided by culture.
Cover PCP;
-TMP‐SMX remains the drug of choice; most effective systemic therapy for PJP.
– Treatment for at least 3 weeks then continue on secondary prophylaxis for 6-12 months.
– 15‐20 mg/kg/day of the TMP component given IV in divided every 6‐8 h; lower doses may be sufficient. In milder disease, two double‐strength tablets can be given po tid
-Alternative agents are less effective and include IV pentamidine isethionate, atovaquone, primaquine and clindamycin if patient is allergic or intolerance
-In severe infections, IV pentamidine is the second‐line agent after TMP‐SMX. S/E: pancreatitis, hypo‐ and hyperglycemia, bone marrow suppression, renal failure, and electrolyte disturbances
Adjunctive corticosteroids:
-The use in non‐HIV PJP infections are contradictory.
-Used in patients with hypoxemia (pAO2 < 70 mm Hg on room air),
-It should be considered early within 72 hours of initiating antimicrobial therapy.
-The optimal dose of corticosteroids has not been established, but 40‐60 mg of prednisone given two to three
times daily for 5‐7 days before gradual tapering over 7‐14 days is recommended to avoid rebound pneumonitis
Secondary prophylaxis:
-TMP‐SMX is the drug of choice for prophylaxis of PJP.
-Dapsone is often used as a second‐line agent for PJP prophylaxis.
As the patient is high risk for CMV pneumonitis; if confirmed:
-Treatment is mandatory in all cases of tissue invasive CMV disease, irrespective of viral load with IV gancyclovir for 14-21 days followed by oral valganciclovir ( adjust for eGFR)
Management of IS:
– Reduce (by 50%) antimetabolites or discontinue if there is evidence of life-threatening infection
-Reduce CNI to lower level.
-Corticosteroids are generally continued
– Monitoring graft function closely for any rejection.
References:
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020;20(1):492. Published 2020 Jul 10. doi:10.1186/s12879-020-05217-x
Kim JE, Han A, Lee H, Ha J, Kim YS, Han SS. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome. BMC Nephrol. 2019;20(1):212. Published 2019 Jun 10. doi:10.1186/s12882-019-1407-x
Fishman, JA, Gans, H; on behalf of the AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13587. https://doi.org/10.1111/ctr.13587
👉Old age recipient , with fever, dry cough and intense desaturation together with radiological finding of parahilar interstitial infiltration starting after the routine prophylaxis for 3 months PCP prophylaxis is highly suggestive of PCP.
👉 Differential diagnosis:
_PCP.
_CMV pneumonitis either alone or convomitant with PCP (after end of 3 months of prophylaxis for this intermediate risk for CMV).
_COVID 19 (however, it tends to have subpleural affection …unlike subpleural sparing in PCP), excluded by PCR and COVID IgM.
_Drug induced interstitial lung disease that can occur with mTORi) so reviewing the patient induction and maintenance therapy is essential. _Risk of PCP is increased with strong induction therapy, TAC and MMf maintenance therapy and use of sirolimus.
👉 Management of the case:
_ICU admission as mortality up to 30%. _OXygen supplementation or non invasive ventilation as CPAP or BIPAP to improve oxygenation and ensure adequate hydration. _Arterial blood gases if PaO2 less than 70 mmHg, use of steroids is indicated. _Confirm diagnosis of PCP by bronchoscopy and BAL with staining with Gomori silver stain or immunofluroscent or PCR. _Sulfamethoxazole and trimethoprim intravenous remains the most important and commonly uses treatment for PCP
_ in case of allergy to SMX_TM , use of pentamidine or dapson with primaquine will be reasonable _CMV PCR to exclude concomitant infection that needs IV ganciclovir treatment for 5 days followed by oral vanganciclovir. _Reduction of IS as stop antiproliferative till stabilization and decrease CNI to the lower therapeutic window to control the infection.
_Cover with steroids by increasing the dose or restart it if steroid free or minimization protocol _Shift from sirolimus to MMF may be considered. _Follow up of CBC, liver and kidney function is essential _LDH level is prognostic marker in PCP. _Life long secondary prophylaxis with oral SMX_TMP is warranted in such high risk patient.
What is your differential diagnosis?
Fever, dry cough, and hypoxemia 4 months post kidney transplantation with the radiological manifestations (chest x-ray showed perihilar and bilateral fine interstitial infiltrates with interstitial edema); I will put Pneumocystis Jirovecii Pneumonia as first differential diagnosis
Chest x-ray (Abnormal in 92–96%):
o Early PJP is manifested by fine, bilateral, perihilar, diffuse infiltrates that progress to an interstitial alveolar butterfly pattern; from the hilar region, the infiltrates often spread to the apices or bases. This pattern often progresses despite therapy with progressive consolidation over 3 to 5 days
o Unusual patterns are common including nodules, unilateral infiltrates, pleural effusions, pneumothoraces, lymphadenopathy, or lobar consolidations
CT chest:
o More sensitive than routine chest radiography
o Often demonstrate abnormalities not appreciated on routine chest radiography and should be obtained in case of normal plain chest radiographs with a consistent clinical presentation
o Bilateral ground glass opacities, pneumatoceles, and diffuse varying in size centrilobular and peribronchovascular consolidation foci
How do you manage this case?
Diagnosis:
o Complete history and clinical examination
o CBC, e GFR, electrolytes, CRP, s. albumin, liver enzymes and blood culture
o O2 saturation and ABG
o Serological tests for atypical bacterial infections
o PCR test for SARS-Covid-2 from nasopharyngeal swab
o Tuberculin skin test (TST) and interferon gamma for tuberculosis
o Viral load for CMV and EBV
o High-resolution chest CT scan is more sensitive and specific for PJP and exclude other causes
Diagnosis of PJP:
1. Measurement of plasma (1→3) b-D-glucan: may suggest diagnosis. Meta-analysis suggests a sensitivity of almost 95%, but with a specificity in the mid-80%
2. LDH: elevated in almost all cases of (over 300 IU/ml)
3. Multiple induced sputum samples: stain using antibodies for PCP (immunoflourescent, immunoperoxidase) and for Pneumocystis and other organisms (Giemsa, Silver, and others). Use PCR-based diagnostics on respiratory secretions. Samples should also be assayed for routine bacterial, fungal, mycobacterial, and other organisms to rule outconcomitant infections. Evaluate for CMV or other respiratory viral coinfection
4. PCR for PJP
5. Bronchoscopy with BAL: yield generally ≥70% in non-AIDS immunocompromised hosts when coupled with antibody staining
6. Bronchoscopy for transbronchial biopsies: increases yield of routine BAL
7. Open lung biopsies when other diagnostic fails or where other concomitant diseases may be a concern. Often considered to be a gold standard, but early patchy disease may decrease yield
Treatment:
v O2 therapy (maintain 0xygen > 92%)
v Reduction in immunosuppression
v Duration of antimicrobial treatment is for at least 14days (21 days in severe infection)
Trimethoprim sulfamethoxazole (TMP-SMX):
o Is the drug of choice and is considered to be the most effective systemic therapy for PCP
o Dose is 15–20 mg/kg/day of the TMP component given IV in divided doses every 6–8 hours often in combination with corticosteroids
o Side effects include bone marrow suppression, rash including Stevens-Johnson syndrome, hepatitis, interstitial nephritis, aseptic meningitis, and pancreatitis
o Hydration should be maintained
o Patients on high-dose TMP-SMX should have regular monitoring of cell counts, creatinine and potassium
Pentamidine isesthionate:
o In severe infection (second line treatment)
o Dose is 4 mg/kg/day IV initially over 1–2 hours
o Side effects include pancreatitis, hypoglycemia, hyperglycemia, bone marrow suppression, renal failure and electrolyte disturbances
Atovaquone:
o Dose is 750 mg po bid (optimal dose uncertain; 1500 bid used anecdotally)
o Available in an oral suspension only
o Has variable oral absorption (best with fatty foods)
o Approved only for mild and moderate PCP
Primaquine and clindamycin:
o Primaquine 15–30 mg po qd in combination with clindamycin 600–900 mg IV or po q6–8 hours This combination studied in mild to moderate PCP in AIDS
o Long-term use of clindamycin can predispose to infection with Clostridium difficile
o Primaquine should be avoided in G6PD deficiency
Dapsone and trimethoprim:
o Dapsone 100 mg po qd used in combination with trimethoprim 15 mg/kg/day po divided tid
o This combination is used with sulfa allergy, though dapsone may elicit sulfa allergies as well
Trimetrexate with folinic acid:
o Trimetrexate 45 mg/m 2/day IV (or 1.5 mg/kg/day IV in patients <50 kg) with folinic acid 20 mg/m2 po or IV every 6 hours (80 mg/m2 total daily)
o Folinic acid therapy extends≥3 days beyond trimetrexate therapy
o Trimetrexate causes bone marrow suppression and must be used with folinic acid, 10 mg po qd Outcomes are inferior to TMP-SMX in AIDS
Pyrimethamine and sulfadiazine:
o Pyrimethamine load of 100–200 mg po, followed by 50–100 mg po qd in combination with sulfadiazine 4 g po qd in divided doses
o Limited data available on this regimen
o Usually with folinic acid 10mg po qd to reduce bone marrow toxicity
Adjunctive agents Corticosteroids:
o 40 mg–60 mg of prednisone (or equivalent) po bid with taper after 5–7 days over a period of 1–2 weeks
o Best administered within 72 hours in the setting of hypoxia (pAO2 < 70 mmHg)
o Commonly used but not well studied in transplantation
o May require prolonged taper to avoid immune reconstitution pneumonitis
Prophylaxis:
For any transplant patient with a history of prior PJP infection, lifelong prophylaxis is often indicated
1. First line therapy: TMP-SMX (80 mg TMP/400 mg SMX or 160 mg TMP/800 mg SMX po (single or double strength) daily or three times weekly)
2. Second line therapy: dapsone (50–100 mg po qd), atovaquone (1500 mg po as single dose), Pentamidine (300 mg administered through aerosolized nebulizer q 3–4 weeks), Clindamycin and pyrimethamine (Up to 300 mg of clindamycin po qd with 15 mg of pyrimethamine po qd)
References
1. Varnas D, Jankauskienė A. Pneumocystis Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after Transplantation: A Case Report and Literature Review. Acta Med Litu. 2021;28(1):136-144. doi: 10.15388/Amed.2020.28.1.5. Epub 2021 Jan 25. PMID: 34393636; PMCID: PMC8311846.
2. Martin, S.I., Fishman, J.A. and (2013), Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of Transplantation, 13: 272-279.
3. Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616.
What is your differential diagnosis? This is a case of cadaveric allograft transplantation, that usually requires aggressive induction immunosuppression. Given the high-risk transplantation and aggressive immunosuppression, patient is at higher risk of infections. During the first 6 months after transplantation, recipients are usually maintained on anti-CMV/HSV and anti-PCP prophylaxis. But the infection risk is not zero. The presence of bilateral interstitial infiltrates, fever, cough and desaturation raises the suspicion of PCP. Although other etiologies cannot be excluded. Differential diagnosis: – PCP – CMV – COVID-19 – Atypical pneumonia – ARDS
CXR findings of PCP are not specific and could be absent in significant number of patients in particular in the early stages. These include: bilateral interstitial infiltrated, bilateral perihilar shadows, reticulonodular marking, bilateral cystic or ground glass appearance and honeycombing.
How do you manage this case?
Initial treatment is organism non-specific and includes oxygen supplementation to achieve SO2> 92% (nasal cannula, face mask or NIV), reduce or discontinuation of MMF, assessment of volume status and achieving euvolemic state.
Diagnostic approach Nasal swab for COVID-19 Swab for Influenza A and B Blood for CMV PCR and sputum PCR Diagnostic tests for PCP that include the following: Gomori methenamine silver staining on samples (sputum or bronchoalveolar lavage fluid). Serum β-D-glucan (BDG) test: Widespread method but lacks species-specificity. PCR analysis: Rapid and more sensitive than GMS staining. Rarely utilized in clinical practice. Variable cut values in different studies. Metagenomic next-generation sequencing: a method for determining the genetic makeup of an organism.
Treatment The empirical treatment should be started as soon as possible and should cover CMV, INFLUENZA, PCP and atypical bacteria. The cornerstone treatment of PCP isSulphamethexazole/Trimethoprim in a dose of 15-20 mg/kg/day of TMP oral or iv in 4 divided doses for 3-4 weeks.
Alternatively, if Sulphamethexazole/Trimethoprim is tolerated or contraindicated, other drug options can be used such asPentamidine, Atovaquone, Primaquine plus clindamycin, and Dapsone.
What is your differential diagnosis?
Atypical viral pneumonia including covid 19 and CMV pneumonitis
PJP
CMV co-infection with PJP
Drug-induced pneumonitis (in the case of everolimus or sirolimus maintenance IS)
The diagnosis of PJP is challenging due to nonspecific clinical presentation and signs in addition to the limited radiological findings so we depend on high clinical suspicion in indexed case post-transplantation with intense IS, induction type, CMV serostatus and the duration of antibiotics prophylaxis ( as the recipient is CMV positive so co-infection with CMV is considered one important risk factor for PJP as can alter the T cell immunity response and reactivation of infection.
Clinical presentation remained nonspecific however Hypoxia, Fever, and dry cough in immunocompromised patients with seropositive CMV after 4 months from transplantation should keep a high index of clinical suspicion of atypical viral infection vs PJP or a combination of CMV co-infection with PJP and need more history about the induction type of immunosuppression and the current maintenance IS ( steroid, MMF, and CNI VS M tor inhibitors Like everolimus or sirolimus with CNI? fever with dry cough and hypoxemia is highly suggestive of PJP, is this patient on PJP prophylaxis or stopped for intolerance or side effects?
The radiological characteristics of PJP include peri-hilar reticular nodular infiltration with pleural sparing. Only 5% still can be unilateral infiltration, and in ¼ could be normal CXR, pleural sparing with apical interstitial infiltration is highly suggestive for PJP, and pleural effusion is still reported in < 5% of cases.
How do you manage this case?
Further investigations needed like full blood count, urea and electrolytes, CNI trough level, liver function test, G6PD screen
noninvasive testing like ABG The single-breath diffusing capacity for carbon monoxide appear to be the most sensitive for PCP. Send for CMV PCR, COVID 19 PCR, hypertonic silane nebulization to induce sputum for PJP q real time PCR
Chest CT scan typical central ground glass appearance sparing the peripheries with pnematocel, cysts , pleural effusion in < 5%, and LAP uncommon
The final diagnosis requires a direct finding of the organism in lower respiratory secretions or tissue. Invasive procedures like bronchoscopy and the use of BAL fluid assay or transbronchial biopsy (however increased risk of bleeding and pneumothorax)
New noninvasive molecular genomic testing with a promise to improve the quality of the diagnosis.
First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may require alternative agents like dapsone, pentamidine, atovaquone, clindamycin in combination with primaquine Echinocandins show some promise for new combination therapies; however, more studies needed to define ideal antimicrobial therapy for PJP as well as the role of corticosteroids in non-HIV infected patients. Patients with immunodeficiency without HIV have a tendency to have more severe symptoms and a higher risk of respiratory failure and death (3).
in the case of CMVpneumonitissalso should be treated with ganciclovir IV 5mg /kg BID for 3 weeks with close monitoring with CMV PCR, and FBC , graft function
if this patient on everolimus or sirolimus should be stopped and modified to alternative IS like MMF or azathioprine with CNI References
1. Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. doi: 10.1080/14656566.2021.1915989. Epub 2021 Apr 19. PMID: 33870843.
2. Zhang Z, Li Q, Shen X, Liao L, Wang X, Song M, Zheng X, Zhu Y, Yang Y. The medication for pneumocystis pneumonia with glucose-6-phosphate dehydrogenase deficiency patients. Front Pharmacol. 2022 Sep 7;13:957376.
3. Krajicek B. J., Limper A. H., Thomas C. F. (2008). Advances in the biology, pathogenesis, and identification of Pneumocystis pneumonia. Curr. Opin. Pulm. Med. 14 (3), 228–234. 10.1097/MCP.0b013e3282f94abc
4. Chatterton JM, Yen DO. Laboratory investigation of Pneumocystis carinii pneumonia. Genitourin Med. 1992 Oct;68(5):336-41. doi: 10.1136/sti.68.5.336. PMID: 1385296; PMCID: PMC1195994.
5. Week five lecture
How do you manage this case?
*ICU admission
*The CPAP or BiPAP availability should be consider early
*Early BAL
*Diagnosis of PJP relies on combination of laboratory findings and diagnostic imaging together with physical examination and history-taking. *Routine investigation:
CBC, RFT, LFT, CRP, D-dimar,Blood culture….) *Quantitative polymerase chain reaction (qPCR)- more accurate way to diagnose PJP *(1-3)-β-d-glucan (BG) –most reliable serologic biomarker for PJP diagnosis *Krebs von den Lungen-6 antigen (KL-6)- together with BG, is the most accurate serologic apptoach for PJP diagnosis *Lactate dehydrogenase (LDH) *S-adenosyl methionine (SAM) *Sputum induction *Imaging studies used in the diagnosis of PJP include: Chest CT Scan– most pertinent finding is ground glass opacity (GGO) indicative of alveolar subtotal consolidation Chest Radiography- nonspecific, can be normal, less common patterns have been reported, including lobar infiltrates, pulmonary nodules, and pneumatoceles and other cystic changes. *Anti-Pneumocystis Agents: Trimethoprim-Sulfamethoxazole TMP-SMX is the first-line agent for the treatment of mild to severe PCP in both HIV and non-HIV-infected patients. Its also the drug of choice for SOT patients because of its high efficacy and its availability in oral and parenteral forms *Atovaquone– one of the oral treatment alternatives for mild and moderate PCP *Pentamidine isethionate- preferred alternative drug regimen to TMP-SMX
Clindamycin and Primaquine-good alternative choice for treatment of mild to moderate PJP *Caspofungin
*KDIGO and the American Society of Transplantation guidelines recommend treatment with adjunctive corticosteroids for SOT recipients with moderate to severe PCP. *Reducing immunosuppressive medications for kidney-transplant recipients who develop PCP
Stop antimetabolites until this patient in the ITU, decrease the CNI. *Prophylaxis
TMP-SMX- recommended prophylactic agent
Aerosolized pentamidine
Atovaquone
Dapsone
Physiotherapy Intervention
Physiotherapy interventions for the treatment of PJP would be the same as treating pneumonia. This includes:
Modified postural drainage
Shaking, vibrations and percussion
Coughing and huffing exercises
Segmental and diaphragmatic breathing exercises
Mobilization of the patient
General body conditioning exercises
# References:
1.Kante, Meenakshi & Racherla, Rishi & Usha, Kalawat. (2019). Pneumocystis jirovecii Pneumonia: A Revisit to the Old Malady. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH retrieved fromhttps://www.researchgate.net/publication/337105006_Pneumocystis_jirovecii_Pneumonia_A_Revisit_to_the_Old_Malady doi:10.7860/JCDR/2019/42636.13318
2. Roblot F., Godet C., le Moal G., Garo B., Faouzi Souala M., Dary M., de Gentile L., Gandji J.A., Guimard Y., Lacroix C., et al. Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Eur. J. Clin. Microbiol. Infect. Dis. 2002;21:523–531. [PubMed] [Google Scholar]
3. Cushion M.T., Linke M.J., Ashbaugh A., Sesterhenn T., Collins M.S., Lynch K., Brubaker R., Walzer P.D. Echinocandin treatment of Pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS ONE. 2010;5:e8524. doi: 10.1371/journal.pone.0008524. [PMC free article] [PubMed] [CrossRef] [Google Scholar
This is post kidney transplant patient from deceased donor present with fever dry cough and hypoxia his CXR showed bilateral infiltration with prominent perihilar shadowing with the given scenario the most likely diagnosis is PCP pneumonia -other differential: -CMV pneumonitis because he was CMV positive before kidney transplant. – Other viral pneumonias like covid 19. -Bacterial pneumonia
How do you manage this case?
-Start with proper history and examination ongoing with resuscitations and supportive treatment by stabilization of oxygen saturation and hemodynamic stabilization .
Investigations ;
-Full blood counts and chemistry -Sputum analysis culture and gram stain -Bronchoalveolar lavage PCR for PCP which is the gold standard test ( Due to higher sensitivity (98.3%) and specificity (91.0%) ) – Metagenomic Next-Generation Sequencing : (mNGS) analysis of a BALF specimen identified a large number of P. jirovecii reads, allowing to confirm the diagnosis of PCP. it is a novel diagnostic method itis sensitive but not specific -Plasma PCR for CMV .
High resolution CT chest:
looking for ground glass appearance ,reticular opacities , septal thickening, a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present, honeycombing, extent of infiltration beside prominent perihilar shadowing and sparing of subpleural area .
Treatment and prognosis:
Reduction of immunosuppression : Stop the antimetabolites continuing on CNI and increase the dose of steroid .
first-line therapy:Trimethoprim-sulfamethoxazole (co-trimoxazole or TMP-SMZ) with 15 to 20 mg/kg IV, switching to oral after clinical improvement in a duration of 14-21 days .
Second-line therapy : Pentamide 4 mg/kg IV o.d., is effective but it has a worse safety profile.
Third-line : Primaquine plus Clindamycin for severe cases and Atovaquone or Dapsone/TMP for mild to moderate cases if patient showed no clinical improvement or do not tolerate the above treatments .
Corticosteroids as adjuvant therapy can be used in this patient 40 mg orally twice daily for five days, followed by 40 mg orally once daily for five days, followed by 20 mg orally once daily for 11 days .
Overall, with prompt treatment, survival is good (50-95%), although relapses are common .
Prophylaxis : This patient needs second prophylaxis for 6 months due to high risk of recurrence .
1- The most important differential diagnosis is Pneumocystitis carenii pneumonia (PCP). especially if prophylaxis is not given or stopped
P. jirovecii is transmitted by airborne route, around ¾ of cases had the organism since early childhood (by the age of 4 years) which become latent and can be reactivated once the immunity is compromised, on the other hand ¼ of cases may not acquire the organism in childhood and acquire it later in life through person to person airborne transmission. (1)
Pneumocystis is exclusively present within the lung alveoli, and once infection develop it presents with alveolitis sparing the bronchial tree, leading to triad of fever, dry cough and hypoxemia (2)
The presence of hypoxia and dry cough in at risk patient (immunocompromised) with CXR showing diffuse, bilateral, interstitial infiltrates is typical for PSC infection
2- CMV pneumonitis
3- Other viral infections including influenza and Covid
4- Bacterial pneumonia
How do you manage this case?
Diagnosis
Routine lab should be done including CBC, C reactive protein, liver and kidney function test, procalcitonin.
Blood gas
Blood culture including fungal cultures, beta d glucan
CMV PCR (In CMV pneumonitis 30% of cases has negative PCR and the main diagnosis is by BAL)
High resolution CT chest
Tacrolimus level
Swab for influenza and covid
Sputum examination including bacterial and fungal cultures and immunofluorescent staining for PCJ and CMV PCR
It may be problematic to have an optimal specimen in a case of dry cough by ordinary cough, so it should be done one of the following ways:
Induction of cough using hypertonic saline
Endotracheal aspirates in mechanically ventilated patients
BAL using bronchoscopy
Diagnosis of PCP depends on the detection of the cystic or trophic forms in respiratory secretions by immunofluorescent staining (the organism cannot be cultured) , PCR has a disadvantage of not differentiating between infection and colonization
Treatment
I- General measures
ICU admission in isolation room till covid swab result
Put the patient on nasal O2 up to 5 liters to have O2 saturation 95-98%, if the target is not achieved use face mask, if the patient still hypoxic or hypoventilation occurs mechanical ventilation is indicated
Circulatory support to maintain mean BP > 65 mmHg
IV fluids should be used cautiously, and depend mainly on normal or enteral feeding
Paracetamol when needed
LMWH prophylactic dose
II- Specific treatment
A- Reduction of immunosuppression if serious infection detected
In the form of reduction of the dose (by 50%) or stopping the antimetabolite (in severe and non-responding disease) since kidney can survive without antimetabolite
Keep CNI at lower trough (do not play with CNI)
Continue on steroids
Close follow up of graft function for early diagnosis of rejection
In case of very high risk patients for rejection, or if the patient develop rejection, the main treatment will be high dose steroids
B- Antimicrobial therapy
Broad spectrum antibiotics till culture result (ceftazidime, zithromax)
Once suspected, treatment of PCP should be initiated immediately till culture result. The standard dose of TMP-SMX is 15 to 20 mg/kg/day (based upon the TMP component) orally or intravenously in three or four divided doses.
In case of CMV pneumonitis, start IV gancyclovir for 5 days then switch to valgancyclovir 900 mg twice daily with follow up of PCR weekly and stop treatment after 21 days of treatment provided the patient is symptom free and PCR negative for 2 successive samples. Then continue on once daily valgancyclovir in a dose of 900 mg daily for 1-3 months to prevent recurrence
If influenza swab is positive start oseltamiver 75 mg twice daily for 5 days
References
1. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978; 61:35.
2. Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jirovecii Pneumonia. Infect Dis Clin North Am 2010; 24:107.
Severe disease (A-a O2 gradient is ≥45 mmHg, PaO2 <60 mmHg, RR> 25 with respiratory muscle fatigue, hypoventilation manifested by hypercapnea).
First line : IV TMP-SMX, and it should be given whenever possible in all cases except in patients with history of severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). The standard dose of TMP-SMX is 15 to 20 mg/kg/day (based upon the TMP component) intravenously in three or four divided doses.
Second line : clindamycin-oral primaquine, patient should tolerate oral when using his regimen
3rd line : IV pentamidine and due to its side effects, switching to less toxic oral therapy is recommended once patient can tolerate oral
Non severe disease
First line : oral TMP-SMX and it should be given whenever possible in all cases except in patients with history of severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). The standard dose of TMP-SMX is 15 to 20 mg/kg/day (based upon the TMP component) intravenously in three or four divided doses.
Second line : dapsone plus trimethoprim or clindamycin plus primaquine
3rd line : atovaquone which is limited to patients with mild disease to complete the course of therapy after TMP-SMX (if the patient develop side effects related to this drug)
Inductions of adjuvant steroid therapy
Resting room air oxygen saturation <92 percent
PaO2 of <70 mmHg on room air
Alveolar-arterial (A-a) oxygen gradient of ≥35 mmHg
In pregnancy
First line : IV or oral TMP-SMX
Second line : dapsone plus trimethoprim
Monitoring patients on treatment –
Monitoring of side effects of the drugs given
Monitoring for the response (typically occur within 4-8 days of therapy)
Duration of therapy
Treatment should be given for 21 days
Secondary prophylaxis
After completion of 21 days of treatment, immunosuppressed patients should receive secondary prophylaxis
A 65-year-old man ,4 months after cadaveric transplantation.
– fever (38 °C) and non-productive (dry) cough.
-CMV negative to CMV positive recipient.
-Oxygen saturation on air was reported at 89% (hypoxic). What is your differential diagnosis? Post kidney transplant with hypoxemia. 1-PCP.(most suspected). 2-Viral induced pneumonia (COVID 19 ,Influenza). 3-CMV pneumonitis . 4-aspergillus. 5-Other causes of CAP. How do you manage this case? 1-Shifting our patient to critical area with supportive o2 therapy in the form of CPAP. 2-Basic investigation (CBC, CRP, LDH, Blood C/S, Sputum C/S, Serial RFT, LFT ). 3-ABG/ serum beta-D-glucan assay. 4-HRCT (looking for par hilar shadows with sub pleural sparing , and ground glass appearance). 5-BAL(The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens.) Treatment: =We recommend starting with TMP-SMX (15 to 20 mg/kg/day of the trimethoprim component) orally or IV given in three or four divided doses, after G6PD enzyme activity. =Alternative agents when TMP-SMX sensitivity is present such as For mild disease, options include: •Atovaquone. •Clindamycin plus primaquine. •TMP plus dapsone. For moderate disease, options include: •Clindamycin plus primaquine. •TMP plus dapsone. For severe disease, options include: •Clindamycin plus primaquine. •Intravenous pentamidine. =Stopping MMF at tine being and continue steroid and CNI with low trough level. =After complete recovery, we can extend prophylaxis Septrin dose up to 2 years. References: 1- Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004;350(24):2487-2498. doi:10.1056/NEJMra032588. 2- Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984;100(5):663-671. doi:10.7326/0003-4819-100-5-663. 3- Wilson JW, Limper AH, Grys TE, Karre T, Wengenack NL, Binnicker MJ. Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity. Diagn Microbiol Infect Dis. 2011;69(2):145-152. doi:10.1016/j.diagmicrobio.2010.10.021. 4- Hughes WT, Feldman S, Sanyal SK. Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J. 1975;112(13 Spec No):47-50.
Viral infections on the top of list PCPbacterial infectionsfungal infectionsacute lung injuryrestrictive (interstitial fibrosis) lung diseaseHow do you manage this case?
co-ordination with microbiologist and pulmonologist
further work up for reaching diagnosis such as BAL, biopsy (silver staining and immunostaining )
supportive care : oxygen (CPAP)if PCP : IV TMP/SMX then oralclose monitoringcontinuous prophylaxis after recovery from disease
Radiological finding in PJP
Bilateral Perihilar opacity
Bilateral ground glass appearance
Sparing subpleural lung tissue
Reticular nodular opacities
Sometime presentation with spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities.
High resolution CT lung has sensitivity of 100% of detecting ground glass appearance but this mean that if the ground glass appearance is not present diagnosis of PJP could not be formulated
Atypical radiological finding could be present so absence of the above radiological finding either in X- Ray / CT will not exclude the diagnosis under high clinical suspension
Ref Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. Block BL, Mehta T, Ortiz GM, Ferris SP, Vu TH, Huang L, Cattamanchi A. Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with AIDS. Case Rep Infect Dis.
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
How do you manage this case?
it is important to establish the patient’s immunization history, travel history
Diagnostic approach:
Complete blood count with differential
Electrolytes, blood urea nitrogen, and creatinine
Blood cultures (minimum of two sets, with at least one peripheral set and one set from any indwelling catheter)
Urine sediment examination and culture
Sputum for Gram stain, fungal smears, and cultures
Imaging of the lungs (chest radiography or, if possible, chest computed tomographic scanning) and imaging of any symptomatic site (eg, abdomen)
Skin examination, looking for evidence of metastatic infection
CMV quantitative molecular testing is often valuable; other viral polymerase chain reaction (PCR) assays as appropriate to the individual (adenovirus, parvovirus B19, severe acute respiratory syndrome coronavirus 2)
Consideration of sample collection for nonculture-based diagnostic tools (eg, specific molecular and antigen tests such as Aspergillus or Pneumocystis PCR, cryptococcal antigen), Aspergillus galactomannan, beta-1,3,-glucan, whole genome sequencing
BAL samples should be coupled to microbiologic studies (cultures, polymerase chain reaction, Aspergillus galactomannan antigen) to improve sensitivity
Treatment: Trimethoprim-sulfamethoxazole: We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients.
Alternative agents by severity of disease: Alternative drugs for the treatment of PCP have been studied primarily in patients with HIV. Regimens that may be used for PCP when TMP-SMX cannot be used include clindamycin plus primaquine, trimethoprim plus dapsone, atovaquone, and intravenous (IV) pentamidine). The choice of regimen for patients who cannot take TMP-SMX depends in part on the severity of the disease.
References: Joos, L., Chhajed, P. N., Wallner, J., Battegay, M., Steiger, J., Gratwohl, A., & Tamm, M. (2007). Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients. Respiratory medicine, 101(1), 93-97.
What is your diffrential diagnosis?
The chest x ray showed bilateral hilarity lymphadenopathy with pnemocyste scarttered in bothe lung field
sub plural sparing is not clear here as it is mild to moderated disrease or it is in the early stage
most proberly this finding due PCP ,usually the patient has chest symptoms with sub clinical course for 3 weeks before full pictuer
usually chest xray will be normal in one fourth of the casese so we can not relay on normal x ray to rule out the PCP, withfalse negative result in 30 to 40 % of the cases.
THe causese include all the causes which leading to bilateral hilar shadow like
pulmonary odeama
bilateral interstitial pnemonitis
For definite diagnosis better to have CT chest which is more sensitive .
89% on what FiO2? Consider CPAP or BiPAP availability at a very short notice.
I agree early BAL
Stopping antimetabolites until this patient is in ITU and reducing CNI to bare minimum with steroid cover.
Please use bold or underline for headings or sub-headings to make it easier to read.
Typing ‘Up to date’ or KGDIO’ guidelines is not good enough a reference.
· How do you manage this case?
· Oral TMP/SMX has excellent bioavailability and may be considered in patients with the mild-moderate disease.
· Severe cases may need hospitalization, supportive therapy, and Oxygen therapy.
· Daily intravenous TMP/SMX (15–20 mg/kg TMP; 75–100 mg/kg SMX) is the most efficacious treatment for mild to severe PcP in SOT. Duration of therapy is a minimum of 14 days, up to 21 days for severe disease
· IV pentamidine is the preferred second-line agent,
· It is recommended to reduce immunosuppression when managing PcP in kidney transplant recipients.
· In SOT patients with moderate to severe disease, twice-daily 40–60 mg prednisone for 5–7 days within 72 h of diagnosis has been recommended, with a gradual reduction in dose over a further 7–14 days
References:
1- Cunha BA, Schoch PE, Berbari N. Cryptococcal vs Pneumocystis (carinii) jiroveci pneumonia (PCP): Clinical & Microbiology differential diagnostic considerations. Infect Dis Pract. 2006. 30:514-517.
2- White, P.; Price, Jessica; Backx, Matthijs (2018). Therapy and Management of Pneumocystis jirovecii Infection. Journal of Fungi, 4(4), 127–. doi:10.3390/jof4040127
PJPCMVBacterial pneumoniaany other viral pneumonia such as COVID19TBDiagnostic tests
Microscopy with stainingType of respiratory specimen —
The most rapid and least invasive method is sputum bronchoscopy with BAL should be performed. Lung biopsy with tissue stains and PCR has excellent sensitivity for diagnosing PCP but is rarely required 2. Polymerase chain reaction — in sputum or BAL fluid, blood, or nasopharyngeal aspirates.
3. Beta-D-glucan assay
4 pcr MCV
KDIGO GUIDELINE
We recommend that KTRs with PCP diagnosed by bronchial alveolar lavage and/or lung biopsy be treated with high-dose intravenous trimethoprim-sulfamethoxazole, corticosteroids, and a reduction in immunosuppressive medication. (1C)
We recommend treatment with corticosteroids for KTRs with moderate to severe PCP (as defined by PaO2 o70mmHg in room air or an alveolar gradient of 435mmHg). (1C)
Trimethoprim-sulfamethoxazole —
We recommend (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV.
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component)
Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
Alternative agents by severity of disease
For mild disease, options include:
•Atovaquone
•clindamycin plus primaquine
•TMP plus dapson
For moderate disease, options include:
•clindamycin plus primaquine
•TMP plus dapson
●For severe disease, options include:
•clindamycin plus primaquine
•Intravenous pentamidine
duration of therapy about 21 days
the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg, or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent).
The most rapid and least invasive method is sputum
bronchoscopy with BAL should be performed.
Lung biopsy with tissue stains and PCR has excellent sensitivity for diagnosing PCP but is rarely required
2. Polymerase chain reaction — in sputum or BAL fluid, blood, or nasopharyngeal aspirates.
3. Beta-D-glucan assay
4 pcr MCV
KDIGO GUIDELINE
We recommend that KTRs with PCP diagnosed by bronchial alveolar lavage and/or lung biopsy be treated with high-dose intravenous trimethoprim-sulfamethoxazole, corticosteroids, and a reduction in immunosuppressive medication. (1C)
We recommend treatment with corticosteroids for KTRs with moderate to severe PCP (as defined by PaO2 o70mmHg in room air or an alveolar gradient of 435mmHg). (1C)
(TMP-SMX) is the treatment of choice for PCP of any severity in patients without HIV.
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component)
Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
Alternative agents by severity of disease
For mild disease, options include:
•Atovaquone
•clindamycin plus primaquine
•TMP plus dapson
For moderate disease, options include:
•clindamycin plus primaquine
•TMP plus dapson
For severe disease, options include:
•clindamycin plus primaquine
•Intravenous pentamidine
duration of therapy about 21 days
the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows
a partial pressure of oxygen <70 mmHg
or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg,
or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent).
Pneumonia in post transplant recipient has wide differential diagnosis
· It may be viral ,bacterial ,fungal ,o parasitic but in this case The radiographic features can narrow the differential diagnosis
· Diffuse, bilateral infiltrates suggest CMV, respiratory viruses, Mycoplasma, Legionella, and Pneumocystis jirovecii (PJP). Diffuse bilateral micronodular infiltrate mostly perihilar raises concern for PJP
Management
1. Hospitalization 2. Stabilization 3. Respiratory support 4. Initial Evaluation include
History
• Recent hospitalizations or illnesses
• Social/exposure history
• Immunization status
• Comorbid conditions
• Current degree of immunosuppression
• Exposure history indicative of possible pathogen Labs and Studies
• Complete blood count with differential
• Electrolyte and kidney function evaluation
• Liver function testing
• Influenza testing (if in season) +/- other respiratory viral
• Blood culture – Sputum cultures
5-Based on history and intial evaluation we may need to proceed to expanded evaluation
is the cornerstone of the initial empiric therapy.
Þacombination therapy with a beta‐lactam agent (±MRSA and ±anipseudomonal ) and an agent active against intracellular organisms (Mycoplasma in and Legionella ) Then adjust according to clinical and microbiological findings.
Trimethoprim-sulphamethexazole is the drug of choice, 15-20 mg/kg/day of TMP oral or iv in 4 divided doses
if allergic to sulfa drugs then alternative can be used pentamidine
Atovaquone 750 mg/12 h
primaquine plus clindamycin
adjunctive glucocorticoid should be given
if room air pao2 <70
evidence of hypoxemia room o2 sat <92
What is your differential diagnosis?
Conventional bacteria – 37 percent (higher with neutropenia and mucositis and early after lung transplantation).
Fungi – 14 percent (higher with prolonged neutropenia).
Viruses (CMV, Coronaviruses, …etc)– 15 percent (common with T cell suppression). P. jirovecii (formerly P. carinii) – 5 to 15 percent (without prophylaxis). Nocardia spp – 7 percent (including sulfa-resistant strains). Mycobacterium tuberculosis – 1 percent (higher in endemic regions).
Mixed infections – 20 percent.
Noninfectious etiologies – malignancies, PE, drug allergies, radiation induced, or pulmonary hemorrhage.
From the data available in the case CMV D+/R- (high risk for CMV), with concomittent PCP infection should be looked for.
How do you manage this case?
Complete detailed history, and clinical examination.
Laboratory: CBC, kidney function test, liver function test, urinalysis, LDH (prognostic tool), albumin, T.protein, blood, sputum and urine cultures.
Radiological: CXR usually perihilar infiltrates, central infiltrates sparing the pleura, no nodules or cavity lesions.
CT Scan- honeycombing, ground glass opacities, subpleural sparing, reticulation, stipes, and pneumatic cysts.
A radiologist, infectious disease, and nephrologist should be involved in management of such cases
Microscopic testing: with low sensitivity and specificity to detect PJP, but me be helpful in CMV and other etiological causes.
D glucan sensitive but not specific.
PCR assay sensitive and specific, but cannot distinguish between infection and carrier state.
Broncho-alveolar lavage, and transbronchial biopsy high yield tool.
The gold standard for PCP diagnosis is VATS/open lung biopsy.
Metagenomic next generation sequencing- is a novel diagnostic tool.
Treatement:
Oxygen therapy – correction of hypoxia.
IV hydration.
Trimethoprim-sulphamethexazole is the drug of choice, if allergic to sulfa drugs then: Atovaquone, pentamidine, dapson, or a combination of clindamycin+pyrimethamine, and pentamidine.
Steroid stress dose (high dose) especially when PJP is the diagnosis.
Lower MMF or stopping it in hemodynamically unstable patients, but continue on CNI.
Adoptive immunotherapy could be used.
If CMV is evident, then IV ganciclovir for 5 days, followed by valgancyclovir, and will continue on PJP prophylaxis.
References:
(1) Lecture of Prof. Gamal Saddi, lectur of PJP in SOT, module 4/ week 5.
(2) Hsu JM, Hass A, Gingras MA, Chong J, Costiniuk C, Ezer N, Fraser RS, McDonald EG, Lee TC. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020 Jul 10;20(1):492. doi: 10.1186/s12879-020-05217-x. PMID: 32650730; PMCID: PMC7350625.
(3) UpToDate- Apprioach to the immunocompromised patients with fever and pulmonary infiltrates.
65 yr old
Four months post cadaveric Tx
Fever
Dry cough
low oxygen
with a CXR showing para hilar shadowing with wide spread infiltrates
All are suggestive of
Pneumocystis Jirovecii pneumonia
However one can consider Bacterial pneumonia as well
The possibility of CMV pneumonia is low with D-/R+ status
Management would require first confirmation of PCP
I will do HRCT chest which might show typical findings of PCP like sub pleural sparing , honeycombing, reticular shadowing with ground glass haze
A BAL has sensitivity of 80% where as induced sputum has sensitivity of 50%
Definitive diagnosis — The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens. This is particularly true of the diagnosis of PCP in patients without HIV infection
Treatment We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV (table 1) [1]. The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract. (Up to date)
Management 1. Diagnosis Non-contrast-enhanced computed tomography (in the case of Pneumocystosis, heterogeneous bilateral interstitial lesion with clinical-radiological dissociation).
sputum test Bronchoalveolar lavage with an investigation for BAAR, Gene Xpert for Tuberculosis, RT PCR for Pneumocystosis, Culture for aerobes, fungi, and Ziehl Neelsen
Specimen biopsy with specific staining (Hematoxylin-Eosin, Gomori Crockott – Silver, PAS) Arterial blood gases – Low levels of PaO2 (PaO2 < 70mmHg) and high difference between alveolar and arterial PaO2 (D(A-a)O2 > 35) suggest pneumocystosis and concomitant need for corticosteroids
2. Clinical management
Define the need for corticosteroids and their progressive withdrawal during treatment
Measures to increase O2 supply with non-invasive pressure-assisted pressure (BIPAP) in case of low PaO2 values
Beginning of treatment with Sulfamethoxazole + Trimethoprim at a therapeutic dose (monitor with blood count, liver transaminases, and nitrogenous slags)
Measure immunosuppressant, mainly cyclosporine, due to the high interaction with Sulfas (Evaluate its replacement for another immunosuppressant)
Investigate and treat CMV reactivation (increases risk of PCP infection)
3. Post-treatment care
Secondary prophylaxis with Sulfas for at least six months after CMV negative
Infection is the second most common cause of death in kidney transplant recipients.
The incidence of most infectious diseases has decreased over the past 15 years.
Pneumocystis jirovecii is an opportunistic pathogen that causes severe pulmonary infection in immunocompromized hosts.
Pneumocystis jirovecii is a common cause of pneumonia in immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV) and in those receiving systemic corticosteroids.
Symptoms include fever, dyspnea, and dry cough.
Prophylaxis is essential to prevent PCP in kidney transplant recipients, with up to 50% mortality.
Differential Diagnosis
Acute respiratory distress syndrome
Viral or bacterial pneumonia
Tuberculosis
Legionella pneumonia
Mycoplasma infections
COVID-19 pneumonia
How do you manage this case?
General health of the patient’s condition stabilizing(improve O2 by high flowoO2 and administer an antipyretic ).
Chest x-ray (characteristically shows diffuse, bilateral perihilar infiltrates, but 20 to 30% of patients have normal x-rays.).
Chest computed tomography.
Metagenomic next-generation sequencing can detect complex and rare pathogens quickly and accurately.
Pulse oximetry (Hypoxemia can be diagnosed by assessing arterial blood gas (ABG) measurements.).
Pulmonary function tests can be used to diagnose Pneumocystis jirovecii pneumonia.(show altered diffusing capacity).
Serum beta-D glucan assays are nonspecific but can support the diagnosis.
PCR
Histopathologic confirmation
Pneumocystis jirovecii is confirmed by histopathologic demonstration using methenamine silver, Giemsa, Wright-Giemsa, modified Grocott, Weigert-Gram.
Sensitivity ranges from 30 to 80% for induced sputum and is > 95% for bronchoscopy with bronchoalveolar lavage.
Treatment
Trimethoprim/sulfamethoxazole
Corticosteroids if PaO2 < 70 mm Hg
Treatment is with trimethoprim/sulfamethoxazole (TMP/SMX) 15-20 mg/kg IV or orally 3 times a day for 14-21 days.
IF sulfa allergies and mild to moderate disease include:
Atavaquone 750 mg, orally twice daily for 21 days (must be taken with food).[
Trimethoprim 15 mg/kg/day by mouth twice daily plus dapsone 100 mg by mouth every day
Primaquine 30 mg daily, plus clindamycin by mouth 450 mg every 6 hours or 600 mg every 8 hours.
Alternative treatments for moderate to severe cases include:
Pentamidine 4 mg/kg IV once daily over 60 minutes
Primaquine 30 mg by mouth every day plus clindamycin IV 600 mg every 6 hours or 900 mg every 8 hours.
The major limitation of pentamidine is the high frequency of toxic adverse effects, including acute kidney injury, hypotension, and hypoglycemia.
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020;20(1):492. Published 2020 Jul 10. doi:10.1186/s12879-020-05217-x
Kelley CF, Checkley W, Mannino DM, Franco-Paredes C, Del Rio C, Holguin F. Trends in hospitalizations for AIDS-associated Pneumocystis jirovecii pneumonia in the United States (1986 to 2005). Chest. 2009;136(1):190–197. doi:10.1378/chest.08-2859
Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, et al. OPTN/SRTR 2015 annual data report: kidney. Am J Transplant. 2017;17(Suppl 1):21–116.
The finding of CXR with other tests like staining of tissue obtained by open lung surgery stained with Gomori methenamine silver stain and immunofluorescence
There are no characteristic radiographic findings for Pneumocystosis. There is even an important clinical-radiological dissociation. We found CT scans with interstitial infiltrate in a patient with low PaO2 indices suggestive of pneumocystosis depending on the epidemiological context (transplantation, HIV, chronic use of corticosteroids).
– Diffuse bilateral interstitial infiltration.
– unusual radiographic patterns include lobar infiltrates.
– solitary and multiple nodules which may become cavitary.
– pneumatocele and pneumothorax.
– in patients received aerosolised pentamidine, upper lobe infiltration to reduce deposition of pentamidine in upper lobe.
– when chest X-ray is normal, high resolution CT scanning demonstrates
Extensive ground glass opacities or cystic lesions.
References:
Uptodate.
Radiological Characteristics Chest x-rays are initially normal in up to one-fourth of patients with PCP. The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates
Upper lobe infiltrates and pneumothoraces can also be seen; however, a higher incidence of both of these findings can be seen in patients using aerosolized pentamidineprophylaxis
Other less common radiographic presentations include
Lobar or segmental infiltrates
Cysts
Nodules
Pleural effusions
Sub pleural sparing is characteristic finding on CT chest along with ground glass haze, reticular shadowing, honey combing.
CXR sensitivity
Findings on chest radiography may be normal in 10-39% of patients with PCP. (Medscape)
What are the radiological characteristics of PCP? CXR: perihilar infiltrates, central infiltrates sparing the pleura, no nodules or cavity lesions. CT-Scan: honeycombing, ground glass opacities, subpleural sparing, reticulation, stipes, and pneumatic cysts. How sensitive CXR in the diagnosis of PCP? it is poorly sensitive nor specific, may be normal in 30% of cases
Reference:
Hsu JM, Hass A, Gingras MA, Chong J, Costiniuk C, Ezer N, Fraser RS, McDonald EG, Lee TC. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020 Jul 10;20(1):492. doi: 10.1186/s12879-020-05217-x. PMID: 32650730; PMCID: PMC7350625.
UpToDate- Apprioach to the immunocompromised patients with fever and pulmonary infiltrates.
The classic presentation of PCP is a bilateral interstitial pattern, which may be characterized as finely granular, reticular, or ground-glass opacities.
The chest radiographic findings may be normal in patients with early mild disease.
Diffuse bilateral infiltrates extending from the perihilar region are visible in most patients with P jiroveci pneumonia (PJP).
Less-common findings include patchy asymmetric infiltrates, pneumothorax, and pneumatoceles.
Pleural effusions and intrathoracic adenopathy are rare.
Usually, chest radiography is the only imaging required; its overall accuracy for the diagnosis of PCP is approximately 75%.
Chest radiographic findings may be normal in 5-30% of patients with a diagnosis of PCP.
The literature reports a false-negative rate of 35- 40% when chest radiography is used for diagnosis of PCP.
When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful, because it is more sensitive than chest radiographs for detecting PCP.
Radiological Characteristics of PCP:
Chest Xray: Bilateral, diffuse, often perihilar finely granular, reticular, or ground-glass opacities
High-resolution CT: Classic CT finding is extensive ground-glass attenuation.
5-30% of individuals with a diagnosis of PCP may have normal chest radiography results.
According to the research, chest radiography has a false-negative rate of 35 to 40% when used to diagnose PCP.
Charles A. Crans & Phillip M. Boiselle (1999) Imaging Features of Pneumocystis carinii Pneumonia, Critical Reviews in Diagnostic Imaging, 40:4, 251-284, DOI: 10.3109/10408379991249194
Plain radiographAlthough up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings 2-4,6,7.
Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include 5:
. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
Its usually bilateral diffuse perihilar, fine granular ground glass interstitial pneumonitis.
Its diagnostic in 75 % of cases. It might be normal in 5-30% of cases.
atypical presentation is encountered in 5 % of cases such as cystic lesion, pneumothorax, and lobar pneumonia.
Reference:
1] Bollée G, Sarfati C, Thiéry G, et al. Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients. Chest. 2007 Oct. 132 (4):1305-10.
bilateral lung infiltration by CXR which is not pathognomonic to PCP
by CT chest it is ground glass appearance and honeycomb appearance
both are suggestive with the clinical scenario but of course BAL and real time PCR are diagnostic
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings
Source
1. Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation
2. Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation
3. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
PCP often manifests itself as a bilateral interstitial pattern, which may be described as having coarsely granular, reticular, or ground-glass opacities. This is the classic presentation of the disease. High-resolution CT may be useful in the diagnosis of PCP when chest radiographic results are normal or equivocal. This is because high-resolution CT has a higher detection sensitivity than chest radiographs do.
Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS are demonstrated by different radiographic patterns: widespread ground-glass opacities in the former and cystic lesions in the latter.
Hardak, E., Brook, O., & Yigla, M. (2010). Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
No radiological characteristic for PCP in CXRY, might be perihilar infiltrations and ground glass appearance and so not sensitive in PCP diagnosis.
BAL with patholigical mircobaterial identifications is required.
Plain radiograph
# Although up to 90% of chest radiographs in patients with pneumocystis pneumonia are abnormal, appearances are often non-specific.
# Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
# Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include 5:
*Small pneumatoceles
*Subpleural blebs
*Fine reticular interstitial changes
*Predominantly perihilar in distribution
# Pleural effusions are normally not a feature, seen in less than 5% of cases.
# High resolution CT:
*Is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs .
*The features include::
# Ground glass pattern
*Considered a principal finding
*Predominantly involving perihilar or mid zones
There may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolized medication.
If they are, then the poorly ventilated upper zones are prone to infection, whereas, in those who are not, the lower zones are more frequently involved.
There may be relative preservation of previously irradiated areas.
Show some peripheral sparing in a considerable number of patients (~40%).
#Reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present.
# Pneumatoceles
*Varying shape, size, and wall thickness
*Are seen in up to 30% of cases
*Pleural effusions are rare
*Lymphadenopathy is uncommon (10%)
# Atypical features, found more frequently in patients treated prophylactically, include :
*Consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
*Nodules (granulomas)
May cavitate
Small nodules and tree in bud opacities are uncommon in patients with AIDS and pneumocysitis pneumonia and usually indicate the presence of intercurrent infectious bronchiolitis from other organisms.
# Lymphadenopathy
# Pleural effusions are also more frequently encountered in this group of patients
# Note: A cystic form of pneumocysitis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis. Features of this pattern include :
*Thin walled cysts: in most cases these are pneumatoceles
*Upper lobe predominance
*May be bilateral
*Increased risk of pneumothorax due to cyst rupture
References:
1. Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation
2. Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation
3. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
What are the radiological characteristics of PCP?, How sensitive CXR in the diagnosis of PCP?
CXR
CXR is normal in around 25% of cases
The most common radiological picture seen is the presence of diffuse, bilateral, interstitial, or alveolar infiltrates sparing subpleural region (1)
Occasionally upper lobe infiltrates and pneumothorax can be seen in patients on aerosolized pantamidine (2-4).
Less commonly PCP may present by lobar or segmental infiltrates, lung cysts, nodules or pleural effusion (5)
High resolution CT
High resolution CT has high sentivity in immunocompromied patietns (6-8). Sensitivityy reaches 100% and specificity was 89% in one study, the diagnosis is suspected on finding patchy or nodular ground-glass attenuation.
On the other hand negative HRCT make the diagnosis of PCP is highly unlikely
References
1- DeLorenzo LJ, Huang CT, Maguire GP, Stone DJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987; 91:323.
2- Jules-Elysee KM, Stover DE, Zaman MB, et al. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med 1990; 112:750.
3- Sepkowitz KA, Telzak EE, Gold JW, et al. Pneumothorax in AIDS. Ann Intern Med 1991; 114:455.
4- Metersky ML, Colt HG, Olson LK, Shanks TG. AIDS-related spontaneous pneumothorax. Risk factors and treatment. Chest 1995; 108:946.
5- Horowitz ML, Schiff M, Samuels J, et al. Pneumocystis carinii pleural effusion. Pathogenesis and pleural fluid analysis. Am Rev Respir Dis 1993; 148:232.
6- Gruden JF, Huang L, Turner J, et al. High-resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings. AJR Am J Roentgenol 1997; 169:967.
7- Hartman TE, Primack SL, Müller NL, Staples CA. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol 1994; 162:547.
8- Hidalgo A, Falcó V, Mauleón S, et al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol 2003; 13:1179.
Is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs .
Features include
– Ground-glass pattern considered a principal finding predominantly involving perihilar or mid zones with peripheral sparing in a considerable number of patients (~40%)
–Reticular opacities or septal thickening may also be present;
-A crazy paving may be seen when both ground-glass opacities and septal thickening are present.
– Pneumatoceles
Peripheral sparing with perihilar and central reticular-interstitial infiltrations sparing the pleura like this CXR finding in the clinical context of hypoxia , fever , dry cough
👉 radiological criteria of PCP:
_Bilateral interstitial infiltration. (parahilar) with subpleural sparing
_Reticular pattern and septations
_Honey combing more apparent in CT chest.
_Upper lobe infltration is atypical pattern of PCP seen in those taking inhaled pentamidine prophylaxis.
_However, these findings are not specific to PCP and can be seen with interstitial lung disease, viral pneumonitis and atypical bacterial infection as mycoplasma.
_Covid 19 infection usually has subpleural infiltration and uncommon to have pleural effusion.
👉 Sensitivity of CXR:
_ 10_30 % may have normal CXR
_ HRCT may be needed with better sensitivity for PCP.
para hilar shadowing, subpleural sparing, upper lobes infiltration
reticulation with septations, stripes, peripheral sparing, pnemoticcytes ( cystic changes), and honeycombing more prominent in CT
CXR abnormalityy in PJ is found in > 91-96% but less sensitive , 30% as these findings can be found in atypical viral or bacterial infections
-No radiographic pattern is pathognomonic for Pneumocystis infection.
-90% of chest radiographs are abnormal, appearances are often non-specific.
-10-15% of patients have normal chest radiographs and
-close to 30% have non-specific or inconclusive finding
-Features which are highly suggestive of PCP include: fine reticular interstitial changes predominantly perihilar in distribution small pneumatoceles, subpleural blebs,
-Patients receiving aerosolized pentamidine classically presents largely or solely in the upper lobes on chest radiograph
HRCT: is more sensitive, used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive CXR. Features on CT include:
Ground glass appearance; considered a principal finding
Subpleural peripheral sparing seen in (~40%)
Other includes: reticular opacities, septal thickening, pneumatocele, honeycomb
References:
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020;20(1):492. Published 2020 Jul 10. doi:10.1186/s12879-020-05217-
Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58.
The radiological characteristics of PCP
1-CXR can be normal in 5-30% of cases of PCP.
2-Interstial pattern.
3-fine granular, reticular, or ground glass opacities.
4- perihilar shadow in the CXR.
5-sparing of subpleural at the early disease stage.
High-resolution CT scan is more sensitive than CXR for detecting PCP and CXR has a 35-40% false negative rate of CXR for detecting PCP.
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
(Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation)
HRCT is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs.
( Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation)
radiological findings:
Para hilar shadowing with subpleural sparing especially in early disease.
ground glass appearance with reticulations & stripes
A bilateral interstitial pattern with coarsely granular, reticular, or ground-glass opacities is the typical presentation of PCP
High-resolution CT may be beneficial when chest radiographic findings are normal or ambiguous because it is more sensitive than chest radiography for detecting PCP.
The classic CT finding is extensive ground glass attenuation.
10-39% of PCP patients may have normal chest radiography findings.
Imaging features of Pneumocystis carinii pneumonia C A Crans Jr 1 , P M Boiselle Pneumocystis jirovecii (carinii) Pneumonia Imaging Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: Eugene C Lin, MD
-The typical radiographic features of PCP are diffuse, bilateral, interstitial infiltrates, ground-glass opacities and foci of consolidation. Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules as well as cavitary lesions; pneumatoceles.
-Chest x ray is non sensitive for diagnosis of PCP but the presence of ground glass on high-resolution chest CT is 100% sensitive for PCP, So absence of ground glass opacities on HRCT ruled out the diagnosis of PCP
Findings on CXR may be normal in 10-39% of patients. Typical CXR findings include; bilateral diffuse, often perihilar, interstitial infiltrates. Atypical features include; cystic lung disease, spontaneous pneumothorax, lobar consolidation, miliary opacities, pleural effusion and lymphadenopathy. CT scan may show ground glass opacification usually perihilar and subpleural space sparing with thickened interlobar septae and focal consolidation.
Classic presentaion of PCP (PCJ) is excpected to be bilateral hilar infiltration (in immunocompromised patients like our patient or who have high dose steroids); usually:
fine granular
reticular
ground -glass (some times)
Chest-x ray is typical, but if doubtful, CT will help (as in secneario 2); This seems typical, though it can be mixed with military TBC !?
What are the radiological characteristics of PCP?
1. Bilateral interstitial pattern which may be characterized as finely granular, reticular, or ground-glass opacities(1).
2. Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS results in a different time lag between symptoms and a correspondingly different radiographic pattern: widespread ground glass opacities in the former and cystic lesions in the latter(2).
3. Perihilar shadows. 4. Septations or stripes. 5. Sparing of subpleural space. 6. Honeycombing
How sensitive CXR in the diagnosis of PCP? 1. CXR test characteristics for detection of pulmonary opacities included: sensitivity 43.5%,specificity 93.0%, positive predictive value 26.9% and negative predictive value 96.5% (3). 2. Findings on chest radiography may be normal in 10-39% of patients with PCP(4). 3. High-resolution CT, however, has a sensitivity of 100% and a specificity of 89%(5). References 1. Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. doi: 10.1080/10408379991249194. PMID: 10514937. 2. Hardak E, Brook O, Yigla M. Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised patients with and without AIDS. Lung. 2010 Apr;188(2):159-63. doi: 10.1007/s00408-009-9214-y. Epub 2010 Jan 5. PMID: 20049469. 3. Self WH, Courtney DM, McNaughton CD, Wunderink RG, Kline JA. High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ED patients: implications for diagnosing pneumonia. Am J Emerg Med. 2013 Feb;31(2):401-5. doi: 10.1016/j.ajem.2012.08.041. Epub 2012 Oct 18. PMID: 23083885; PMCID: PMC3556231. 4. Medscape; Pneumocystis jirovecii (carinii) Pneumonia Imaging Updated: Jun 29, 2022 Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: Eugene C Lin, MD 5. Benito N, Moreno A, Miro JM, et al; Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012 Mar39(3):730-45. doi: 10.1183/09031936.00200210. Epub 2011 Sep 1.
The typical radiographic features of PCP in patients without HIV are diffuse, bilateral, interstitial infiltrates . Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules, which may become cavitary; pneumatoceles; pneumothorax; and, in patients receiving aerosolized pentamidine, upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes. When chest radiograph findings are normal, high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
Kennedy CA, Goetz MB. Atypical roentgenographic manifestations of Pneumocystis carinii pneumonia. Arch Intern Med. 1992 Jul;152(7):1390-8. PMID: 1627019.
Hidalgo A, Falcó V, Mauleón S, Andreu J, Crespo M, Ribera E, Pahissa A, Cáceres J. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003 May;13(5):1179-84. doi: 10.1007/s00330-002-1641-6. Epub 2002 Sep 25. PMID: 12695843.
High resolution CT scan is diagnostic to show PCP which demonstrate diffuse ground glass opacity and bilateral interstitial infiltration in perihiler region Chest X ray not specific and not sensitive; However may appear normal in 5 to 30% of cases in presence of infection
Radiographic features Plain radiograph
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings
Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include
Pleural effusions are normally not a feature, seen in less than 5% of cases
CT High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs 3.
Features include
considered a principal finding
predominantly involving perihilar or mid zones § there may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolised medication § if they are, then the poorly ventilated upper zones are prone to infection , whereas, in those who are not, the lower zones are more frequently involved § there may be relative preservation of previously irradiated areas § show some peripheral sparing in a considerable number of patients (~40%)
varying shape, size, and wall thickness
are seen in up to 30% of cases
pleural effusions are rare
lymphadenopathy is uncommon (10%)
Atypical features, found more frequently in patients treated prophylactically, include
consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
nodules (granulomas)
may cavitate
small nodules and tree-in-bud opacitiesare uncommon in patients with AIDS and pneumocystis pneumonia and usually indicate the presence of intercurrent infectious bronchiolitis from other organisms
lymphadenopathy
pleural effusions are also more frequently encountered in this group of patients
A cystic form of Pneumocystis pneumonia is also recognised; again, more frequently in patients receiving aerosolised prophylaxis. Features of this pattern include
thin walled cysts: in most cases these are pneumatoceles
upper lobe predominance
may be bilateral
increased risk of pneumothorax due to cyst rupture
Radiological Features of PCP
-CXR: Classical Early changes are bilateral perihilar fine reticulonodular infiltrates. Atypical findings such as lobar pneumonia are possible, as is a normal CXR.
-CT: Bilateral Perihilar groundglass opacities with sub-pleural sparing in the early stages. Later stages show separations, honeycombing, stripes, pneumatic cysts
CXR is poorly sensitive for PCP as a normal CXR can be seen in 5-30% of cases
Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. doi: 10.1080/10408379991249194. PMID: 10514937.
Almost 90% of chest xrays of patients with PCP will be abnormal. Whereas 10 to 15% will have no radiological finding in x ray.
The key radiological features highly suggestive of PCP are
-Bilateral interstitial perihilar pattern , characterized by finely granular, reticular, or ground-glass opacities. –CXR retains a key role in the diagnosis of pneumonia in immune compromised individuals. CXR may be normal in 10-39% of patients with PCP. CT scanning is more sensitive and more specific. Reference -Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84
-Khan A N .Pneumocystis jirovecii (carinii) Pneumonia Imaging Medscape 2022
The radiological pattern of PCP include:
CXR finding
Bilateral diffuse reticulonodular perihilar infiltrate .atypical finding may include pneumatocele , lober pneumonia, and rarely pleural effusion. The CXR finding in PCP may be normal in up to 5-30% of cases. It is less sensitive nor specific. The Chest CT finding include :
ground glass appearance, honeycomb, subpleural sparing , pneumocystis, and septation. It’s more sensitive
In general the radiological finding inPCP is not specific.
Predominately involve peri-hilar or mid-zone, (areas of predilection depends on whether the patient is on aerosolized medication or not), (if there is a poorly ventilated area prone to infection If not the lower zone is mostly affected).
2. Reticular opacities or septal thickening ( a crazy paving pattern may be seen if both ground glass and septal thickening are present). 3.Pneumatoceles
Varying shape, size, and wall thickness.
Seen in up to 30% of cases.
Rarely pleural effusion.
Lymphadenopathy is uncommon.
4. Atypicall features if the patient receives prophylactic treatment;
Consolidation.
Nodules (granulomas).
Lymphadenopathy.
Pleural effusion.
5. Cystic changes in case of receiving aerosolized therapy
What are the radiological characteristics of PCP? Radiological findings: CXR: Typical finding in PJP includes(1,2)
bilateral,
symmetrical,
perihilar,
interstitial infiltrates/fine to medium reticular opacities
Subpleural sparing
HRCT: Typical findings in PJP includes(1,2) At the symptom onset
ground glass opacities
perihilar,
with sparing of lower lung zones and subpleural regions
Evolution in case of ineffective therapy
mosaic pattern,
architectural distortion(linear and irregular opacities, reticulation, and traction bronchiolectasis)
increasing density of infiltrates
distribution of disease is same (perihilar, lower zone and subpleural sparing)
Atypical and less frequent HRCT findings in PJP(Table 1)(1)
How sensitive CXR in the diagnosis of PCP?
5-30% of initial cases may have normal chest X Ray
References:
Cereser L, Dallorto A, Candoni A, Volpetti S, Righi E, Zuiani C, et al. Pneumocystis jirovecii pneumonia at chest High-resolution Computed Tomography (HRCT) in non-HIV immunocompromised patients: Spectrum of findings and mimickers. European Journal of Radiology. 2019; 116: 116-27.
Martin SI, Fishman JA, Practice ASTIDCo. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:272-9.
Classically, pneumocystis carinii pneumonia (PCP) presents with chest showing ground glass opacities, granular or reticular lesions in bilateral lung fields. These findings might not be present in up to one third of cases (1). In those cases, a high resolution computed tomogram (HRCT) of chest can be done, which shows extensive ground glass attenuation, upper lobe distribution of lung parenchymal opacities, or cystic lung lesions (2). HRCT chest has a sensitivity of 100% with specificity of 83.3% (3).
References:
Kanne JP, Yandow DR, Meyer CA. Pneumocystis jiroveci pneumonia: high-resolution CT findings in patients with and without HIV infection. AJR Am J Roentgenol. 2012 Jun;198(6):W555-61. doi: 10.2214/AJR.11.7329. PMID: 22623570.
Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. doi: 10.1080/10408379991249194. PMID: 10514937.
Hidalgo A, Falcó V, Mauleón S, Andreu J, Crespo M, Ribera E, Pahissa A, Cáceres J. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003 May;13(5):1179-84. doi: 10.1007/s00330-002-1641-6. Epub 2002 Sep 25. PMID: 12695843.
– 90% of the radiographs are abnormal while 10-15% of patients have normal radiographs and 30% have nonspecific inconclusive findings
– the classic chest radiograph features of PCP is a bilateral interstitial pattern characterized by diffuse, finely granular, reticular or ground-glass opacities
– other findings include small pneumatoceles, subpleural blebs, perihilar fine reticular interstitial changes
– HRCT (high resolution computed tomography) Chest is more sensitive than a chest radiograph – it can be done when the radiograph findings are normal or equivocal
– the classic HRCT finding is perihilar or mid-zone ground-glass pattern
– other features include reticular opacities, septal thickening, pneumatoceles
– rarely, pleural effusion, lymphadenopathy
– atypical features (present in patients treated prophylactically) include consolidation, nodules (granulomas)
– overall accuracy of CXR in the diagnosis of PCP is ~75%
– 5-30% of patients may have a normal CXR
– literature reports 35-40% false negative rate
– overall accuracy of HRCT chest in the diagnosis of PCP is ~94%
References
1. Crans CA, Jr., Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Critical reviews in diagnostic imaging. 1999 Aug;40(4):251-84. PubMed PMID: 10514937. Epub 1999/10/09. eng.
2. Opravil M, Marincek B, Fuchs WA, Weber R, Speich R, Battegay M, et al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. Journal of acquired immune deficiency syndromes. 1994 Jan;7(1):39-45. PubMed PMID: 8263751. Epub 1994/01/01. eng.
3. Singh D. Imaging of Pulmonary Infections: Thoracic Imaging. 2019 Jan 15:147-72. doi: 10.1007/978-981-13-2544-1_6.
4. Kunihiro Y, Tanaka N, Matsumoto T, Yamamoto N, Matsunaga N. The usefulness of a diagnostic method combining high-resolution CT findings and serum markers for cytomegalovirus pneumonia and pneumocystis pneumonia in non-AIDS patients. Acta radiologica (Stockholm, Sweden : 1987). 2015 Jul;56(7):806-13. PubMed PMID: 25031277. Epub 2014/07/18. eng.
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific.
Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings
Features which are highly suggestive of pneumocystis pneumonia
small pneumatoceles
subpleural blebs
fine reticular interstitial changes
predominantly perihilar in distribution
Pleural effusions are normally not a feature, seen in less than 5% of cases.
CT
High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs
Features include:
ground-glass pattern
considered a principal finding
predominantly involving perihilar or mid zones
there may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolized medication.
if they are, then the poorly ventilated upper zones are prone to infection, whereas, in those who are not, the lower zones are more frequently involved.
there may be relative preservation of previously irradiated areas
show some peripheral sparing in a considerable number of patients (~40%)
reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present
pneumatoceles
varying shape, size, and wall thickness
are seen in up to 30% of cases
pleural effusions are rare
lymphadenopathy is uncommon
Atypical features, found more frequently in patients treated prophylactically, include:
consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
nodules (granulomas)
may cavitate
small nodules and tree-in-bud opacities are uncommon in patients with AIDS and pneumocystis pneumonia and usually indicate the presence of intercurrent infectious bronchiolitis from other organisms
lymphadenopathy
pleural effusions are also more frequently encountered in this group of patients
A cystic form of Pneumocystis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis. Features of this pattern include:
thin-walled cysts: in most cases these are pneumatoceles
upper lobe predominance may be bilateral
increased risk of pneumothorax due to cyst rupture
Nuclear medicine
Gallium-67 lung scintigraphy is highly sensitive for PCP, and a normal gallium scan renders the diagnosis of PCP very unlikely. The gallium scan in patients with PCP demonstrates diffuse pulmonary uptake, which may be heterogeneous or homogeneous.
How sensitive CXR in the diagnosis of PCP?
CXR findings may be normal in 5-30%
false-negative rate of 35- 40%
Referrence Amini B, Milton B, Weerakkody Y, et al. Pulmonary Pneumocystis jiroveci infection. Reference article, Radiopaedia.org (Accessed on 23 Feb 2023) https://doi.org/10.53347/rID-1901
Chest X Ray
Chest X ray in patients with PCP are normal in about 10-15% , while 85-90% may show changes. -Feature of PCP include :
Small Pneumatoceles
Subpleural blebs
Fine reticular interstitial changes
Usually perihilar distribution
Pleural effusion in 5% HRCT Chest
Ground glass pattern
Septal thickening
Pneumatoceles
Pleural effusion – Rare
Lymphadenopathy – Uncommon Cystic form of PCP— Thin walled cysts, Upper lobe predominance, Bilaterality, High risk of pneumothorax
What are the radiological features of PCP:
X ray:
-Up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, but non-specific.
-10-15% of patients have normal chest radiographs and 30% have non-specific or inconclusive findings.
Features which are highly suggestive of pneumocystis pneumonia:
· small pneumatoceles
· subpleural blebs
· fine reticular interstitial changes
· predominantly perihilar in distribution Pleural effusions are normally not a feature, seen in less than 5% of cases.
CT: High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs.
Features include:
· Ground-glass pattern
· Reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present
· pneumatoceles
· pleural effusions are rare
· lymphadenopathy is uncommon (10%)
Atypical features, found more frequently in patients treated prophylactically, include:
· consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
· nodules (granulomas)
· lymphadenopathy
· pleural effusions are also more frequently encountered in this group of patients.
A cystic form of Pneumocystis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis.
Nuclear medicineGallium-67 lung scintigraphy is highly sensitive for PCP, and a normal gallium scan renders the diagnosis of PCP very unlikely. The gallium scan in patients with PCP demonstrates diffuse pulmonary uptake, which may be heterogeneous or homogeneous.
Despite this, the specificity of the gallium scan is low; hence, it is most useful in patients in whom bronchoalveolar lavage may be less diagnostic (e.g. in suspected relapse).
References:
Pulmonary Pneumocystis jiroveci infection
Last revised by Blake Milton on 07 Feb 2023
Dear All What are the radiological characteristics of PCP? A- Plain Chest X-ray: 1- Small pneumatoceles. 2- Subpleural blebs. 3- Fine reticular interstitial changes. 4- Predominant perihilar distribution. 5- Pleural effusion is seen in 5% of case but is not a feature of PJP.
B- HRCT:1- More sensitive than CXR.
2- Ground glass pattern mainly in peri-hilar and mid-zonal areas.Peripheral sparing in more than 40% of cases.
3- Reticular opacities or septal thickening or crazy paving pattern.
4- Pnematoceles: are seen in 30% of cases of variable shapes, sizes and wall thickness.
5- Pleural effusion: rare.
6- Lymphadenpathy: uncommon, in 10% of cases.
7- Atypical features especially in patients on prophylactic treatment and include the following:
a- Consolidation
b- Nodules or granulomas that may cavitate
c- Small nodules and tree-in-bud opacities are uncommon.
8- Ruptured pnumatoceles can lead to pneumothorax.
C- Nuclear Medicine:
1- Gallium 67 lung Scintigraphy is very sensitive to PJP that shows diffuse pulmonary intake either homogenous or heterogenous.
2- Gallium scan is of low specificity.
3- Very useful in those with probable less diagnostic BAL (in suspected relapse).
How sensitive CXR in the diagnosis of PCP?
1- 90% are abnormal and non-specific. 2- 10-15% normal CXR. 3- 30% have non-specific or inconclusive findings.
References:
1. Boiselle PM, Crans CA, Kaplan MA. The changing face of Pneumocystis carinii pneumonia in AIDS patients. AJR Am J Roentgenol. 1999;172 (5): 1301-9. AJR Am J Roentgenol (abstract) – Pubmed citation
2. Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation
3. Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation
4. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
5. Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58. Radiographics (abstract)– Pubmed citation
· In patients with PCP, chest radiographs classically demonstrate bilateral, diffuse, often perihilar, fine, reticular interstitial opacification, which may appear somewhat granular.
· This opacification progresses to air-space consolidation over 3 to 4 days, which may be followed by coarse reticulation as infection resolves.
· Findings on chest radiography may be normal (in 10-39% of patients)
· Chest radiography’s overall accuracy for the diagnosis of PCP is approximately 75%.
· The hallmark finding of PCP on HRCT scans is ground-glass attenuation, which is seen in more than 90% of patients and represents exudative alveolitis.
· Although patients with PCP may present with parenchymal nodules, this feature is more common in CMV infection; thus, the combination of ground-glass attenuation and nodularity is more likely to be secondary to CMV infection.
· In patients with PCP, chest radiographs classically demonstrate bilateral, diffuse, often perihilar, fine, reticular interstitial opacification, which may appear somewhat granular.
· This opacification progresses to air-space consolidation over 3 to 4 days, which may be followed by coarse reticulation as infection resolves.
· Findings on chest radiography may be normal (in 10-39% of patients)
· Chest radiography’s overall accuracy for the diagnosis of PCP is approximately 75%.
· The hallmark finding of PCP on HRCT scans is ground-glass attenuation, which is seen in more than 90% of patients and represents an exudative alveolitis.
· Although patients with PCP may present with parenchymal nodules, this feature is more common in CMV infection; thus, the combination of ground-glass attenuation and nodularity is more likely to be secondary to CMV infection.
typical radiographic features of PCP in patients without HIV are diffuse, bilateral, interstitial infiltrates . Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules , which may become cavitary; pneumatoceles ; pneumothorax; and, in patients receiving aerosolized pentamidine , upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes. high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions
findings on chest radiograph may be normal in 10 – 39 % of patients >>> low sensitivity
Radiographic manifestations in PCP; Chest radiographs; -Chest x-rays are initially normal in up to one-fourth of patients with PCP. -The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates. -Upper lobe infiltrates and pneumothoraces can also be seen; however, a higher incidence of both of these findings can be seen in patients using aerosolized pentamidine prophylaxis. -Other less common radiographic presentations include: ●Lobar or segmental infiltrates ●Cysts ●Nodules ●Pleural effusions High resolution computed tomography; -High resolution computed tomography (HRCT) has a high sensitivity for PCP among HIV-positive patients. -One study, for example, evaluated 51 patients with suspected PCP and normal, equivocal, or nonspecific chest x-ray findings; -HRCT had a sensitivity of 100 % and a specificity of 89 % when the presence of patchy or nodular ground-glass attenuation was used to indicate possible PCP. -While such findings are suggestive, they are not diagnostic. -However, a negative high resolution computed tomography scan makes the diagnosis of PCP highly unlikely.
Gallium-67 citrate scanning; -Gallium-67 citrate scanning is sometimes used to screen for PCP in suspected individuals with a normal chest radiograph but in whom a HRCT cannot be obtained. -Nuclear scanning is a highly sensitive test in patients with PCP, demonstrating intense, diffuse bilateral uptake. -This test is rarely used for diagnosis today.
References; -Up To Date;Clinical presentation and diagnosis of Pneumocystis pulmonary infection in patients with HIV;Dec 08, 2020.
PJP can present with wide range of radiological patterns specially perihilar reticulation ,honey comb appearance, ground glass opacities with characteristic sub pleural sparing and in 10 % of cases CXR may be completely normal , but none of these radiological findings is specific to PJP.
The typical radiographic features of PCP: · Diffuse, bilateral, interstitial infiltrates. · Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules, which may become cavitary. · Pneumatoceles · Pneumothorax
· Upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes.
· When chest radiograph findings are normal, high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions.
The classic presentation of PCP is a bilateral interstitial pattern, which may be finely granular, reticular, or ground-glass opacities mainly central .
When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful, because it is more sensitive than chest radiographs for detecting PCP.
The classic CT finding is extensive ground glass attenuation.
Increasingly recognized characteristic patterns of PCP in AIDS patients include cystic lung disease, spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities. Although the radiographic findings in PCP are similar for AIDS and non-AIDS immunosuppressed patients, cystic lung disease has not been described in the latter patient population.
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
What are the radiological characteristics of PCP?
CXR: diffuse, bilateral, interstitial infiltrates. Unusual radiographic patterns include lobar infiltrates, solitary or multiple nodules which may become cavitary; pneumatoceles up to pneumothorax. PErihilar pattern sparing the periphery.
High-resolution CT: ground-glass opacities or cystic lesions
How sensitive CXR in the diagnosis of PCP?
Findings on chest radiography may be normal (in 10-39% of patients), or radiographic changes may lag behind clinical symptoms.
DD:PCP infection ,mtor induced interstitisial pneumonitis ,Aspergillois,viral pneumonia ,atypical bacterial infection
Management :
Investigations:CBC ,sputum culture ,BAL for PCP BCR,respiratory panel,CMV PCR
CXR ,HRCT,BAL
Treatment:
Trimethoprim/sulfamethoxazole
in case of contraindications:Pyrimethamine/trimethoprim ,Atovaquine,Pentamidine
Radiological characteristics of PCP:
Perihilar infiltrations with subpleural sparing
Bilateral interstitial infiltrations
Honey comb appearance
reticulations
Cysts
CT scan:bilateral ground glass apeearance
Pneumocysts
reticulations
CXR is not specific for diagnosis of PCP
Differential diagnosis includes:
-Cytomegalovirus, PCP infection, Atypical bacterial infections, COVID19, Legionella, Tuberculosis.
Management:
-CBC, CRP with titer, sputum bio fire, culture and sensitivity, blood culture and sensitivity, CMV PCR quantitative analysis.
Treatment
-TMP-SMX is the drug of choice , with pentamidine , primaquine and dapsone as secondary lines .
A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%. CXR done revealed bilateral interstitial infiltrates.
Issues/ concerns
– fever, dry cough, oxygen saturation 89%
– 4 months post cadaveric transplantation
– CMV serostatus D-/ R+
– CXR shows bilateral interstitial infiltrates
What is your differential diagnosis?
Chest x-ray showing interstitial infiltrates perihilar with sparing of periphery.
– Bacterial: either typical or atypical organism in such immunocompromised patient
– Viral pneumonia: (Cytomegalovirus (CMV), SARSCOV2)
-fungal: like Pneumocystis jiroveci
How will you manage this case?
–Respiratory panel screening (gene expert) showed be obtained as early as possible.
–Multidisciplinary approach including infectious disease, microbiologists, nephrologist, pulmonologists.
-Based on high clinical suspicious IV co-trimoxazole can be started especially if the patient wasn’t on prophylactic treatment 4months post-transplant.
-BAL should be arranged by chest team with screening for CMV, PCP, TB in BAL.
-According to clinical presentation with life threatening infection all immunosuppression should be stopped and stress dose of IV steroids should be started with proper counselling of the patient or his relatives about risks and benefits of holding immunosuppression 4months post-transplant.
IF PCP proven based on PCR duration of antibiotics should be ~21days followed by PCP prophylaxis for at least 6-12 months or even extended courses can be used.
References
1. Martin SI, Fishman JA. Pneumocystis pneumonia in solid organ transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Mar;13 Suppl 4:272-9. PubMed PMID: 23465020. Epub 2013/03/08. eng.
2. Grover SA, Coupal L, Suissa S, Szentveri T, Falutz J, Tsoukas C, et al. The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. Clinical and investigative medicine Medecine clinique et experimentale. 1992 Aug;15(4):309-17. PubMed PMID: 1516288. Epub 1992/08/01. eng.
3. Fauchier T, Hasseine L, Gari-Toussaint M, Casanova V, Marty PM, Pomares C. Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients. Journal of clinical microbiology. 2016 Jun;54(6):1487-95. PubMed PMID: 27008872. Pubmed Central PMCID: PMC4879311. Epub 2016/03/25. eng.
4. Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. The Journal of antimicrobial chemotherapy. 2016 Sep;71(9):2386-96. PubMed PMID: 27550991. Epub 2016/08/24. eng.
5. LaRocque RC, Katz JT, Perruzzi P, Baden LR. The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2003 Nov 15;37(10):1380-3. PubMed PMID: 14583873. Epub 2003/10/30. eng.
6. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2007 Feb;13(1):1-7. PubMed PMID: 17334722. Epub 2007/03/06. eng.
The probable differential diagnosis is mainly PCP vs CMV pneumonia or ARDS.
PCP main characteristic is being early post-transplant especially after heavy induction and high doses of immunosuppression initially, and the presence of dry cough signifies this.
Confirmation of diagnosis is done by negative CMV serology, BAL is positive for PCP as well as tissue biopsy.
Management of this case primarily needs reduction of immunosuppression, oxygen supply by mechanical ventilation on need, treatment by TMP using to renally adjusted doses.
● What is your differential diagnosis?
Fever and dry cough after 4 month cadaveric transplant in older recipient with CXR shows bilateral central perihilar infiltrates sparing the periphery consists mostly with PCP but other differential diagnosis include:
☆ CMV pneumonia
☆ Bacterial pneumoniae
☆ Fungal pneumoniae
☆ TB
☆ Other pneumoniae as covid 19
☆ Mycoplasma infection
● How do you manage this case?
Laboratory evaluation
CBC,CRP, ABG, TST, IGRA, PCR for CMV , PCJ, and covid 19 , liver tests and renal function.
Chest CT scan
Supportive management as hydration and oxygen.
In PCP pneumonia:
TMP-SMX IV with high doses in case of PCP and pentamide in case of no response to TMP-SMX
Steroid can be useful in severe hypoxia
What is your differential diagnosis?
· In view of dry cough and hypoxia, PJP comes on the top of the list
· DD:
· Viral: Influenza, parainfluenza , cytomegalovirus(Unlikely with D-/R+ Sero status)
· Fungal: PCP
· Bacterial: community acquired bacteria and Mycobacteria
· Parasites
How would you manage this case?
· MDT approach involving pulmonologist, ICU and Nephrologist
· ITU admission and ventilatory support
· Detailed history and full physical examination
· Supportive treatment with IV fluids and Nutritional support
· Initial investigations including FBC,ESR, CRP, RFTs. LFTs, and blood culture including TB cultures. Check for Tacrolinus trough level transplant graft US.
· Viral throat swab to diagnose viral infections including COVID 19, Influenza and para-influenza and Mycoplasma pneumonia
· Urine sample for Legionella urinary antigen
· CMV-DNA by PCR test(D-/R+).Unlikely positive with such sero-status
· Bronchoscopy & BAL ( including CMV PCR on the BAL)
· Immunosuppression modification: stop anti-metabolites and continue on CNIs and steroids.
· Broad spectrum antibiotics including cover for atypical pneumonia
· Definitive treatment:
· In case of CMV: IV gancycolvir 5mg/kg BD for 5 days followed by oral valgancyclovir 900 mg od until 2 X PCR are negative.If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV IVIG.
· In case of PJP: TMP-SMT given initially IV at a high dose of 15 to 20 mg/kg IV then switching to oral treatment after clinical improvement. Second-line therapy is pentamide 4 mg/kg IV OD with comparable efficacy but worse safety profile Primaquine plus Clindamycin for severe cases. Increasing steroid dose can be useful in severe hypoxia(Sat <70%)
· In case of CMV: IV gancycolvir 5mg/kg BD for 5 days followed by oral valgancyclovir 900 mg OD until 2 X PCR are negative.If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV IVIG.
· Monitor graft function during treatment
Radiological features of PJP:
· No pathognomonic radiologic features for Pneumocystis infection.
· 90% of chest X rays are abnormal but 10-15% have normal chest radiographs
· Features highly suggestive of PCP include:
· Bilateral, diffuse, interstitial or alveolar infiltrates sparing sub-pleural region
· It is predominantly peri-hilar in distribution
· Patients receiving aerosolized pentamidine classically presents largely or solely in the upper lobes on chest X rays
· HRCT:
· More sensitive and specific compared to X ray.
· Features on CT include nodular or patchy ground glass appearance.
References:
1. Dulek DE, Mueller NJ; AST Infectious Diseases Community of Practice. Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13545.
2. Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587.
3. Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58.
CxR showing Bilateral interstitial hilar extending from hilum.
What is your differential diagnosis?
PCP infection
Cytomegalovirus infection
Viral Pnemonia
ARDS
Tuberculosis
Mycoplasma infection
Managment
Diagnosis-The diagnosis of PCP should be considered in patients with risk factors for PCP who present with pneumonia and suggestive radiographic findings. Microbiologic identification of the organism when possible . Detection of the organism in respiratory specimens is most commonly achieved by microscopy with staining of an induced sputum specimen or BAL fluid .The serum beta-D-glucan assay can be used as an adjunct to the diagnosis of PCP.
Treatment–
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract. For renal dose adjustment recommendations, refer to TMP-SMX drug information.
Duration-21 days
Differential Diagnosis:
The most likely cause of the patient’s symptoms, including dry cough, 4 months post-cadaveric transplantation, CMV positivity, and oxygen saturation of 89%, is Pneumocystis pneumonia. Chest X-ray shows a perihilar ground glass appearance, with sparing of the subpleuritic region. Other possible differential diagnoses include viral pneumonia (such as CMV pneumonia or COVID pneumonia), fungal pneumonia (such as Aspergillus pneumonia), bacterial pneumonia (including TB, Legionella, or Mycoplasma), sarcoidosis, and ARDS.
Management:
The patient should be admitted to the intensive care unit for close observation, in case escalation of ventilatory support is required. Currently, respiratory support can be provided through a nasal oxygen cannula. Investigations that should be conducted include CBC, LDH, β-D-Glucan (BDG), ABG, serum creatinine, BUN, urine analysis, ALT, AST, blood culture, induced sputum culture, CMV PCR test, and monitoring of immunosuppressives such as CNI trough levels. BAL with Pneumocystitis quantitative PCR from respiratory fluid, stained samples, or metagenomic next-generation sequencing can also be performed. Pulmonary function tests should be conducted, and the severity of the illness can be determined based on the alveolar-arterial gradient and room air partial pressure of oxygen.
Treatment:
Prompt initiation of treatment is crucial, and the first-line agent is cotrimoxazole, which can be administered orally or intravenously in 3-4 daily doses for a minimum of 3-4 weeks. It is important to consider any potential interaction with cyclosporine, another medication the patient is receiving. Second-line treatment options include pentamidine, dapsone (often used in combination with pyrimethamine), or atovaquone.
What is your differential diagnosis?
The differential diagnosis is of Viral associated Pneumonia (CMV pneumonia, COVID-19, ARDS)
How do you manage this case?
Tests for CBC, ABG, Sputum test, BAL, HRCT of chest, Bronchoscopy and lung biopsy
Management with IV ganciclovir in case of CMV pneumonia, Prednisolone or steroids
Q1: ΔΔ:
1. Pneumocystic jirovani pneumonia
2. CMV pneumonitis, fungal, bacterial, or parasitic pneumonia
3. Covid-19 pneumonia
4. Other types of atypical pneumonia
Q2: management includes:
1. ICU admission
2. Oxygen supplementation
3. Cotrimoxazole (15-20 mg/kg/day) TMP divided Q6-8 hours preferably IV oral doses with two double-strength tablets Q8h in mild cases.
4. Alternatives pentamedine(4 mg/kg/day), atovaquone (750 mg ), clindamycine (600-900mg/Q8h) with primaquine dapsone and TMP
5. Lab test: PCR test for CMV, covid, and other viruses, BAL specimen test for cytology, gram stain, acid-fast bacilli, and PCR for PCP, CMV, and other respiratory viruses.
6. If influenza positive: oseltamivir
7. Wide-spectrum empirical antibiotics
8. Reduction of immunosuppression. Stop MMF adjust CNI
Possible differential diagnoses would be:
– Community pneumonia
– Pneumocystis jiroveci
– CMV pneumonitis
– Tuberculosis
– Pneumonitis secondary to drug
I would perform more accurate tests:
– Chest CT: for a better evaluation of the alterations present on the chest X-ray, with a view to excluding any of the suspected infectious pulmonary conditions.
– Boncoscopy with bronchoalveolar lavage: CT scan of the chest would not exclude all etiologies, so a bronchoscopy with bronchoalveolar lavage would also be necessary with collection of:
– PCR for Pneumocystis
– PCR for Tuberculosis
– Cultures of pathogenic germs
– Galactomana
What is your differential diagnosis?
1-Typical and atypical pneumonia .
2-Fungal infection ;
Pneumocyst carinii
Spergellous
3-Viral infection ;
CMV ,EBV , adenovirus ,Covid .
2-How do you manage this case?
1-The diagnostic approach ;
A-None invasive approach;
a-Blood ,sputum .
b-Serum antibodies against EBV ,CMV ,Ligionella and mycoplasma .
c-Galactomannan test( GM test), and Interferon-γ release assays (T-SPOT).
B-The invasive approach ;
The guidelines recommend fiberoptic bronchoscopy with BAL in patient with negative findings .
2-The therapeutic approach ;
1-The empirical antimicrobial therapy included;
A- For early onset pneumonia (the presented case );
moxifloxacin, ganciclovir, and trimethoprim-sulfamethoxazole (TMP-SMX) .
B-For late onset pneumonia ;
moxifloxacin plus ganciclovir .
C- The guidelines recommend antifungal therapy in cases of suspicion or confirmed fungal infection.
D-The dosages of all the drugs should be adjusted based on the allograft function.
E- The antimicrobial should adjusted within 24 h after the results of the microbiological cultures and serum tests became available.
F-Reduction immunosuppressant ;
1-None ICU admission;
Withdrawn of anti proliferative agent ,continue CNI and steroids .
2-ICU admission;
In critically ill patients. all the immunosuppressants should be withdrawn on admission to the ICU, methylprednisolone (1 mg/kg every 12 h) can be initiated, followed by gradual tapering . Calcineurin inhibitors can be resumed at a low dose when the intravenous methylprednisolone dose was reduced to 1.0 mg/kg/d.
G-The management of other aspects of care, such as blood glucose control, nutritional support, thromboembolic prophylaxis, sedation, and analgesia, was performed according to the current guidelines .
References:
1- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358588/ Int J Clin Exp Med. 2015; 8(1): 1324–1332. Published online 2015 Jan 15. Early- and late-onset severe pneumonia after renal transplantation .
2https://ukkidney.org/sites/renal.org/files/Coronavirus%20transplant%20information%2021%20October%202020.pdf
The patient has fever, dry cough. No expectations and desaturation
DD include
1. Viral infections including respiratory virusrs, CMV and other herpes viruses
2. Bacterial infections less possibility
3. Fungal as PCP, histoplasmosis, cryptococcosis
And even parasites
In such patient with CMV positive recipient, desaturation, dry cough and fever most probably PCP
Management include
1 complete history and clinical examination including immunosuppression protocols and induction history
2. Lab tests including routine tests, inflammatory markers, virology, cultures, and immunosuppression trough levels
3. Imaging after CXR we should perform HRCT
4. In case of sputum we shall perform cytology and culture even BAL with virology markers
5. Being CMV positive recipient so risk of reactivation is high and CMV PCR
Regarding treatment
ICU administration owing to hypoxia
Empirical antibiotics should be started including beta lactame antibiotics
Pcp empirical treatment including Trimethoprin sulphamethoxazole
If confirmed continue for 3 weeks if allergic or CI give pentamidine
If negative stop the drug
If CMV manage for CMV treatment
Regarding immunosuppression
Stop MMF and adjust CNI according to trough level
Plus continue supportive care
In the above case, likely diagnosis is PCP because of history of fever, dry cough ,hypoxia and X-ray Chest showing bilateral perihilar shadowing with bilateral infiltrates. Though x-ray chest has only 5-30% sensitivity. Other differentials which should be considered include: viral pneumonia like CMV, COVID infection, bacterial and fungal pneumonias
Patient should be admitted and oxygen therapy should be started immediately along with broad spectrum antibiotics .Intensivist and pulmonologist should be taken on board and assessment for noninvasive ventilation i.e., CPAP or BiPAP should be done by them. Immunosuppression should be modified i.e., antimetabolites stopped and CNIs reduced . Investigations should be done to confirm the diagnosis which include: CBC, serum LDH, B-glucan, PCR for CMV DNA and PCP , CT scan chest (sub pleural sparing , honeycombing, reticular shadowing with ground glass haze, spontaneous pneumothorax)and then BAL or sputum samples for microbiological diagnosis with special staining. Metagenomic next-generation sequencing is the new diagnostic test which will help in detecting rare pathogens easily. First line treatment for PCP is Trimethoprim-Sulfamethoxazole (TMP-SMX)in a dose of 15mg/kg -20mg/kg in 3-4 divided doses for a duration of 14-21 days. After that prophylaxis is continued for 6-12 mths. Second line options include Intravenous pentamidine, Atovaquone, clindamycin-primaquine, or dapsone-TMP. Steroids in a dose of 40–60 mg of prednisone /day with tapering in 1–2 weeks is recommended in those patients with PaO2 <70 mmHg on room air, A-a oxygen gradient ≥35 mmHg,or SpO2 <92%.
REFERENCES:
1-Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587
What is your differential diagnosis?
4 months post-transplant, cadaveric donor, CMV (D-/R+), presented with fever, non-productive cough and hypoxia (PaO2 89%). CXR shows diffuse reticulo-nodular opacity.
differential diagnosis:
· Viral pneumonia: Influenza, parainfluenza, CMV
· Fungal: Pneumocystis jirovecii (PJP), Aspergillus, histoplasma, Cryptococcus
· Tuberculosis
· Bacterial pneumonitis (atypical)
In view of hypoxia and non-productive cough, probability of PCP is high.
In view of CMV status D-/R+, CMV pneumonia possibility is less (it may present with patchy ground glass opacities, small nodules, or consolidation).
Bacterial etiology of the clinical picture is unlikely (no expectoration).
How do you manage this case?
1. detailed history – Induction therapy and agent; immunosuppressive regime being used; examination – resp rate, saO2, chest auscultation for crepitations, look for pneumothorax
2. Laboratory testing – CBC, RFT, LFT, CRP, Tac C0 drug level
3. HRCT chest
Viral assays – CMV DNA PCR, influenza testing, H1N1 (swine flu) testing
Serum beta D Glucan, Serum LDH
3. Induced sputum examination – cytology, gram stain, AFB and culture.
If no sputum – may need BAL – fluid test for CMV and PJP
4.Treatment:
– Admission and monitoring in HDU / ICU
– oxygen therapy in view of hypoxia.
May need non-invasive ventilation (CPAP or BiPAP) or ventilatory support if worsen
– Bronchoscopy with bronchoalveolar lavage (BAL) with or without transbronchial lung biopsy
– PCR for respiratory viruses, CMV, pneumocystis etc, and histopathological analysis.
– Start empiric treatment:
1) Influenza season: Antiviral against influenza (Oseltamivir) till the results for respiratory virus panel is available.
2) Empirical antibiotics: Co-amoxy-clav / Azithromycin
3) PCP treatment – considering the clinical scenario, co-trimoxazole double strength (TMP 160 +SMX 800) 2tab PO tid should be started, pending the investigation results.
– Steroids to be added if hypoxemia PaO2 <70% on room air develops.
– Anti-PCP treatment can be stopped once investigations for pneumocystis are negative.
4) Immunosuppression reduction: Antimetabolites to be stopped, CNI doses to be minimal adjusted as per trough levels.
Further management as per the laboratory reports:
Ø If Sputum / BAL fluid / biopsy shows PCP: TMP-SMX. Treatment should be given for 3 weeks, followed by secondary prophylaxis with low dose of TMP-SMX for 6-12months.
– If TMP=SMX is contraindicated (patient is allergic) or not effective – then second line drugs Pentamidine, Atovaquone, Dapsone, Primaquine + clindamycin can be used.
Ø If BAL shows CMV: Treatment with Valgancyclovir 900mg PO bid or Inj Ganciclovir (5mg/kg IV 12 hourly) adjusted to creatinine clearance
– To be continued for 2 weeks until resolution of clinical symptoms and radiological findings with clearance of CMV in blood.
– Complete blood count and serum creatinine should be monitored weekly during the treatment.
– If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG).
– Secondary prophylaxis with oral Valganciclovir post-treatment can be given for 3-6 months in patients with high-risk of relapse.
References:
What are differential diagnosis?
As the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest the differential could be,
1. PCP, can present with parihylar infiltrates and sphering of peripheral lungs, with hypoxemia.
2. CMV pneumonitis,
3. Bacterial infection,
4. Influenza, other viral pneumonia,
5. Other fungal infection,
6. COVID-19
7. Tuberculosis.
How do you manage this case?
As the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Further high resolution CT chest,
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, genexpert, blood C/S, procalcitonine, CRP.
General management;
Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange CPAP.
Empirical broad spectrum antibiotic.
If persistently hypoxemic start corticosteroids.
Specific management;
. The next treatment will be according to labs evidence, and
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day,
If responsive or allergic to sulfa group switch to second line agent, depson, pentamidine 4mg IV od, atorviquine 750mg bd, primaquine 30mg tid.
References;
1. https://journals.scholarsportal.info/details/21938229/v10i0003/1733_mnsftdinpars.xml&sub=all.
2. https://www.sciencedirect.com/science/article/abs/pii/S1341321X07708802.
3. https://www.uptodate.com/contents/search?search=pcp%20prophylaxis%20adult&sp=0&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=1&autoComplete=true&language=&max=0&index=5~10&autoCompleteTerm=pcp&rawSentence.
*Differential diagnosis include
PCP pneumonia or CMV pneumonia
*CXR show bilateral perhailer infiltrate with sparing of the peripheral lung tissue which goes mostly with PCP
treatment with high dose septrin
From given sceneri and CXR, i have following differentials-
– PCP
– CMV pneuminia
– Other viral pneumonia
– ARDS
a) Hospitalization in HDU/ ICU
b) Respiratory support to maintain SpO2 >94%
c) Investigations-
– CBC, CRP, ABG
– Renal function test, LFT
– LDH
– HRCT of chest( subpleural spearing, honey combing, ground glass opacity, reticulation, stripes)
– Diagnostic specimen – BAL, Transbronchial biopsy, open lung biopsy/ VATS, induced sputum.
– Diagnostic technique- immunofluorescence assay, real time PCR, nucleic acid testing, silver staining.
– Lung biopsy specimen -lymphocytic infiltration, Gonori methenamine silver staining ( dark brown oval or cup shaped organism in alveolar spaces)
d)Trealment-
1. TMP (15 – 20 mg/ kg)- SMX (75 – 100mg/kg)- IV or p o divided into 3 – 4 doses.
2. Prednisolone
40 mg 12 hourly for 5 days
40 mg daily from day 6 to day 11
20 md daily from day 12 to day 21
3. APAs ( pentamidine, atovaquone, dapsone)
Differential diagnosis:
PCP
CMV pneumonia
COVID pneumonia
Management:
ICU admission
Oxygen therapy for hypoxia
BAL for PCP diagnosis
HRCT
Reduction of immunosuppression, Stop MMF/AZA, CNI levels
Monitoring for rejection
TMP-SMX 15-20 mg/kg for 21days
This is a 65 year patient S/P cadaveric transplantation before 4 months presented with fever , dry couph .and hypoxemia , on CXR perihilar shadows and Diffuse bilateral interstitial infiltration. so our differential diagnosis :
1- PCP on the top of differential
2- other fungal infection
3- Viral infection mainly CMV
4- TB
5- Bacterial infection
6- COVID 19 infection
1- More detailed history especially about the induction therapy , maintenance immunosupression , CMV and PCP prophylaxis , viral status for both donor and recipient before transplantation
2- This patient needs to be admitted to ICU with MDT including ( Nephrologist , Infectious and ICU specialist )
3- supportive management with IV fluid , O2 supplement , antipathetic
4- laboratory test : CBC , KFT , LFT , CRP , ESR , urine analysis , blood urine and sputum Cx , LDH ( high in PCP ) , Tac level , β-D-Glucan (BDG), ABG
5- Consider HRCT : more informative than CXR
6- BAL with transbronchial biopsy and staining is a highly sensitive method of identifying pulmonary disease. looking for PCP , CMV , TB and other common infection .
7- Broad spectrum antibiotics until the results of cultures and BAL ,
8- First-line treatment is with TMP-SMX 15 to 20 mg/kg for 21 days. Treatment of severe disease should include adjunctive steroids as for HIV-infected persons with PJP (60 mg/day initially, then taper).
9- Second-line agents include intravenous pentamidine (4 mg/kg/day), dapsone-trimethoprim (100 mg dapsone daily with trimethoprim 100 mg twice daily), or clindamycin plus primaquine (600 mg 4 times daily clindamycin with 30 mg base daily primaquine).
10- Look carefully for the adverse effects of trimethoprim which include nephrotoxicity, pancreatitis, and bone marrow suppression. Dapsone is associated with hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.
Mild-to-moderate PJP can be treated with atovaquone (750 mg orally twice daily for 21 days) in patients allergic to TMP-SMX.
11- continue Prophylactic agents,for 6 months .
References :
1) Hand book of Kidney Transplantation 6th edition
2) Prof Gamal Saadi lecture Pneumocystis Pneumonia in SOT
Differential diagnosis in this patient…The patient is a recent post transplant case (4 months ago), CMV negative donor to CMV positive recipient…. 4 months post transplant the patient has presented with fever, non productive cough and desaturation….The clinical diagnosis is suggestive of pneumonia for which the following possibilities are possible
By order of preference the first diagnosis will be PCP in view of fever, non productive cough and hypoxia
Management of the patient includes investigations and treatment… Patient needs to be admitted….Detailed history regarding the use of immunosuppressives post transplant needs to be elicited out…Laboratory testing includes CBC, RFT, Liver function test, LDH..I would always keep bacterial sepsis in mind and send procalcitonin and Blood cultures and start on empirical antibiotics…
Patient needs CNI trough level to be monitored at baseline….CT chest will give better understanding of the opacities and introduce us to any cavities which cannot be seen in CXR…Sputum examination is not possible in the case due to non productive cough and induced sputum examination with 3% saline, may help in few cases…Sputum to be stained for gram stain, culture, AFB stain, PCP stain including giemsa or toulidine blue….CMV PCR testing should be done although it is unlikely in this scenario…..
Patient needs NIV like CPAP or high flow oxygen to maintain the oxygen saturation…
Antimetabolites needs to be stopped…CNI dose should be adjusted as per the trough levels….
Treatment with empirical antibiotics like Piperaccilin tazobactum should be considered…Oseltamivir should be started if there is an outbreak of influenza and the results can be stopped later… PCP treatment should be started with high dose Trimethoprim/sulfamethaoxazole 160/800 mg IV twice daily for 3 weeks, followed by secondary prophylaxis with low dose TMP-SMX for 6 months atleast.. Potassium levels need to be monitored while on TMP-SMX…In PCP steroids have to be added for hypoxia ..The dose being higher than the regular maintenance dosage…Second line agents like dapsone, atovoquone, primaquine with clindamycin can be used in patients who develop allergic reactions to TMP-SMX….
Radiological characteristics of PCP are perihilar shadowing, reticulonodular opacities with sparing of sub pleural stages at an early stage…These findings are not specific for PCP…CXR is not sensitive in the diagnosis of PCP and it can be normal also
What are differential diagnosis?
. According to history the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest the differential could be,
1. PCP, can present with parihylar infiltrates and sphering of peripheral lungs, with hypoxemia.
2. CMV pneumonitis,
3. Bacterial infection,
4. Influenza, other viral pneumonia,
5. Other fungal infection,
6. COVID-19
7. Tuberculosis.
How do you manage this case?
. According to history the patient is immunocompromised and there is high risk of opportunistic infection (with no history of prophylaxes) symptoms dry cough, hypoxemia, and x ray finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Further high resolution CT chest,
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, genexpert, blood C/S, procalcitonine, CRP.
General management;
. Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange CPAP.
Empirical broad spectrum antibiotic.
If persistently hypoxemic start corticosteroids.
Specific management;
. The next treatment will be according to labs evidence, and
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day,
If responsive or allergic to sulfa group switch to second line agent, depson, pentamidine 4mg IV od, atorviquine 750mg bd, primaquine 30mg tid.
References;
1. https://journals.scholarsportal.info/details/21938229/v10i0003/1733_mnsftdinpars.xml&sub=all.
2. https://www.sciencedirect.com/science/article/abs/pii/S1341321X07708802.
3. https://www.uptodate.com/contents/search?search=pcp%20prophylaxis%20adult&sp=0&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=1&autoComplete=true&language=&max=0&index=5~10&autoCompleteTerm=pcp&rawSentence.
this patient with history of respiratory symptoms in nearly post-transplant period the condition most probably caused by opurtunistic infection .
Q 1- differntial diagnosis include :
Ø Pneumocystic jirvocii pneumonia
Ø COVID 19
Ø CMV
Ø TB
Ø Others EBV, HSV …
Q 2- How do you manage this case?
This patient is critical state needs
1- Admition to ICU.
2- Monitoring of the vital signs , O2 saturation .
3- O2 therapy – o2 supply by mask or nasal prang , non-invasive o2 support , invasive mechanical ventilation .
4- IV hydration .
5- WORK UP to prove the most probable diagnosis (PCP ) .
5-1 Chest x RAY – radiographic feature include
May be normal or there is bilateral, symmetric, diffuse, reticular, or granular opacities ,( although are non-specific). It is perihilar in mild presentations or diffuse in severe presentations . Typically, reticular and poorly defined ground-glass opacities progress to alveolar consolidation in 3–4 days .
5-2 High-resolution computed-tomography scans (HRCT) are more sensitive than chest radiography at detecting PCP. With a sensitivity and specificity of 100% and 89%, respectively, a normal HRCT may allow exclusion of PCP. Pulmonary cysts occur in 3%–6% of PCP .
5-3 Microbiological diagnosis: type of sputum sensitivity for diagnosis
Routine sputum Poor
Induced sputum 30–55%
Bronchoalveolar lavage 80–95%
Bronchoalveolar lavage and transbronchial biopsy, Open-lung biopsy >95%
Note: Pneumocystis remains a non-cultivable microorganism.
5-4 – Polymerase Chain Reaction:
PCR is a highly effective at diagnosing . the negative predictive value of this method, close to 100%, allows PCP to be excluded .
5-5- Plasmatic Markers
– the level of serum LDH is elevated (>300 IU) in most patients with PCP .
– serum levels of β-d-glucan (BDG), a polysaccharide present in the Pneumocystis cyst wall, as a noninvasive diagnostic test for PCP. with sensitivities ranging from 90% to 100% and specificities of 88%–96% .
6- WORK UP to exclude other possible cause .
1- SPUTUM for covid 19 PCR and chest ct scan .
2- CMV PCR.
3- T B – sputum for AFB, IgRA , Gen Expert .
4- PCR for EBV , SHV ..
TREATMENT :
Trimethoprim-Sulfamethoxazole (TMP-SMX) TMP-SMX is the first-line agent for the treatment of mild to severe PCP . The recommended daily dose is TMP 15–20 mg/kg plus SMX 75–100 mg/kg, preferably by IV administration for severe PCP. Recommended duration of treatment is 21 days.
Intravenous pentamidine is about as effective as TMP-SMX and it is the best second-line agent after TMP-SMX for SOT recipients .
second-line treatment
Atovaquone, clindamycin-primaquine, or dapsone-TMP have only been evaluated in mild to moderate PCP. The clindamycin-primaquine combination seems to be the most effective regimen, particularly in cases where TMP-SMX has failed .
patients with moderate-to-severe PCP, the use of adjunctive glucocorticoids remains questionable and is highly controversial. KDIGO and the American Society of Transplantation guidelines recommend treatment with adjunctive corticosteroids for SOT recipients with moderate to severe PCP (as defined by PaO2 <70 mmHg in room air). American Society of Transplantation guidelines suggest that 40–60 mg of prednisone is administered per os twice daily and tapered after 5–7 days over a period of 1–2 weeks
references :
Jay A, etal: Pneumocystis Jirovecii in solid organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9
1.oxygen supply.
2.reduction of immunosuppression.
3.TMP-SMX its a first choice line treatment in PCP, upto to 20 mg/kg IV, switching to oral after clinical improvement.
Second line (sulfa allergies): Atovaquone, dapsone, or aerosolized pentamidine
TMP-SMX also reduces the incidence of Toxoplasma gondii, Listeria monocytogenes, and Nocardia asteroides and reduces the incidence of UTI in kidney transplant recipients. Check glucose-6-phosphate dehydrogenase before initiation of dapsone
– Prednisone if oxygen saturation
65-year-old man transplanted
patient was admitted with a fever (38 °C) dry cough and Oxygen saturation on air was
reported at 89%.
CXR was done showing fine
bilateral interstitial infiltrates with ground-glass opacities more central sparing subpleural space.
Dry cough with hypoxia early on presentation With the x ray findings
in transplant recipient suggests PCP infection.
*Differential diagnosis
PCP.
CMV.
COVID- 19.
Bacterial pneumonia.
TB
*Investigation
-Cbc,CRP
-ABG
-Kidney function test
– Tuberculin skin test (TST) and
Interferon-gamma release assay.
-PCR tests for SARS-CoV-2.
-PCR for PCP,CMV,EBV.
-sputum and blood cultures
-Chest CT scan.
*Management
-oxygen supply to increase saturation .
-adjust immunosuppression.
– In case of PCP, treatment with TMP-SMX is the first-line therapy with 15 to 20 mg/kg IV, switching to oral after clinical improvement.
-Second-line therapy for
severe cases would be pentamide 4 mg/kg IV o.d., though with comparable
efficacy but worse safety profile .
– Primaquine plus Clindamycin for severe cases.
-Atovaquone or Dapsone/TMP for mild to moderate cases are
third-line options that can be considered for patients who do not tolerate the
above treatments or show no clinical improvement.
– Prednisone if oxygen saturation
declined to < 70 mmhg on room air.
*Reference
Dominykas Varnas and Augustina Jankauskienė.Pneumocystis
Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after
Transplantation: A Case Report and Literature Review.Acta Med Litu. 2021;
28(1): 136–144.
Differential diagnosis:
· Pneumocystis pneumonia (PCP)
· CMV pneumonia
· Active TB
Approach to diagnosis:
· It should include microbiologic identification of the PCP when possible (ie, when a sample such as an induced sputum or bronchoalveolar lavage [BAL] fluid can be obtained safely). In situations in which a respiratory specimen cannot be obtained safely, treatment can be initiated based upon the patient’s risk, clinical presentation, and use of serum diagnostic assays such as beta-D-glucan testing as the basis for presumptive diagnosis.
· CRP,ESR, PCT
· CMV PCR and Covid test
· HRCT scan.
· Respiratory culture
· AFB smear and culture
Differential diagnosis:
Management:
– To correct hypoxia: Oxygen inhalation, non-invasive / invasive ventilation according to demand.
– Anti-pyretic for fever.
– I/V fluid if necessary.
– CBC, CRP
– Blood culture, urine culture, sputum culture
– PCR for CMV, PCP
– Serum beta D-glucan: is non-specific but if positive it supports diagnosis of fungal infection.
– LDH for the assessment of severity of PCP and prognosis
– BAL should be checked for gram stains, silver stain or IF for PCJ, ZN stain, and sent for microbial cultures including fungus.
– CT scan of Chest
– Sputum for GeneXpert TB test
– Following confirm diagnosis, treatment of PCP drug of choice is TMP SMX we need to give at least for 3 weeks at a dose of 15-20 mg/ kg IV of TMP
– Close monitoring for side effects of drugs is important as may need to decrease the dose.
– Alternative agents are less effective such as IV pentamidine, Dapsone with Pyrimethamine plus Leucovorin, aerosolized Pentamidine and Atovaquone.
– Modification of immunosuppressive medications:
Hold MMF or Azathioprine.
Reduce the dose of CNIs, aiming at lower target level.
Increase the dose of steroid
– Secondary prophylaxis for life.
References:
(i) UpTodate
(ii) Jay A, etal: Pneumocystis Jirovecii in solid organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9
(iii) Sunsane B, etal: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
OUR CASE;
65 yr old man.
4/12 post transplant.
CMV D-VE/R+VE.
Fever 38 degrees. dry cough,SPO2 89%
CXR- Heterogenous opacification.
DX ;PCP
DDX;
MGT.
REFERENCES.
Differential diagnosis
Pneumocystis pneumonia
Cmv pneumonitis
Covid 19 pneumonia
Other viral pneumonias- Influenza, Rsv
Management
Through history and physical examination
Oxygen supplementation to maintain SP02 >92%
Blood works: CBC, UEC, LFT,CRP,ESR, PCT, CNI trough level, Serum LDH levels, Serum β D glucan levels, CMV PCR
BAL- for direct immunofluorescence antibody staining is the diagnostic modality of choice or Gomori methanamine silver stain which stain the wall of the cysts.
Treatment
TMP/SMX is the drug of choice
Steroids should be given for HIV negative patients who are desaturating due to the associated high mortality.
Patients who are allergic to sulpha alternatives include:
Radiological characteristic of PCP
CXR- bilateral diffuse perihilar reticular opacities
CT scan- extensive ground glass attenuation
Sensitivity of CXR
Accuracy of diagnosing using CXR is approximately 75%.
Maybe normal in 5-30% of patients.
False negative CXR may occur in 35-40% of patients.
Atypical findings may be seen in 5% and may include cysts, pneumothorax, lobar consolidation.
References.
Diagnosis and management of Pneumocystis jirovecii infection P Lewis White, Matthijs Backx, Rosemary A Barnes
Pneumocystis Pneumonia in Solid Organ Transplantation S.I. Martin J.A. Fishman The AST Infectious Diseases Community of Practice
Imaging features of Pneumocystis carinii pneumonia.C A Crans, P M Boiselle
1- This kidney transplant recipient presented with fever , dry cough and desaturation , 4 months after transplantation ( after stopping the prophylaxis against CMV).His X ray show fine perihilar reticulations ,all that are highly suggestive of PJP
DD:
-PJ pneumonia
– Viral pneumonia : CMV pneumonia (either alone or associated with PJP)
– Covid-19 pneumionia but tend to affect lung prephery rather than perihilar.
-Drug induced pneumonitis specially m TOR inhibitors.
2- Management
A- Confirm the diagnosis of PJP: bronchoscopy and BAL for PCR , immunofluresent and Gomori silver stain .
– Exclude other concomitant infections with
– Nasal swap and PCR for covid , CMV PCR.
– Withdrawl of m TOR if the patient was receiving them.
– CBC, CRP ,procalcitonin.
B- Treatment :
1- ICU admission , o2 therapy and stabilization of the general condition.
2- IS doses :withdraw m TOR , decrease dose of antiproliferative drugs as MMF and increase steroid doses .
3- Specific treatment :
-For PJP: TM-SMX is the initial drug of choice .If the patient is allergic to sulfa use pentamidine or dapsone with primaquine .
– For CMV pneumonia : IV gancyclovir 5 mg /kg for 5 days followed by oral valgancyclovir .
D/D
PCP
Aspergillosis
Bacterial Pneumonis
Covid-19 pneumonia.
CMV pneumonia
Management?
hospitalization in ICU care
sputum sample by coughing or even broncho-alveolar lavage, for Giemsa stain.
PCR tests for Covid-19 & CMV.
Serum beta D-glucan: is non-specific but if positive it supports diagnosis of fungal infection.
Metagenomic next generation sequencing., CT-Chest
What are the radiological characteristics of PCP?
CXR: perihilar infiltrates, central infiltrates sparing the pleura
How sensitive CXR in diagnosis of PCP?
Chest radiography may be normal in 10-39% of patients.Chest Xray: of PCP patient shows diffuse, often perihilar finely granular, reticular, or ground-glass opacities on chest HRCT perihilar shadowing and septa are there but real time PCR is diagnostic
DDX
1- PJP
2-CMV
3-Covid 19
4-TB
5-Atypical Pneumonia
Management
Admission to ICU
O2 supply
Hydration
Complete work up
Start TMP/ SMX at a dose of 15-20/ 75-100 mg/ kg intravenous for 3 weeks then as the patient tolerated moved to oral 480 mg single dose daily , for 6-12 months.
It there is allergy to sulfa or intolerance due to AEs second line treatment can be started as dapson with trimethoprim , pentamidine spray ,
Atovaquone 750 mg/12 h
primaquine plus clindamycin.
If CMV treated by gancyclovir I.v then valgancyclovir 900 mg for 200 days.
Management of her IS by stopping antimetabolites , reduce the dose of Tac by 50% and adjunctive glucocorticoid should be given
if room air pao2 <70 by increasing the dose of steriod to 20-40 mg dialy.
Regular monitoring of RFT and LFT and drug level.
What is your differential diagnosis?
– According to history and chest x-ray most likely PCP
-CMV peumonia
– pulmonary TB
-Covid pneumonia.
How do you manage this case?
-ICU admission.
-Detail history and examination.
-CBC ,CRP,ESR, RFT, LFT ,immunosuppression level,CMV and Covid PCR,and screening for TB
– sputum and bronchoscopy with BALF for staining.
-HRCT scan.
-O2 supply .
– If PCP confirm :TMP-SMX 15-20 mg/kg for 21days.
-After improvement :secondary prophylaxis of PCP.
Reference:
Danovitch G.M .Handbook of kidney transplantation. sixth edition. Wolters Kluwer .Press:2017.
>What is your differential diagnosis?
mostly a case of PCP.
Differential diagnosis:
1- COVID pneumonia.
2- CMV pneumonia.
3- TB pneumonia.
4- Bacterial pneumonia.
>How do you manage this case?
Investigations:
-serum beta D-glucan, serum LDH, CBC, pan cultures, RFTs, LFTs, CRP
– sputum examination for PCP, acid fast bacilli.
– Respiratory syndromic panel
– Nasopharyngeal swapping for COVID 19
– CMV PCR
– BAL examination, metagenomic next generation sequencing analysis & lung biopsy may be considered
– HRCT chest
Treatment:
1- ICU settings for the hypoxia management
2- Supportive management
3- Reduction of immunosuppression:
– Hold antimetabolites (MMF)
– Keep tacrolimus guided by trough level around 6-8, follow graft function assessment
– Consider Increase dose of steroid up to 40-60 mg/d
4- Antibiotics:
– Empirical broad spectrum antibiotic coverage till culture results
– For PCP:
>Start IV TMP/SMX (15-20 mg/kg/d for TMP & 75-100mg/kg/d for SMX)
>other options: dapsone, atovaquone, clindamycin plus primaquine & aerosolized pentamidine
– if CMV +ve: start IV ganciclovir 5mg/kg/d in 2 divided doses
4- extend prophylaxis with TMP/SMX ds tab 3 times per week for 6-12 months
>How sensitive CXR in the diagnosis of PCP?
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
(Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation)
HRCT is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs.
( Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation)
>What are the radiological characteristics of PCP?
Para hilar shadowing with subpleural sparing especially in early disease.
ground glass appearance with reticulations & stripes
honeycombing
pneumatic cyst
(Professor Gamal Alsaadi’s lecture)
Differential Diagnosis:
· PCP
· CMV Pnemonia
· TB
· COVID 19
Management :
Admission to ICU . because this patient has low oxygen saturation and connected to oxygen
Detailed history and examination ,ask if he received prophylaxis after tx like septrin and valganciclovir
Investigations:
To do CBC,CRP,RFT and electrolytes,TB screen .ESR,CMV screen ,Blood culture ,sputum culture ,CT chest ,lung function test ,HIV screen ,lactate dehydrogenase ,B-glucan
Bronch alveolar lavage and PCR
Transbronchial biopsy
Staining by silver and immune fluorescent stained
Microscopic examination of stained sputum and Broncho Alveolar Lavage Fluid (BALF) .
Meta genomic next generation sequencing (mNGS )analysis
Of BALF specimen .
Treatment :
TMP:15-20mg/kg
SMX:75-100mg/kg
Iv or oral divided into 3-4 doses daily .or
Pentamidine :
4mg/kg as induction reduced to 2-3 mg/kg /day or
Atovaquone :
75omg per oral bd up to 1500mg bd or Primaquine plus clindamycine .
References :
1-Prof Jamal lecture
2-Hand book of kidney tx
Scenario 1
Our 65 year old patient presented with a fever, non-productive (dry) cough 4 months after cadaveric transplantation and Spo2 on air was reported at 89% ,giving hx CMV negative to CMV positive recipient
CXR shows bilateral para hilar infiltration and diffuse interstitial infiltrates all make PJP highly suggestive.
Viral infection influenza a,b ,COVID 19, CMV pneumonitis
Bacterial pneumonia
TB
Fungal infection PJP,Aspergillosis
Pneumocystis pneumonia can be life threatening. It can cause respiratory failure that can lead to death. People with this condition need early and effective treatment.
So MDT( nephrologist ,pulmonologist,ICU ,infectious ) is mandatory in management.
Brief history including drug hx and prophylaxis
Physical examination
Routine labs including CBC ,KFT ,LFT,Serum electrolytes,RBS
LDH for prognosis
Urine analysis
Septic work up including blood cx ,urine cx and if available sputum cx
ABG if po2 < 70 to consider high dose steroids
Cxr
HR chest CT
Beta-1,3 glucan level in the blood and/or lavage fluid from bronchoscopy
>>>> Given the lack of specificity of beta-D-glucan testing for PCP, the possibility of other fungal infections should be kept in mind.
BAL with transbronchial biopsy and staining is a highly sensitive method of identifying pulmonary disease
>>> The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens. This is particularly true of the diagnosis of PCP in patients without HIV infection, since the number of organisms is significantly lower than in patients with HIV.
==================================================
Keep on o2 nasal cannula to improve saturation
First line treatment is with TMP-SMX 15 to 20 mg/kg for 21 days.
Treatment of severe disease should include adjunctive steroids as for HIV-infected persons with PJP (60 mg/day initially, then taper).
Second line agents include intravenous pentamidine (4 mg/kg/day), dapsone-trimethoprim (100 mg dapsone daily with trimethoprim 100 mg twice daily), or clindamycin plus primaquine (600 mg 4 times daily clindamycin with 30 mg base daily primaquine).
Mild-to-moderate PJP can be treated with atovaquone (750 mg orally twice daily for 21 days) in patients allergic to TMP-SMX.
Prophylactic agents, in order of efficacy, include TMP-SMX (single-strength tablet 3 times weekly), monthly aerosolized pentamidine, daily dapsone, and daily atovaquone.
Prophylaxis against disease should be reinstituted following augmentation of immunosuppression, such as steroid bolus or ATG administration for acute rejection.
Patients reporting sulfa allergies should be questioned regarding the nature of their reaction; desensitization may be possible with mild reactions. For those with severe allergies, dapsone should also be avoided, and PJP prophylaxis provided using atovaquone.
Reference
Uptodate
SIXTH EDITION Handbook of Kidney Transplantation ,Edited by Gabriel M. Danovitch, MD
Medical Director, Kidney and Pancreas Transplant Program Ronald Reagan Medical Center at UCLA John J. Kuiper Chair of Nephrology and Renal Transplantation Distinguished Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles, California
Medscape
This is an immunocompromised recipient within 6 months of transplantation, has fever, dry cough, hypoxia, CMV viremia, and bilateral lung infiltration, all are risk factors and suggestive of Pneumocystis jirovecii pneumonia.
Differential Diagnosis of Pneumocystis jiroveci Pneumonia
· Acute Respiratory Distress Syndrome
· Cytomegalovirus
· Lymphocytic Interstitial Pneumonia
· Mycoplasma Infections
· Viral Pneumonia
· Pulmonary Embolism
· Legionellosis
· Tuberculosis
· Mycobacterium avium Complex (MAC) Infection
Laboratory Studies
· LDH is done as a part of the initial workup. It has a high sensitivity (78%-100%), and LDH levels may reflect the degree of lung injury.
· Quantitative PCR for pneumocystis may be useful in distinguishing between colonization and active infection.
· PCR of respiratory fluid, in particular BAL, is increasingly used to make the diagnosis of PCP
· Sputum P jirovecii PCR testing may be a viable alternative to invasive testing.
Chest Radiography
· Can be normal in patients with early mild disease.
· Diffuse bilateral infiltrates extending from the perihilar region are seen in most patients with PJP.
· Less-common findings include patchy asymmetric infiltrates, pneumothorax, and pneumatoceles.
· Pleural effusions and intrathoracic adenopathy are rare
Computed Tomography
· The typical appearance is patchy areas of ground-glass attenuation with a background of interlobular septal thickening.
Pulmonary function tests
· Decreased DLCO of less than 75% predicted has a high sensitivity (89%-100%) but poor specificity (53%).
· PJP is unlikely if DLCO is normal.
Pulse oximetry
· The oxygen saturation should be measured both at rest and with exertion.
· In case of any detected hypoxemia, ABG should be done for the possible need for steroid therapy
Treatment of PJP
· TMP-SMX is the drug of choice and is the preferred initial therapy during pregnancy
· second-line agents including pentamidine, dapsone (often in combination with pyrimethamine), or atovaquone
· For the treatment of infections that are resistant to TMP-SMX, the combination of clindamycin and primaquine is likely to be more effective than intravenous pentamidine.
· Adjunctive steroids are not recommended in patients without HIV infection.
Prevention of PJP
· Smoking cessation. As smokers are at an increased risk of P jiroveci pneumonia (PJP) and have a more complicated treatment course.
· Chemoprophylaxis. TMP-SMX one double-strength tablet (160 mg TMP to 800 mg SMX) daily. One single-strength tablet (80 mg TMP to 400 mg SMX) daily is also effective
https://emedicine.medscape.com/article/225976-overview#a19:~:text=Pneumocystis%20jiroveci%20Pneumonia%20(PJP)%20Overview%20of%20Pneumocystis%20jiroveci%20Pneumonia
65 year man, 4 months post- transplant, with fever and nonproductive cough, D-, R+, with hypoxia and CXR showed: diffuse bilateral interstitial infiltrates with perihilar involvement.
1. What is the differential diagnosis?
2. How do you manage this case?
Medications:
References
1. Jay A, ETAL: Pneumocystis Jiroveci in solid Organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33, 9
2. Sunsane B, etL: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
3. Xavir, etal: Pneumocystis pneumonia in solid organ trasnplnt receipients, journal of fungi,MDPI,28 SEP, 2018
4. Ji Eun Kim1, Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome, BMC Nephrology (2019) 20:212
What is your differential diagnosis?
65-year-old male, 4 months post-renal-transplant, CMV D/R -ve/+ve, presented with Fever (38), low oxygen saturation at 89% associated with dry cough.
Chest x-ray: bilateral prominent broncho-vascular markings and perihilar infiltrates, few pneumatoceles are seen.
Differential diagnosis includes:
1- Fungal infection like PJP is the first possible DD because of clinical manifestations mainly fever, dry cough and low oxygen saturation associated with minimal chest X-ray finidings.
2- Aspergillosis.
3- Viral infection: CMV, EBV, Covid-19.
4- Bacterial infection.
5- TB pneumonia.
How do you manage this case?
General Non-specific measures:
1- Hypoxia: Oxygen, serial ABG, escalation to non-invasive ventilation (CPAP or BIPAP)
2- Keep ITU in the loop in case of deterioration.
3- Fever: anti-pyretic.
Septic work up:
1- CRP, Blood culture, urine culture, induced sputum culture.
2- CMV PCR, PJP PCR
3- Serum beta D-glucan: is non-specific but if positive it supports diagnosis of fungal infection.
4- Metagenomic next generation sequencing.
5- CT-Chest
6- Bronchoscopy and broncho-alveolar lavage: PJP can be detected using stains like Giemsa, modified Grocott, Weigert-Gram, or methenamic silver.
Modification of immunosuppression medications:
1- Consider stopping MMF or Azathioprine.
2- Monitor level of CNIs, aiming at lower target level.
3- Consider increasing steroids especially if hypoxic.
Specific treatment for PJP:
1- PJP lines of treatment includes TMP/SMX (either IV or orally 15-20mg/Kg/day divided on 12 hours, course for 2-3 weeks), using steroids if ABG shows hypoxaemia PaO2 below 70mmHg.
2- If patient is allergic to TMP/SMX, alternatives include Atovaquone, Dapson, or Primaquine, or IV pentamidine.
Treatment of other pathogens according to results of septic work up.
Monitor for side effects of medications
Monitor renal function.
Reference:
Uptodate.
1-Pneumocystic Jeroveci Pneumonia
2-Viral pneumonia
3-Bacterial pneumonia
Detailed history of his presentation, duration, associated weight loss, sweating, desaturation on exertion. History of chest problems before.
Any prophylaxis for PJP, TB and CMV after transplantation, type, any interruption.
Septic workup, including routine lab, CBC differentials, CRP, sputum culture (induced sputum), CMV PCR, sputum for ZN stain, AFB.
Admission to high dependency unit or ICU.
Pulmonology consultation.
Empirical antibiotics to cover bacterial, CMV and PCP infections.
If no improvement within 48hours to start anti PCP with a reduction of immmmonsuppresion. Starting by the antimetabolite.
Anti PCP include cotrimoxazole. If contra indicated, like G6PD deficiency, alternatives are pentamidine, dapsone or primaquine.
References:
Pulmonary Pneumocystis Jiroveci infection
Last revised by Blake Milton on 07 Feb 2023
What is your differential diagnosis?
This patient has dry cough, high grade fever and hypoxia. He is 4 month post transplant and CMV – to CMV +.
Chest X Ray shows hilar shadowing.
Differential will include-
PCP pneumonia
CMV Pnemonitis
Covid 19
Tuberculosis
Asperagillosis
Bacterial chest infections
How do you manage this case?
This patient will require resuscitation, investigation and treatment accordingly.
He may require admission to ITU / HDU
A multimodality approach involving Nephrologist, respiratory, ID and ITU physician will be required.
· Basic Investigations will include, Full blood counts, Renal and liver functions, CRP, ABGs, Beta D -Glucan.
· HRCT Chest
· CMV PCR
· Covid 19 PCR
· Bronchoscopy and Broncholaveolar lavage- PCP PCR from respiratory specimen
Patient can treated with trimethoprim ( 15-20 mg/kg) and sulphamethoxazole.75-100 mg/kg in divided doses.
Those allergic to sulpha drugs can have -Atavaquone 750 mg, orally twice daily for 21 days , Trimethoprim 15 mg/kg/day by mouth twice daily plus dapsone 100 mg by mouth every day, Primaquine 30 mg daily, plus clindamycin by mouth 450 mg every 6 hours or 600 mg every 8 hours.
White PL, Price JS, Backx M. Therapy and Management of Pneumocystis jirovecii Infection. J Fungi (Basel). 2018 Nov 22;4(4):127.
What is your differential diagnosis?
The etiology of infectious pneumonitis in immunocompromised patients
In one series using invasive diagnostic approaches for pulmonary infiltrates in immunocompromised hosts, a specific diagnosis was obtained in 162 of the 200 cases evaluated (81 percent)
An infectious etiology was found in 125 patients (77 percent) and a noninfectious etiology in 37 (23 percent); 38 (19 percent) remained undiagnosed.
Among infectious causes, bacteria were documented in 24 percent, fungi in 17 percent, and viruses in 10 percent. In 7 percent, the etiology was polymicrobial.
●Conventional bacteria – 37 percent (higher with neutropenia and mucositis and early after lung transplantation)
●Fungi – 14 percent (higher with prolonged neutropenia)
●Viruses – 15 percent (common with T cell suppression)
●P. jirovecii (formerly P. carinii) – 5 to 15 percent (without prophylaxis)
●Nocardia spp – 7 percent (including sulfa-resistant strains)
●Mycobacterium tuberculosis – 1 percent (higher in endemic regions)
●Mixed infections – 20 percent
The spectrum of pulmonary fungal infection includes infection with non-fumigatus Aspergillus spp, Fusarium spp, Scedosporium spp, and the Mucorales in patients with neutropenia and/or in association with graft-versus-host disease (GVHD)
Azole-resistant mold infection may emerge during therapy
Mixed infections with combinations of respiratory viruses, cytomegalovirus (CMV), Aspergillus spp, and/or gram-negative bacilli are common in neutropenic hosts and hematopoietic cell transplant (HCT) recipients
Pneumocystis pneumonia (PCP) is most common in patients receiving glucocorticoids as a part of a chemotherapeutic or maintenance regimen
Invasive CMV disease may be difficult to distinguish from viral shedding (or activation in the setting of severe systemic illness) in the immunocompromised host with pulmonary infiltrates. Confirmation of invasive CMV pneumonitis can be achieved using assays from blood samples (eg, CMV viral load by nucleic acid testing) and/or tissue histology
Noninfectious etiologies for pulmonary infiltrates are common in immunocompromised patients, including pulmonary embolus, tumor, radiation pneumonitis, cancer, fibrosis, atelectasis with pulmonary edema, drug allergy or toxicity, and pulmonary hemorrhage
How do you manage this case?
Diagnostic approach — The initial evaluation for immunocompromised patients with fever with or without pulmonary findings, at a minimum, should include:
●Rapid assessment of vital signs, including oxygen saturation
●Complete blood count with differential
●Electrolytes, blood urea nitrogen, and creatinine
●Blood cultures (minimum of two sets, with at least one peripheral set and one set from any indwelling catheter)
●Urine sediment examination and culture
●Sputum for Gram stain, fungal smears, and cultures
●Imaging of the lungs (chest radiography or, if possible, chest computed tomographic scanning) and imaging of any symptomatic site (eg, abdomen)
●Skin examination, looking for evidence of metastatic infection
●CMV quantitative molecular testing is often valuable; other viral polymerase chain reaction (PCR) assays as appropriate to the individual (adenovirus, parvovirus B19, severe acute respiratory syndrome coronavirus 2)
●Consideration of sample collection for nonculture-based diagnostic tools (eg, specific molecular and antigen tests such as Aspergillus or Pneumocystis PCR, cryptococcal antigen), Aspergillus galactomannan, beta-1,3,-glucan, whole genome sequencing)
Hypoxemia — The presence or absence of hypoxemia can assist in the differential diagnosis of pulmonary infiltrates in immunocompromised patients. Hypoxemia with an elevation in lactic dehydrogenase or beta-1,3-glucan and minimal radiographic findings are common in Pneumocystis pneumonia (PCP),
whereas the absence of hypoxemia with pulmonary consolidation is more common in nocardiosis, tuberculosis, and fungal infections until later in the course.
TREATMENT
We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
if the patient has a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis), TMP-SMX should be avoided
Regimens that may be used for PCP when TMP-SMX cannot be used include clindamycin plus primaquine, trimethoprim plus dapsone, atovaquone, and intravenous (IV) pentamidine
For mild disease, options include:
•Atovaquone
•Clindamycin plus primaquine
•TMP plus dapsone
All of these agents can be given orally. Although there are limited data, we prefer oral atovaquone in patients with mild disease.
For moderate disease, options include:
•Clindamycin plus primaquine
•TMP plus dapsone
Although there are limited data, we prefer clindamycin plus primaquine for patients with moderate disease.
For severe disease, options include:
•Clindamycin plus primaquine
•intravenous pentamidine
Clindamycin can be given intravenously, but primaquine is available only as an oral formulation. Pentamidine should be given intravenously.
For severe disease, we prefer intravenous clindamycin plus oral primaquine because this regimen is less toxic than IV pentamidine. Patients should receive clindamycin intravenously until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract, at which point they can be switched to oral clindamycin.
Adjunctive glucocorticoids are recommended in patients with HIV and moderate or severe PCP because their use improves clinical outcomes and mortality without increasing the risk of other opportunistic infections.
we suggest the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg, or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent). Patients who worsen clinically and meet criteria for glucocorticoids while receiving anti-Pneumocystis therapy are also candidates for adjunctive glucocorticoids.
REFERENCES UpToDate
6. Wieruszewski PM, Barreto JN, Frazee E, et al. Early Corticosteroids for Pneumocystis Pneumonia in Adults Without HIV Are Not Associated With Better Outcome. Chest 2018; 154:636
7.Ding L, Huang H, Wang H, He H. Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies. Ann Intensive Care 2020; 10:34.
The patient is 4 months post-transplant, cadaveric transplant (D-/R+), presented with fever, non-productive cough, and hypoxia. The chest x ray shows diffuse reticulo-nodular pattern.
The differential diagnosis:
With the clinical scenario and exertional hypoxia, PCP high likely
The management
Huang, L.; Cattamanchi, A.; Davis, J.L.; den Boon, S.; Kovacs, J.; Meshnick, S.; Miller, R.F.; Walzer, P.D.; Worodria, W.; Masur, H. HIV-associated Pneumocystis pneumonia. Proc. Am. Thorac. Soc. 2011, 8, 294–300. [CrossRef] [PubMed] 2. Thomas, C.F., Jr.; Limper, A.H. Pneumocystis pneumonia. N. Engl. J. Med. 2004, 350, 2487–2498.
Chest radiograph demonstrated (1):
Differential diagnosis
How do you manage this case?
In this setting, the likely diagnosis is pneumocystis carinii pneumonia. This is supported by fever, prolonged dry cough and hypoxia post renal transplant with the described cheast radiograph.
References
Chest radiograph demonstrated (1):
Differential diagnosis
How do you manage this case?
In this setting, the likely diagnosis is pneumocystis carinii pneumonia. This is supported by fever, prolonged dry cough and hypoxia post renal transplant with the described cheast radiograph.
References
1. A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%. CXR done revealed bilateral interstitial infiltrates.
Issues/ concerns
– fever, dry cough, oxygen saturation 89%
– 4 months post cadaveric transplantation
– CMV serostatus D-/ R+
– CXR shows bilateral interstitial infiltrates
What is your differential diagnosis?
– Pneumocystitis jiroveci pneumonia – hypoxia, dry cough, bilateral interstitial infiltrates
– Bacterial pneumonia
– Viral pneumonia
– Cytomegalovirus (CMV) pneumonitis
– Pulmonary tuberculosis
– SARSCOV2 pneumonia
– Mycobacterium avium complex (MAC) infection
– Acute respiratory distress syndrome (ARDS)
– Mycoplasma infections
– Lymphocytic interstitial pneumonia
– Pulmonary embolism
How will you manage this case? (1)
– multidisciplinary approach – invite the infectious disease specialists, microbiologists, pulmonologists
– comprehensive history i.e., additional history of progressive exertional dyspnoea, weight loss, chest discomfort/ pain, drenching night sweats, weight loss, treatment for rejection, induction therapy
– thorough physical examination i.e., pulmonary symptoms, tachypnoea, tachycardia, fever, lymphadenopathy
– admit to HDU/ ICU, initiate on oxygen therapy, IV paracetamol
– adjust his immunosuppression prescription accordingly i.e., reduce the CNI dose to the bare minimum, hold antimetabolite until the patient recovers, maintain on corticosteroids (as adjunctive therapy)
– assess for risk factors for PCP: – (1)
– laboratory investigations: – (2-4)
– 3 distinct morphologic stages of the organism have been described: –
– diagnostic method of choice is demonstration of the organism in the respiratory tract or secretions using invasive or noninvasive methods
– use of immunofluorescent/ immunoperoxidase monoclonal antibody stains against the organism have greatly improved the diagnosis of PCP (5)
– direct antibody staining of samples binds to both the cyst and trophozoite forms of pneumocystis increasing the sensitivity of detecting the organism
– on the other hand, routine stains like gomori methanamine-silver stains the cyst form only, giemsa and wright’s stain can also stain trophozoites the most common form of the organism in the alveolus
– imaging: – (6)
– therapeutic options: – (1)
– other options if the patient cannot tolerate TMP-SMX
– corticosteroids are used as adjunctive initial treatment in patients with severe disease – best given within 72hours of initiating antibiotics in states of hypoxia i.e., pAO2 < 70 mmHg on room air
– duration of antibiotics should be ~21days
– preventive measures include chemoprophylaxis, smoking cessation play an important role
– relapse of PCP is uncommon with completion of therapy
– offer CMV prophylaxis
– Indications for PCP prophylaxis: –
– prophylactic agents include: – TMP-SMX, Dapsone, Atovaquone, Pentamidine, Clindamycin + Pyrimethamine
References
1. Martin SI, Fishman JA. Pneumocystis pneumonia in solid organ transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Mar;13 Suppl 4:272-9. PubMed PMID: 23465020. Epub 2013/03/08. eng.
2. Grover SA, Coupal L, Suissa S, Szentveri T, Falutz J, Tsoukas C, et al. The clinical utility of serum lactate dehydrogenase in diagnosing pneumocystis carinii pneumonia among hospitalized AIDS patients. Clinical and investigative medicine Medecine clinique et experimentale. 1992 Aug;15(4):309-17. PubMed PMID: 1516288. Epub 1992/08/01. eng.
3. Fauchier T, Hasseine L, Gari-Toussaint M, Casanova V, Marty PM, Pomares C. Detection of Pneumocystis jirovecii by Quantitative PCR To Differentiate Colonization and Pneumonia in Immunocompromised HIV-Positive and HIV-Negative Patients. Journal of clinical microbiology. 2016 Jun;54(6):1487-95. PubMed PMID: 27008872. Pubmed Central PMCID: PMC4879311. Epub 2016/03/25. eng.
4. Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. The Journal of antimicrobial chemotherapy. 2016 Sep;71(9):2386-96. PubMed PMID: 27550991. Epub 2016/08/24. eng.
5. LaRocque RC, Katz JT, Perruzzi P, Baden LR. The utility of sputum induction for diagnosis of Pneumocystis pneumonia in immunocompromised patients without human immunodeficiency virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2003 Nov 15;37(10):1380-3. PubMed PMID: 14583873. Epub 2003/10/30. eng.
6. Fujii T, Nakamura T, Iwamoto A. Pneumocystis pneumonia in patients with HIV infection: clinical manifestations, laboratory findings, and radiological features. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2007 Feb;13(1):1-7. PubMed PMID: 17334722. Epub 2007/03/06. eng.
1- DD:
2- Management:
CMV-PCR and COVID-PCR
oral doses can be used 2 DS tablets /8hrs
1- Pentamidine : 4mg/kg/day
2- Atovaquone: 750 mg bid oral
3- Clindamycine (600-900 mg /8hr oral or IV)+ primaquine (15-30 mg po)
4- Dapson (100 mg po) +trimethoprim (15 mgkg/day)
What is your differential diagnosis?
How do you manage this case?
The index patient is a recent (4 months post-transplant), CMV negative to CMV positive cadaveric transplant (D-/R+), who presented with fever, non-productive cough, and hypoxia (89% oxygen saturation on room air). The chest x ray shows diffuse reticulo-nodular shadows.
The clinical symptoms are suggestive of pneumonia. The differential diagnosis in such a scenario would be (1):
1) Viral: Respiratory viruses (Influenza, parainfluenza etc), Herpesviruses (like cytomegalovirus, CMV)
2) Fungal: Pneumocystis jirovecii (PCP), histoplasma, Cryptococcus
3) Bacterial: community acquired like streptococcus, tuberculosis etc.
4) Parasitic
In view of hypoxia and non-productive cough, probability of PCP is high (2).
Bacterial etiology of the clinical picture is unlikely (no expectoration).
In view of D-/R+ CMV status, CMV pneumonia possibility is less (it may present with patchy ground glass opacities, small nodules, or consolidation) (3,4).
The management of the index case involves:
1. A detailed history and clinical examination. History regarding induction therapy use and the immunosuppressive regime being used is especially important.
2. Laboratory testing including complete blood count, renal function tests, liver function tests, C reactive protein, blood culture, chest X ray, influenza testing (if in influenza season) and other respiratory viral testing (biofire), serum beta D Glucan, Serum LDH, Calcineurin inhibitor (CNI) trough levels (if on CNIs).
3. Induced sputum examination for cytology, gram stain and acid fast bacilli stain, and culture.
4. High resolution computed tomogram (HRCT) of chest.
5. CMV PCR testing: To rule out CMV infection (although unlikely in this setting).
6. Admission in intensive care unit (ICU): With oxygen therapy in view of hypoxia. May need non-invasive ventilation (CPAP or BiPAP) or ventilatory support if worsening takes place.
7. Bronchoscopy with bronchoalveolar lavage (BAL) with or without transbronchial lung biopsy (although biopsy usually not required): For stain and culture, as well as PCR for respiratory viruses, CMV, pneumocystis etc, and histopathological analysis.
8. Empiric initial treatment (1):
1) If influenza season: Antiviral against influenza (Oseltamivir) till the results for respiratory virus panel is available.
2) Empirical antibiotics: Beta lactam agent and agent against intracellular organisms should be started.
3) Considering the clinical status, empirical anti PCP treatment in form of co-trimoxazole (trimethoprim-sulfamethoxazole, TMP-SMX) should be started pending the investigation results. Steroids to be added if hypoxemia with oxygen saturation <70% on room air develops. Anti-PCP treatment can be stopped once investigations for pneumocystis are negative.
9. Immunosuppression: Antimetabolites to be stopped, CNI doses to be adjusted as per trough levels.
10. Further management as per the laboratory reports:
1) If BAL or biopsy shows PCP: continue TMP-SMX. Treatment should be given for 3 weeks, followed by secondary prophylaxis with low dose of TMP-SMX. If TMP=SMX is contraindicated, or patient is allergic to it, then second line drugs like Pentamidine, Atovaquone, Dapsone, Primaquine with clindamycin can be used.
2) If BAL shows CMV: Treatment with intravenous ganciclovir (5mg/kg IV 12 hourly, to be adjusted according to creatinine clearance). It should be continued for minimum 2 weeks (can be changed to oral valganciclovir, if improves earlier), and until resolution of clinical symptoms and radiological findings with clearance of CMV in blood, if present (5). Complete blood count and serum creatinine should be monitored weekly during the treatment. If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV immunoglobulin or intravenous immunoglobulin (IVIG) (5). Secondary prophylaxis with oral valganciclovir post-treatment can be given for 1-2 months in patients with high-risk of relapse.
11. Supportive care: Intravenous fluids, nutrition.
References:
What is your differential diagnosis?
Considering the below mentioned findings in an immunosuppressed kidney transplant recipient:
Signs/symptoms: fever, dry cough and reduction in oxygen saturation
CXR findings: Bilateral, symmetrical, perihilar, interstitial infiltrates/fine to medium reticular opacities
Diagnosis is highly suggestive of Pneumocystis Pneumonia(PCP)
Differential diagnosis may include:
How do you manage this case?
Confirmation of diagnosis:
1.HRCT: typically findings includes
Ground glass opacities(GGO) which may be
Less common findings may include
2. Non-microbiological supportive laboratory investigations:
3. Microbiological confirmation of PJP:
Gold standard for diagnosis on induced sputum/BAL samples: either of below
4. In case of suspicion of other aetiologies after seeing HRCT:
Induced sputum and BAL samples should be assayed for
CMV DNA/Viral PCR
5. Trans-bronchial /open lung /video-assisted thoracoscopic biopsy:
Required in cases
Treatment:
Duration of therapy: At least 14 days, extended to 21 days for severe cases
Frontline/drug of choice:
For milder disease
Maintain Hydration
Regular monitoring of TLC, potassium and creatinine
In case of sulfa allergy:
Second line:
Look for toxicities/side effects in case of IV Pentamidine:
D/D: PJP, ARDS, DPLD, Acute Pulmonary oedema.
Supportive & specific management according to cause( e.g. TMP-SMX for PJP, justify the use of I/V steoid etc..)
differential diagnosis?
-Pneumocystis jirovecii.
-CMV Pneumonitis.
-COVID infection with ARDS
-Pulmonary aspergillosis.
-Tuberculous pneumonia
-Nosocomial Infections
-Respiratory syncytial virus, adenoviruses, and human metapneumovirus
-Drug-induced interstitial pneumonitis (mTOR)
Radiological finding favoring PCP
PCP often manifests as a bilateral interstitial pattern, could be coarsely granular, reticular, or ground-glass opacities in appearance.
High-resolution CT may be useful in the diagnosis of PCP, because of high-resolution leading to higher detection.
Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
How to manage
–High flow O2 (BIPAP CPAP) and maintaining O2 >95%
–Multidisciplinary Teams (Nephrology / ICU / Pulmonology / ID).
meanwhile sending the following investigations
CBC CRP, LFTs, LDH, RFTs
-BAL staining for PCP (Gomori methenamine silver (GMS) staining).
also send for respiratory panel (Influenza type A,B, Adenovirus ,covid-19 , etc).
CMV PCR) – As the patient is at high risk for CMV.
-sputum for C/S and AFB.
Treatment of PJP;
-Trimethoprim-sulfamethoxazole (TMP-SMZ)
-corticosteroids in patients with moderate to severe infections.
-In case of allergy or contraindication can be given the following medicines;
–Dapsone , Inhaled pentamidine , Atovaquone , Primaquine combined with
clindamycin , Combined dapsone and trimethoprim , Pyrimethamine and
sulphadiazine.
with treatment, survival is good (50-95%), but relapses are common.
Needs long term prophylaxis for minimum of 1 year or even life long.
References;
Up To Date; diagnosis of Pneumocystis pneumonia Aug 02, 2022.
PCP often manifests itself as a bilateral interstitial pattern, which may be described as having coarsely granular, reticular, or ground-glass opacities. This is the classic presentation of the disease. High-resolution CT may be useful in the diagnosis of PCP when chest radiographic results are normal or equivocal. This is because high-resolution CT has a higher detection sensitivity than chest radiographs do.
Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS are demonstrated by different radiographic patterns: widespread ground-glass opacities in the former and cystic lesions in the latter.
Hardak, E., Brook, O., & Yigla, M. (2010). Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
CHEST X RAY shows prominent interstitial infiltration and some ground glass appearances
in the setting of transplant and immunosuppression , opportunistic infections are very likely like PCP
in general CXR is not diagnostic of PCP infection , but few findings are specific to PCP , like pneumatocele formation , honey-comb pattern
sensitivity is low at 5-30 % to detect PCP
management
stabilization with nasal O2 ,
SPUTUM OR BAL MICROSCOPY AND CULTURE( NOT FOR PCP BUT FOR OTHER ORGANISM LIKE BACTERIA )
COTRIAMAXAZOLE IN PCP
DIFF DIAGNOSIS
OTHER VIRAL PNEUMONIA LIKE CMV, BACTERIAL PNEUMONIA
FLARE UP OF CHEST TB
Differential diagnosis
Management
According to the Amrican society of transplantation (Infectious disease community practice) Updated Guidelines in the prophylaxis, diagnosis, and management of PJP;
3.In case of drug resistance; the alternative is;
Refferences;
Huang, L.; Cattamanchi, A.; Davis, J.L.; den Boon, S.; Kovacs, J.; Meshnick, S.; Miller, R.F.; Walzer, P.D.; Worodria, W.; Masur, H. HIV-associated Pneumocystis pneumonia. Proc. Am. Thorac. Soc. 2011, 8, 294–300. [CrossRef] [PubMed] 2. Thomas, C.F., Jr.; Limper, A.H. Pneumocystis pneumonia. N. Engl. J. Med. 2004, 350, 2487–2498. [CrossRef] [PubMed] 3. Utsunomiya, M.; Dobashi, H.; Odani, T.; Saito, K.; Yokogawa, N.; Nagasaka, K.; Takenaka, K.; Soejima, M.; Sugihara, T.; Hagiyama, H. Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: Results from a non-blinded, randomized controlled trial. Arthirits Res. Ther. 2017, 19, 7.
Carini A. Formas de eschizogonia de Trypanosoma lewisii. Arch Soc Med Ci Sao Paulo 1910;204 2. Chagas C. Nova trypanomiazaea humanan. Über eine neue Trypanomiasis der Menchen. Mem Inst Osvaldo Cruz 1909;1: 159–218 3. Delanoe P, Delanoe M. Sur les supports des kystes Pneumocystis carinii du poumon des rats avec Tryponosoma lewisi. C R Acad Sci (Paris) 1912;155:658–660 4. van der Meer MG, Brug SL. Infection à Pneumocystis chez l’homme et chez les animaux. Am Soc Belge Méd Trop 1942;22:301–309
◇ Differential diagnosis [1]:
◇ Management of the case:
1. Generalmanagement–
– ICU admission.
– Non invasive ventilation/ give the patient an oxygen therapy.
– Fluid management
2. Investigations:
– Measure ABGs.
– CBCsLFTs and RFTs
– Viral screening ( CMV, HIV). CMV- PCR
– To confirm the diagnosis of PCP: The gold standard method for the diagnosis of PCP mainly relies on microscopic detection for cysts in respiratory specimens (sputum or a sample that is obtained by bronchoalveolar lavage) and PCR (which is sensitive).
3. Treatment [1]:
▪︎ Treatment for a presumed PCP should not be withheld while diagnostic measures are pending.Treatment should be initiated in patients with known risk factors and when clinical suspicion of infections exists.
▪︎IV Sulfamethoxazole and Trimethoprim are the most important drugs and commonly uses treatment for PCP.
▪︎ In patients with a mild allergy to TMP-SMX, desensitization should be attempted as this is the most effective drug of choice. ▪︎In patients with severe allergies to TMP-SMX, desensitization is no longer recommended, and choosing a different drug regimen is more appropriate. Alternative drug regimens for the treatment of PCP in those with sulfa allergies and mild to moderate disease include: pentamidine or dapson with primaquine.
▪︎ Give steroids by increasing the dose or restart it if the patient is steroid free.
▪︎ If the investigatios revealed any other causes then treat accordingly
————————–
References:
[1] Truong J, Ashurst JV. et al. Pneumocystis Jirovecii Pneumonia
–Differential diagnosis
Pneumocystitis pneumonia is most likely due multiple predisposing factors present including dry cough , 4 months after cadaveric transplantation, CMV positive recipient, oxygen saturation 89%.
Chest xray finding of perihilar ground glass appearance sparing subpleuritic region
Other DD
Viral pneumonia as CMV pneumonia,COVID pneumonia
Fungal pneumonia asAspergillus pneumonia
Bacterial pneumonia as TB ,legionella , Mycoplasma
Sarcoidosis
ARDS
–Management
Admission to intensive care to be under close observation in case needed escalation of ventilatory support.
He can need nasal oxygen cannula for respiratory support for now
Investigations :
CBC,LDH, β-D-Glucan (BDG),ABG
serum creatinine , BUN , urine analysis ,ALT ,AST ,blood culture , induced sputum culture
CMV PCR test
Immunosuppresives as CNI trough levels need to be followed
BAL with Pneumocystitis quantitative PCR from respiratory fluid, or stained samples or metagenomic next generation sequencing
Chest xray findings show perihilar interstitial pattern with subpleural sparing
Pulmonary function test
Illness degree is based on the alveolar-arterial gradient: mild (< 35 mm Hg), moderate/severe (35-45 mm Hg), or severe (>45 mm Hg).
Severe disease is also categorised by a room air partial pressure of oxygen lower than 70 mm Hg.
Treatment
Cotrimoxazole oral or IV in 3-4 daily doses must be started as soon as possible for at least 3-4 weeks.
Interaction with cyclosporine must be considered
second-line agents are pentamidine, dapsone (often in combination with pyrimethamine), or atovaquone.
Reference
-Gilroy SA , Pneumocystis jiroveci Pneumonia (PJP) Overview of Pneumocystis jiroveci Pneumonia.Medscape 2022
-Iriart X, Bouar ML, Kamar N, Berry A. Pneumocystis Pneumonia in Solid-Organ Transplant Recipients. J Fungi (Basel). 2015;1(3):293-331.
DIFFERENTIAL DIAGNOSIS:
The above chest radiograph shows parahilar opacities bilaterally with prominent bronchivascular markings.
This feature in otherwise non transplanted individual is suggestive of a viral pneumonia like COVID 19 which also applies to the patient unde discussion.
But apart from viral pneumonia, the second most common possibility PJP.
MANAGEMENT:
1. Assessment of vitals and hemodynamics to decide whether patient requires ICU care.
2. Immediate vlood gas to decide need of O2 support and/or non-invasive vs invasive ventilation
3. If vitals and hemodynamics compromised then IV fluids and vasopressors
4. Initial baseline investigations with sepsis markers, COVID RT PCR, PJP PCR, beta D glucan
5. Start broad spectrum antibiotics
6. In case PCP positive, then patient will require specific therapy for the same. The first line includes IV TMP-SMX given every 6 hourly.
7. Reduction of immunosupression: Exact guideline not available but would be advisable to taper down B cell inhibitor drug , MMF
REF:
1. Norihiko Goto, Kenta Futamura, Manabu Okada, Takayuki Yamamoto, Makoto Tsujita, Takahisa Hiramitsu, Shunji Narumi, and Yoshihiko Watarai .Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak. Clin Med Insights Circ Respir Pulm Med. 2015; 9(Suppl 1): 81–90. doi: 10.4137/CCRPM.S23317
A 65-year-old man was admitted with a fever (38 °C) and non-productive (dry) cough 4 months after cadaveric transplantation. CMV negative to CMV positive recipient. Oxygen saturation on air was reported at 89%.
Transplant recipient with fever, cough desaturation up to 6 months after transplantation and history of. CMV positive
Chest X-ray showed:
Bilateral differ pulmonary infiltration increased susceptibility to PCP especially if patient is not received prophylaxis.
Management.
1- hospital admission ICU (reverse isolation).
2- respiratory support with target SPO2 > 92%.
3- start empirical antibiotics:
1st line:
Trimethoprime-sulphamethoxazole (15-20) mg/kg for 21 intravenous or orally three to four divided doses , patient must continue intravenously until pao2 > 60 or respiratory rate < 25 with functioning gastrointestinal tract so, can shift to oral therapy.
2nd line:
If patient had avsevere allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrosis).
according to disease severity.
>>>>>>Mild disease:
Atovaquine
Clindamycin I.
-primaquine
TMP +dapsone
. >>>moderate disease :
Clindamycin.
-primaquine –
TMP +dapson
sever disease,
clindamycin+ primaquaine – intravenous pentamidine
>>Glucocorticoid:
Inpatients with HIV with moderate to severe PCP.
.Full Lab
CRP CBC FERRTIN
blood culture aerobic
urine culture
PCR CMV
BAL
References
uptodate
handbook of kidney transplant 6th edition (6 edition)
1-What is your differential diagnosis?
-Pneumocystis jirovecii (formerly P. carinii) pneumonia) (most likely).
-CMV Pneumonitis.
-Pulmonary aspergillosis.
-Respiratory viruses;
Respiratory syncytial virus, adenoviruses, and human metapneumovirus
COVID-19 – ARDS.
-Idiopathic Pneumonia Syndrome.
-Tuberculous pneumonia (M. haemophilum and M. avium complex)
-Drug-induced interstitial pneumonitis( mTOR)
2-How do you manage this case?
-Maintain the O2 above 94% by giving High flow O2 (BIPAP CPAP) & Request ABG,
-Check Vital signs, to evaluate the need for ICU or high dependency unit.
-Multidisciplinary Teams (Nephrology / ICU / Pulmonology / ID).
-Further Investigations;
CBC (search for leukopenia and thrombocytopenia)
CRP (often normal) – LDH
Liver function tests, and Renal function tests.
BAL staining for PCP (Gomori methenamine silver (GMS) staining)& serum beta-D-glucan assay .
BAL and send for respiratory panel (Influenza type A,B, Adenovirus ,covid-19 , etc).
(CMV PCR) – As the patient is at high risk for CMV.
Full septic screen (including sputum C/S).
-Management;
Treatment of PJP;
-Trimethoprim-sulfamethoxazole (TMP-SMZ) given in a high dose, combined with corticosteroids in patients with moderate to severe infections.
-If there is allergy or side effects to trimethoprim-sulfamethoxazole, alternative drugs can be used including;
–Dapsone , Inhaled pentamidine , Atovaquone , Primaquine combined with clindamycin , Combined dapsone and trimethoprim , Pyrimethamine and sulphadiazine.
-Prophylaxis is highly efficacious in preventing PJP in transplant patients.
-Overall, with prompt treatment, survival is good (50-95%), relapses are common.
Treatment of CMV tissue invasive disease (cmv pneumonitis);
-Consider decreasing the IS; (stop the antiproliferative medication, and decrease the CNI by 50%, with monitoring Graft Functions.
-IV ganciclovir (5 mg/kg every 12 hours) for 2-3 weeks; should be used in place of valganciclovir. (after ID recommendations)
-IV ganciclovir can be transitioned to oral valganciclovir once the patient has demonstrated clear clinical improvement, viral loads are down-trending, and the patient can tolerate/absorb oral medications.
-While treating with either ganciclovir or valganciclovir, we monitor the serum creatinine at regular intervals in case dose adjustment is needed.
-Monitoring on therapy; RFTS / LFTS / Blood cell counts / LDH.
-References;
Up To Date; diagnosis of Pneumocystis pneumonia in patients without HIV: Aug 02, 2022.
PCP
CMV infection
TB infection
COVID-19 chest infection
ARDS
Drug induce interstitial pneumonitis
Maintain air way by oxygen (ventori mask)
ABG
CBC, ESR, CRP , Procalcitonin RFT, LFT,
CXR
Monitoring of renal function and drug level of calcinurine inhibitor’s
de novo DSA
PCR of pneumocystis
HRCT scan for chest
Bronchoalveolar lavage
Open lung biopsy
Treatment by trimethoprim/sulfamethoxazole for 3 weeks
stop anti metabolites
reduce dose of calcinurine inhibitors
DDx
-PCP
-Atypical Pneumonia
-Community Acquired Pneumonia
-CMV Pneumonitis
-Covid Pneumonia
-Fungal pneumonia
Management:
-Futher imaging with CT Thorax, which may show ground glass opacities with sub pleural sparring, reticulations, separations, stripes, honeycombing and pneumatic cysts
-LAbs: ABGs, LDH, CMV serology, Serum 1,3,B D Glucan, Induced Sputum microscopy and PCR or Metagenomic Next Generation Sequencing if available
-Further tests would be Bonchoscopy with BAL and trans-bronchial biopsy, consideration for VATS if necessary.
-Treatment with Cotrimoxazole will be indicated. IV if severe, but this case seems mild, so two tabs DS CTX may be sufficient. Oxygen therapy also necessary. Consider Drug interactions particularly CNIs: Monitor levels, Keep low. Consider reducing MMF as well and keeping on higher steroid doses
Xie D, Xu W, You J, Yuan X, Li M, Bi X, Zhang K, Li H, Xian Y. Clinical descriptive analysis of severe Pneumocystis jirovecii pneumonia in renal transplantation recipients. Bioengineered. 2021 Dec;12(1):1264-1272. doi: 10.1080/21655979.2021.1911203. PMID: 33896387; PMCID: PMC8806328.
What are the radiological characteristics of PCP?
Chest x ray finding :
Ø Para hillar shadow
CT chest :
Ø Sub pleural space
Ø Strips honey comb
Ø Ground glass
Ø Pneumatic cyst
Ø Pneumatic patches
DD:
-Pneumocystis pneumonia: most likely.
_CMV pneumonitis or superadded to PCP.
_COVID 19 despite it tends to have subpleural affection ; to be ruled out by PCR & COVID IgM.
_Drug induced interstitial lung disease; with mTOR ;to check drug list.
Management: need ICU for associated mortality of 30%.
-O2 supplementation or non invasive ventilation as CPAP or BIPAP to combat hypoxemia in addition to well hydration.
– BAL with staining with Gomori silver stain or IF or PCR to confirm diagnosis.
-SMX TMP is the preferred line of treatment.
– Pentamidine or Dapson with primaquine are alternatives.
– IV ganciclovir treatment for 5 days followed by oral vanganciclovir for concomitant CMV.
-Antiproliferative stopping till stabilization and decrease CNI to the lower therapeutic target to reduce immunosuppression; with steroid use as complementary.
-Replacing of sirolimus by MMF, as it is a risk factor of PCP.
-Routine lab follow up.
-Monitoring LDH; usually more than 300 iu/ml
– SMX_TMP as secondary prophylaxis.
CXR may be totally normal in 5-30% of cases or showing classic pattern of perihilar and interstitial ground glass infiltrates. CT scanning is more sensitive to the diffuse interstitial and nodular pattern than CXR.CXR has false negative rate of 35-40%.
What is your differential diagnosis?
KTR with pre-transplant CMV serostatus of D-/R+ which is risky for CMV infection and reactivation.
History of dry cough and low oxygen saturation on air beside non-specific bilateral interstitial lung findings with sparing of subpleural space, all point towards PCP.
The likely differential diagnoses are:
· PCP
· CMV Pneumonitis.
· COVID-19 pneumonia.
· Miliary TB.
· Other viral infection e.g. RSV, HSV.
· Bacterial infection.
How do you manage this case?
1. To admit the patient in HDU or ICU.
2. Respiratory support with oxygen via N/C, FM or even MV when needed.
3. Laboratory tests:
· CBC, RFT,ABG, LFT, CRP, RBG & LDH.
· Sputum for C&S(looking for concomitant bacterial infection).
· Silver methenamine staining and PCR for PCJ (from sputum, respiratory secretions or BAL).
· CMV IgG & IgM beside PCR for CMV may be needed.
· Screening for TB.
4. PCP is the most likely diagnosis(dry cough, hypoxia and CXR findings) and specific management for PCP is warranted:
· Respiratory support with oxygen supply.
· Reduction and adjustment of immunosuppression.
· TMP-SMX is the first line of therapy; low to intermediate dose of TMP-SMX is preferred as it is effective and associated with low adverse effects(1).
5. Drug treatment options for PCP(2):
a) The first choice: trimethoprim-sulfam ethoxazoleat a dose of 2tablets DS every 8h or IVTrimethoprim 5 mg/kg with sulfamethoxazole 20 mg/kg every 8 h.
b) Alternatives:
I. Dapsone( 100 mg daily) plus trimethoprim(320 mg every 8 h).
II. Clindamycin(PO 300–450 mg every 6 h) plus primaquine (IV 30 mg daily).
III. Pentamidine IV at 4mg/kg/day.
IV. Atovaquone PO 750 mg BID.
c) Adjunctive therapy: Prednisone in patients with room air pAO2 < 70 mmhg (9.3 kPa)
· 40 mg twice daily for 5 days.
· 40 mg daily; days 6 through 11.
· 20 mg daily, days 12 through 21 while on anti-PCP therapy.
d) Dapsone has not been studied as a single drug and thus should not be used alone for treatment. Dapsone–trimethoprim is effective, however, and probably has potency that is comparable to TMP–SMX.
References:
1. Haseeb A, Abourehab MAS, Almalki WA, Almontashri AM, Bajawi SA, Aljoaid AM, Alsahabi BM, Algethamy M, AlQarni A, Iqbal MS, Mutlaq A, Alghamdi S, Elrggal ME, Saleem Z, Radwan RM, Mahrous AJ, Faidah HS. Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review. Int J Environ Res Public Health. 2022 Feb 28;19(5):2833. doi: 10.3390/ijerph19052833. PMID: 35270525; PMCID: PMC8910260.
2. Drug Resistance in Pneumocystis jirovecii Jannik Helweg-Larsen, Thomas Benfield, Joseph Kovacs & Henry Masur.
PJP
CMV
Pulmonary Tuberculosis
Fungal infection
COVID-19
ARDS
Admission
O2 to maintain sop2 more than 92%( nasal prong/face mask or noninvasive ventilation)
Sputum profile(gram statin /AFB 1,2/Culture)
Can be induce sputum- if not possible broncho alveolar lavage
Cbc, rft, lft, crp, ABG, blood c/s, urine c/s
PJP pcr in sputum
Beta D Glucan
LDH for prognosis
HRCT CHEST
Anti-Pneumocystis Agents:
Trimethoprim-Sulfamethoxazole TMP-SMX – (160/800mg) double strength thrice a dayfor 2 to 3 weeks
Alternative
Pentamidine isethionate
Clindamycin and Primaquine
Atovaquone
Dapsone
Adjuctive
Corsticosteroid
Stop antimetabolites, decrease the CNI dose
References
1)Lecture :Pneumocystis Pneumonia in SOT, Prof Gamal Saadi
2) Iriart X, Bouar ML, Kamar N, Berry A. Pneumocystis Pneumonia in Solid-Organ Transplant Recipients. J Fungi (Basel). 2015 Sep 28;1(3):293-331. doi: 10.3390/jof1030293. PMID: 29376913; PMCID: PMC57531
MY DIFFERNTIAL DIAGNOSIS,
PCP CMV PNEMONITIS COVID 19 TB PNEMUMONITIS How do you manage this case?
Admission to HDU or icu according to ABG of the patientDleivering oxygen throgh nasal canula or venturi mask Pulmonology consulatioanSend fbc,full chmistrey panel,esr,crp, procalcitonin, bllod culture , respiartory multiplex,sputu, cluture , qiantiferon test.Ct chest Ask pulmonolgist for brnchosscopy and broncholavelora lavage .In this index case with long standing hoistory of dry cough fever, with this cxr finding mostprobably its is acase of pcp,as the patient is recently transplanted from cadveric donor , using for sure high aggresive immunosuppresion.tretment of pcp is chaleniging most of gude line recomend the following,Bactrim 15/20mg iv/kg divedev q/6, iv for 2-3 weeks if patient recoverd , contiue propylaxis for 3-6 month , some centers prefere to give prophlaxis for life .if allergic to bactrim or seiroius side effects happens ,which is bad sign pentamidine can be given .Hold mmf , target tac is 4-6 , steroids sholud be doubled to till patient recovery.
1.Bil pneumonitis due to Pneumocystis jirovecii (formerly P. carinii), Nocardia asteroides, Cryptococcus neoformans, varicella-zoster virus, community-acquired respiratory viruses (influenza, respiratory syncytial virus, severe acute respiratory syndrome coronavirus 2), or Legionella spp.
2 .COVID pneumonia
Management:
1.0xygen as required,
2.sputum for gm stain ,c/s,fungal stain ,and c/s,
3.PCR pneumocystis,ligionella,corona
4.other test:CBC,ABG,BAL,HRCT of chest
5. Treatment: According to organism.
6.Adjustment of immunosuppressive dose
This is a patient who has a possible pneumonia 4 months after transplantation. He is CMV donor -/CMV recipient +.
His CXR is showing increase bronchopulmonary lung markings with sparing of the costophrenic angles – batwing appearance
The differential diagnosis includes:
Management:
The management will include:
1.Doing a further work up:
2.The treatment will include:
Remember it is a fungus.
High index of suspicion is the degree of hypoxia out of proportion to this CXR.
Yes Professor
Pulmonary Pneumocystis jiroveci infection
Radiographic featuresPlain radiograph– up to 90% of chest radiographs are abnormal, appearances are often non-specific.
– Between 10-15% of patients have normal chest radiographs
– close to 30% have non-specific or inconclusive findings 2-4,6,7.
– Features which are highly suggestive in patients with CD4 counts below 200/mm3 include 5:
Pleural effusions are normally not a feature, seen in less than 5% of cases 9.
High-resolution computed tomography
is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs 3.
Features include 2,3,7:
Atypical features, found more frequently in patients treated prophylactically, include 7:
References
· What is your differential diagnosis?
Symmetrical infiltration is the chest radiographic
PCP
Covid-19.
CMV pneumonia.
Pulmonary T.B.
Fungal infection.
Bacterial pneumonia.
· How do you manage this case?
Investigation:
CBC.
RFT.
Sputum smear for AFB, CBNAAT, and COVID-19 RTPCR.
CT chest.
Flexible bronchoscopy.
Bronchial washings.
For Gram stain, bacterial culture, AFB smear, CBNAAT, AFB culture, fungal smear,
Fungal Culture, cytology, Galactomannan assay, Nocardia stain, Pneumocystis
Jirovecii stain, And Cytomegalovirus (CMV) quantitative PCR.
Plasma CMV quantitative PCR.
Treatment:
Oxygen.
Admission.
Trimethoprim-sulfamethoxazol IV or orally.
Alternative:
•Clindamycin plus primaquine
•Intravenous pentamidine.
Reduction in Immunosuppressive Medications
The National Kidney Foundation recommends reducing immunosuppressive medications
for kidney-transplant recipients who develop PCP .
References :
Xavier Iriart, Marine Le Bouar,Nassim Kamar,and Antoine
Berry.. pneumocystis Pneumonia in Solid-Organ Transplant recipient .J Fungi
(Basel). 2015 Dec; 1(3): 293–331..
Differential diagnosis:
differential diagnosisIn the current scenario of transplant patient on immunosuppression with respiratory symptoms of non productive cough with hypoxemia and in view of chest x ray findings of bilateral pulmonary infiltrates with fluffy cotton appearance,most probably indicating PCP (The most significant risk factors for PCP in patients with organ transplantation are glucocorticoid use and defects in cell-mediated immunity).
-For confirmation:
Laboratory findings:
– Elevated LDH in the setting of pulmonary infiltrates without another apparent cause.
-High Beta-D-glucan in view of clinical suspicion.
-Definitive diagnosis of PCP is by microbiological test of an induced sputum or bronchoalveolar lavage [BAL] fluid which can be obtained safely.
Radiological findings:
diffuse, bilateral, interstitial infiltrates, ground-glass opacities and foci of consolidation.
DD: Physicians have to be vigilant to other diagnoses like:
ARDS
bacterial pneumonia
pulmonary tuberculosis
Managment:
Antimicrobial therapy directed against P. jirovecii is the mainstay of treatment for PCP
-Patients with mild disease have a PO2 ≥70 mmHg:The treatment of choice is oral trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of (15 to 20 mg/kg/day, for at least21 days.
-Patients with moderate disease with PO2≥60 and <70 mmHg oral trimethoprim-sulfamethoxazole plus adjunctive steroids (Prednisone40 mg orally twice daily for five days, followed by 40 mg orally once daily for five days, followed by 20 mg orally once daily for 11 days).
-Patients with Severe disease with PO2 <60 mmHg: recommend parentral TMP-SMX plus Adjunctive corticosteroids.
Alternative regimens:
-TMP plus dapsone
–Primaquine plus clindamycin
–Atovaquone suspension750 mg orally twice daily
-Pentamidine 4 mg/kg IV once daily
References:
Sepkowitz KA, Brown AE, Armstrong D. Pneumocystis carinii pneumonia without acquired immunodeficiency syndrome. More patients, same risk. Arch Intern Med 1995; 155:1125.
Smego RA Jr, Nagar S, Maloba B, Popara M. A meta-analysis of salvage therapy for Pneumocystis carinii pneumonia. Arch Intern Med 2001; 161:1529
Differential diagnosis
Management
Treatment – Given for 21 days.
Reference
Chest radiographs–
-Chest x-rays are initially normal in up to one-fourth of patients with PCP.
-The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates.
-Upper lobe infiltrates and pneumothoraces can also be seen.
2-CMV PNEUMONIA EITHER WITH PCP OR WITHOUT
3-COVID 19 INFECTION COMPLICATED PNEUMONIA
4-Atypical pneumonia with an atypical bacterial infection such as legionella.
5- pneumonia due to fungal infection
What are the radiological characteristics of PCP?
Chest radiographs with following features are highly suggestive of PJP:
Chest HRCT are highly sensitive and can exclude PJP:
How sensitive CXR in the diagnosis of PCP?
4 months following cadaveric transplantation, a 65-year-old male with 38 °C temperature and an ineffective (dry) cough, who is CMV negative but CMV positive.
The air’s oxygen saturation level was recorded at 89%. (hypoxic).
Differential diagnoses are;
1-PcP pneumonia
2-Superimposed infection on top of PCP
3-CMV pneumonia
4-Others viral pneumonia like COVID, influenza
5-Aspergillus
Managment
Supportive therapy in the form of oxygen, admit in HDU, evaluate hydration status.
Full investigation including ABGs, Complete blood picture, blood culture and sensitivity, CRP, LDH, D-dimmers and electrolytes, serum 1,3 beta-D-glucan asaay metabolic profile.
Radiological; HRCT, and BAL or bronchial secretion for PCP PCR
After G6PD enzyme activity, we advise commencing with TMP-SMX (15 to 20 mg/kg/day of the trimethoprim component), administered orally or intravenously in three or four divided doses.
Rest of treatment thatv can be ysed for treatment and prevention are;
Atovaquon, TMP plus dapson, clindamycine plus primaquine,
Pneumocystis Pneumonia Charles F. Thomas, Jr., M.D., and Andrew H. Limper, M.D
Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Jay A. Fishman, Hayley Gans, on behalf of the AST Infectious Diseases Community of Practice
4 months post- KT, CMV status D-/ R+, presented with symptoms suggestive for pneumonia ( fever, non-productive cough) with hypoxia 82 % Spo2. CXR showed; diffuse, bilateral, interstitial infiltrates.
The etiology of infectious pneumonitis in immunocompromised patients is diverse.
Differential diagnosis is the setting of immunocompromised host:
– PJP pneumonia.
– Viral pneumonia; CMV, HSV, Covid .
– Bacterial pneumonia
– Tuberculosis.
– Fungal infection.
– Drug-induced Interstitial pneumonitis.
*Hypoxemia out of proportion to plain radiographic imaging is highly suggestive for PCP.
-PCP it still remains an important causative pathogen among SOT recipients . However, the survival of non-HIV patients with PCP is worse than those with AIDS and reaches up to 50% even with adequate therapy.
-Incidence of symptomatic CMV infection is 15-20% for D-/R+ patients.
-Several studies have identified CMV as a clear risk factor for PCP in SOT patients, studies shows that 20%–53% of SOT recipients with PCP had a CMV infection compared to 0.6%–24% of those who did not develop PCP. However, it is unclear whether CMV infections simply reflect the degree of immunosuppression or if CMV can directly increase the risk of PCP.
-Presentation of PCP is usually non-specific and insidious, the most common symptoms being dyspnea and/or non-productive cough and hypoxia.
How do you manage this case?
Further history is needed about the induction therapy, current IS regimen and levels, CMV prophylaxis and PJP prophylaxis, any recent contact with
Recent virual load as part of pre-emptive therapy.
Management:
General measures:
– HDU / ICU; Stabilized the patient
– ABC; O2 and respiratory support to maintain Spo2 > 94%
– Manage the fever with antipyretic.
– Patient should be managed empirically till we have the results.
– Fluid management.
Work up required:
– CBC with differential, CRP, procalcitonin.
– VBG
– RFT, LFT.
– LDH
– Blood culture.
– Respiratory culture, and viral panel.
– COVID PCR
– Viral load; CM PCR, , EBV PCR.
– Sputum for microscopy, staining, CMV, PJP and aspergillus (It may be difficult to obtain a sample as patient has dry cough) hypertonic saline can be used to induce sputum. The sensitivity of induced sputum is only 30%‐55%, compared with 80%‐95% with BAL
– BAL bronchoscopy; staining with Gomori methenamine‐silver stain, PCR( can’t distinguish colonization from infection)
– Immunosuppression level Tacrolimus level.
– serum levels of beta-D-glucan. a high sensitivity (>90%) with lower specificity (<80%)
– CXR; abnormal up to 90 %, No radiographic pattern is pathognomonic for PJP is a diffuse interstitial
– HRCT chest. often demonstrates abnormalities not appreciated on routine chest radiography and should be obtained, especially if CXR is normal with a consistent clinical presentation
Cover for bacterial pneumonitis:
– Generally start broad spectrum antibiotics then guided by culture.
Cover PCP;
-TMP‐SMX remains the drug of choice; most effective systemic therapy for PJP.
– Treatment for at least 3 weeks then continue on secondary prophylaxis for 6-12 months.
– 15‐20 mg/kg/day of the TMP component given IV in divided every 6‐8 h; lower doses may be sufficient. In milder disease, two double‐strength tablets can be given po tid
-Alternative agents are less effective and include IV pentamidine isethionate, atovaquone, primaquine and clindamycin if patient is allergic or intolerance
-In severe infections, IV pentamidine is the second‐line agent after TMP‐SMX. S/E: pancreatitis, hypo‐ and hyperglycemia, bone marrow suppression, renal failure, and electrolyte disturbances
Adjunctive corticosteroids:
-The use in non‐HIV PJP infections are contradictory.
-Used in patients with hypoxemia (pAO2 < 70 mm Hg on room air),
-It should be considered early within 72 hours of initiating antimicrobial therapy.
-The optimal dose of corticosteroids has not been established, but 40‐60 mg of prednisone given two to three
times daily for 5‐7 days before gradual tapering over 7‐14 days is recommended to avoid rebound pneumonitis
Secondary prophylaxis:
-TMP‐SMX is the drug of choice for prophylaxis of PJP.
-Dapsone is often used as a second‐line agent for PJP prophylaxis.
As the patient is high risk for CMV pneumonitis; if confirmed:
-Treatment is mandatory in all cases of tissue invasive CMV disease, irrespective of viral load with IV gancyclovir for 14-21 days followed by oral valganciclovir ( adjust for eGFR)
Management of IS:
– Reduce (by 50%) antimetabolites or discontinue if there is evidence of life-threatening infection
-Reduce CNI to lower level.
-Corticosteroids are generally continued
– Monitoring graft function closely for any rejection.
References:
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020;20(1):492. Published 2020 Jul 10. doi:10.1186/s12879-020-05217-x
Kim JE, Han A, Lee H, Ha J, Kim YS, Han SS. Impact of Pneumocystis jirovecii pneumonia on kidney transplant outcome. BMC Nephrol. 2019;20(1):212. Published 2019 Jun 10. doi:10.1186/s12882-019-1407-x
Fishman, JA, Gans, H; on behalf of the AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13587. https://doi.org/10.1111/ctr.13587
Thank you and well done
👉Old age recipient , with fever, dry cough and intense desaturation together with radiological finding of parahilar interstitial infiltration starting after the routine prophylaxis for 3 months PCP prophylaxis is highly suggestive of PCP.
👉 Differential diagnosis:
_PCP.
_CMV pneumonitis either alone or convomitant with PCP (after end of 3 months of prophylaxis for this intermediate risk for CMV).
_COVID 19 (however, it tends to have subpleural affection …unlike subpleural sparing in PCP), excluded by PCR and COVID IgM.
_Drug induced interstitial lung disease that can occur with mTORi) so reviewing the patient induction and maintenance therapy is essential.
_Risk of PCP is increased with strong induction therapy, TAC and MMf maintenance therapy and use of sirolimus.
👉 Management of the case:
_ICU admission as mortality up to 30%.
_OXygen supplementation or non invasive ventilation as CPAP or BIPAP to improve oxygenation and ensure adequate hydration.
_Arterial blood gases if PaO2 less than 70 mmHg, use of steroids is indicated.
_Confirm diagnosis of PCP by bronchoscopy and BAL with staining with Gomori silver stain or immunofluroscent or PCR.
_Sulfamethoxazole and trimethoprim intravenous remains the most important and commonly uses treatment for PCP
_ in case of allergy to SMX_TM , use of pentamidine or dapson with primaquine will be reasonable
_CMV PCR to exclude concomitant infection that needs IV ganciclovir treatment for 5 days followed by oral vanganciclovir.
_Reduction of IS as stop antiproliferative till stabilization and decrease CNI to the lower therapeutic window to control the infection.
_Cover with steroids by increasing the dose or restart it if steroid free or minimization protocol
_Shift from sirolimus to MMF may be considered.
_Follow up of CBC, liver and kidney function is essential
_LDH level is prognostic marker in PCP.
_Life long secondary prophylaxis with oral SMX_TMP is warranted in such high risk patient.
Excellent
Thanks dear professor
What is your differential diagnosis?
Fever, dry cough, and hypoxemia 4 months post kidney transplantation with the radiological manifestations (chest x-ray showed perihilar and bilateral fine interstitial infiltrates with interstitial edema); I will put Pneumocystis Jirovecii Pneumonia as first differential diagnosis
Other differential diagnoses include:
1. Pulmonary tuberculosis
2. CMV disease
3. EBV disease
4. SARS-Covid-2 infection
5. Atypical bacterial infections
Radiological features of PJP:
Chest x-ray (Abnormal in 92–96%):
o Early PJP is manifested by fine, bilateral, perihilar, diffuse infiltrates that progress to an interstitial alveolar butterfly pattern; from the hilar region, the infiltrates often spread to the apices or bases. This pattern often progresses despite therapy with progressive consolidation over 3 to 5 days
o Unusual patterns are common including nodules, unilateral infiltrates, pleural effusions, pneumothoraces, lymphadenopathy, or lobar consolidations
CT chest:
o More sensitive than routine chest radiography
o Often demonstrate abnormalities not appreciated on routine chest radiography and should be obtained in case of normal plain chest radiographs with a consistent clinical presentation
o Bilateral ground glass opacities, pneumatoceles, and diffuse varying in size centrilobular and peribronchovascular consolidation foci
How do you manage this case?
Diagnosis:
o Complete history and clinical examination
o CBC, e GFR, electrolytes, CRP, s. albumin, liver enzymes and blood culture
o O2 saturation and ABG
o Serological tests for atypical bacterial infections
o PCR test for SARS-Covid-2 from nasopharyngeal swab
o Tuberculin skin test (TST) and interferon gamma for tuberculosis
o Viral load for CMV and EBV
o High-resolution chest CT scan is more sensitive and specific for PJP and exclude other causes
Diagnosis of PJP:
1. Measurement of plasma (1→3) b-D-glucan: may suggest diagnosis. Meta-analysis suggests a sensitivity of almost 95%, but with a specificity in the mid-80%
2. LDH: elevated in almost all cases of (over 300 IU/ml)
3. Multiple induced sputum samples: stain using antibodies for PCP (immunoflourescent, immunoperoxidase) and for Pneumocystis and other organisms (Giemsa, Silver, and others). Use PCR-based diagnostics on respiratory secretions. Samples should also be assayed for routine bacterial, fungal, mycobacterial, and other organisms to rule outconcomitant infections. Evaluate for CMV or other respiratory viral coinfection
4. PCR for PJP
5. Bronchoscopy with BAL: yield generally ≥70% in non-AIDS immunocompromised hosts when coupled with antibody staining
6. Bronchoscopy for transbronchial biopsies: increases yield of routine BAL
7. Open lung biopsies when other diagnostic fails or where other concomitant diseases may be a concern. Often considered to be a gold standard, but early patchy disease may decrease yield
Treatment:
v O2 therapy (maintain 0xygen > 92%)
v Reduction in immunosuppression
v Duration of antimicrobial treatment is for at least 14days (21 days in severe infection)
Trimethoprim sulfamethoxazole (TMP-SMX):
o Is the drug of choice and is considered to be the most effective systemic therapy for PCP
o Dose is 15–20 mg/kg/day of the TMP component given IV in divided doses every 6–8 hours often in combination with corticosteroids
o Side effects include bone marrow suppression, rash including Stevens-Johnson syndrome, hepatitis, interstitial nephritis, aseptic meningitis, and pancreatitis
o Hydration should be maintained
o Patients on high-dose TMP-SMX should have regular monitoring of cell counts, creatinine and potassium
Pentamidine isesthionate:
o In severe infection (second line treatment)
o Dose is 4 mg/kg/day IV initially over 1–2 hours
o Side effects include pancreatitis, hypoglycemia, hyperglycemia, bone marrow suppression, renal failure and electrolyte disturbances
Atovaquone:
o Dose is 750 mg po bid (optimal dose uncertain; 1500 bid used anecdotally)
o Available in an oral suspension only
o Has variable oral absorption (best with fatty foods)
o Approved only for mild and moderate PCP
Primaquine and clindamycin:
o Primaquine 15–30 mg po qd in combination with clindamycin 600–900 mg IV or po q6–8 hours This combination studied in mild to moderate PCP in AIDS
o Long-term use of clindamycin can predispose to infection with Clostridium difficile
o Primaquine should be avoided in G6PD deficiency
Dapsone and trimethoprim:
o Dapsone 100 mg po qd used in combination with trimethoprim 15 mg/kg/day po divided tid
o This combination is used with sulfa allergy, though dapsone may elicit sulfa allergies as well
Trimetrexate with folinic acid:
o Trimetrexate 45 mg/m 2/day IV (or 1.5 mg/kg/day IV in patients <50 kg) with folinic acid 20 mg/m2 po or IV every 6 hours (80 mg/m2 total daily)
o Folinic acid therapy extends≥3 days beyond trimetrexate therapy
o Trimetrexate causes bone marrow suppression and must be used with folinic acid, 10 mg po qd Outcomes are inferior to TMP-SMX in AIDS
Pyrimethamine and sulfadiazine:
o Pyrimethamine load of 100–200 mg po, followed by 50–100 mg po qd in combination with sulfadiazine 4 g po qd in divided doses
o Limited data available on this regimen
o Usually with folinic acid 10mg po qd to reduce bone marrow toxicity
Adjunctive agents Corticosteroids:
o 40 mg–60 mg of prednisone (or equivalent) po bid with taper after 5–7 days over a period of 1–2 weeks
o Best administered within 72 hours in the setting of hypoxia (pAO2 < 70 mmHg)
o Commonly used but not well studied in transplantation
o May require prolonged taper to avoid immune reconstitution pneumonitis
Prophylaxis:
For any transplant patient with a history of prior PJP infection, lifelong prophylaxis is often indicated
1. First line therapy: TMP-SMX (80 mg TMP/400 mg SMX or 160 mg TMP/800 mg SMX po (single or double strength) daily or three times weekly)
2. Second line therapy: dapsone (50–100 mg po qd), atovaquone (1500 mg po as single dose), Pentamidine (300 mg administered through aerosolized nebulizer q 3–4 weeks), Clindamycin and pyrimethamine (Up to 300 mg of clindamycin po qd with 15 mg of pyrimethamine po qd)
References
1. Varnas D, Jankauskienė A. Pneumocystis Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after Transplantation: A Case Report and Literature Review. Acta Med Litu. 2021;28(1):136-144. doi: 10.15388/Amed.2020.28.1.5. Epub 2021 Jan 25. PMID: 34393636; PMCID: PMC8311846.
2. Martin, S.I., Fishman, J.A. and (2013), Pneumocystis Pneumonia in Solid Organ Transplantation. American Journal of Transplantation, 13: 272-279.
3. Fishman JA, Gans H; AST Infectious Diseases Community of Practice. Pneumocystis jiroveci in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13587. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616.
Thank you and well done
What is your differential diagnosis?
This is a case of cadaveric allograft transplantation, that usually requires aggressive induction immunosuppression.
Given the high-risk transplantation and aggressive immunosuppression, patient is at higher risk of infections. During the first 6 months after transplantation, recipients are usually maintained on anti-CMV/HSV and anti-PCP prophylaxis. But the infection risk is not zero.
The presence of bilateral interstitial infiltrates, fever, cough and desaturation raises the suspicion of PCP.
Although other etiologies cannot be excluded.
Differential diagnosis:
– PCP
– CMV
– COVID-19
– Atypical pneumonia
– ARDS
CXR findings of PCP are not specific and could be absent in significant number of patients in particular in the early stages. These include: bilateral interstitial infiltrated, bilateral perihilar shadows, reticulonodular marking, bilateral cystic or ground glass appearance and honeycombing.
How do you manage this case?
Initial treatment is organism non-specific and includes oxygen supplementation to achieve SO2> 92% (nasal cannula, face mask or NIV), reduce or discontinuation of MMF, assessment of volume status and achieving euvolemic state.
Diagnostic approach
Nasal swab for COVID-19
Swab for Influenza A and B
Blood for CMV PCR and sputum PCR
Diagnostic tests for PCP that include the following:
Gomori methenamine silver staining on samples (sputum or bronchoalveolar lavage fluid).
Serum β-D-glucan (BDG) test: Widespread method but lacks species-specificity.
PCR analysis:
Rapid and more sensitive than GMS staining.
Rarely utilized in clinical practice.
Variable cut values in different studies.
Metagenomic next-generation sequencing: a method for determining the genetic makeup of an organism.
Treatment
The empirical treatment should be started as soon as possible and should cover CMV, INFLUENZA, PCP and atypical bacteria. The cornerstone treatment of PCP is Sulphamethexazole/Trimethoprim in a dose of 15-20 mg/kg/day of TMP oral or iv in 4 divided doses for 3-4 weeks.
Alternatively, if Sulphamethexazole/Trimethoprim is tolerated or contraindicated, other drug options can be used such as Pentamidine, Atovaquone, Primaquine plus clindamycin, and Dapsone.
Thank you and well done
I agree, BDG test lacks specificity and sensitivity
What is your differential diagnosis?
Atypical viral pneumonia including covid 19 and CMV pneumonitis
PJP
CMV co-infection with PJP
Drug-induced pneumonitis (in the case of everolimus or sirolimus maintenance IS)
The diagnosis of PJP is challenging due to nonspecific clinical presentation and signs in addition to the limited radiological findings so we depend on high clinical suspicion in indexed case post-transplantation with intense IS, induction type, CMV serostatus and the duration of antibiotics prophylaxis ( as the recipient is CMV positive so co-infection with CMV is considered one important risk factor for PJP as can alter the T cell immunity response and reactivation of infection.
Clinical presentation remained nonspecific however Hypoxia, Fever, and dry cough in immunocompromised patients with seropositive CMV after 4 months from transplantation should keep a high index of clinical suspicion of atypical viral infection vs PJP or a combination of CMV co-infection with PJP and need more history about the induction type of immunosuppression and the current maintenance IS ( steroid, MMF, and CNI VS M tor inhibitors Like everolimus or sirolimus with CNI? fever with dry cough and hypoxemia is highly suggestive of PJP, is this patient on PJP prophylaxis or stopped for intolerance or side effects?
The radiological characteristics of PJP include peri-hilar reticular nodular infiltration with pleural sparing. Only 5% still can be unilateral infiltration, and in ¼ could be normal CXR, pleural sparing with apical interstitial infiltration is highly suggestive for PJP, and pleural effusion is still reported in < 5% of cases.
How do you manage this case?
Further investigations needed like full blood count, urea and electrolytes, CNI trough level, liver function test, G6PD screen
noninvasive testing like ABG The single-breath diffusing capacity for carbon monoxide appear to be the most sensitive for PCP.
Send for CMV PCR, COVID 19 PCR, hypertonic silane nebulization to induce sputum for PJP q real time PCR
Chest CT scan typical central ground glass appearance sparing the peripheries with pnematocel, cysts , pleural effusion in < 5%, and LAP uncommon
The final diagnosis requires a direct finding of the organism in lower respiratory secretions or tissue. Invasive procedures like bronchoscopy and the use of BAL fluid assay or transbronchial biopsy (however increased risk of bleeding and pneumothorax)
New noninvasive molecular genomic testing with a promise to improve the quality of the diagnosis.
First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may require alternative agents like dapsone, pentamidine, atovaquone, clindamycin in combination with primaquine Echinocandins show some promise for new combination therapies; however, more studies needed to define ideal antimicrobial therapy for PJP as well as the role of corticosteroids in non-HIV infected patients. Patients with immunodeficiency without HIV have a tendency to have more severe symptoms and a higher risk of respiratory failure and death (3).
in the case of CMVpneumonitissalso should be treated with ganciclovir IV 5mg /kg BID for 3 weeks with close monitoring with CMV PCR, and FBC , graft function
if this patient on everolimus or sirolimus should be stopped and modified to alternative IS like MMF or azathioprine with CNI
References
1. Weyant RB, Kabbani D, Doucette K, Lau C, Cervera C. Pneumocystis jirovecii: a review with a focus on prevention and treatment. Expert Opin Pharmacother. 2021 Aug;22(12):1579-1592. doi: 10.1080/14656566.2021.1915989. Epub 2021 Apr 19. PMID: 33870843.
2. Zhang Z, Li Q, Shen X, Liao L, Wang X, Song M, Zheng X, Zhu Y, Yang Y. The medication for pneumocystis pneumonia with glucose-6-phosphate dehydrogenase deficiency patients. Front Pharmacol. 2022 Sep 7;13:957376.
3. Krajicek B. J., Limper A. H., Thomas C. F. (2008). Advances in the biology, pathogenesis, and identification of Pneumocystis pneumonia. Curr. Opin. Pulm. Med. 14 (3), 228–234. 10.1097/MCP.0b013e3282f94abc
4. Chatterton JM, Yen DO. Laboratory investigation of Pneumocystis carinii pneumonia. Genitourin Med. 1992 Oct;68(5):336-41. doi: 10.1136/sti.68.5.336. PMID: 1385296; PMCID: PMC1195994.
5. Week five lecture
Thank you and well done
What is your differential diagnosis?
*PCP
*Bacterial pneumonia
*ARDS
*Viral pneumonia
*Pulmonary Tuberculosis
*Pulmonary Embolism
*Mycobacterium Avium Complex
*CMV
*Histoplasmosis
How do you manage this case?
*ICU admission
*The CPAP or BiPAP availability should be consider early
*Early BAL
*Diagnosis of PJP relies on combination of laboratory findings and diagnostic imaging together with physical examination and history-taking.
*Routine investigation:
CBC, RFT, LFT, CRP, D-dimar,Blood culture….)
*Quantitative polymerase chain reaction (qPCR)- more accurate way to diagnose PJP
*(1-3)-β-d-glucan (BG) –most reliable serologic biomarker for PJP diagnosis
*Krebs von den Lungen-6 antigen (KL-6)- together with BG, is the most accurate serologic apptoach for PJP diagnosis
*Lactate dehydrogenase (LDH)
*S-adenosyl methionine (SAM)
*Sputum induction
*Imaging studies used in the diagnosis of PJP include:
Chest CT Scan– most pertinent finding is ground glass opacity (GGO) indicative of alveolar subtotal consolidation
Chest Radiography- nonspecific, can be normal, less common patterns have been reported, including lobar infiltrates, pulmonary nodules, and pneumatoceles and other cystic changes.
*Anti-Pneumocystis Agents:
Trimethoprim-Sulfamethoxazole TMP-SMX is the first-line agent for the treatment of mild to severe PCP in both HIV and non-HIV-infected patients. Its also the drug of choice for SOT patients because of its high efficacy and its availability in oral and parenteral forms
*Atovaquone– one of the oral treatment alternatives for mild and moderate PCP
*Pentamidine isethionate- preferred alternative drug regimen to TMP-SMX
Clindamycin and Primaquine-good alternative choice for treatment of mild to moderate PJP
*Caspofungin
*KDIGO and the American Society of Transplantation guidelines recommend treatment with adjunctive corticosteroids for SOT recipients with moderate to severe PCP.
*Reducing immunosuppressive medications for kidney-transplant recipients who develop PCP
Stop antimetabolites until this patient in the ITU, decrease the CNI.
*Prophylaxis
TMP-SMX- recommended prophylactic agent
Aerosolized pentamidine
Atovaquone
Dapsone
Physiotherapy Intervention
Physiotherapy interventions for the treatment of PJP would be the same as treating pneumonia. This includes:
Modified postural drainage
Shaking, vibrations and percussion
Coughing and huffing exercises
Segmental and diaphragmatic breathing exercises
Mobilization of the patient
General body conditioning exercises
# References:
1.Kante, Meenakshi & Racherla, Rishi & Usha, Kalawat. (2019). Pneumocystis jirovecii Pneumonia: A Revisit to the Old Malady. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH retrieved fromhttps://www.researchgate.net/publication/337105006_Pneumocystis_jirovecii_Pneumonia_A_Revisit_to_the_Old_Malady doi:10.7860/JCDR/2019/42636.13318
2. Roblot F., Godet C., le Moal G., Garo B., Faouzi Souala M., Dary M., de Gentile L., Gandji J.A., Guimard Y., Lacroix C., et al. Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Eur. J. Clin. Microbiol. Infect. Dis. 2002;21:523–531. [PubMed] [Google Scholar]
3. Cushion M.T., Linke M.J., Ashbaugh A., Sesterhenn T., Collins M.S., Lynch K., Brubaker R., Walzer P.D. Echinocandin treatment of Pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS ONE. 2010;5:e8524. doi: 10.1371/journal.pone.0008524. [PMC free article] [PubMed] [CrossRef] [Google Scholar
Thank you and well done
This is post kidney transplant patient from deceased donor present with fever dry cough and hypoxia his CXR showed bilateral infiltration with prominent perihilar shadowing with the given scenario the most likely diagnosis is PCP pneumonia -other differential:
-CMV pneumonitis because he was CMV positive before kidney transplant.
– Other viral pneumonias like covid 19.
-Bacterial pneumonia
-Start with proper history and examination ongoing with resuscitations and supportive treatment by stabilization of oxygen saturation and hemodynamic stabilization .
Investigations ;
-Full blood counts and chemistry
-Sputum analysis culture and gram stain
-Bronchoalveolar lavage PCR for PCP which is the gold standard test ( Due to higher sensitivity (98.3%) and specificity (91.0%) )
– Metagenomic Next-Generation Sequencing : (mNGS) analysis of a BALF specimen identified a large number of P. jirovecii reads, allowing to confirm the diagnosis of PCP. it is a novel diagnostic method itis sensitive but not specific -Plasma PCR for CMV .
looking for ground glass appearance ,reticular opacities , septal thickening, a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present, honeycombing, extent of infiltration beside prominent perihilar shadowing and sparing of subpleural area .
Treatment and prognosis:
Prophylaxis : This patient needs second prophylaxis for 6 months due to high risk of recurrence .
Reference :
3.Infect Drug Resist. 2020 Aug 13;13:2829-2836. doi: 10.2147/IDR.S257587. eCollection 2020.
Thank you and well done
What is your differential diagnosis?
1- The most important differential diagnosis is Pneumocystitis carenii pneumonia (PCP). especially if prophylaxis is not given or stopped
2- CMV pneumonitis
3- Other viral infections including influenza and Covid
4- Bacterial pneumonia
How do you manage this case?
Diagnosis
It may be problematic to have an optimal specimen in a case of dry cough by ordinary cough, so it should be done one of the following ways:
Diagnosis of PCP depends on the detection of the cystic or trophic forms in respiratory secretions by immunofluorescent staining (the organism cannot be cultured) , PCR has a disadvantage of not differentiating between infection and colonization
Treatment
I- General measures
II- Specific treatment
A- Reduction of immunosuppression if serious infection detected
B- Antimicrobial therapy
References
1. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978; 61:35.
2. Catherinot E, Lanternier F, Bougnoux ME, et al. Pneumocystis jirovecii Pneumonia. Infect Dis Clin North Am 2010; 24:107.
Thank you and well done
What would you give in case of TMP-SMX allergy or intolerance?
Severe disease (A-a O2 gradient is ≥45 mmHg, PaO2 <60 mmHg, RR> 25 with respiratory muscle fatigue, hypoventilation manifested by hypercapnea).
Non severe disease
Inductions of adjuvant steroid therapy
In pregnancy
Monitoring patients on treatment –
Duration of therapy
Secondary prophylaxis
References
1- up-to-date
A 65-year-old man ,4 months after cadaveric transplantation.
– fever (38 °C) and non-productive (dry) cough.
-CMV negative to CMV positive recipient.
-Oxygen saturation on air was reported at 89% (hypoxic).
What is your differential diagnosis?
Post kidney transplant with hypoxemia.
1-PCP.(most suspected).
2-Viral induced pneumonia (COVID 19 ,Influenza).
3-CMV pneumonitis .
4-aspergillus.
5-Other causes of CAP.
How do you manage this case?
1-Shifting our patient to critical area with supportive o2 therapy in the form of CPAP.
2-Basic investigation (CBC, CRP, LDH, Blood C/S, Sputum C/S, Serial RFT, LFT ).
3-ABG/ serum beta-D-glucan assay.
4-HRCT (looking for par hilar shadows with sub pleural sparing , and ground glass appearance).
5-BAL(The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens.)
Treatment:
=We recommend starting with TMP-SMX (15 to 20 mg/kg/day of the trimethoprim component) orally or IV given in three or four divided doses, after G6PD enzyme activity.
= Alternative agents when TMP-SMX sensitivity is present such as
For mild disease, options include:
•Atovaquone.
•Clindamycin plus primaquine.
•TMP plus dapsone.
For moderate disease, options include:
•Clindamycin plus primaquine.
•TMP plus dapsone.
For severe disease, options include:
•Clindamycin plus primaquine.
•Intravenous pentamidine.
=Stopping MMF at tine being and continue steroid and CNI with low trough level.
=After complete recovery, we can extend prophylaxis Septrin dose up to 2 years.
References:
1- Thomas CF Jr, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004;350(24):2487-2498. doi:10.1056/NEJMra032588.
2- Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies. Ann Intern Med. 1984;100(5):663-671. doi:10.7326/0003-4819-100-5-663.
3- Wilson JW, Limper AH, Grys TE, Karre T, Wengenack NL, Binnicker MJ. Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity. Diagn Microbiol Infect Dis. 2011;69(2):145-152. doi:10.1016/j.diagmicrobio.2010.10.021.
4- Hughes WT, Feldman S, Sanyal SK. Treatment of Pneumocystis carinii pneumonitis with trimethoprim-sulfamethoxazole. Can Med Assoc J. 1975;112(13 Spec No):47-50.
Thank you and well done
DDX.:
Viral infections on the top of list PCPbacterial infectionsfungal infectionsacute lung injuryrestrictive (interstitial fibrosis) lung diseaseHow do you manage this case?
co-ordination with microbiologist and pulmonologist
further work up for reaching diagnosis such as BAL, biopsy (silver staining and immunostaining )
supportive care : oxygen (CPAP)if PCP : IV TMP/SMX then oralclose monitoringcontinuous prophylaxis after recovery from disease
Thank you Dalshad
There are many typos. Please proof-read before uploading.
Radiological finding in PJP
Bilateral Perihilar opacity
Bilateral ground glass appearance
Sparing subpleural lung tissue
Reticular nodular opacities
Sometime presentation with spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities.
High resolution CT lung has sensitivity of 100% of detecting ground glass appearance but this mean that if the ground glass appearance is not present diagnosis of PJP could not be formulated
Atypical radiological finding could be present so absence of the above radiological finding either in X- Ray / CT will not exclude the diagnosis under high clinical suspension
Ref
Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84.
Block BL, Mehta T, Ortiz GM, Ferris SP, Vu TH, Huang L, Cattamanchi A. Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with AIDS. Case Rep Infect Dis.
Thank you and well done
-What is your differential diagnosis?
-How do you manage this case?
Management is MDT & involved admission to ICU for better monitoring and aggressive treatment including fluids resuscitation
Other investigations
Antibiotics for at least 2 weeks
Source:
Oxford handbook of nephrology 6 th edition, drug resistance in pneumocystis by Jannik Helweng -Larsen et al.
Thank you and well done
Wlcm, prof
it is important to establish the patient’s immunization history, travel history
Diagnostic approach:
Complete blood count with differential
Electrolytes, blood urea nitrogen, and creatinine
Blood cultures (minimum of two sets, with at least one peripheral set and one set from any indwelling catheter)
Urine sediment examination and culture
Sputum for Gram stain, fungal smears, and cultures
Imaging of the lungs (chest radiography or, if possible, chest computed tomographic scanning) and imaging of any symptomatic site (eg, abdomen)
Skin examination, looking for evidence of metastatic infection
CMV quantitative molecular testing is often valuable; other viral polymerase chain reaction (PCR) assays as appropriate to the individual (adenovirus, parvovirus B19, severe acute respiratory syndrome coronavirus 2)
Consideration of sample collection for nonculture-based diagnostic tools (eg, specific molecular and antigen tests such as Aspergillus or Pneumocystis PCR, cryptococcal antigen), Aspergillus galactomannan, beta-1,3,-glucan, whole genome sequencing
BAL samples should be coupled to microbiologic studies (cultures, polymerase chain reaction, Aspergillus galactomannan antigen) to improve sensitivity
Treatment:
Trimethoprim-sulfamethoxazole: We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients.
Alternative agents by severity of disease: Alternative drugs for the treatment of PCP have been studied primarily in patients with HIV. Regimens that may be used for PCP when TMP-SMX cannot be used include clindamycin plus primaquine, trimethoprim plus dapsone, atovaquone, and intravenous (IV) pentamidine). The choice of regimen for patients who cannot take TMP-SMX depends in part on the severity of the disease.
References:
Joos, L., Chhajed, P. N., Wallner, J., Battegay, M., Steiger, J., Gratwohl, A., & Tamm, M. (2007). Pulmonary infections diagnosed by BAL: a 12-year experience in 1066 immunocompromised patients. Respiratory medicine, 101(1), 93-97.
-Uptodate
Thank you and well done
What is your diffrential diagnosis?
The chest x ray showed bilateral hilarity lymphadenopathy with pnemocyste scarttered in bothe lung field
sub plural sparing is not clear here as it is mild to moderated disrease or it is in the early stage
most proberly this finding due PCP ,usually the patient has chest symptoms with sub clinical course for 3 weeks before full pictuer
usually chest xray will be normal in one fourth of the casese so we can not relay on normal x ray to rule out the PCP, withfalse negative result in 30 to 40 % of the cases.
THe causese include all the causes which leading to bilateral hilar shadow like
pulmonary odeama
bilateral interstitial pnemonitis
For definite diagnosis better to have CT chest which is more sensitive .
referrences
uptodate
I suggest:
Please use bold or underline for headings or sub-headings to make it easier to read.
Typing ‘Up to date’ or KGDIO’ guidelines is not good enough a reference.
Thank you and well done
· What is your differential diagnosis?
1. Pneumocystis jirovecii Infection
2. Acute Respiratory Distress Syndrome
3. Cytomegalovirus
4. Lymphocytic Interstitial Pneumonia
5. Mycoplasma Infections
6. Viral Pneumonia
7. Pulmonary Embolism
8. Legionellosis
9. Tuberculosis
10. Mycobacterium avium Complex (MAC) Infection
· How do you manage this case?
· Oral TMP/SMX has excellent bioavailability and may be considered in patients with the mild-moderate disease.
· Severe cases may need hospitalization, supportive therapy, and Oxygen therapy.
· Daily intravenous TMP/SMX (15–20 mg/kg TMP; 75–100 mg/kg SMX) is the most efficacious treatment for mild to severe PcP in SOT. Duration of therapy is a minimum of 14 days, up to 21 days for severe disease
· IV pentamidine is the preferred second-line agent,
· It is recommended to reduce immunosuppression when managing PcP in kidney transplant recipients.
· In SOT patients with moderate to severe disease, twice-daily 40–60 mg prednisone for 5–7 days within 72 h of diagnosis has been recommended, with a gradual reduction in dose over a further 7–14 days
References:
1- Cunha BA, Schoch PE, Berbari N. Cryptococcal vs Pneumocystis (carinii) jiroveci pneumonia (PCP): Clinical & Microbiology differential diagnostic considerations. Infect Dis Pract. 2006. 30:514-517.
2- White, P.; Price, Jessica; Backx, Matthijs (2018). Therapy and Management of Pneumocystis jirovecii Infection. Journal of Fungi, 4(4), 127–. doi:10.3390/jof4040127
I suggest
Thanks a lot dear professor..
Differential diagnosis
PJPCMVBacterial pneumoniaany other viral pneumonia such as COVID19TBDiagnostic tests
Microscopy with stainingType of respiratory specimen —
The most rapid and least invasive method is sputum bronchoscopy with BAL should be performed. Lung biopsy with tissue stains and PCR has excellent sensitivity for diagnosing PCP but is rarely required 2. Polymerase chain reaction — in sputum or BAL fluid, blood, or nasopharyngeal aspirates.
3. Beta-D-glucan assay
4 pcr MCV
KDIGO GUIDELINE
We recommend that KTRs with PCP diagnosed by bronchial alveolar lavage and/or lung biopsy be treated with high-dose intravenous trimethoprim-sulfamethoxazole, corticosteroids, and a reduction in immunosuppressive medication. (1C)
We recommend treatment with corticosteroids for KTRs with moderate to severe PCP (as defined by PaO2 o70mmHg in room air or an alveolar gradient of 435mmHg). (1C)
Trimethoprim-sulfamethoxazole —
We recommend (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV.
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component)
Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
Alternative agents by severity of disease
For mild disease, options include:
•Atovaquone
•clindamycin plus primaquine
•TMP plus dapson
For moderate disease, options include:
•clindamycin plus primaquine
•TMP plus dapson
●For severe disease, options include:
•clindamycin plus primaquine
•Intravenous pentamidine
duration of therapy about 21 days
the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows a partial pressure of oxygen <70 mmHg or an alveolar-arterial (A-a) oxygen gradient ≥35 mmHg, or hypoxemia on pulse oximetry (eg, room air oxygen saturation <92 percent).
REFERENCES
Uptodate
Kdigo guideline
Here I ll correct my typing mistakes
Differential diagnosis
Diagnostic tests
Type of respiratory specimen —
2. Polymerase chain reaction — in sputum or BAL fluid, blood, or nasopharyngeal aspirates.
3. Beta-D-glucan assay
4 pcr MCV
KDIGO GUIDELINE
(TMP-SMX) is the treatment of choice for PCP of any severity in patients without HIV.
The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component)
Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract.
Alternative agents by severity of disease
For mild disease, options include:
•Atovaquone
•clindamycin plus primaquine
•TMP plus dapson
For moderate disease, options include:
•clindamycin plus primaquine
•TMP plus dapson
For severe disease, options include:
•clindamycin plus primaquine
•Intravenous pentamidine
duration of therapy about 21 days
the use of glucocorticoid therapy in patients with PCP who, while breathing room air, have an arterial blood gas measurement that shows
REFERENCES
Uptodate
Kdigo guideline
Typing ‘Up to date’ or KGDIO’ guidelines is not good enough a reference.
It seems copying and pasting from KGDIO is not good enough. Apologies to you if I am sounding abrupt.
Thank you professor for your notes. I appreciate your efforts and your notes.
I ll be more precise and careful the next time .
So nice of you Dr Ghalia to make note of my suggestions
I suggest:
Please use bold or underline for headings or sub-headings to make it easier to read.
Typing ‘Up to date’ or KGDIO’ guidelines is not good enough a reference.
You are right. Thank you prof.
Pneumonia in post transplant recipient has wide differential diagnosis
· It may be viral ,bacterial ,fungal ,o parasitic but in this case The radiographic features can narrow the differential diagnosis
· Diffuse, bilateral infiltrates suggest CMV, respiratory viruses, Mycoplasma, Legionella, and Pneumocystis jirovecii (PJP). Diffuse bilateral micronodular infiltrate mostly perihilar raises concern for PJP
Management
1. Hospitalization
2. Stabilization
3. Respiratory support
4. Initial Evaluation include
History
• Recent hospitalizations or illnesses
• Social/exposure history
• Immunization status
• Comorbid conditions
• Current degree of immunosuppression
• Exposure history indicative of possible pathogen
Labs and Studies
• Complete blood count with differential
• Electrolyte and kidney function evaluation
• Liver function testing
• Influenza testing (if in season) +/- other respiratory viral
• Blood culture – Sputum cultures
5-Based on history and intial evaluation we may need to proceed to expanded evaluation
· Serologic and/or antigen evaluation for endemic fungal infection
· Legionella antigen and/or PCR testing
· Fungal biomarker testing (Galactomannan) from serum
· CMV QNAT
· Chest CT scan
6-Procedural Evaluation Consider
ÞBAL / Transbronchial biopsy
ÞIR guided biopsy
ÞOpen Lung biopsy +/- VATS
7-Tissue speicment testing
ÞCultures: Bacterial, Fungal, AFB, Viral
ÞStains: Fungal/PJP directed
8-BALF Specimen Testing
ÞCultures: Bacterial, Fungal, AFB, Viral
ÞStains: Fungal/PJP directed (Silver, GMS, )
ÞAntigen/Biomarker: Galactomannan; endemic fungi
ÞPCR/DNA: Respiratory viruses, CMV, Mycoplasma spp., Ureaplasma spp., Legionella spp. PJP, Legionella spp., Nocardia spp., Invasive molds
9-Antibacterial therapy
is the cornerstone of the initial empiric therapy.
Þacombination therapy with a beta‐lactam agent (±MRSA and ±anipseudomonal ) and an agent active against intracellular organisms (Mycoplasma in and Legionella ) Then adjust according to clinical and microbiological findings.
Trimethoprim-sulphamethexazole is the drug of choice,
15-20 mg/kg/day of TMP oral or iv in 4 divided doses
if allergic to sulfa drugs
then alternative can be used
pentamidine
Atovaquone 750 mg/12 h
primaquine plus clindamycin
adjunctive glucocorticoid should be given
if room air pao2 <70
evidence of hypoxemia room o2 sat <92
It is not clear from your reply if you would be:
We should stop MMF or AZA and target lower tac level until the patient is clinically stable with improvement in respiratory symptoms
Yes, I agree
What is your differential diagnosis?
Conventional bacteria – 37 percent (higher with neutropenia and mucositis and early after lung transplantation).
Fungi – 14 percent (higher with prolonged neutropenia).
Viruses (CMV, Coronaviruses, …etc)– 15 percent (common with T cell suppression).
P. jirovecii (formerly P. carinii) – 5 to 15 percent (without prophylaxis).
Nocardia spp – 7 percent (including sulfa-resistant strains).
Mycobacterium tuberculosis – 1 percent (higher in endemic regions).
Mixed infections – 20 percent.
Noninfectious etiologies – malignancies, PE, drug allergies, radiation induced, or pulmonary hemorrhage.
From the data available in the case CMV D+/R- (high risk for CMV), with concomittent PCP infection should be looked for.
How do you manage this case?
Complete detailed history, and clinical examination.
Laboratory: CBC, kidney function test, liver function test, urinalysis, LDH (prognostic tool), albumin, T.protein, blood, sputum and urine cultures.
Radiological: CXR usually perihilar infiltrates, central infiltrates sparing the pleura, no nodules or cavity lesions.
CT Scan- honeycombing, ground glass opacities, subpleural sparing, reticulation, stipes, and pneumatic cysts.
A radiologist, infectious disease, and nephrologist should be involved in management of such cases
Microscopic testing: with low sensitivity and specificity to detect PJP, but me be helpful in CMV and other etiological causes.
D glucan sensitive but not specific.
PCR assay sensitive and specific, but cannot distinguish between infection and carrier state.
Broncho-alveolar lavage, and transbronchial biopsy high yield tool.
The gold standard for PCP diagnosis is VATS/open lung biopsy.
Metagenomic next generation sequencing- is a novel diagnostic tool.
Treatement:
Oxygen therapy – correction of hypoxia.
IV hydration.
Trimethoprim-sulphamethexazole is the drug of choice, if allergic to sulfa drugs then: Atovaquone, pentamidine, dapson, or a combination of clindamycin+pyrimethamine, and pentamidine.
Steroid stress dose (high dose) especially when PJP is the diagnosis.
Lower MMF or stopping it in hemodynamically unstable patients, but continue on CNI.
Adoptive immunotherapy could be used.
If CMV is evident, then IV ganciclovir for 5 days, followed by valgancyclovir, and will continue on PJP prophylaxis.
References:
(1) Lecture of Prof. Gamal Saddi, lectur of PJP in SOT, module 4/ week 5.
(2) Hsu JM, Hass A, Gingras MA, Chong J, Costiniuk C, Ezer N, Fraser RS, McDonald EG, Lee TC. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020 Jul 10;20(1):492. doi: 10.1186/s12879-020-05217-x. PMID: 32650730; PMCID: PMC7350625.
(3) UpToDate- Apprioach to the immunocompromised patients with fever and pulmonary infiltrates.
Adoptive immunotherapy: very promising but of unproven benefits
Thank you Prof. Ajay.,sure no proven benefit yet.
Yes, I appreciate that.
65 yr old
Four months post cadaveric Tx
Fever
Dry cough
low oxygen
with a CXR showing para hilar shadowing with wide spread infiltrates
All are suggestive of
Pneumocystis Jirovecii pneumonia
However one can consider Bacterial pneumonia as well
The possibility of CMV pneumonia is low with D-/R+ status
Management would require first confirmation of PCP
I will do HRCT chest which might show typical findings of PCP like sub pleural sparing , honeycombing, reticular shadowing with ground glass haze
A BAL has sensitivity of 80% where as induced sputum has sensitivity of 50%
Definitive diagnosis — The definitive diagnosis of PCP requires identification of the organism either by tinctorial (dye-based) staining, fluorescent antibody staining, or polymerase chain reaction (PCR)-based assays of respiratory specimens. This is particularly true of the diagnosis of PCP in patients without HIV infection
Treatment
We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV (table 1) [1]. The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg (dosing is based upon the TMP component and expressed as mg/kg per day of TMP) intravenously or orally daily in three or four divided doses. Dose may need to be adjusted if creatinine clearance changes during therapy. Patients should receive intravenous therapy until they are clinically stable (eg, PaO2 ≥60 mmHg, respiratory rate <25) and have a functioning gastrointestinal tract. (Up to date)
Please use bold or underline for headings or sub-headings to make it easier to read.
Differential diagnosis
– Pneumocystosis
– Mycobacteria (especially Tuberculosis)
– Histoplasmosis
– atypical pneumonia
Management
1. Diagnosis
Non-contrast-enhanced computed tomography (in the case of Pneumocystosis, heterogeneous bilateral interstitial lesion with clinical-radiological dissociation).
sputum test
Bronchoalveolar lavage with an investigation for BAAR, Gene Xpert for Tuberculosis, RT PCR for Pneumocystosis, Culture for aerobes, fungi, and Ziehl Neelsen
Specimen biopsy with specific staining (Hematoxylin-Eosin, Gomori Crockott – Silver, PAS)
Arterial blood gases – Low levels of PaO2 (PaO2 < 70mmHg) and high difference between alveolar and arterial PaO2 (D(A-a)O2 > 35) suggest pneumocystosis and concomitant need for corticosteroids
2. Clinical management
3. Post-treatment care
History
====================================================================
Differential Diagnosis
How do you manage this case?
Treatment
IF sulfa allergies and mild to moderate disease include:
Alternative treatments for moderate to severe cases include:
==================================================================
Reference
Many thanks Prof.Sharma for important information
Many thank Dr Wadi for making note of my suggestions.
Many thanks Prof. Sharma for your support
Dear All
What are the radiological characteristics of PCP?
How sensitive CXR in the diagnosis of PCP?
Radiological findings
All of the above findings are not specific to PJP
The finding of CXR with other tests like staining of tissue obtained by open lung surgery stained with Gomori methenamine silver stain and immunofluorescence
When you state radiology, do you mean CT scan?
There are no characteristic radiographic findings for Pneumocystosis. There is even an important clinical-radiological dissociation. We found CT scans with interstitial infiltrate in a patient with low PaO2 indices suggestive of pneumocystosis depending on the epidemiological context (transplantation, HIV, chronic use of corticosteroids).
Thank you, I agree, it is non-specific but there are radiological features that suggest PCP. What are these features?
– Diffuse bilateral interstitial infiltration.
– unusual radiographic patterns include lobar infiltrates.
– solitary and multiple nodules which may become cavitary.
– pneumatocele and pneumothorax.
– in patients received aerosolised pentamidine, upper lobe infiltration to reduce deposition of pentamidine in upper lobe.
– when chest X-ray is normal, high resolution CT scanning demonstrates
Extensive ground glass opacities or cystic lesions.
References:
Uptodate.
Thank you Amal
Do not forget the perihilar pattern sparing the periphery which is a common radiological feature
Ok
Thanks our prof
Many thanks Prof.Halawa
What are the radiological characteristics of PCP?
How sensitive CXR in the diagnosis of PCP?
Reference
Thank you
Radiological Characteristics
Chest x-rays are initially normal in up to one-fourth of patients with PCP. The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates
Upper lobe infiltrates and pneumothoraces can also be seen; however, a higher incidence of both of these findings can be seen in patients using aerosolized pentamidineprophylaxis
Other less common radiographic presentations include
Lobar or segmental infiltrates
Cysts
Nodules
Pleural effusions
Sub pleural sparing is characteristic finding on CT chest along with ground glass haze, reticular shadowing, honey combing.
CXR sensitivity
Findings on chest radiography may be normal in 10-39% of patients with PCP. (Medscape)
Thank you
X-RAY
the X-ray may be normal in10-39% of case and may lag behind clinical symptoms
CT
Thank you
What are the radiological characteristics of PCP?
CXR: perihilar infiltrates, central infiltrates sparing the pleura, no nodules or cavity lesions.
CT-Scan: honeycombing, ground glass opacities, subpleural sparing, reticulation, stipes, and pneumatic cysts.
How sensitive CXR in the diagnosis of PCP?
it is poorly sensitive nor specific, may be normal in 30% of cases
Reference:
The classic presentation of PCP is a bilateral interstitial pattern, which may be characterized as finely granular, reticular, or ground-glass opacities.
The chest radiographic findings may be normal in patients with early mild disease.
Diffuse bilateral infiltrates extending from the perihilar region are visible in most patients with P jiroveci pneumonia (PJP).
Less-common findings include patchy asymmetric infiltrates, pneumothorax, and pneumatoceles.
Pleural effusions and intrathoracic adenopathy are rare.
Usually, chest radiography is the only imaging required; its overall accuracy for the diagnosis of PCP is approximately 75%.
Chest radiographic findings may be normal in 5-30% of patients with a diagnosis of PCP.
The literature reports a false-negative rate of 35- 40% when chest radiography is used for diagnosis of PCP.
When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful, because it is more sensitive than chest radiographs for detecting PCP.
REFERENCES
Thank you
Radiological Characteristics of PCP:
Chest Xray: Bilateral, diffuse, often perihilar finely granular, reticular, or ground-glass opacities
High-resolution CT: Classic CT finding is extensive ground-glass attenuation.
5-30% of individuals with a diagnosis of PCP may have normal chest radiography results.
According to the research, chest radiography has a false-negative rate of 35 to 40% when used to diagnose PCP.
Thank you
Plain radiographAlthough up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings 2-4,6,7.
Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include 5:
Pleural effusions are normally not a feature, seen in less than 5% of cases.
What is your differential diagnosis?
reference :
. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
Thank you
The Chest X-ray picture may be normal in 25 % of patients
May be showing bilateral diffuse hazy pulmonary reticular interstitial infiltrates with hilar opacity , pneumothorax and hazy ground glass changes
Unilateral cavities or nodules
Bats wing pattern with hilar prominence
Rarely pleural effusion
Thank you
Its usually bilateral diffuse perihilar, fine granular ground glass interstitial pneumonitis.
Its diagnostic in 75 % of cases. It might be normal in 5-30% of cases.
atypical presentation is encountered in 5 % of cases such as cystic lesion, pneumothorax, and lobar pneumonia.
Reference:
1] Bollée G, Sarfati C, Thiéry G, et al. Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients. Chest. 2007 Oct. 132 (4):1305-10.
Thank you
Radiological characteristics of PCP are:
Chest x-ray sensitivity ;
sensitivity is low it could be normal upto 30% of patients.
Reference
UpToDate
Thank you
bilateral lung infiltration by CXR which is not pathognomonic to PCP
by CT chest it is ground glass appearance and honeycomb appearance
both are suggestive with the clinical scenario but of course BAL and real time PCR are diagnostic
Thank you
Radiology
1.CXR:
2.HRCT:
CXR in diagnosis of PCP
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings
Source
Thank you
wlcm prof
PCP often manifests itself as a bilateral interstitial pattern, which may be described as having coarsely granular, reticular, or ground-glass opacities. This is the classic presentation of the disease. High-resolution CT may be useful in the diagnosis of PCP when chest radiographic results are normal or equivocal. This is because high-resolution CT has a higher detection sensitivity than chest radiographs do.
Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS are demonstrated by different radiographic patterns: widespread ground-glass opacities in the former and cystic lesions in the latter.
Hardak, E., Brook, O., & Yigla, M. (2010). Radiological features of Pneumocystis jirovecii pneumonia in immunocompromised patients with and without AIDS. Lung, 188, 159-163.
Thank you
No radiological characteristic for PCP in CXRY, might be perihilar infiltrations and ground glass appearance and so not sensitive in PCP diagnosis.
BAL with patholigical mircobaterial identifications is required.
Thank you.
chest CT Scan more sensitive than CXR.
radiological features: although no one specific to PCP , with clinical presentations ,give you an idea about it
Thank you.
Plain radiograph
# Although up to 90% of chest radiographs in patients with pneumocystis pneumonia are abnormal, appearances are often non-specific.
# Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
# Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include 5:
*Small pneumatoceles
*Subpleural blebs
*Fine reticular interstitial changes
*Predominantly perihilar in distribution
# Pleural effusions are normally not a feature, seen in less than 5% of cases.
# High resolution CT:
*Is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs .
*The features include::
# Ground glass pattern
*Considered a principal finding
*Predominantly involving perihilar or mid zones
There may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolized medication.
If they are, then the poorly ventilated upper zones are prone to infection, whereas, in those who are not, the lower zones are more frequently involved.
There may be relative preservation of previously irradiated areas.
Show some peripheral sparing in a considerable number of patients (~40%).
#Reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present.
# Pneumatoceles
*Varying shape, size, and wall thickness
*Are seen in up to 30% of cases
*Pleural effusions are rare
*Lymphadenopathy is uncommon (10%)
# Atypical features, found more frequently in patients treated prophylactically, include :
*Consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
*Nodules (granulomas)
May cavitate
Small nodules and tree in bud opacities are uncommon in patients with AIDS and pneumocysitis pneumonia and usually indicate the presence of intercurrent infectious bronchiolitis from other organisms.
# Lymphadenopathy
# Pleural effusions are also more frequently encountered in this group of patients
# Note: A cystic form of pneumocysitis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis. Features of this pattern include :
*Thin walled cysts: in most cases these are pneumatoceles
*Upper lobe predominance
*May be bilateral
*Increased risk of pneumothorax due to cyst rupture
References:
1. Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation
2. Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation
3. Opravil M, Marincek B, Fuchs WA et-al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. J. Acquir. Immune Defic. Syndr. 1994;7 (1): 39-45. – Pubmed citation
Thank you
Radiological characteristic of PCP
Perihilar shadow
Sub pleural sparing.
Ground glass apperence
Stripes
Reticulations
Peumatic cyst
How sensitive CXR in diagnosis of PCP
92-96%
Thank you
What are the radiological characteristics of PCP?, How sensitive CXR in the diagnosis of PCP?
CXR
High resolution CT
References
1- DeLorenzo LJ, Huang CT, Maguire GP, Stone DJ. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987; 91:323.
2- Jules-Elysee KM, Stover DE, Zaman MB, et al. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med 1990; 112:750.
3- Sepkowitz KA, Telzak EE, Gold JW, et al. Pneumothorax in AIDS. Ann Intern Med 1991; 114:455.
4- Metersky ML, Colt HG, Olson LK, Shanks TG. AIDS-related spontaneous pneumothorax. Risk factors and treatment. Chest 1995; 108:946.
5- Horowitz ML, Schiff M, Samuels J, et al. Pneumocystis carinii pleural effusion. Pathogenesis and pleural fluid analysis. Am Rev Respir Dis 1993; 148:232.
6- Gruden JF, Huang L, Turner J, et al. High-resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings. AJR Am J Roentgenol 1997; 169:967.
7- Hartman TE, Primack SL, Müller NL, Staples CA. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol 1994; 162:547.
8- Hidalgo A, Falcó V, Mauleón S, et al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol 2003; 13:1179.
Thank you and well done
Plain radiograph:
It is abnormal in up to 90% of cases but usually non specific Between 10-15% of patients have normal chest radiographs .
Features which are highly suggestive of pneumocystis pneumonia:
Pleural effusions are normally not a feature, seen in less than 5% of cases .
High-resolution computed tomography:
Is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs .
Features include
– Ground-glass pattern considered a principal finding predominantly involving perihilar or mid zones with peripheral sparing in a considerable number of patients (~40%)
–Reticular opacities or septal thickening may also be present;
-A crazy paving may be seen when both ground-glass opacities and septal thickening are present.
– Pneumatoceles
Thank you and well done
Peripheral sparing with perihilar and central reticular-interstitial infiltrations sparing the pleura like this CXR finding in the clinical context of hypoxia , fever , dry cough
Thank, short and sweet,
👉 radiological criteria of PCP:
_Bilateral interstitial infiltration. (parahilar) with subpleural sparing
_Reticular pattern and septations
_Honey combing more apparent in CT chest.
_Upper lobe infltration is atypical pattern of PCP seen in those taking inhaled pentamidine prophylaxis.
_However, these findings are not specific to PCP and can be seen with interstitial lung disease, viral pneumonitis and atypical bacterial infection as mycoplasma.
_Covid 19 infection usually has subpleural infiltration and uncommon to have pleural effusion.
👉 Sensitivity of CXR:
_ 10_30 % may have normal CXR
_ HRCT may be needed with better sensitivity for PCP.
Thanks, Mai
Please do not use underscore (_).
para hilar shadowing, subpleural sparing, upper lobes infiltration
reticulation with septations, stripes, peripheral sparing, pnemoticcytes ( cystic changes), and honeycombing more prominent in CT
CXR abnormalityy in PJ is found in > 91-96% but less sensitive , 30% as these findings can be found in atypical viral or bacterial infections
references
week five lecture by prof Gamal Saady.
Thank you
-No radiographic pattern is pathognomonic for Pneumocystis infection.
-90% of chest radiographs are abnormal, appearances are often non-specific.
-10-15% of patients have normal chest radiographs and
-close to 30% have non-specific or inconclusive finding
-Features which are highly suggestive of PCP include: fine reticular interstitial changes predominantly perihilar in distribution small pneumatoceles, subpleural blebs,
-Patients receiving aerosolized pentamidine classically presents largely or solely in the upper lobes on chest radiograph
HRCT: is more sensitive, used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive CXR. Features on CT include:
Ground glass appearance; considered a principal finding
Subpleural peripheral sparing seen in (~40%)
Other includes: reticular opacities, septal thickening, pneumatocele, honeycomb
References:
Hsu JM, Hass A, Gingras MA, et al. Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study. BMC Infect Dis. 2020;20(1):492. Published 2020 Jul 10. doi:10.1186/s12879-020-05217-
Shah RM, Kaji AV, Ostrum BJ et-al. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics. 17 (1): 47-58.
Short and sweet
The radiological characteristics of PCP
1-CXR can be normal in 5-30% of cases of PCP.
2-Interstial pattern.
3-fine granular, reticular, or ground glass opacities.
4- perihilar shadow in the CXR.
5-sparing of subpleural at the early disease stage.
High-resolution CT scan is more sensitive than CXR for detecting PCP and CXR has a 35-40% false negative rate of CXR for detecting PCP.
I agree.
We need to appreciate that hypoxia is a prominent feature in early stage when chest X ray may be normal.
(Hartman TE, Primack SL, Müller NL et-al. Diagnosis of thoracic complications in AIDS: accuracy of CT. AJR Am J Roentgenol. 1994;162 (3): 547-53. AJR Am J Roentgenol (abstract) – Pubmed citation)
( Hidalgo A, Falcó V, Mauleón S et-al. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003;13 (5): 1179-84. doi:10.1007/s00330-002-1641-6 – Pubmed citation)
radiological findings:
(Professor Gamal Alsaadi’s lecture)
I agree.
We need to appreciate that hypoxia is a prominent feature in early stage when chest X ray may be normal.
What are the radiological characteristics of PCP?
-Bilateral interstitial pattern which may be granular, reticular, or ground glass
-perihilar shadows
-honeycombs appearance
-sparing sub pleural area
How sensitive CXR in the diagnosis of PCP?
may be normal in 30% of cases
A bilateral interstitial pattern with coarsely granular, reticular, or ground-glass opacities is the typical presentation of PCP
High-resolution CT may be beneficial when chest radiographic findings are normal or ambiguous because it is more sensitive than chest radiography for detecting PCP.
The classic CT finding is extensive ground glass attenuation.
10-39% of PCP patients may have normal chest radiography findings.
Imaging features of Pneumocystis carinii pneumonia C A Crans Jr 1 , P M Boiselle
Pneumocystis jirovecii (carinii) Pneumonia Imaging Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: Eugene C Lin, MD
I agree
-The typical radiographic features of PCP are diffuse, bilateral, interstitial infiltrates, ground-glass opacities and foci of consolidation. Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules as well as cavitary lesions; pneumatoceles.
-Chest x ray is non sensitive for diagnosis of PCP but the presence of ground glass on high-resolution chest CT is 100% sensitive for PCP, So absence of ground glass opacities on HRCT ruled out the diagnosis of PCP
Findings on CXR may be normal in 10-39% of patients. Typical CXR findings include; bilateral diffuse, often perihilar, interstitial infiltrates. Atypical features include; cystic lung disease, spontaneous pneumothorax, lobar consolidation, miliary opacities, pleural effusion and lymphadenopathy. CT scan may show ground glass opacification usually perihilar and subpleural space sparing with thickened interlobar septae and focal consolidation.
Thankyou
CT is always helpful when added to clinical picture .
BAL
PCR.
What are the radiological characteristics of PCP?
Radiographic feature of PCP is the presence of bilateral, symmetric, diffuse, reticular, or
granular opacities.
The interstitial infiltrates are mostly bilateral and are also frequently observed in SOT
recipients .
These opacities are typically per hilar in mild presentations or diffuse in severe
presentations.
Typically, reticular and poorly defined ground-glass opacities progress to alveolar
consolidation in 3–4 days.
How sensitive CXR in the diagnosis of PCP?
these chest-radiographic images are non-specific and may be normal at diagnosis.
Thankyou ,correct.
Classic presentaion of PCP (PCJ) is excpected to be bilateral hilar infiltration (in immunocompromised patients like our patient or who have high dose steroids); usually:
fine granular
reticular
ground -glass (some times)
Chest-x ray is typical, but if doubtful, CT will help (as in secneario 2); This seems typical, though it can be mixed with military TBC !?
or detecting PCP.
Fine but not to be confused with milliary TB.
What are the radiological characteristics of PCP?
1. Bilateral interstitial pattern which may be characterized as finely granular, reticular, or ground-glass opacities(1).
2. Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS results in a different time lag between symptoms and a correspondingly different radiographic pattern: widespread ground glass opacities in the former and cystic lesions in the latter(2).
3. Perihilar shadows.
4. Septations or stripes.
5. Sparing of subpleural space.
6. Honeycombing
How sensitive CXR in the diagnosis of PCP?
1. CXR test characteristics for detection of pulmonary opacities included: sensitivity 43.5%,specificity 93.0%, positive predictive value 26.9% and negative predictive value 96.5% (3).
2. Findings on chest radiography may be normal in 10-39% of patients with PCP(4).
3. High-resolution CT, however, has a sensitivity of 100% and a specificity of 89%(5).
References
1. Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. doi: 10.1080/10408379991249194. PMID: 10514937.
2. Hardak E, Brook O, Yigla M. Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised patients with and without AIDS. Lung. 2010 Apr;188(2):159-63. doi: 10.1007/s00408-009-9214-y. Epub 2010 Jan 5. PMID: 20049469.
3. Self WH, Courtney DM, McNaughton CD, Wunderink RG, Kline JA. High discordance of chest x-ray and computed tomography for detection of pulmonary opacities in ED patients: implications for diagnosing pneumonia. Am J Emerg Med. 2013 Feb;31(2):401-5. doi: 10.1016/j.ajem.2012.08.041. Epub 2012 Oct 18. PMID: 23083885; PMCID: PMC3556231.
4. Medscape; Pneumocystis jirovecii (carinii) Pneumonia Imaging Updated: Jun 29, 2022 Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR; Chief Editor: Eugene C Lin, MD
5. Benito N, Moreno A, Miro JM, et al; Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012 Mar39(3):730-45. doi: 10.1183/09031936.00200210. Epub 2011 Sep 1.
The typical radiographic features of PCP in patients without HIV are diffuse, bilateral, interstitial infiltrates . Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules, which may become cavitary; pneumatoceles; pneumothorax; and, in patients receiving aerosolized pentamidine, upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes.
When chest radiograph findings are normal, high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings.
References
Kennedy CA, Goetz MB. Atypical roentgenographic manifestations of Pneumocystis carinii pneumonia. Arch Intern Med. 1992 Jul;152(7):1390-8. PMID: 1627019.
Hidalgo A, Falcó V, Mauleón S, Andreu J, Crespo M, Ribera E, Pahissa A, Cáceres J. Accuracy of high-resolution CT in distinguishing between Pneumocystis carinii pneumonia and non- Pneumocystis carinii pneumonia in AIDS patients. Eur Radiol. 2003 May;13(5):1179-84. doi: 10.1007/s00330-002-1641-6. Epub 2002 Sep 25. PMID: 12695843.
High resolution CT scan is diagnostic to show PCP which demonstrate diffuse ground glass opacity and bilateral interstitial infiltration in perihiler region
Chest X ray not specific and not sensitive; However may appear normal in 5 to 30% of cases in presence of infection
Radiographic features
Plain radiograph
Although up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, appearances are often non-specific. Between 10-15% of patients have normal chest radiographs and close to 30% have non-specific or inconclusive findings
Features which are highly suggestive of pneumocystis pneumonia in patients with CD4 counts below 200/mm3 include
Pleural effusions are normally not a feature, seen in less than 5% of cases
CT
High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs 3.
Features include
considered a principal finding
predominantly involving perihilar or mid zones
§ there may be a mid, upper or lower zone predilection depending on whether the patient is on prophylactic aerosolised medication
§ if they are, then the poorly ventilated upper zones are prone to infection , whereas, in those who are not, the lower zones are more frequently involved
§ there may be relative preservation of previously irradiated areas
§ show some peripheral sparing in a considerable number of patients (~40%)
varying shape, size, and wall thickness
are seen in up to 30% of cases
Atypical features, found more frequently in patients treated prophylactically, include
may cavitate
small nodules and tree-in-bud opacitiesare uncommon in patients with AIDS and pneumocystis pneumonia and usually indicate the presence of intercurrent infectious bronchiolitis from other organisms
A cystic form of Pneumocystis pneumonia is also recognised; again, more frequently in patients receiving aerosolised prophylaxis. Features of this pattern include
Reference
Amini B, Milton B, Weerakkody Y, et al. Pulmonary Pneumocystis jiroveci infection. Reference article, Radiopaedia.org (Accessed on 20 Feb 2023) https://doi.org/10.53347/rID-1901
DOI:
https://doi.org/10.53347/rID-1901
Permalink:
https://radiopaedia.org/articles/1901
rID:
1901
Radiological Features of PCP
-CXR: Classical Early changes are bilateral perihilar fine reticulonodular infiltrates. Atypical findings such as lobar pneumonia are possible, as is a normal CXR.
-CT: Bilateral Perihilar groundglass opacities with sub-pleural sparing in the early stages. Later stages show separations, honeycombing, stripes, pneumatic cysts
CXR is poorly sensitive for PCP as a normal CXR can be seen in 5-30% of cases
Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84. doi: 10.1080/10408379991249194. PMID: 10514937.
Almost 90% of chest xrays of patients with PCP will be abnormal. Whereas 10 to 15% will have no radiological finding in x ray.
The key radiological features highly suggestive of PCP are
-Bilateral interstitial perihilar pattern , characterized by finely granular, reticular, or ground-glass opacities.
–CXR retains a key role in the diagnosis of pneumonia in immune compromised individuals.
CXR may be normal in 10-39% of patients with PCP.
CT scanning is more sensitive and more specific.
Reference
-Crans CA Jr, Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Crit Rev Diagn Imaging. 1999 Aug;40(4):251-84
-Khan A N .Pneumocystis jirovecii (carinii) Pneumonia Imaging Medscape 2022
The radiological pattern of PCP include:
CXR finding
Bilateral diffuse reticulonodular perihilar infiltrate .atypical finding may include pneumatocele , lober pneumonia, and rarely pleural effusion. The CXR finding in PCP may be normal in up to 5-30% of cases. It is less sensitive nor specific.
The Chest CT finding include :
ground glass appearance, honeycomb, subpleural sparing , pneumocystis, and septation. It’s more sensitive
In general the radiological finding inPCP is not specific.
Radiology
CXR:
CT:
CXR sensitivity: Although 90% of patients may have abnormal CXR
The radiological finding
Plain x-ray;
CT finding
1. Ground glass appearance
2. Reticular opacities or septal thickening ( a crazy paving pattern may be seen if both ground glass and septal thickening are present).
3.Pneumatoceles
4. Atypicall features if the patient receives prophylactic treatment;
5. Cystic changes in case of receiving aerosolized therapy
Nuclear medicine
Sensitivity and specificity;
Plain x-ray;
CT;
Nuclear medicine;
What are the radiological characteristics of PCP?
Radiological findings:
CXR:
Typical finding in PJP includes(1,2)
HRCT:
Typical findings in PJP includes(1,2)
At the symptom onset
Evolution in case of ineffective therapy
Atypical and less frequent HRCT findings in PJP(Table 1)(1)
How sensitive CXR in the diagnosis of PCP?
References:
Radiological features of PCP
Classically, pneumocystis carinii pneumonia (PCP) presents with chest showing ground glass opacities, granular or reticular lesions in bilateral lung fields. These findings might not be present in up to one third of cases (1). In those cases, a high resolution computed tomogram (HRCT) of chest can be done, which shows extensive ground glass attenuation, upper lobe distribution of lung parenchymal opacities, or cystic lung lesions (2). HRCT chest has a sensitivity of 100% with specificity of 83.3% (3).
References:
1- Radiological finding of PCP:
2- sensitivity of x ray:
overall accuracy for the diagnosis of PCP is approximately 75%.
it may be normal in 5-30% of cases
What are the radiological characteristics of PCP? (1)
– 90% of the radiographs are abnormal while 10-15% of patients have normal radiographs and 30% have nonspecific inconclusive findings
– the classic chest radiograph features of PCP is a bilateral interstitial pattern characterized by diffuse, finely granular, reticular or ground-glass opacities
– other findings include small pneumatoceles, subpleural blebs, perihilar fine reticular interstitial changes
– HRCT (high resolution computed tomography) Chest is more sensitive than a chest radiograph – it can be done when the radiograph findings are normal or equivocal
– the classic HRCT finding is perihilar or mid-zone ground-glass pattern
– other features include reticular opacities, septal thickening, pneumatoceles
– rarely, pleural effusion, lymphadenopathy
– atypical features (present in patients treated prophylactically) include consolidation, nodules (granulomas)
How sensitive CXR in the diagnosis of PCP? (1)
– overall accuracy of CXR in the diagnosis of PCP is ~75%
– 5-30% of patients may have a normal CXR
– literature reports 35-40% false negative rate
– overall accuracy of HRCT chest in the diagnosis of PCP is ~94%
References
1. Crans CA, Jr., Boiselle PM. Imaging features of Pneumocystis carinii pneumonia. Critical reviews in diagnostic imaging. 1999 Aug;40(4):251-84. PubMed PMID: 10514937. Epub 1999/10/09. eng.
2. Opravil M, Marincek B, Fuchs WA, Weber R, Speich R, Battegay M, et al. Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia. Journal of acquired immune deficiency syndromes. 1994 Jan;7(1):39-45. PubMed PMID: 8263751. Epub 1994/01/01. eng.
3. Singh D. Imaging of Pulmonary Infections: Thoracic Imaging. 2019 Jan 15:147-72. doi: 10.1007/978-981-13-2544-1_6.
4. Kunihiro Y, Tanaka N, Matsumoto T, Yamamoto N, Matsunaga N. The usefulness of a diagnostic method combining high-resolution CT findings and serum markers for cytomegalovirus pneumonia and pneumocystis pneumonia in non-AIDS patients. Acta radiologica (Stockholm, Sweden : 1987). 2015 Jul;56(7):806-13. PubMed PMID: 25031277. Epub 2014/07/18. eng.
What are the radiological characteristics of PCP?
Plain CXR
Features which are highly suggestive of pneumocystis pneumonia
CT
High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs
Features include:
Atypical features, found more frequently in patients treated prophylactically, include:
A cystic form of Pneumocystis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis. Features of this pattern include:
Nuclear medicine
Gallium-67 lung scintigraphy is highly sensitive for PCP, and a normal gallium scan renders the diagnosis of PCP very unlikely. The gallium scan in patients with PCP demonstrates diffuse pulmonary uptake, which may be heterogeneous or homogeneous.
How sensitive CXR in the diagnosis of PCP?
CXR findings may be normal in 5-30%
false-negative rate of 35- 40%
Referrence
Amini B, Milton B, Weerakkody Y, et al. Pulmonary Pneumocystis jiroveci infection. Reference article, Radiopaedia.org (Accessed on 23 Feb 2023) https://doi.org/10.53347/rID-1901
Chest X Ray
Chest X ray in patients with PCP are normal in about 10-15% , while 85-90% may show changes. -Feature of PCP include :
Small Pneumatoceles
Subpleural blebs
Fine reticular interstitial changes
Usually perihilar distribution
Pleural effusion in 5%
HRCT Chest
Ground glass pattern
Septal thickening
Pneumatoceles
Pleural effusion – Rare
Lymphadenopathy – Uncommon
Cystic form of PCP— Thin walled cysts, Upper lobe predominance, Bilaterality, High risk of pneumothorax
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What are the radiological features of PCP:
X ray:
-Up to 90% of chest radiographs in patients with Pneumocystis pneumonia are abnormal, but non-specific.
-10-15% of patients have normal chest radiographs and 30% have non-specific or inconclusive findings.
Features which are highly suggestive of pneumocystis pneumonia:
· small pneumatoceles
· subpleural blebs
· fine reticular interstitial changes
· predominantly perihilar in distribution
Pleural effusions are normally not a feature, seen in less than 5% of cases.
CT: High-resolution computed tomography is more sensitive and may be used to exclude PCP in patients with clinical suspicion for PCP but normal or inconclusive chest radiographs.
Features include:
· Ground-glass pattern
· Reticular opacities or septal thickening may also be present; a crazy paving pattern may, therefore, be seen when both ground-glass opacities and septal thickening are present
· pneumatoceles
· pleural effusions are rare
· lymphadenopathy is uncommon (10%)
Atypical features, found more frequently in patients treated prophylactically, include:
· consolidation: can be more common in patients without HIV infection and tends to develop more rapidly, reflecting pulmonary damage from the host immune response.
· nodules (granulomas)
· lymphadenopathy
· pleural effusions are also more frequently encountered in this group of patients.
A cystic form of Pneumocystis pneumonia is also recognized; again, more frequently in patients receiving aerosolized prophylaxis.
Nuclear medicineGallium-67 lung scintigraphy is highly sensitive for PCP, and a normal gallium scan renders the diagnosis of PCP very unlikely. The gallium scan in patients with PCP demonstrates diffuse pulmonary uptake, which may be heterogeneous or homogeneous.
Despite this, the specificity of the gallium scan is low; hence, it is most useful in patients in whom bronchoalveolar lavage may be less diagnostic (e.g. in suspected relapse).
References:
Pulmonary Pneumocystis jiroveci infection
Last revised by Blake Milton on 07 Feb 2023
Dear All
What are the radiological characteristics of PCP?
A- Plain Chest X-ray:
1- Small pneumatoceles.
2- Subpleural blebs.
3- Fine reticular interstitial changes.
4- Predominant perihilar distribution.
5- Pleural effusion is seen in 5% of case but is not a feature of PJP.
B- HRCT:1- More sensitive than CXR.
2- Ground glass pattern mainly in peri-hilar and mid-zonal areas.Peripheral sparing in more than 40% of cases.
3- Reticular opacities or septal thickening or crazy paving pattern.
4- Pnematoceles: are seen in 30% of cases of variable shapes, sizes and wall thickness.
5- Pleural effusion: rare.
6- Lymphadenpathy: uncommon, in 10% of cases.
7- Atypical features especially in patients on prophylactic treatment and include the following:
a- Consolidation
b- Nodules or granulomas that may cavitate
c- Small nodules and tree-in-bud opacities are uncommon.
8- Ruptured pnumatoceles can lead to pneumothorax.
C- Nuclear Medicine:
1- Gallium 67 lung Scintigraphy is very sensitive to PJP that shows diffuse pulmonary intake either homogenous or heterogenous.
2- Gallium scan is of low specificity.
3- Very useful in those with probable less diagnostic BAL (in suspected relapse).
How sensitive CXR in the diagnosis of PCP?
1- 90% are abnormal and non-specific.
2- 10-15% normal CXR.
3- 30% have non-specific or inconclusive findings.
References:
· In patients with PCP, chest radiographs classically demonstrate bilateral, diffuse, often perihilar, fine, reticular interstitial opacification, which may appear somewhat granular.
· This opacification progresses to air-space consolidation over 3 to 4 days, which may be followed by coarse reticulation as infection resolves.
· Findings on chest radiography may be normal (in 10-39% of patients)
· Chest radiography’s overall accuracy for the diagnosis of PCP is approximately 75%.
· The hallmark finding of PCP on HRCT scans is ground-glass attenuation, which is seen in more than 90% of patients and represents exudative alveolitis.
· Although patients with PCP may present with parenchymal nodules, this feature is more common in CMV infection; thus, the combination of ground-glass attenuation and nodularity is more likely to be secondary to CMV infection.
https://emedicine.medscape.com/article/359972-overview#a3:~:text=Pneumocystis%20jirovecii%20(carinii)%20Pneumonia%20Imaging
· In patients with PCP, chest radiographs classically demonstrate bilateral, diffuse, often perihilar, fine, reticular interstitial opacification, which may appear somewhat granular.
· This opacification progresses to air-space consolidation over 3 to 4 days, which may be followed by coarse reticulation as infection resolves.
· Findings on chest radiography may be normal (in 10-39% of patients)
· Chest radiography’s overall accuracy for the diagnosis of PCP is approximately 75%.
· The hallmark finding of PCP on HRCT scans is ground-glass attenuation, which is seen in more than 90% of patients and represents an exudative alveolitis.
· Although patients with PCP may present with parenchymal nodules, this feature is more common in CMV infection; thus, the combination of ground-glass attenuation and nodularity is more likely to be secondary to CMV infection.
https://emedicine.medscape.com/article/359972-overview#a3:~:text=Pneumocystis%20jirovecii%20(carinii)%20Pneumonia%20Imaging
typical radiographic features of PCP in patients without HIV are diffuse, bilateral, interstitial infiltrates .
Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules , which may become cavitary; pneumatoceles ; pneumothorax; and, in patients receiving aerosolized pentamidine , upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes.
high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions
findings on chest radiograph may be normal in 10 – 39 % of patients >>> low sensitivity
uptodate
medscape
Radiographic manifestations in PCP;
Chest radiographs;
-Chest x-rays are initially normal in up to one-fourth of patients with PCP.
-The most common radiographic abnormalities are diffuse, bilateral, interstitial, or alveolar infiltrates.
-Upper lobe infiltrates and pneumothoraces can also be seen; however, a higher incidence of both of these findings can be seen in patients using aerosolized pentamidine prophylaxis.
-Other less common radiographic presentations include:
●Lobar or segmental infiltrates
●Cysts
●Nodules
●Pleural effusions
High resolution computed tomography;
-High resolution computed tomography (HRCT) has a high sensitivity for PCP among HIV-positive patients.
-One study, for example, evaluated 51 patients with suspected PCP and normal, equivocal, or nonspecific chest x-ray findings;
-HRCT had a sensitivity of 100 % and a specificity of 89 % when the presence of patchy or nodular ground-glass attenuation was used to indicate possible PCP.
-While such findings are suggestive, they are not diagnostic.
-However, a negative high resolution computed tomography scan makes the diagnosis of PCP highly unlikely.
Gallium-67 citrate scanning;
-Gallium-67 citrate scanning is sometimes used to screen for PCP in suspected individuals with a normal chest radiograph but in whom a HRCT cannot be obtained.
-Nuclear scanning is a highly sensitive test in patients with PCP, demonstrating intense, diffuse bilateral uptake.
-This test is rarely used for diagnosis today.
References;
-Up To Date;Clinical presentation and diagnosis of Pneumocystis pulmonary infection in patients with HIV;Dec 08, 2020.
PJP can present with wide range of radiological patterns specially perihilar reticulation ,honey comb appearance, ground glass opacities with characteristic sub pleural sparing and in 10 % of cases CXR may be completely normal , but none of these radiological findings is specific to PJP.
The typical radiographic features of PCP:
· Diffuse, bilateral, interstitial infiltrates.
· Unusual radiographic patterns include lobar infiltrates; solitary or multiple nodules, which may become cavitary.
· Pneumatoceles
· Pneumothorax
· Upper lobe infiltrates due to reduced deposition of pentamidine in the upper lobes.
· When chest radiograph findings are normal, high-resolution computed tomography scanning may demonstrate extensive ground-glass opacities or cystic lesions.
Reference:
Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV – UpToDate
The classic presentation of PCP is a bilateral interstitial pattern, which may be finely granular, reticular, or ground-glass opacities mainly central .
When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful, because it is more sensitive than chest radiographs for detecting PCP.
The classic CT finding is extensive ground glass attenuation.
Increasingly recognized characteristic patterns of PCP in AIDS patients include cystic lung disease, spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities. Although the radiographic findings in PCP are similar for AIDS and non-AIDS immunosuppressed patients, cystic lung disease has not been described in the latter patient population.
Plain radiograph