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2. A 61-year-old CKD 5 secondary to diabetic nephropathy had a deceased donor kidney transplantation. Currently she is on Tacrolimus-based triple immunosuppression. Her kidney function has improved and started to pass more urine. On day 11 she developed dry cough, low grade temperature (37.8 °C). Clinically there were very few physical findings only of few scattered crepes. She has dyspnoea (respiratory rate is 38/min) but chest X-Ray showed bilateral perihilar infiltrates (see below). CT chest showed ground glass appearance. Blood gas showed PaO2 of 8 kPa and picture of compensated respiratory alkalosis.
- What is the differential diagnosis?
- How do you manage this case?
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DD:
PCP infection
CMV infection
Atypical bacterial pneumonia
Aspergillosis
This is most likely PCP infection although it came early in this patient
may be because of high dose of induction immunosuppression ,DGF,CMV infection ,diabetes
Management:
Trimethoprim sulfamethoxazole
in case of contraindications or allergy >atovaquine ,pentamidine ,dapsone ,pyrimethamine
Differential diagnosis of lung infiltrates, in DM recently transplanted patient with dry cough, low grade fever, with heavy immunosuppression is PCP.
Other differential diagnoses include CMV pneumonia, ARDS, bacterial infections, fungal infections, other viral infections as influenza, SARS COV 19 viral infections, and military TB.
Management of this case is searching for viral serology by PCR technique, Bronchoalveolar lavage for PCP or TB, tissue biopsy for detection of microbial related cytopathic changes.
Multidisciplinary team approach is a must.
Broad spectrum antibiotics (avoidance of nephrotoxic medications is better)
Oxygen supplementation according to need, even by mechanical ventilation if mandatory.
Reduction of immunosuppression doses (keeping drug levels at low doses as well as holding the antimetabolites as MMF).
Use of IV Trimethoprim sulfamethoxazole renally adjusted doses according to disease severity. Second lines as Dapsone in case of bad response to TMS or allergy.
Initiation of dialytic support upon demand.
Supportive care by proper fluids and nutritional support.
Antiviral therapy if proved to be of viral origin.
IVIG can be administered being an immunomodulator.
● What is the differential diagnosis?
☆ Immunocompromised individual with fever, dry cough, hypoxemia and the radiographic appearance is a bilateral interstitial pneumonia with diffuse patchy consolidative and ground-glass opacities that consist with PJP .
☆ Other D.D are to ruled out:
*Bacterial pneumonia
*Viral pneumonia
☆ The PCP is presented earlier at 11 day so may be the exposure was in the transplant unit from the air hospital or from inter-individual transmissions between receptive patients, colonized medical workers or colonized patients .
● How do you manage this case?
☆ BAL fluid sample or induced sputum.
☆ Detection of the β-d-glucan antigen in blood samples
☆ Bronchoalveolar lavage and transbronchial biopsy
☆ Real time PCR
☆ Anti-Pneumocystis Agents (TMP-SMX)
The recommended daily dose is TMP 15–20 mg/kg plus SMX 75–100 mg/kg, preferably by IV administration for severe PCP. the optimal duration has not been fully studied but is generally 14 days . This duration of therapy can be extended to 21 days in severe infections or when clinical improvement is prolonged
☆ Intravenous pentamidine is the best second-line agent after TMP-SMX
☆ The clindamycin-primaquine combination seems to be the most effective regimen, particularly in cases where TMP-SMX has failed
☆ 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)
☆ The National Kidney Foundation recommends reducing immunosuppressive medications for kidney-transplant recipients who develop PCP
Reference :
Xavier Iriart, Marine Le Bouar,Nassim Kamar, and Antoine Berry .
Pneumocystis Pneumonia in Solid-Organ Transplant Recipients . J Fungi (Basel) . 2015 Dec; 1(3): 293–331.
· What is the differential diagnosis?
The clinical presentation with low grade fever, non-productive cough and hypoxia with an x ray showing bilateral peri-hilar shadows and a CT chest showing ground glass appearance put PJP on the top of the list. However the early time of presentation is unusual(time at which prophylaxis is given) may be attributed to the DGF, the use of heavy induction therapy, the original kidney disease (Diabetic nephropathy) or the concurrent CMV infection.
Other DD:
Viral: influenza, para-influenza and CMV
Bacterial: community acquired bacterial causes including atypical forms and mycobacteria TB
Fungal infection
Parasitic infections.
· How do you manage this case?
Diagnosis:
o MDT approach involving pulmonologist, ICU and Nephrologist
o ITU admission and ventilatory support
o Detailed history and full physical examination
o Supportive treatment with IV fluids and Nutritional support
o Initial investigations including FBC,ESR, CRP, RFTs. LFTs, and blood culture including TB cultures, serum beta D Glucan, Serum LDH. Check for Tacrolinus trough level transplant and graft US.
o Viral throat swab to diagnose viral infections including COVID 19, Influenza and para-influenza and Mycoplasma pneumonia
o Urine sample for Legionella urinary antigen
o CMV-DNA by PCR test.
o Sputum sample examination for microscopy, staining and cultures for CMV, PJP and aspergillus (It may be difficult to obtain a sample as the patient has dry cough); hypertonic saline can be used to induce sputum(sensitivity of induced sputum is only 30%‐55%).
o Bronchoscopy & BAL for stain (Gomori methenamine‐silver stain) and culture, as well as PCR for respiratory viruses like pneumocystis and CMV.
Treatment:
o Immunosuppression modification: stop anti-metabolites and continue on CNIsand steroids.
o Broad spectrum antibiotics including cover for atypical pneumonia
o Definitive treatment:
o In case of PJP:
o TMP-SMX:
o First drug of choice
o Given IV or oral
o Given initially IV at a high dose of (TMP 15 to 20 mg/kg and SMX 75-100 mg/kg) or oral 2 DS tablets TDS.
o Duration: Given for 3 weeks followed by a lower dose for prophylaxis extended to 6-12 months
o Side effects: rash, fever, neutropenia, hepatitis, nephritis, and hyperkalemia, pancreatitis, renal calculi, and anaphylactoid reaction.
o In case of allergy or contraindication to use TMP-SMX then the second line drugs like Pentamidine, Atovaquone, Dapsone, Primaquine with clindamycin can be used.
o Early initiation(within the first 3 days) of adjuvant steroid doses was found to reduce mortality in moderate to severe disease
o Steroids can reduce inflammation, reduces the need for mechanical ventilation and ITU admission in those already on mechanical ventilation.
o Indications: resting PaO2 of <70 mmHg, oxygen saturation <92 % or alveolar-arterial (A-a) oxygen gradient of ≥35 mmHg
o Dose: 40mg BD prednisone (or equivalent) from day 1 to 5, then 40mg OD from day 6 to 11then tapered to 20mg OD up to 3 weeks.
o In case of CMV:
o IV gancicolvir 5mg/kg BD for 5 days followed by oral valganciclovir 900 mg OD until resolution of clinical symptoms and radiological findings with clearance of CMV in blood(2 X PCR are negative). If no response in 2 weeks, assess for ganciclovir resistance and shift to Foscarnet and additional CMV IVIG. Secondary prophylaxis with oral valganciclovir post-treatment can be given for 1-2 months in patients with high-risk of relapse.
o Monitor graft function during treatment.
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. Martin SI, Fishman JA, Practice ASTIDCo. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:272-9.
4. 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.
What is the 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.
Duration-21 days
Glucocorticoid–
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
Female patient with diabetic nephropathy had a deceased donor kidney transplantation. Currently she is on Tacrolimus-based triple immunosuppression. Her kidney function has improved and started to pass more urine. On day 11 she developed dry cough, low grade temperature (37.8 °C) with few physical findings, dyspnoea (respiratory rate is 38/min).
chest X-Ray showed bilateral perihilar infiltrates.
CT chest showed ground glass appearance.
Blood gas showed PaO2 of 8 kPa and picture of compensated respiratory alkalosis.
1-What is the differential diagnosis?
–Pneumocystis Pneumonia.
-CMV Pneumonitis.
-bacterial Pneumonitis. .
-Respiratory viruses, as Influenza virus
-COVID-19 .
-Drug-induced interstitial pneumonitis (mTOR).
2-How do you manage this case?
Investigations;
-CBC ,CRP.
-graft function.
-sputum culture
-BAL staining for PCP Gomori methenamine- silver staining).
-Serum 1-3 beta-D-glucan assay which is highly sensitive but not specific.
-BALF and culture
– CMV PCR
-Blood culture.
-Tacrolimus level.
Treatment
first supportive treatment to Maintain the sufficient O2 saturation with follow up of the ABG and the alkalosis.
Antipyretics for fever.
Keep good hydration with fluid chart to keep fluid balance.
Pulmonology consultation is important.
Treatment of PJP;
-reduce MMF or even discontinue
-Reducing CNI dose but keep steroid as it is, for fear of rejection .
–In case of PCP, treatment with TMP-SMX is considered as a first-line therapy with 15 to 20 mg/kg IV, switching to oral after clinical improvement with dose adjustment according to graft function .
Second-line therapy for severe cases would be pentamide 4 mg/kg IV o.d., and better to be used as inhaled though with comparable efficacy but worse safety profile.
Primaquine plus Clindamycin for severe cases and 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.
PCP prophylaxis Current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend TMP-SMX as a first-line therapy for 3–6 months after KTx and at least 6 weeks during and after treatment for acute rejection. Alternative therapies with dapsone, aerosolized pentamidine or atovaquon should be considered in the event of allergic reactions or severe side effects
-References;
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.
Up To Date; Over view of Pneumocystis jirovecii pneumonia in patients without HIV: Aug 02, 2022.
The above scenario is likely a case of PCP as the patient develops symptoms 11 days post-transplant and the Chest X-ray showing bilateral interstitial infiltrates and HRCT chest showing ground glass opacities with honeycombing and sub pleural sparing Other differentials which can be considered include: Viral pneumonia; CMV, COVID, Tuberculosis ,Fungal infection(Aspergillus),HCAP.
How do you manage this case?
First, we will get basic investigations like CBC, CRP, LDH ,RFT, LFT followed by Blood C/S, Sputum C/S, ABG/ serum beta-D-glucan assay. Diagnosis is confirmed via staining of induced sputum sample or BAL sample with special stains or getting PCR done on respiratory samples. Multidisciplinary team should be involved including renal transplant physician ,intensivist , infectious disease specialist and pulmonologist. First step in the treatment of PCP in renal transplant recipient is modification of immunosuppression i.e., withholding MMF and achieving lower target of tacrolimus and then starting IV TMP-SMX in a dose of 15 to 20 mg/kg/day (based upon the TMP component) in three or four divided doses, later on switching to oral when tolerating for a duration of 21 days. Steroids in the form of oral prednisolone 40 mg twice a day for 6-10 days then 40 mg once daily for 11-21 days. . Other drugs which can be administered if patient is intolerant to TMP-SMX are Atovaquone, Dapsone +TMP, clindamycin and oral primaquine, Inhalational pentamidine .After treatment, patient should be placed on prophylaxis for at least 06 months to 01 year.
REFERENCES:
1-Lecture of Prof. Gamal Saddi, lectur of PJP in SOT.
2- Fishman JA. Infection in renal transplant recipients. Seminars in nephrology. 2007 Jul;27(4):445-61. PubMed PMID: 17616276.
What is the differential diagnosis?
The differential diagnosis is of CMV pneumonia, Pneumocystis pneumonia
How do you manage this case?
Tests for CBC, ABG, Sputum test, BAL, HRCT of chest, Bronchoscopy and lung biopsy
Management with IV ganciclovir and Valganciclovir in case of CMV pneumonia, Trimethoprim-sulfamethoxazole, Prednisone
Q1: differential diagnosis includes:
1. PCP pneumonia
2. Other viral pneumonia (CMV, influenza, parainfluenza, RSV, Covid-19)
3. Bacterial pneumonia
4. Fungal or parasitic pneumonia
Q2: management includes:
1. ICU admission
2. 2. Oxygen supply or even mechanical ventilation
3. Proper test: CBC, LDH, serum D-glucagon or stain, culture, or BDG treatment should be started with empiric TMP/ SMX, TMP 15-20 mg/kg/day IV every 6-8 hours, and wide-spectrum antibiotics.
In case of PCP confirmation, Prednisolone should be started immediately.
If allergic or resistant to TMP/SMX, nebulized pentamidine, primaquine, and clindamycin. Atovaquone, dapsone and TMP are alternatives.
The images suggest a picture with bilateral pulmonary infiltrate and formation of nodules and cavity.
Possible differential diagnoses would be:
– Hospital pneumonia
– Staphylococcal donor pneumonia
– Nocardiosis pneumonia
– Donor-acquired tuberculosis
I would not fully exclude, but I would not expect a result to find fungal or CMV or PPC infection in this first month of transplantation
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
– Pyogenic germ cultures
– Galactomana
Initiate ATB scheme for coverage of care-related pathogens (coverage for ESBL and MRSA resistance), as a result of the other tests.
· 1-Bacterial infection ;
· Typical and atypical pneumonia .
· 2-Viral infection ;
· CMV ,EBV , adenovirus ,Covid .
· 3-Fungal infection ;
· Pneumocyst carinii
· Spergellous.
How do you manage this case?
1-Microbiological diagnostic approach ;
None invasive approach;
a-Blood ,sputum and urine culture .
b-Serum antibodies against EBV ,CMV ,Ligionella and mycoplasma .
c-Galactomannan test( GM test), and Interferon-γ release assays (T-SPOT).
The invasive approach ;
· The guidelines recommend fiberoptic bronchoscopy with BAL in patient with negative findings .
2-Therapeutic approach ;
Hospital admission
Patient should be started on IV antibiotics like broad spectrum antibiotics and they should be continued till the cultures report.
Antimetabolites should be stopped and Patient should be managed with CNI based on trough levels and increased dose of steroids.
IV TMP SMX or 160/800mg 2 tablets twice daily should be given for 21 days and then followed by low dose prophylaxis for 6 months .
Steroids in PCP are indicated if there is hypoxia
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
And CT chest shwoing ground glass heterogenous opacities
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
Clinical scenario, CXR and CT scan indicate towards
– PJP
– CMV pneumonia
– Covid 19 pneumonia
– Influenza
– Nosocomial pneumonia – atypical bacterial
– Fungal (Aspergillus) infection
Admission n monitoring in HDU/ ICU
a) Oxygen supplement to maintain SpO2 >94%
b) Investigations
– CBC, CRP, ABG, RFT, LFT
– LDH (>220 is suggestive of PJP)
– HRCT Chest: (perihilar opacity, subpleural sparing, ground glass opacity, reticulation, stripes, honey combing, pneumocystis, effusion)
– Induced sputum / BAL fluid testing is diagnostic
(if, fail to detect) – Transbronchial biopsy, open lung biopsy / VATS.
– Diagnostic technique- immunofluorescence assay, PCR, nucleic acid testing (QNAT), silver staining.
– Lung biopsy specimen – lymphocytic infiltration; Gomori methenamine silver staining (dark brown oval or cup shaped organism in alveolar spaces)
c) Treatment:
1.Tab TMP-SMX 160+800mg x 2 tab 2-3 times daily
If no response in 7days à Injection TMP-SMX (TMP 15 – 20mg/kg + SMX 75 – 100mg/kg) IV in 3 divided doses.
Duration of Tt for 21days
2. steroids in patients with moderate or severe disease (PaO2 < 70 mm Hg)
Prednisolone PO
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. Alternate therapy: APAs (pentamidine, atovaquone, dapsone)
4. Reduction of immunosuppression – Stop MMF/AZA, CNI minimal dose (Tac C0 level 8-10ng/ml); monitoring for rejection
References:
1) Pneumocystis jiroveci Pneumonia (PJP) Overview of Pneumocystis jiroveci Pneumonia Shelley A Gilroy, MD, FACP, FIDSA2) Hand book of Kidney Transplantation 6th edition
3) Prof Gamal Saadi lecture Pneumocystis Pneumonia in SOT
Discussion: Reply to Qn by Prof Ahmed Halawa
It is uncommon to have PCP infection 11 days post-transplantation. Will you explain what happened here in the index case?
Early PCP (< 30 days post transplantation) may occur in the current case due to the following
· Its occurrence in elderly diabetic patient
· If aggressive induction was used including high dose steroids and ATG
· If no prophylactic therapy was used
· If there was neutropenia or low CD4+ count lymphocyte counts
· If there was a concurrent CMV infection
What is the role of steroids in the treatment of PCP?
Role of steroids in PCP:
· Steroid use was found to decrease mortality in patients with PCP (both HIV and non-HIV) with moderate to severe disease (with hypoxemia or respiratory failure)
· Early initiation (within 3 days) of corticosteroids in these subsets of patients was associated with reduced need for mechanical ventilation and shortened the period of mechanical ventilation and IVU admission in those already on mechanical ventilation (1)
· No benefit and possible harm seen in mild cases without hypoxemia
· High dose steroids (equivalent of ≥60 mg prednisolone) for up to 5 days may be preferred over low dose (equivalent of ≤30 mg of prednisone) as it was found that it is associated with lower mortality (2)
So, adjuvant steroid therapy is indicated if one of the following is present
· Resting room air oxygen saturation <92 percent
· PaO2 of <70 mmHg on room air
· Alveolar-arterial (A-a) oxygen gradient of ≥35 mmHg
References
1. 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.
2. Pareja JG, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest 1998; 113:1215.
What is the differential diagnosis:
PCP is very rare in first month post-transplantation, but there risk factors strong immunosuppression tacrolimus, diabetes, slow graft function.
According to the history, clinical presentation and radiological finding the provisional diagnosis is PCP.
Other differentials could be,
. CMV pneumonitis,
. Bacterial infection,
. Viral pneumonia,
. Atypical pneumonia.
. Other fungal infection,
. COVID-19.
How do you manage this case:
According to history the patient is immunocompromised, diabetic, slow graft function all these make prone the recipient vulnerable for opportunistic infections, and there is high risk of opportunistic infection (with no history of prophylaxes), symptoms dry cough, hypoxemia, and radiological finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, blood C/S, procalcitonin, CRP.
General management;
Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange and put on CPAP, if not responding and persistently hypoxemic need to discuss with family for intubation.
Empirical broad spectrum antibiotic.
Start corticosteroids.
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day, according to eGFR.
If not responsive or allergic to sulfa group switch to second line agent, clindamycin 600mg bid plus primaquine 30mg.
Then secondary prophylaxes for next six months.
Reference;
1. https://pubmed.ncbi.nlm.nih.gov/10530464/.
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734213/
3. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv?search=Role%20of%20corticosteroids%20in%20treatment%20of%20PCP&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H6.
4. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv/abstract/11.
5. https://journals.scholarsportal.info/details/21938229/v10i0003/1733_mnsftdinpars.xml&sub=all.
6. https://www.sciencedirect.com/science/article/abs/pii/S1341321X07708802.
7. 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 a bilateral interstitial lung infiltration with hypoxia and cough most probably it a pcp pneumonia especially if the patient not on septrin prophylaxis
mangment include high dose septrin plus or minus pentamidine
we should stop the antimetabolites and increase the steroid dose to improve the oxygenation
From the given scenerio & CXR and CT chest, i have following differentials-
– PCP
– Nosocominal pneumonia
– Donor drived bacterial pneumonia
– Influenza
– Fungal (Aspergillus) infection
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
Reduction of immunosuppression, Stop MMF/AZA, CNI levels
Monitoring for rejection
TMP-SMX 15-20 mg/kg for 21days
corticosteroids in patients with moderate or severe disease.
(PaOs < 70 mmhg)
This patient has many risk factor to develop PCP , he is old age , diabetic , deceased donor kidney transplantation so his induction therapy is ATG , he developed DGF so most probably he did not take PCP prophylaxis in addition he had hypoxemia , chest X-Ray showed bilateral perihilar infiltrates and CT chest showed ground glass appearance
Confirmation of PCP infection :
1- A lactic dehydrogenase (LDH) study is performed as part of the initial workup. [25] LDH levels are usually elevated (>220 U/L) in patients with P jiroveci pneumonia (PJP).
2- 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 . A disadvantage is that PCR cannot distinguish between colonization and disease .
3- Sputum P jirovecii PCR testing may be a viable alternative to invasive testing.
4- β-D-Glucan (BDG) Level
5- Lung biopsy Open lung biopsy is the most invasive procedure and yields 100% sensitivity and specificity because it provides the greatest amount of tissue for diagnosis.
Treatment of PCP infection :
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).
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.
continue Prophylactic agents,for 6 months
References :
1) Pneumocystis jiroveci Pneumonia (PJP) Overview of Pneumocystis jiroveci Pneumonia Shelley A Gilroy, MD, FACP, FIDSA2) Hand book of Kidney Transplantation 6th edition
3) Prof Gamal Saadi lecture Pneumocystis Pneumonia in SOT
What is the differential diagnosis?
PCP is very rare in first month post-transplantation, but there risk factors strong immunosuppression tacrolimus, diabetes, slow graft function.
According to the history, clinical presentation and radiological finding the provisional diagnosis is PCP.
Other differentials could be,
. CMV pneumonitis,
. Bacterial infection,
. Viral pneumonia,
. Atypical pneumonia.
. Other fungal infection,
. COVID-19.
How do you manage this case?
According to history the patient is immunocompromised, diabetic, slow graft function all these make prone the recipient vulnerable for opportunistic infections, and there is high risk of opportunistic infection (with no history of prophylaxes), symptoms dry cough, hypoxemia, and radiological finding suggest PCP pneumonitis, but further to confirm the diagnosis needed.
Baseline investigations, galactomenone, CMV PCR, BAL, for biopsy, microscopy, gram stain, cytology, blood C/S, procalcitonin, CRP.
General management;
Keep well hydrated,
Keep Fio2 >90, otherwise give maximum O2, arrange and put on CPAP, if not responding and persistently hypoxemic need to discuss with family for intubation.
Empirical broad spectrum antibiotic.
Start corticosteroids.
Trimethoprim-sulphamethoxazole 20mg/kg split dose /day, according to eGFR.
If not responsive or allergic to sulfa group switch to second line agent, clindamycin 600mg bid plus primaquine 30mg.
Then secondary prophylaxes for next six months.
Reference;
1. https://pubmed.ncbi.nlm.nih.gov/10530464/.
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734213/
3. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv?search=Role%20of%20corticosteroids%20in%20treatment%20of%20PCP&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H6.
4. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv/abstract/11.
5. https://journals.scholarsportal.info/details/21938229/v10i0003/1733_mnsftdinpars.xml&sub=all.
6. https://www.sciencedirect.com/science/article/abs/pii/S1341321X07708802.
7. 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.
The patient has diabetic nephropathy and CKD…She had a deceased donor renal transplantation 11 days back and has improved renal function with normal urine output…She has developed fever and cough with desaturation with ABG showing respiratory alkalosis.. There is hypoxia in ABG… CXR shows right peri hilar opacities…CT chest shows bilateral peri hilar shadowing with right more than left with crazy pavement pattern of interstitial pneumonia in the lungs with peripheral sparing…
The patient has developed early onset pnemonia after transplant… I will consider the following
I would keep PCP as the first diagnosis given the hypoxia, typical radiological picture in a post transplant patient
Although Early PCP (30 days of transplant) is rare, it is seen in diabetic patients, in those patient whom ATG or high dose steroids were given for rejection, when no prophylaxsis was used due to graft dysfunction or allergy to TMP-SMX..If there was neutropenia due to any other cause like CMV, TMP SMX could not have been started before hence without prophylaxis could be another reason for the PCP occurence…
Patient needs admission, Baseline investigations like CBC, RFT, Liver function test, CRP, Procalcitonin and Blood culture needs to be taken… Patient should be started on IV antibiotics like broad spectrum antibiotics and they should be continued till the cultures report… Antimetabolites should be stopped…Patient should be managed with CNI based on trough levels and increased dose of steroids…Sputum examination is necessary after saline induction for gram stain, culture, PCP stain with toluidine blue or giemsa stain…. Bronchoscopy BAL examination have a better diagnostic yield in PCP… IV TMP SMX or 160/800mg 2 tablets twice daily should be given for 21 days and then followed by low dose prophylaxis for 6 months atleast…. Steroids in PCP are indicated if there is hypoxia… the role of early steroids (within 3 days) in addition to IV TMP-SMX has been shown to reduced the mortality and morbidity in many patients both HIV and non HIV individuals…indications for steroids in PCP are hypoxia<92%, Pao2 <70 mm of Hg, Alveolar arterial oxygen gradient > 35mm of Hg…cases with benefit are of moderate to severe PCP and mild cases of PCP it is not indicated… high dose steroids 60mg of prednisolone for 5 days and followed by gradual tapering is recommended
1- Patient admission in hospital
2- ABC treatment; clear airway- O2 supplement
3- lab test
CBC – LDH (non specific)- CRP- procalcitonin-
BAL analysis and culture
PCR (CMV)
PCR(PCP)
β-d-Glucan antigen
4- immunosuppression reducing
5- in the case of PCP thd best treatment is TMP-SMX 15- 20 mg /kg Tmp intravenous for 14 to 21 days
6- alternative therapy for PCP
pentamidine for SOT recipient
Atovaquone
lindamycin+ primaquine
dapsone- Tmp
For patients Who do not tolerate
TMP-SMX aerosolized pentamidine is the alternative Treatment
7- corticosteroid may be indicated is some serious cases
Patients with a PaO2 of <70 mmhg initially .
additional steroids (e.g. methylprednisolone 30mg bid for days 1- 5, tapering over 10-15 days) should be given for severe PCP episodes, as they have been shown to reduce mortality
8- prophylaxis treatment for CMV is indicated
REFERENCE
Oxford Academic
https://academic.oup.com › suppl_4
IV.7.1 Pneumocystis carinii pneumonia Guidelines
Q1- What is the differential diagnosis?
Differential diagnosis include
a- Pneumocystis jirvocii pneumonia
b- Covid 19 infection
c- CMV
d- In early post-transplant period (1 month )- hospital acquired infection – nosocomial infection .
e- Other viral infection EBV, HSV ….
Q2- How do you manage this case?
1- Admition to hospital and multi-disciplinary team management .
2- Monitoring of the vital signs , O2 saturation .
3- O2 therapy – if indicated
4- IV hydration .
5- WORK UP to prove the most probable diagnosis (PCP ) .
Note : Chest x RAY and computed-tomography scans (HRCT) are both are suggestive of pneumocystis jirovocii pneumonia.
This case need further test for diagnosis which include
1- Microbiological diagnosis: sputum sensitivity for diagnosis is differ
Routine sputum has poor outcome and Induced sputum has about 30–55%. Bronchoalveolar lavage increase the sensitivity to 80–95% but the most sensitive way are Bronchoalveolar lavage and transbronchial biopsy, Open-lung biopsy with sensitivity of >95%.
Note: Pneumocystis remains a non-cultivable microorganism.
2 – 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), with sensitivities ranging from 90% to 100% and specificities of 88% – 96% .
Other tests
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 :
When the PCP is diagnosed this case should be treated
Manipulation of immunsupresant : stopping MMF and Azathioprine.
Reduce the CNI dose to half .
Increase the steroid dose .
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
after treatment and recovery it is important to keep patient on TMP-SMX secondary prophylaxis.
references
1- Sunsane B, etL: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
2- Jay A, ETAL: Pneumocystis Jiroveci in solid Organ Transplantation: Guidelines from the American Society of Infectious Disease Community of Practice, Clinical Transplantation volume 33.
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) Lecture: Prof. Gamal Saadi on Pneumocystis Pneumonia in SOT
Differential Diagnosis
How do you manage this case?
Treatment:
I would start IV broad spectrum antibiotics
PCP treatment
Antimetabolite reduced by 50% and may need to stop it if infection gets life threatening.
Reduce CNI to the lowest 25%-50% of initial dose.
If proved to be PCP, secondary prophylaxis should be initiated for 12 months and some studies recommended prophylaxis for life.
References
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
Sunsane B, etL: Prophylaxis and Treatment of Pneumocystis Jeroveci Pneumonia after Solid Organ Transplantation, Pharmacological Research Volume 134, August 2018, 61-67
OUR CASE;
61 yr old female pt, CKD from DM nephropathy.
Deceased donor kidney transplantation.
Tacrolimus based triple therapy.
Better eGFR with better urine output.
Dry cough with fever on day 11.
Has crepitation with bilateral perihilar infiltrates on CXR, Ground glass opacification on HRCT.
BGA shows compensated respiratory alkalosis.
RISK FACTORS;
DX ;PCP.
DDX;
MANAGEMENT.
REFRENCES.
1.Jay et al;PCP in solid organ transplant, Guidelines from American Society of Infectious Disease ,Clinical Transplantation,vol33,9
2.Alanco et al; ECIL guidelines for diagnosis of PCP in pts with hematological malignancies and stem cell transplant recipients, the journal of antimicrobial chemo.2016 sep;71(9);2386-96
What is the differential diagnosis?
PCP,Viral Pneumonia,Aspergillosis
Xray and CT findings are atypical and shows bilateral perihilar infiltrates
and ground glass appearance
How do you manage this case?
Treatment :
1- ICU admission is very much necessary and send general and specific investigation like blood and PCR nd radialogy along with that controlling of fever ,maintain good hydration ,strict monitoring of blood suger level, ABG monitoring .
3- Specific treatment :
TM –SMX is drug of choice and replace with pentamidine or dapsone with primaquine if the patient is allergic .
– CMV pneumonia : 5 mg /kg IV gancyclovir for 5 days followed by oral vlgancyclovir..
– Other antibiotics : based on C&S.
– Modification of immunosppuression doses: decrease MMF and increase steroid .
This kidney recipient is old age and diabetic that increase the risk of early onset PJP pneumonia
DD:
1- PJP
2- CMV pneumonia alone or concomitant with PJP.
3- Covid 19 pneumonia.
4- Drug induced pneumonitis .
5- TB pneumonia
6- Aspergilosis
7- Bacterial pneumonia
Management:
Lab investigation
– CBC, CRP ,procalcitonin , sputum culture ans sensitivity
– Blood suger monitoring strict control .
– Bronchoscopy and BAL with PCR for PJP , TB
– CMV PCR .
– Covid swap and PCR .
– Monitor graft function.
Treatment :
1- ICU admission , control fever , maintain good hydration , monitoring of blood suger.
2- ABG .
3- Specific treatment :
– PJP : TM –SMX as ist choice and replace with pentamidine or dapsone with primaquine if the patient is allergic .
– CMV pneumonia : 5 mg /kg IV gancyclovir for 5 days followed by oral vlgancyclovir.
– For TB : INH+ rifambicin .
– Other antibiotics : based on C&S.
– Modify IS doses: decrease MMF and increase steroid .
2. A 61-year-old CKD 5 secondary to diabetic nephropathy had a deceased donor kidney transplantation. Currently she is on Tacrolimus-based triple immunosuppression. Her kidney function has improved and started to pass more urine. On day 11 she developed dry cough, low grade temperature (37.8 °C). Clinically there were very few physical findings only of few scattered crepes. She has dyspnoea (respiratory rate is 38/min) but chest X-Ray showed bilateral perihilar infiltrates (see below). CT chest showed ground glass appearance. Blood gas showed PaO2 of 8 kPa and picture of compensated respiratory alkalosis.
concerns/ issues
– 61yo, CKD5, Diabetes nephropathy, deceased donor kidney transplantation
– Tacrolimus-based triple regimen
– good kidney function
– Day 11 – dry cough, low grade fever, scattered crepitations, dyspnoea, RR 38, BGA respiratory alkalosis
– CXR – bilateral perihilar infiltrates
– CT Chest – ground glass appearance
What is the differential diagnosis?
– Pneumocystis pneumonia
– Bacterial pneumonia
– Viral pneumonia
– Cytomegalovirus (CMV) pneumonitis
– SARSCOV2 pneumonia
– Pulmonary embolism
How do you manage this case?
– multidisciplinary approach i.e., engage the infectious disease specialist, microbiologist, endocrinologist, pulmonologist
– comprehensive history
– thorough physical examination
– baseline investigations including: –
– admit ICU/ HDU
– initiate on oxygen therapy
– use insulin to achieve glycemic control
– consider tapering down the dose of Tacrolimus to the bare minimum, hold/ reduce antimetabolite dose until the patient recovers
– to get corticosteroids as adjunctive therapy
– offer CMV prophylaxis
– specific treatment: – (4)
– TMP-SMX is given at a dose of 1920mg TID for 21 days
– Prednisone 40mg BD 5days, 20mg BD 5days then 20mg OD 11days
– assess for risk factors: –
o risk increases with number/ episodes of rejection treatment (5)
o induction with lymphocyte depleting agents (6)
o use of biologic agents – antiCD20, antiCD52 (7)
o corticosteroids – interfere with many pathways within the immune system by decreasing circulating monocytes, macrophages, CD4 lymphocytes (8)
o mycophenolic acid analogues – affect proliferation of B and T lymphocytes by inhibiting an enzyme that is implicated in purine synthesis (9)
o CNIs – reduce proliferation and differentiation of T lymphocytes by preventing IL-2 production; so far, the studies are showing conflicting results (10)
o mTORi – sirolimus blocks activation of T and B cells by inhibiting response to IL-2 hence it is associated with development of PCP (7, 8, 10)
– offer prophylaxis
References
1. 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.
2. 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.
3. 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.
4. 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.
5. Radisic M, Lattes R, Chapman JF, del Carmen Rial M, Guardia O, Seu F, et al. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case-control study. Transplant infectious disease : an official journal of the Transplantation Society. 2003 Jun;5(2):84-93. PubMed PMID: 12974789. Epub 2003/09/17. eng.
6. Fishman JA. Infection in renal transplant recipients. Seminars in nephrology. 2007 Jul;27(4):445-61. PubMed PMID: 17616276. Epub 2007/07/10. eng.
7. Reid AB, Chen SC, Worth LJ. Pneumocystis jirovecii pneumonia in non-HIV-infected patients: new risks and diagnostic tools. Current opinion in infectious diseases. 2011 Dec;24(6):534-44. PubMed PMID: 21986616. Epub 2011/10/12. eng.
8. De Castro N, Xu F, Porcher R, Pavie J, Molina JM, Peraldi MN. Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after discontinuation of prophylaxis: a case–control study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2010 Sep;16(9):1375-7. PubMed PMID: 20041898. Epub 2010/01/01. eng.
9. Ransom JT. Mechanism of action of mycophenolate mofetil. Therapeutic drug monitoring. 1995 Dec;17(6):681-4. PubMed PMID: 8588241. Epub 1995/12/01. eng.
10. Neff RT, Jindal RM, Yoo DY, Hurst FP, Agodoa LY, Abbott KC. Analysis of USRDS: incidence and risk factors for Pneumocystis jiroveci pneumonia. Transplantation. 2009 Jul 15;88(1):135-41. PubMed PMID: 19584693. Epub 2009/07/09. eng.
D/D: PJP, CMV pneumonia, Viral pneumonia ( covid-19, RSV, inflenza), atypical bacterial pneumonia ( TB, Mycoplasma, Legionella), Aspergillosis.
Mx: admission in ICU, supporive therapy( o2 support, maintain fluid balance), Do all necessary test( CBC, CRP, all possible culture, RFT, LFT, LDH, CMV PCR, HIV, induced sputum / BAL for staining of PJP).
Stop temporary MMF, reduce dose of TAC, increase dose of steroid, start TMP/ SMX.
Differential Diagnosis:
· Legionella and Pseudomonas pneumonia
· CMV, community-acquired respiratory viruses
· Nocardia, Aspergillus, or Cryptococcus pneumonia
· Pneumocystis jiroveci
The history, chest XR and CT suggestive of infiltration and possible pneumatoceles, may indicate PJP in this severely immunocompromised patient.
PJP frequently occurs within 6 months after kidney transplantation, which is a critically immunocompromised period.
Risk Factors for PJP: Cumulative doses of tacrolimus, mycophenolate mofetil, corticosteroids, ATG use, history of acute rejection, number of anti-rejection treatments, cytomegalovirus (CMV) infection, bacterial pneumonia, tuberculosis, and hepatitis C virus infection.
Sputum Induction
· Pneumocystis organisms are frequently found in sputum induced by inhalation of a hypertonic saline solution.
· Sputum induction is the quickest and least-invasive method for definitively diagnosing PJP.
· The sensitivity of sputum induction varies widely (< 50% to >90%), but could be less sensitive in patients without HIV infection
· Specificity is high (99%-100%)
Bronchoalveolar lavage
· BAL is the most common invasive procedure used to diagnose P jiroveci pneumonia (PJP).
· It has a diagnostic yield that exceeds 90% (could be higher if multiple lobes are sampled).
Lung biopsy
· Open lung biopsy is the most invasive procedure and yields 100% sensitivity and specificity
· Should be reserved for rare cases when bronchoscopy findings are nondiagnostic
Treatment
· depends on the degree of illness at diagnosis which is determined 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 indicated by a room air partial pressure of oxygen lower than 70 mm Hg.
· TMP-SMX has been shown to be as effective as IV pentamidine and more effective than other alternative treatment regimens.
· The parenteral route may be considered in patients who present with serious illness or in those with GI side effects.
· For the treatment of infections that are resistant to TMP-SMX, the combination of clindamycin and primaquine is likely to be more effective than IV pentamidine.
· Atovaquone 750 mg by mouth twice daily may be given as an alternative treatment, but its use is contraindicated in pregnancy.
· Adjunctive steroids are not recommended in patients without HIV infection.
· Treatment of severe disease should include adjunctive steroids as for HIV-infected persons with PJP (60 mg/day initially, then taper)
·
1) https://emedicine.medscape.com/article/225976-overview#a17:~:text=Pneumocystis%20jiroveci%20Pneumonia%20(PJP)%20Overview%20of%20Pneumocystis%20jiroveci%20Pneumonia
2) Handbook of Kidney Transplantation Edited by Gabriel M. Danovitch, MD
Diferential diagnosis :
Ø CMV pneumonia
Ø Bacterial pneumonia ( TB,hospital acquired infection)
Ø COVID 19
Ø PCP ( Older recipient ,known case of DM and presented with pneumonia plus hpoxia and CT finding )
Management :
Admission to ICU and connect to oxygen .
Multi disciplinary team (pulmonologist ,radiologist ,nephrologists ,ICU doctor and clinical pharmacist )
Take detailed history and examination
To do CBC ,CRP,RFT and electrolytes ,TB Screen, CMV screen ,HIV screen, ABG ,lung function test liver function test ,blood culture ,urine culture ,broncho alveolar lavage and PCR ,lactate dehydrogenase β-D-glucan and KL-6
Microscopic examination of stained sputum and BALF and ( mGNS ) analysis.
Start for this patient : TMP-SMX is considered as a 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 and 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
Reduced the dose of immunosupression medication
What is the role of steroids in the treatment of PCP?
Corticosteroid prevent early deterioration in patient with moderately severe PCP and HIV .
References ::
1. Gilroy SA, , Bennett NJ. Pneumocystis pneumonia. Semin Respir Crit Care Med. 2011;32(6):775-782. doi:10.1055/s-0031-1295725 [PubMed] [Google Scholar]
2. Morris A, , Wei K, , Afshar K, , Huang L. Epidemiology and Clinical Significance of Pneumocystis Colonization. J INFECT DIS. 2008;197(1):10-17. doi:10.1086/523814 [PubMed] [Google Scholar]
3. Fillatre P, Decaux O, Jouneau S, et al… Incidence of Pneumocystis jiroveci pneumonia among groups at risk in HIV-negative patients. Am J Med. 2014;127(12):1242.e11-17. doi:10.1016/j.amjmed.2014.07.010 [PubMed] [Google Scholar]
4 Goto N, Futamura K, Okada M, et al… Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak. Clin Med Insights Circ Respir Pulm Med. 2015;9s1:CCRPM.S23317. doi:10.4137/CCRPM.S23317 [PMC free article] [PubMed] [Google Scholar
5. Adjunctive corticosteroid therapy for Pneumocystis carinii pneumonia.
Pottratz ST.Chest. 1998 Nov;114(5):1230-1. doi: 10.1378/chest.114.5.1230.PMID: 9823990
Here we have a patient day 11 post transplant with respiratory symptoms mainly infectious cause
PCP consider the first differential based on the above data given in scenario also we should to think about
> Viral infection influenza a,b ,COVID 19, CMV pneumonitis ….
> Bacterial pneumonia
> TB
> Aspergillosis
To manage this patient well , MDT including nephrology,pulmonologist,infectious and ICU consultants must be involved and Admission to ICU for close observation and monitoring.
Hx and clinical examination
Routine labs including CBC ,KFT,LFT,LDH ,CRP
Urine analysis and culture
PCR >>> CMV,COVID ,PCP
Blood culture
initial screening via multiple induced sputum samples .
All respiratory secretions should be stained using antibodies for PCP (immunoflourescent, immunoperoxidase, or similar) as well as routine stains for Pneumocystis and other organisms (Giemsa, Silver, and others) . Use of PCR-based diagnostics on respiratory secretions can be considered .Samples should also be assayed for routine bacterial, fungal, mycobacterial, and other organisms to rule out concomitant infections. Evaluation for CMV or other respiratory viral coinfection, in particular, should be considered .
bronchoscopy with BAL to obtain diagnostic samples .This may have the dual advantage of increasing the yield and helping expedite the diagnosis of other and/or concomitant infections.
bronchoscopy should be considered for transbronchial biopsies. Increased yield is likely obtained by multiple samples .
Measurement of plasma (1→3) β-d-glucan levels can be considered and may suggest the diagnosis .This assay lacks specificity for Pneumocystis, however, and can be positive in the setting of other invasive fungal infections.
Open lung biopsies can be obtained when other diagnostic approaches have been unrevealing or where other concomitant diseases may be a concern .Video-assisted thoracoscopic (VATS) biopsies may be appropriate for some patients in this regard.
O2 support to improve oxygenation
Good hydration
Trimethoprim-sulfamethoxazole (TMP-SMX) 15–20 mg/kg/day of the TMP component , SMX component 75–100 mg/kg/day given IV in divided doses every 6–8 hours often in combination with corticosteroids ;for milder disease, two double-strength tablets can be given po bid-tid.
TMP-SMX is the drug of choice and is considered to be the most effective systemic therapy for PCP. Hydration should be maintained• Patients on high-dose TMP-SMX should have regular monitoring of cell counts, creatinine ,potassium
In severe infections, intravenous pentamidine probably remains the second-line agent after TMP-SMX .Pentamidine isesthionate 4 mg/kg/day IV initially over 1–2 hours; dose reduction to 2–3 mg/kg/day if needed
Pentamidine side effects include pancreatitis, hypoglycemia, hyperglycemia, bone marrow suppression, renal failure and electrolyte disturbances•
>>> Atovaquone is a second-line agent, although it is used only for mild-to-moderate PJP.
Dapsone and trimethoprim Dapsone 100 mg po qd used in combination with trimethoprim 15 mg/kg/day po divided tid
This combination has been used with sulfa allergy, though dapsone may elicit sulfa allergies as well
In patients with hypoxemia (pAO2 < 70 mmHg on room air), adjunctive corticosteroids should be administered with antimicrobial therapy, ideally within 72 hours of initiating antimicrobial therapy for maximum benefit (Grade II-1). Though the optimal dose of corticosteroids has not been well-established, recommendations of 40–60 mg of prednisone (or equivalent) given twice daily for 5–7 days before being tapered over a period of at least 7–14 days is often recommended (Grade III).
Duration of antimicrobial therapy should be extended for at least 14 days, although clinicians treat for 21 days total in severe infection
reduction in immunosuppression is a common initial approach to PJP management. We discontinue MMF as antimetabolite for 14–21 days with adjunctive glucocorticoids. When PJP patients requiring ICU care need saving their lives rather than maintaining grafts function, we discontinue temporarily both MMF and CNIs with pulse therapy of methylprednisolone injection.
As CMV infection increases a risk of PCP so treatment with valgancyclovir. Until the definitive diagnosis .
Reference
Pneumocystis Pneumonia in Solid Organ Transplantation
S. I. Martin, J. A. Fishman, the AST Infectious Diseases Community of Practice
Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak
Norihiko Goto, Kenta Futamura, […], and Yoshihiko Watarai
Pneumocystis Pneumonia in Solid-Organ Transplant Recipients
Xavier Iriart, Marine Le Bouar, […], and Antoine Berry
What is your differential diagnosis?
A case of pneumonia in early post-transplant period, mostly 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
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
– Increase dose of steroid to 40-60 mg/d for
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
5- Prophylaxis for CMV with valganciclovir ( CMV status of the donor & recipient needed)
this clinical picture is suggestive of acute lung infection in an immunocompromised post transplant recipient.
Differential diagnosis can be acute bacterial pneumonia, CMV infection , COVID 19 ,
PCP ( rare )
CXR – bilateral peri hilar infiltration and ground glass opacity in midzone on both side
CT scan – GG opacity , some pneumatocele and infiltrations
SHE needs ICU care with multidisciplinary team , nasal O2, BAL microscopy, blood labs to be monitored along with renal functions
if BAL shows PCP, cotriamaxazole is the drug of choice
reduction in immunosuppression is also helpful till the acute phase is settled
she will be on secondary prophyalaxis later on
why this happened ?
excessive immunosuppression can be the reason behind this infection
Thank you All
It is uncommon to have PCP infection 11 days post-transplantation. Will you explain what happened here in the index case?
What is the role of steroids in the treatment of PCP?
Regrding what happened , I gusess that that she may had delayed graft dysfunction. Bactim planned but was postponed for a while.
Regarding steroid (commented below)
yes, it’s uncommon if the patient was on PJP prophylaxis, which may be due to DGF, induction with ATG and PMP, and above 60s years old being diabetics all consider more risks to getting an early infection, regarding steroids role in the treatment of PCP, most the data limited to HIV related PJP which is recommended in moderate to sever PJP ( most the evidence from small observational studies ).
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.
Role of corticosteroids in treatment of PCP (Grade 3 recommendation)(1):
Optimal dose of corticosteroids:
References:
For better control of inflammatory process.
It is uncommon to have PCP infection 11 days post-transplantation. Will you explain what happened here in the index case?
Early PCP (< 30 days post transplantation) may occur in the current case due to the following
What is the role of steroids in the treatment of PCP?
So, adjuvant steroid therapy is indicated if one of the following is present
References
1. 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.
2. Pareja JG, Garland R, Koziel H. Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest 1998; 113:1215.
The patient has diabetes make her prone to infections, she might recieved ATG induction therapy , and did not recieve PCP prophylaxis , and she is on MMF,CNI,and steroids, and aged 61 years.
From the senario -no data about the CMV serostatus, so she might have a concurrent CMV infection
The role of steroid as adjunctive therapy when PaO2 less than 70 mmHg or 9.3 kPa, which is 8 kPa in index case
Q1
Q2
Its uncommon to have PJP as early as 11 days post transplantation, unless the patient is already immune suppressed in the first place [such as uncontrolled diabetes mellitus], that has worsened progressively with addition of immune suppressants post transplantation.
Use of steroid is controversial and of debatable benefit. It was speculated that early commencement of steroid with anti-PJP antibiotic is beneficial in preventing pulmonary inflammatory reaction integral tp PJP.
References:
1]Patrick M. Wieruszewski et al. Early Corticosteroids for Pneumocystis Pneumonia in Adults Without HIV Are Not Associated With Better Outcome. CHEST INFECTIONS| VOLUME 154, ISSUE 3, P636-644, SEPTEMBER 2018
role of steroid in pcp treatment to decrease inflammatory process and decrease need for mechanical ventilation hence decrease mortality and can be given in mild to moderate cases with po2 less than 70
Hannah Ewald, Heike Raatz, Remy Boscacci, Hansjakob Furrer, Heiner C Bucher, Matthias Briel. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015 Apr; 2015(4): CD006150.
Uncommon but possible
Elderly, diabetic patient
With history of improving urine output at 11 days hinted for delayed graft dysfunction so he might have received treatment of rejection
Prophylactic therapy and dose of tacrolimus was not mentioned which also effect early infection.more over prophylaxis of bactrium might be delayed due to delayed graft dysfuction, low tlc count, G6PD deficiency.
Clinical feature and radiology consistence with the PJP diagnosis
Role of steroid
Four randomized, controlled trials demonstrated that corticosteroids could reduce mortality in patients with moderate or severe disease.
On the basis of these results, adjunctive steroids are now recommended for all patients with severe disease (PaOs < 70 mmhg)
Reference
Chapter 68 Drug Resistance in Pneumocystis jirovecii Jannik Helweg-Larsen, Thomas Benfi eld, Joseph Kovacs, and Henry Masur
Indeed it is rather early for PCP infection at 11 days post transplant. Possible explanations include:
-No PCP prophylaxis being used
-Concurrent CMV infection
-Heavy induction therapy
-Pre-existing immunoparesis from another condition such as HIV infection
Steroids are used for moderate to severe hypoxemia to prevent worsening and improve outcome.
Possible causes of early PCP infection (1)
– Age >55years
– comorbidities i.e., diabetes
– lack of chemoprophylaxis
– CMV coinfection
– graft rejection i.e., exposure to high-dose corticosteroid therapy
– overall load of immunosuppressive therapy e.g., induction with ATG
– prolonged episodes of neutropenia and lymphopenia
Role of steroids in the treatment of PCP (2)
– prevent early deterioration in patients moderately severe PCP
– adjunctive corticosteroid therapy is indicated in HIV positive patients with severe PCP as defined by PaO₂ < 70 mmHg on room air or an arterial-alveolar O₂ gradient >35mmHg
– once PCP therapy is begun, there is microbial degradation and clearance which can provoke a severe inflammatory response in the lungs which may worsen with the treatment
– corticosteroid adjunctive therapy blunts this inflammatory response resulting in better clinical outcomes among non-HIV PCP patients with respiratory failure
References
1. Iriart X, Challan Belval T, Fillaux J, Esposito L, Lavergne RA, Cardeau-Desangles I, et al. Risk factors of Pneumocystis pneumonia in solid organ recipients in the era of the common use of posttransplantation prophylaxis. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2015 Jan;15(1):190-9. PubMed PMID: 25496195. Epub 2014/12/17. eng.
2. 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. Annals of Intensive Care. 2020 2020/03/20;10(1):34.
Probably PCP prophylaxis was not started, as she developed adverse side effects to immune suppressants, e.g thrombocytopenia, leukopenia.
Adjunctive glucocorticoids are recommended in patients with moderate or severe PCP because their use improves clinical outcomes and mortality without increasing the risk of other opportunistic infections.
However, In contrast to patients with HIV, The available limited data do not provide support for the routine use of adjunctive glucocorticoids in patients without HIV but with PCP who have mild to moderate disease.
In a retrospective cohort study evaluating the outcomes of 323 hospitalized patients without HIV who had P. jirovecii pneumonia, there were no differences in mortality, length of stay, admission to the intensive care unit, or need for mechanical ventilation in the 258 patients who received adjunctive corticosteroids versus the 65 who did not. A second retrospective study of 31 patients without HIV but with PCP also found no difference in the need for mechanical ventilation or mortality between the glucocorticoid-treated and -untreated groups.
However, in severe disease, data suggest adjunctive glucocorticoids may be beneficial. In one of the retrospective studies included in the meta-analysis that looked at 30 patients without HIV but with severe PCP, 16 patients who received the equivalent of ≥60 mg of prednisone per day had a significantly shorter duration of mechanical ventilation, intensive care unit admission, and supplemental oxygenation than the 14 patients who received the equivalent of ≤30 mg of prednisone per day or were on a glucocorticoid taper. However, similar rates of mechanical ventilation and in-hospital mortality were observed.
It remains unclear whether corticosteroids are beneficial, however, the greater degree of inflammation in the lungs of patients without HIV provides some rationale for glucocorticoid therapy.
Reference:
Treatment and prevention of Pneumocystis pneumonia in patients without HIV – UpToDate
It is uncommon to have PCP infection 11 days post-transplantation. Will you explain what happened here in the index case?
PCP infections were common in first 1-6 months, hence the recommendation regarding PCP prophylaxis for first 6-12 months post-transplant (1). It can present earlier (within first few weeks) in patients who have history of receiving immunosuppressants or steroids pre-transplant, as part of treatment of basic disease- autoimmune disease like SLE (2). The risk factors for early PCP include pre-transplant desensitization, history of acute rejection, and higher dose requirement for Tacrolimus (3). The other risk factors for PCP include associated CMV, TB or hepatitis C virus infection, use of more potent immunosuppression, or primary prophylaxis failure (4).
What is the role of steroids in the treatment of PCP?
Steroids are recommended in patients with severe PCP, to be administered within 72 hours of presentation, in patients with severe hypoxia (pAO2<70 mmHg) (2). They should be given for a total period of 3 weeks.
Reference:
1) Kasiske BL, Zeier MG, Chapman JR, Craig JC, Ekberg H, Garvey CA, Green MD, Jha V, Josephson MA, Kiberd BA, Kreis HA, McDonald RA, Newmann JM, Obrador GT, Vincenti FG, Cheung M, Earley A, Raman G, Abariga S, Wagner M, Balk EM; Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010 Feb;77(4):299-311. doi: 10.1038/ki.2009.377. Epub 2009 Oct 21. PMID: 19847156.
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. doi: 10.1111/ctr.13587. Epub 2019 Jul 1. PMID: 31077616
3) Lee G, Koo TY, Kim HW, Lee DR, Lee DW, Oh J, Kim BS, Kim MS, Yang J; KOTRY Study Group. Comparison of early and late Pneumocystis jirovecii Pneumonia in kidney transplant patients: the Korean Organ Transplantation Registry (KOTRY) Study. Sci Rep. 2022 Jun 23;12(1):10682. doi: 10.1038/s41598-022-14580-5. PMID: 35739203; PMCID: PMC9226063.
4) Radisic M, Lattes R, Chapman JF, del Carmen Rial M, Guardia O, Seu F, Gutierrez P, Goldberg J, Casadei DH. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case-control study. Transpl Infect Dis. 2003 Jun;5(2):84-93. doi: 10.1034/j.1399-3062.2003.00018.x. PMID: 12974789.
Role of steroids in management of PCP?
Ewald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015 Apr 2;2015(4):CD006150. doi: 10.1002/14651858.CD006150.pub2. PMID: 25835432; PMCID: PMC6472444.
https://emedicine.medscape.com/article/225976-overview#a17
More risk factors for immunosuppression increased risk of early PCP – elderly, DM, ESRD, Immunosuppression, Aggressive induction with ATG.
Steroids are indicated in those with moderate to severe PCP with an arterial – alveolar oxygen gradient more than 35mmhg or room arterial oxygen pressure less than 70mmhg to decrease inflammation.
REF;
MEDSCAPE -PCP
Yes it is unlikely for opportunistic infection to occur within first postoperative month, as it occur after first month.
But this happened in index case probabley because of
1- Elderly patient
2- Diabetic history
3- There may excessive immunosuppression ( ATG, triple immunosuppression )
4- HIV history should be assessed ? .
5- Concomitant CMV infection ?
6- Use of PCP prophylaxis.
7- the close contact to other patients with PJP
What is the role of steroids in the treatment of PCP?
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
As your first question is concern according to literature PCP is uncommon, but in those patients who has other comorbids like diabetes, history of induction with ATG for rejection or induction, elderly patients.
Second, the role of steroid without HIV do not provide support routine use of adjunctive glucocorticoids. No differences in mortality, length of stay, admission to intensive care unit. however, there are evidence meta-analysis they found steroid was associated with lower mortality, need of mechanical ventilation and ICU admission.
Reference;
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734213/.
2. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv?search=Role%20of%20corticosteroids%20in%20treatment%20of%20PCP&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H6.
3. https://www.uptodate.com/contents/treatment-and-prevention-of-pneumocystis-pneumonia-in-patients-without-hiv/abstract/11.
4. https://pubmed.ncbi.nlm.nih.gov/10530464/.
Thank you
*Early PCP can occur in-
– Elderly patient
– Diabetic patient
– Aggessive immunosuppression
– CMV infection
In this index case the patient diabetic, 61 years old and ATG induction may be used for DGF
* Steroid is required if patient is hypoxaemic ( Pa02 < 70mmHg or 9.33 KPa
Yup Indeed it is rather early for PCP infection at 11 days post transplant. Possible explanations include:
-No PCP prophylaxis being used
-Concurrent CMV infection
-Heavy induction therapy
-Pre-existing immunoparesis from another condition such as HIV infection.
Steroids are used for moderate to severe hypoxemia to prevent worsening and improve outcome.
Q1: If the patient is diabetic, induction therapy with ATG and especially if prophylaxis with TMP/SMX was held or reduced because of bone marrow suppression and neutropenia or thrombocytopenia, and concurrent CMV infection.
Q2: steroids are used for the treatment of moderate to severe PCP pneumonia with early initiation of 60 mg prednisolone up to 5 days and cause lower mortality.
Dear Prof,
Our recipient is an elderly diabetic patient with a deceased donor , definitely received rATG as induction , may have acquired DGF , along with the usual IS , may be the causes for her unusual early PCP infection .
Steroids are beneficial in severe cases (impending respiratory failure) 2-3 days after presentation.
What is the differential diagnosis?
The chest X ray shows bilateral pulmonary infiltrates and CT shows ground glass appearance.
The differentials will include-
· CMV Pneumonia
· Covid 19
· Bacterial pneumonia
· PCP pneumonia
· Aspergillosis
How do you manage this case?
This patient will require hospital admission. The management should be multimodality with involvement of respiratory physician , ITU consultant , Nephrologist and Radiologist.
Initial management -will start with resuscitation with oxygen and IV access. Depending on oxygen saturation patient may need BIPAP.
Investigation will include– Full blood count, ABGs, renal and liver functions, clotting profile, CRP.
PCR for CMV
BAL when stable and then perform PCP PCR
Beta D- Glucan
Blood culture if febrile
Dry cough with hypoxia and radiological findings favour PCP diagnosis.
Treatment starts with trimethoprim 15 mg/kg and sulphamethoxazole at 75 mg/kg for 2 to 3 weeeks.
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.
Corticosteroids should be administered concomitantly within 72 hours of start of antmicrobials.
Immune suppession modification– Antimetabolites can be reduced or stoppped whilst patient is in ITU and reducing CNI to minimum levels with steroid cover.
White PL, Price JS, Backx M. Therapy and Management of Pneumocystis jirovecii Infection. J Fungi (Basel). 2018 Nov 22;4(4):127.
Avino L.J., Naylor S.M., Roecker A.M. Pneumocystis jirovecii pneumonia in the non-HIV infected population. Ann. Pharmacother. 2016;50:673–679.
Thank you Dr kHAN
What is the role of steroid in the treatment of PCP
Clasiically corticosteroid is used as conjunctive therapy to PJP antibyotherapy. Earlier small numbered trails showed the benefit of steroids. The main role thought is to help control inflammation and by this contribute to improved oxygenation
Thank you Dr Islam
61 years old, DN, on TAC triple therapy, day 11 postTx, fever and dry cough , few physical findings ,chest XR: bilateral interstitial infiltrates with perhilar involvement and CT chest: ground glass appearance with PaO2 of 8 Kpa.
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
Thank you
What is your differential diagnosis?
61-year-old female, 11 days post-deceased-renal-transplant, on Tacrolimus triple IS, presented with Fever (37.8), Tachypnea, dyspnea, low oxygen saturation in ABG associated with respiratory alkalosis, associated with dry cough.
Chest x-ray: bilateral peri-hilar infilterates.
CT chest: ground glass appearance.
Differential diagnosis includes:
1- Fungal infection like PJP is the first possible DD because of clinical manifestations mentioned earlier.
2- Aspergillosis.
3- Viral infection: CMV, EBV, Covid-19.
4- Bacterial infection.
How do you manage this case?
General Non-specific measures:
1- ITU admission.
2- Hypoxia: Oxygen, serial ABG, escalation to non-invasive ventilation (CPAP or BIPAP).
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 functions and electrolytes.
Reference:
Uptodate.
Thank you
Early post transplant chest infection:
1-Bacterial pneumonia, hospital acquired
2-Viral pneumonia, CMV and others,
3-Atypical infection
4-PCP
Detailed history, including donor history of recent infection, prophylaxis medication for PCP and CMV.
Routine lab, CBC differential , septic workup, sputum culture, BAL.
Admission to ICU or HDU, support with oxygen, non invasive or intubation as needed.
Empiric antibiotics to cover gram negative, gram positive, fungal and viral infection.
After culture to give antibiotics according to culture result.
If BAL is positive for PCP, to give:
First line cotrimoxazole 5mg( trimethoprine /kg 8hourly, alternarive are:
Clindamycin, Pentamidine IV at 4mg/kg/day or atovaquone PO 750 mg BID
Reference
Dugraidas hand book of transplantation 5th edition
Thank you
A 61-year-old CKD 5 secondary to diabetic nephropathy had a deceased donor kidney transplantation. Currently she is on Tacrolimus-based triple immunosuppression. Her kidney function has improved and started to pass more urine. On day 11 she developed dry cough, low grade temperature (37.8 °C). Clinically there were very few physical findings only of few scattered crepes. She has dyspnoea (respiratory rate is 38/min) but chest X-Ray showed bilateral perihilar infiltrates (see below). CT chest showed ground glass appearance. Blood gas showed PaO2 of 8 kPa and picture of compensated respiratory alkalosis.
What is the differential diagnosis?X-rays showed perihilar infiltration while CT showed ground glass opacitis with honey comb appearance
Early post-transplantinfection developed within one month post kidney transplant
>Nosocomial infection :-
MDRO: MRSA VRE ESLB/CRE
C. difficile colitis.
Surgical site infection.
Urinary tract infection
Catheter related blood stream infection
Infection
Pneumonia
> donor derived infections:-
Atypical post transplant course.LCMV WNV HCV T. Cruzi bactermia and endemic mycosis.
> recipient derived infections:-
Incubating or colonising
~ here the most differential diagnosis :
-PCP
-CMV pneumonitis
-HAP
-TB
-COVID-19 pneumonia
How do you manage this case?ICU admission.
Respiratory support with target SPO2 > 92%
Pan culture ( blood culture aerobic, anaerobic and urine culture)CMV PCR
Blood chemistry :- CBC, D-dimer, renal panel, liver panel
LDH : it more than 495 denotes very bad survival outcomes.
***As regard to immunosuppression
– Glucocorticoid: If used alone no risk for PCP but it used with other immunosuppressive medication can be predisposed for PCP eg mTOR inhibitors
-Mucophenolate mofetil increased risk for PCP while mycophenolate sodium is not proved to cause that.
– sirolemus, studies showed that it considered risk factor for PCP.
for management :
1- first line of therapy : TMP-SMX 15-20mg/kg for 21 days , if disease associated with HIV , we give steroid gong then titrated.
2- second line of therapy intravenous pentamidine 4 mg/kg/d, dapsone-trimethoprim 100 mg dapsone daily + trimethoprim 100 mg twice daily) or clindamycin + primaquine (600 mg/6H daily + clindamycin 30mg with base daily primaquine
References:
uptodate
week 5 lecture
On day 11 post transplant
Differential diagnosis
Management
Thank you
What is your differential diagnosis?
●Conventional bacteria –
●Fungi –
●Viruses –
●P. jirovecii (formerly P. carinii)
●Nocardia spp –
●Mycobacterium tuberculosis –
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)
Noninfectious etiologies
pulmonary embolus, tumor
radiation pneumonitis,
cancer
fibrosis
atelectasis with pulmonary edema
drug allergy or toxicity
pulmonary hemorrhage
How do you manage this case?
Admission ICU ISOLATION ROOM
ID CONSULTATION
SEPTIC SCREEN (CRP -LDH-BLOOD -URINE SPUTUM CULTURES )
Complete blood count with differential
Sputum for Gram stain, fungal smears, and cultures
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
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).
Thank you
A clinical scenario of deceased donor recipient with background history of diabetic nephropathy with improving graft function ,After just 11 days post transplant she developed respiratory tract infection symptoms and signs with chest x ray showing bilateral infiltrate and CT chest revealed a ground glass appearance .PO2 low at 8 kpa (10.5-12) ,there is a few physical signs.
This scenario raises a question of :can PCP developed so early post transplant and in patient presumed covered with prophylactic antibacterial agent either Bactrim or Atovaquone? picture of compensated respiratory alkalosis? Hyperventilation.
Pulmonary infections after renal transplantation are most common in the first 6 months with a peak at about 3 months. During the first month, infections are similar to patients undergoing other thoracic and abdominal surgeries. During this period, the common infections are pneumonia due to gram negative bacterial infections and septic emboli due to intravenous lines. COVID 19 can be included in DD in view of HRCT findings.
The presentation of pulmonary infections in the setting of renal transplant may be either acute or subacute/chronic. An acute process which evolves over hours may be due to bacterial pneumonia. A subacute/chronic process which presents over days to weeks may be due to PCP, viruses, mycobacteria, or fungi.
Management of suspected PCP :
As microbiological diagnosis is often delayed, an empirical therapy is started on the likely diagnosis of infection based on the clinical and radiological patterns.
According to severity:
-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 nebulizer
Thank you MOHAMED
DDX of early posttransplant infection :
1-Bacterial infection such as nosocomial infection, line infection, mycoplasma pneumonia, pulmonary TB..
2-Viral infection such as Covid 19, CMV , influenza virus A&b , varecilla.
3-fungal infection like aspergillosis , PCP.
The most probable diagnosis her is PJP from the clinical picture and radiological findings.
Management plan include :
Admission to ICU
O2 administration and if needed CPAP , PiPAP or even mechanical ventilation to increase the PaO2 above 92%.
Hemodynamic stabilization
Manage fever
Empirical AB till results of investigations reach.
Proper history and physical examination
Investigations include :
CBC , ESR , CRP ,LDH , RFT ,LFT, TB screen , cultures , PCR for Covid 19 and CMV , Tac level , sputum or induced sputum for PCP PCR , bronchoscopy for BAL and transbronchial biopsy for PCP cyst isolation by IF staining and if needed open lung biopsy for confirming the diagnosis.
Treatment start by adding TMP SMX at a dose of 15-20 / 75- 100mg /kg i.v every 6-8 hrs then orally once patient tolerated for 3 weeks . And continue on prophylactic single dose of 480 mg OD 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.
References :
lecture of Dr. Jamal Sadi
uptodate
Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management:
A Systematic Review
Abdul Haseeb 1,* , Mohammed A. S. Abourehab 2 , Wesam Abdulghani Almalki 1,
Thank you
What is the differential diagnosis?
· PCP
· CMV Pneumonitis.
· COVID-19 pneumonia.
· Miliary TB.
· Other viral infection e.g. RSV, VZV and HSV.;
· Bacterial infection; Atypical 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. Antipyretic to relieve pyrexia ( Paracetamol PO or IV).
4. Laboratory tests:
· CBC, RFT,ABG, LFT, CRP, RBG & LDH.
· Screening for COVID-19.
· 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.
5. PCP is the most likely diagnosis(dry cough, hypoxia and radiological findings) and specific management for PCP is warranted:
a) Respiratory support with oxygen supply.
b) Reduction and adjustment of immunosuppression.
a) 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). The first choice: trimethoprim-sulfamethoxazoleat a dose of 2tablets DS every 8h or IV Trimethoprim 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.
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.
Thank you
1- DD
viral infection (CMV, COVID)
bacterial pneumonia (nosocomial inection)
fungal: aspergillosis
2- Management:
Thank you
· Dry cough ,hypoxemia, thee finding of bilateral perihilar Infiltrates in X ray in addition to the ground glass appearance in CT raise the concern of PCP
· Other top differential CMV pneumonia
· We also should consider other causes of pneumonia (bacterial ,viral, fungal )
Lab studies
· CBC diff/ inflammatory markers
· CMV PCR
· Blood and sputum culture
· Respiratory virus panel
For pcp
· Direct fluorescent antibody staining
· PCR
(Sample sputum induced or bronchoscopy with BAL )
· Beta-D-glucan assay
Specific therapy for pcp
TMP -sulphamthexazole15-20 mg/kg/day in 4divided doses
Adjunctive glucocorticoid
Thank you
What is the differential diagnosis?
How do you manage this case?
Thank you
What is the differential diagnosis?
Radiological findings along with dry cough, fever, hypoxemia, scattered creps and compensated respiratory alkalosis, post transplant is highly suggestive of pneumocystis pneumonia(PJP)
Differential may include:
How do you manage this case?
Investigations
Serum LDH
Serum Procalcitonin
(1-3)Beta-D-Glycan
Confirmation of diagnosis (Gold standard): Induced sputum or BAL for either
Cultures
COVID RT PCR
Treatment:
Supportive Care
First line/drug of choice(Grade 1 recommendation)(1,2):
Maintain Hydration
Regular monitoring of TLC, potassium and creatinine
In case of sulfa allergy:
Second line(in severe or resistant cases)(Grade 2 recommendation)(1,2):
Should look for potential toxicities/side effects if using IV pentamidine:
Corticosteroids(Grade 3 recommendation)(1,2):
Optimal dose of corticosteroids:
References:
Thank you
The index patient is a 61-year-old diabetic female with fresh (11 days post-transplant) cadaveric transplant (D-/R+), on tacrolimus, MMF and steroids, having good graft function, developed low grade fever and non-productive cough with tachypnea. The chest x ray shows bilateral perihilar shadows while the CT chest showed ground glass appearance. The clinical symptoms are suggestive of post-transplant pneumonia. The differential diagnosis in such a scenario would be (1):
1. Viral: Respiratory viruses (Influenza, parainfluenza etc), Herpesviruses (cytomegalovirus, CMV etc)
2. Fungal: Pneumocystis jirovecii, histoplasma, Cryptococcus
3. Bacterial: community acquired like streptococcus, tuberculosis etc.
4. Parasitic
In view of hypoxia and non-productive cough, and the radiological changes, probability of PCP is high (2).
Bacterial etiology of the clinical picture is unlikely (low-grade fever, no expectoration).
Although the CMV serostatus of the recipient and the donor has not been given, CMV pneumonia possibility is less likely (it may present with patchy ground glass opacities, small nodules, or consolidation but usually does not present in immediate post-transplant period) (3,4).
The management of the index case involves:
1. A detailed history and clinical examination including history of recent fever prior to transplant.
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, Tacrolimus trough levels.
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 CPAP or BiPAP or invasive ventilation if worsening takes place.
7. Bronchoscopy with bronchoalveolar lavage (BAL) with or without transbronchial lung biopsy: 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: 15-20 mg/kg/day of TMP with 75-100 mg/kg/day of SMX intravenous) should be started pending the investigation results. Steroids should be added.
9. Immunosuppression: Antimetabolites to be stopped, CNI doses to be adjusted as per trough levels.
10. Further management as per the laboratory reports:
11. 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.
1) TMP-SMX: It is the drug of choice, and can be used orally or parenterally. It may cause rash, fever, neutropenia, hepatitis, nephritis, and hyperkalemia, pancreatitis, renal calculi, and anaphylactoid reaction.
2) Dapsone (100 mg/day) plus TMP: It can be used as an alternative, but may cause rash, nausea, fever, vomiting, hepatotoxicity, and hemolysis in G6PD deficiency.
3) Clindamycin (600-900 mg 6-8 hourly) plus Primaquine (15-30 mg/day): It may cause diarrhea, nausea, vomiting, hepatitis, and rash. Oral primaquine is not easily available.
4) Pentamidine (4 mg/kg/day): Given as slow intravenous infusion, it is highly effective, but has toxicity including nephrotoxicity, hypoglycemia, pancreatitis, pancytopenia, and Q-T prolongation.
5) Atovaquone (750 mg twice a day): It is expensive, given orally, and is useful only for mild to moderate disease in patients who cannot tolerate TMP-SMX. Hence not useful in the index patient.
6) Adjunctive steroids (Prednisone 40-60 mg twice a day for one week, and then tapered over next 2 weeks): Used in moderate to severe PCP with low pAO2 (<70 mm Hg), although associated with metabolic effects like glucose and electrolyte abnormalities.
12. 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.
13. Supportive care: Intravenous fluids, nutrition.
References:
Thank you Amit
Are you interested to write a review article on PCP?
Yes Professor. It would be an honour to do that.
Differential diagnosis
This patient who developed a cough, tachypneic and desaturating 11 days post transplant the differentials are broad.
Could be a hospital acquired pneumonia .
The findings of perihilar infiltrates and ground glass opacities is highly suspicious though not definitive for Pneumocystis pneumonia.
The CMV status for donor/recipients have not been given however a differential for CMV pneumonitis should be entertained.
Other differentials include:
Viral pneumonia- eg RSV, influenza, Covid 19
Bacterial pneumonia
Management
This patient requires monitoring in an intensive care unit.
Oxygen supplementation to maintain oxygen saturation SP02 > 92%
Blood works- CBC, UECS,LFT,CRP,ESR
Serum LDH and β D glucan levels- elevated levels are suspicious for PCP.
Induce sputum sample with nebulised normal saline and for microscopy and culture.
For definitive diagnosis of PCP, PCR and immunofluorescence staining of the sputum samples and lung biopsy. However this should only be done in a clinically stable patient, thus in most cases clinical suspicion is enough to make a diagnosis.
To rule out other diagnosis:
Treatment
Drug of choice is TMP-SMX.
This is moderate to severe disease, TMP-SMX should be administered IV (TMP 15 to 20 mg/kg/day SMX 75-100 mg/kg/day) and switch to oral when the patient improves.
Other alternative treatment for patients allergic to sulphur:
Steroids are recommended in non-HIV patients due to the associated high mortality. Should be initiated immediately or within 72 hours. Dosing should be prednisolone 40mg bd for 5 days then 40mg od for 5 days then 20mg od for 10days. IV methylprednisolone can be used in patients who can’t take oral prednisolone.
References
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
Truong J , Ashurst J V . Pneumocystis Jirovecii Pneumonia. [Updated 2022 Nov 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan
Thank you
What is the differential diagnosis
Pneumocystic jeroveci
Bacterial pneumonia
Viral pneumonitis
CMV pneumonia
Covid 19
Pulmonary Tuberculosis
How do you manage this case?
First we stabilize the patient giving oxygen .
Investigations :
CBC, CRP, RFT, ESR, blood culture, PCR for TB, PCR forCMV, Tacrolimus level.
PCR for covid, line and urine culture.
PCR for PJP
Bronchoscopy with BAL.
Bronchoscopy for transbronchial biopsies
Open lung biopsies if we not reach the diagnosis which is most sensitive .
After stablish the diagnosis we treat the PCP as:
Trimethoprim sulphamethazole TMP 15-20 mg/kg ..SMX 75-100 mg/kg oral or IV in 3 to 4 doses per day.
Primaquine and clindamycin .
Reducing of immune supressions.
refereces
1. Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. American Journal of Transplantation. 2009;9:S1-S155. doi:10.1111/j.1600-6143.2009.02834. .
2. Orlando G, Tariciotti L, Manzia TM, et al. Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia. Transpl Infect Dis. 2010;12(1):11–5
3. Eitner F, Hauser IA, Rettkowski O, et al. Risk factors for Pneumocystis jiroveci pneumonia (PcP) in renal transplant recipients. Nephrol Dial Transplant. 2011;26(6):2013–7
Thank you
Nice to see your contribution Murwan
differential diagnosis
Pneumocystis pneumonia is most likely because of cadaveric renal transplantation presented with dry, tachypnea with bilateral perihilar infiltrates and ground glass appearance.
Other Differential diagnosis
Viral or bacterial pneumonia
Legionella pneumonia
Mycoplasma infections
Tuberculosis
COVID-19 pneumonia
Management
Admission for close monitoring of the vitals and Oxygen supplementation.
Investigation
Treatment
TMP-SMX, (TMP 15 to 20 mg/kg/day and SMX 75-100 mg/kg/day) are given intravenously (IV) every 8 hours with a switch to oral when the patient shows clinical improvement.
Allergies to TMP-SMX choose an alternative treatment as:
Pentamidine 4 mg/kg IV once daily
Primaquine 30 mg by mouth every day plus clindamycin IV 600 mg every 6 hours.
Prednisone should be started as soon as possible.
if patients develop respiratory failure, then mechanical ventilation in ICU would be required.
Tacrolimus dose can be reduced or switched over to Cyclosporin as it is one of the risk factors for PCP.
Reference
Thank you
KTR with acute respiratory illness with:
CXR showed bilateral perihilar infiltrates.
CT: showed a perihilar ground glass pattern with peripheral subpleural sparing, honeycomb appearance, and small cyst.
These radiological finding, with the presence of hypoxia and dry cough, is highly suspicious for PCP.
Hypoxemia out of proportion to plain radiographic imaging is highly suggestive of PCP.
Differential diagnosis:
– Pneumocystis pneumonia.
– Viral pneumonia: COVID, CMV, Influenzas, HSV, VZV
– Bacterial pneumonia.
– Other fungal; aspergillus
– Drug-induced interstitial pneumonitis.
-PCP remains an important causative pathogen among SOT recipients. However, the survival of non-HIV patients with PCP is worse than those with AIDS, reaching up to 50% even with adequate therapy.
-Presentation of PCP is usually non-specific and insidious, the most common symptoms being dyspnea and/or non-productive cough and hypoxia.
– Early post-transplantation (11 days); usually patient will be covered with chemoprophylaxis.
-A definitive diagnosis of PCP is made by demonstration of organisms in lung tissue or lower respiratory tract secretions. Because no specific diagnostic pattern exists on any given imaging test, it is imperative that the diagnosis of PCP be confirmed by lung biopsy or bronchoalveolar lavage.
How do you manage this case?
A further detailed history is needed about the induction therapy, current IS regimen and levels, CMV prophylaxis and PJP prophylaxis, and any recent contact.
Recent viral load as part of pre-emptive therapy.
Management:
General supportive 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.
Workup required:
– CBC with differential, CRP, and procalcitonin.
– VBG: the patient has hypoxia with a respiratory alkalosis ( washing Co2 tachypneic)
– RFT, LFT.
– LDH
– Blood culture.
– Respiratory culture and a viral panel (multiplex)
– COVID PCR
-Viral load; CM PCR, , EBV PCR.
– Sputum sample for; microscopy, staining, CMV, PJP and aspergillus (It may be difficult to obtain a sample as the patient has a 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
Antimicrobial management:
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 divided every 6‐8 h; lower doses may be sufficient.
– In milder diseases, two double‐strength tablets can be given PO tid
-Alternative agents are less effective considered (if the patient has an allergy to sulfa or intolerance or if there is resistance )and include: pentamidine, Dapsone plus trimethoprim, atovaquone, primaquine and clindamycin if the patient is allergic or intolerance
-In severe infections, IV pentamidine is the second‐line agent after TMP‐SMX; for side effect profile, mainly hypotension should run slow infusion. Aerosolized pentamidine is usually used in prevention.
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 or an alveolar gradient of >35 mm Hg )
-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 at 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 a lower level.
-Corticosteroids are generally continued
– Monitoring graft function closely for any rejection ( kidney function, drug level)
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
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(Suppl 3):S1-155.
Thank you, well done Hadeel
1-What is the differential diagnosis?
–Pneumocystis Jirovecii Pneumonia (most likely).
-CMV Pneumonitis.
-Pulmonary aspergillosis.
-Respiratory viruses;
Respiratory syncytial virus, adenoviruses, and human metapneumovirus
COVID-19 – ARDS.
– Bacterial Pneumonia (atypical bronchopneumonia).
-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 vs 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 – CRP – LDH.
-Liver function tests & Renal function tests.
-BAL staining for PCP (Gomori methenamine silver (GMS) staining).
-Serum 1-3 beta-D-glucan assay.
-BAL and send for respiratory panel (Influenza type A,B, Adenovirus , covid-19 , etc).
-Virology (including HIV) , (CMV PCR)
-Full septic screen (including sputum C/S).
Treatment of PJP;
Hospitalized patients with PCP;
-Should be cared for using standard precautions, although they should not be placed in the same room with other immunocompromised individuals due to the potential for person-to-person spread.
Regarding I.S. ;
-Holding antimetabolites until this patient is in ICU.
-Reducing CNI dose with steroid cover.
Preferred regimen;
-I recommend (TMP-SMX) as the preferred medication for the treatment of Pneumocystis pneumonia (PCP) in patients without HIV.
-The dose of TMP-SMX for patients with normal renal function is 15 to 20 mg/kg.
-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.
-Monitoring potassium levels before and periodically after the institution of TMP-SMX therapy.
-Patients are usually symptomatically better after 21 days of therapy for PCP.
Alternative regimens;
-If there is allergy or side effects to trimethoprim-sulfamethoxazole, alternative drugs can be used including;(after ID recommendation)
-Dapsone , Inhaled pentamidine , Atovaquone , Primaquine combined with clindamycin , Combined dapsone and trimethoprim , Pyrimethamine and sulphadiazine.
-For patients with allergy to TMP-SMX, desensitization should ideally be performed since TMP-SMX is the most effective regimen.
-Exceptions include patients with a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).
-In these cases, TMP-SMX should be avoided and desensitization should not be performed.
Adjunctive glucocorticoids;
-Using adjunctive glucocorticoids in patients without HIV 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%.
Prophylaxis;
-Is highly efficacious in preventing PJP in transplant patients.
–For most patients who require PCP prophylaxis,TMP-SMX is recommended.
-For patients with normal renal function, TMP-SMX may be given as one double-strength tablet daily or three times per week or as one single-strength tablet daily.
-References;
Up To Date; Over view of Pneumocystis jirovecii pneumonia in patients without HIV: Aug 02, 2022.
Thankyou but he was not on mTOR! and if he was it does not happen that fast!
Thanks our; Prof.
-Administration of m-TOR inhibitors is potential risk factor for late- onset PCP after SOT.
-Targeted PCP prophylaxis -based on recipients’ risk factors rather universal prophylaxis may lessen the risk.
(Ghadimi M,etal.European Journal of clinical pharmacology2019).
The top differential is PJP
Others are;
Management;
According to his immunosuppressants protocol and the deceased donation, the patient is considered as a high risk, (although it is too early for the PJP on day 11)
so PJP prophylaxis is vital in such high-risk patients.
The standard treatment of PJP is the TMP-SMX, the recommended dose is 15-20 mg/kg every 6-8 hrs IV route then orally.
Optimization of the dose is associated with AEs and if resistant develop the alternative is considered;
References
Lee, S.H.; Huh, K.H.; Joo, D.J.; Kim, M.S.; Kim, S.I.; Lee, J.; Park, M.S.; Kim, Y.S.; Kim, S.K.; Chang, J.; et al. Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients. Sci. Rep. 2017, 7, 1571. [CrossRef] 5. Li, R.; Tang, Z.; Liu, F.; Yang, M. Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of Pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis. PLoS ONE 2021, 16, e0248524. [CrossRef] 6. White, P.L.; Price, J.S.; Backx, M. Therapy and management of Pneumocystis jirovecii infection. J. Fungi 2018, 4, 127. [CrossRef] 7. Autmizguine, J.; Melloni, C.; Hornik, C.P.; Dallefeld, S.; Harper, B.; Yogev, R.; Sullivan, J.E.; Atz, A.M.; Al-Uzri, A.; Mendley, S.; et al. Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children. Antimicrob. Agents Chemother
Thankyou but do you think (interstitial lung fibrosis is easily accepted for TX.).
Thank you prof
I think ILD hardly accepted for kidney transplantation in advanced cases based on the degree of fibrosis.
In this case I mean post infection ILD associated with PJP which is reported I’m many cases although early to color
And also many cases reported as a complication of CyA and EVL
Everolimus-related pulmonary toxicity in heart transplant recipientsJ Heart Lung Transplant
Sirolimus and everolimus induced pneumonitis in adult renal allograft recipients: experience in a centerTransplant Proc
Radiological findings imply infectious process in the lungs, however, findings are nonspecific. It may suggest interstitial thickening, partial alveolar filling or collapse, increased blood supply, or a combination of these.
Initial tests
1- Serum 1-3 b-D-glucan/Galactomannan
2. LDH
3. Sputum culture
4. PJP-PCR
5. BAL-for culture, Galactomannan, PCR TB, CMV, PCP, MAC to confirm the etiology.
6. Transbronchial biopsies via bronchoscopy enhance BAL yield.
7. Open lung biopsies for failed diagnostics
8. Covid-19 swab
9. PCR CMV, although not indicative of invasive disease
10. Procalcitonin elevated in bacterial pneumonia
Treatment
Management of this case start with oxygen supplementation to achieve a SO2 OF 92%, shifting of the patient to critical care for closed monitoring, assessment of volume status and achieving euvolemic state, lowering the immunosuppression- reduce antimetabolite by 50%, optimize CNI dose.
Empirical treatment should be started with antibiotic/antiviral to cover typical and typical bacteria, influenza, PCP and CMV, awaiting for requested tests results. Immunosuppressive drugs should be adjusted to minimize the risk of infection and infection progression. Tacrolimus level should be optimized to lower trough levels. MMF dose should be reduced by 50 %.
If the investigations are compatible with PCP, then the duration of treatment is 21 days.
TMP-SMX – 15 to 20 mg/kg/day orally or intravenously in 3 to 4 doses
Alternatively, or in cases of TMP-SMX allergy the following regimens are recommended.
TMP plus dapsone – TMP: 5 mg/kg orally three times per day and Dapsone, 100 mg orally once per day
Primaquine plus clindamycin – Primaquine, 30 mg orally daily, clindamycin, 900 mg IV 8-hourly, or 600 mg three times daily.
Atovaquone 750 mg twice daily orally
Nebulized pentamidine
Well done.
PJP Pneumonia(likely)
CMV pneumonia
Pulmonary TB
hospital acquired pneumonia.
COVID-19
Care of ABC
O2 inhalation to increase pao2 (noninvasive ventilation if needed)
Diagnosis
Sputum /induce sputum or BAL– gram stain, culture, AFB, immunofluorescence, if not conclusive qPCR or mNGS
Serum
CBC, RFT, LFT, LDH (prognosis), G6PD
Treatment
Trimethoprim-sulfamethoxazole (TMP-SMX), TMP 15 to 20 mg/kg/day and SMX 75-100 mg/kg/day are given intravenously (IV) every 6 to 8 hours with a switch to oral when the patient shows clinical improvement with prednisolone 40 mg bd for 6-10 days then 40 mg of for 11-21 days.
Alternative when TMP/sulfamethoxazole sensitive or resistant
Dapsone +TMP
Clindamycin +primaquine
atovaquone
IV or Aerosole pentamidine
Caspofungine
Reference
Lecture: prof gamal saadi Pneumocystis Pneumonia in SOT
Salzer H, J, F, Schäfer G, Hoenigl M, Günther G, Hoffmann C, Kalsdorf B, Alanio A, Lange C: Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia. Respiration 2018;96:52-65. doi: 10.1159/000487713
Thankyou but remember PCJ can not be cultured exvivo.
After receiving a cadaveric transplant 11 days prior, this patient developed pneumonia.
Perihilar infiltrates are seen on the CXR, and ground glass opacities with honeycombing are visible on the CT scan.
It would be crucial to understand whether the patient was receiving PJP prophylaxis, what her CMV status was before the transplant, and whether she was on CMV prophylaxis.
D/D
PCP Pneumonia
CMV pneumonia
Pulmoanry TB
Bacterial pneumonia
COVID-19
TREATMENT
In patients with moderate to severe infections, trimethoprim-sulfamethoxazole (TMP-SMZ) is administered in a high dose in combination with corticosteroids.
Other medications can be used if there are any allergies to or side effects from trimethoprim-sulfamethoxazole, such as dapsone, inhaled pentamidine, atovaquone, primaquine mixed with clindamycin, combination dapsone and trimethoprim, and pyrimethamine and sulphadiazine.
The use of prophylaxis in transplant patients is very effective in preventing PJP.
-Relapses are common, but overall survival is favorable (50-95%) with early treatment.
Up To Date; diagnosis of Pneumocystis pneumonia in patients without HIV: Aug 02, 2022
Well done.
A 61-year-old CKD 5, day 11 post a deceased KTX, on Tacrolimus-based triple immunosuppression, developed dry cough, low grade temperature (37.8 °C) with very few physical findings only of few scattered crepes, dyspnea (respiratory rate is 38/min) but chest X-Ray showed bilateral perihilar infiltrates.
CT chest showed ground glass appearance. Blood gas showed PaO2 of 8 kPa and picture of compensated respiratory alkalosis.
What is the differential diagnosis?
1-PCP.(most suspected).
2-Hospital acquired pneumonia.
2-Viral induced pneumonia (COVID 19 ,Influenza).
3-CMV pneumonitis .
4-aspergillus.
5-Other causes of CAP.
How do you manage this case?
2-Basic investigation (CBC, CRP, LDH, Blood C/S, Sputum C/S, Serial RFT, LFT ).
3-ABG/ serum beta-D-glucan assay.
4-Covid 19 swab.
5-HRCT (looking for par hilar shadows with sub pleural sparing , and ground glass appearance).
6-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.
Very good
Pentamidine is better used as an nebulizer.
-differential diagnosis
Pneumocytitis pneumonia is most likely in this case of cadaveric renal transplant on Tac based immunosuppressive therapy ,post transplant presented with dry cough ,fever ,hypoxia ,tachypnea
chest X-Ray showed bilateral perihilar infiltrates . CT chest showed ground glass appearance.
Other Differential diagnosis
Acute respiratory distress syndrome
Viral or bacterial pneumonia
Tuberculosis
Legionella pneumonia
Mycoplasma infections
COVID-19 pneumonia
-Management
ICU admission is needed for respiratory support and close monitoring of the vitals
Patient PO2 60 mmHg so CPAP or invasive ventilatory support can be needed
Investigation
CBC , Serum beta-D-glucagon, LDH ,kidney function tests ,liver function test
ABG is needed in hypoxic patients with tachycardia and signs of respiratory distress and results will likely show an elevated Alveolar-arterial (A-a) oxygen gradient .
CXR and CT done were done and suggestive of PCP
Induced sputum analysis
Bronchoscopy and BAL for analysis of respiratory secretions by special stain or metagenomic next generation sequencing analysis ,quantitative Pneumocystitis PCR
Treatment
Trimethoprim-sulfamethoxazole (TMP-SMX), TMP 15 to 20 mg/kg/day and SMX 75-100 mg/kg/day are given intravenously (IV) every 6 to 8 hours with a switch to oral when the patient shows clinical improvement.
In cases with a mild allergy to TMP-SMX, desensitization need to be tried as this is the most effective drug .
In patients with severe allergies to TMP-SMX, desensitization is no longer advicded, and choosing an alternative treatment can be done as:
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.
Prednisone should be started as soon as possible or within 72 hours of starting treatment for PCP
IV methylprednisone can be given at 75% of the prednisone dose if oral therapy cannot be tolerated.
Patients with severe disease and respiratory failure who require mechanical ventilation and intensive care unit (ICU) admission have mortality rates as high as 84%.
Tacrolimus dose has to be reduced as it represent a risk factor for PCP
Reference
Truong J , Ashurst J V . Pneumocystis Jirovecii Pneumonia. [Updated 2022 Nov 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan.
Exellent but Pentamidine is restricted to nebuliser as iv. route causes severe hypotension even over a long time.
Differential diagnosis
Management
Treatment – Given for 21 days.
Reference
Thankyou but dont forget PCJ PCR.
WHAT IS THE DIFFERENTIAL DIAGNOSIS
1. Bacterial pneumonia
2. COVID
3. Other viral pneumonia
4. PJP
HOW DO YOU MANAGE THIS CASE
So the basic management of this case which includes diagnostics and definitive therapy is similar to scenario 1.
But there are few key points which needs to be discussed.
1. Respiratory involvement has occured just eleven days post transplant. In this situation PCP appears unlikely as its incubation period is minimum 7 days. This can happen only if patient got exposed to pneumocystis within 3 days after transplant.
2. Acute respiratory illness causing respiratory alkalosis is quite rare and can happen only if patient is hyperventilation for prolonged period or has chronic lung involvement. This needs to be evaluated in detail. And as per respiratory status she will require urgent non invasive ventilation through high frequency nasal cannula along with other routine measure of pneumonia as discussed in scenario 1.
You are fine with the management but what about confirmation of diagnosis.!
Maam I shall go ahead with following specific investigations:
1. COVID RT PCR
2. Beta D glucan
3. CMV PCR
4.BAL
If diagnostic dilemma still persists then patient might need lung biopsy
DDX:
-PCP
-CMV Pneumonitis
-Atypical Pneumonia
-Bacterial Pneumonia
-Covid19 Pneumonia
-PTB
Management:
-I would manage this patient in a high care setting with supportive Oxygen therapy, iv fluids and imperic antibiotics while rapidly working her up
-GIven a dry cough, I would do sputum induction with hypertonic saline and send for microscopy and PCR studies.
-Serum LDH, BDGlucan, CMV serology,
-Bronchoscopy with BAL and transbronchial Biopsy would be next. Will do mNG Sequencing on the BAL samples and histology on the biopsy samples
-Treatment will include Cotrimoxazole, with TMP at 15-20mg/gk/day and SMX at 75-200mg/kg/day.
-REview of immunosuppression: taper Tacrolimus to minimum, reduce or stop MMF and increase steroid cover. Will consider addition of Caspofungin (see below)
Tu GW, Ju MJ, Xu M, Rong RM, He YZ, Xue ZG, Zhu TY, Luo Z. Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients. Nephrology (Carlton). 2013 Nov;18(11):736-42. doi: 10.1111/nep.12133. PMID: 24571744.
Thankyou what other drugs to be used.?
Differential diagnosis:
PCP
CMV infection
TB infection
Viral infection
Mycobacterial infection
COVID 19 infection
ARDS
How to mange:
High resolution CT scan demonstrate diffuse ground glass opacity.
LDH reflect lung injury
PCR for pneumocystis
and bronchoalveolar lavage for PCR pneumocystis
β-D-Glucan (BDG) is a cell-wall component of many fungi, including Candida, Aspergillus, and Pneumocystis, It is sensitive test to detect PJP.
Monitoring renal function and drug level/ DSA level, CMV igg, igm
Treatment
Oxygen therapy
Trimethoprim-sulfamethoxazole (TMP-SMX) is the first line of treatment,
intravenous pentamidine are more effective
Intravenous Antibiotic ( Ciprofloxacin)
Corticosteroids are used as adjunctive initial therapy
Stop anti metabolites
reduce calcinurine inhibitors
Thankyou but PENTAMIDINE iv is with drastic side effects ,used as inhaler.
CXR findings are bilateral homogenous opacity and reticulonodular infiltrations.
CT scan of chest reveals bilateral perihilar ground glass appearance with honeycombing and sparing of subpleural area.
DD: includes PCP.COVID-19 & CMV pneumonia.
Checking of compliance to PCP &CMV prophylaxis protocols as both infections are not common in the first month following transplantation with checking status of CMV D/R.
Lab work up: LDH, sputum PCR ,using BAL if needed; or lung biopsy through different ways if indicated. Sample staining is processed by Gomori methenamine silver polychrome stain and IF .In addition, a swab for COVID-19 and CMV PCR to be done.
-Treatment of PCP severe infection:
-One month IV TMP/SMX : 15-20/75-100mg/kg in 3 divided doses, with close monitoring of S. creatinine and CNI levels.
-Alternative regimens if allergy to sulfa or non toleration:
-I.V Pentamidine 4mg/kg initially, then reduce to 2-3mg/kg or Primaquine &Clindamycin ;1500mg and 600mg g6 hourly or Dapson & Trimethoprim;100mg daily and 15mg/kg.
-Primary prophylaxis following recovery; if not given at single doses for 6 -12 months.
-CMV prophylaxis (Valganciclovir 900mg daily oral) for 200 days if not given.
References:
Emily G. McDonald, Guillaume Butler-Laporte, Olivier Del Corpo, et al. On the treatment of Pneumocystis Jirovechii Pneumonia: Current Practice Based on Outdated Evidence. OFID. 2021.
P. Lewis White, Jessica S. Price, Matthis Backx. Therapy and management of Pneumocystis Infection. Journal of Fungi. 2018; 4: 127
Well done.
What is the differential diagnosis?
Three patterns of infections after transplantation have been reported:
(1) up to 1 month characterized by nosocomial infections and donor-source infections
(2)a pattern of profound immunosuppression for up to 6 months associated with opportunistic infections; like PJP, CMV, BKV
(3) pattern of reduced immunosuppression with community-acquired and rare infectious agents, latent reactivation.
So our indexed case fits the first pattern,0-1 month, need to know about donor sources of infection like donor, recipient CMV status( High risk from D+ve /R-VE ), did he received adequate prophylaxis like anti-fungal, B lactamase antibacterial course, is he on CMV, and PJP chemoprophylaxis?
Early 0–1-month post-transplant period infection risk
Includes, HAP, Nosocomial infections including MDR microbes, gram-negative and gram-positive MSSA, MRSA, fungal infection, enterococcus spp, and nonfermenting gram-negative bacteria occurred at high rates during the first 180 and 150 days respectively (2). another important DDX with hypoxemia and tachycardia tachypnea with respiratory alkalosis is pulmonary embolism (PE), infective exacerbation, and decompensated heart failure however atypical infections like PJP and CMV are less likely, and usually, patients should be on chemoprophylaxis like cotrimoxazole and valganciclovir
How do you manage this case?
FBC, CRP, blood culture, sputum culture if no sputum, use saline induced sputum, respiratory viral screen, CMV PCR, LDH, LFT, ABG, D DIMER, and doppler US to rule out DVT, 12 lead ECG, Cardiac BNP, assess volume status and in/out chart
O2 therapy with high nasal flow o2 or NIV
Empirical AB includes covering MDR and staph aureus, MSSA, MRSA, and gram-negative bacteremia.
Adjust immunosuppression therapy with a 50% reduction of antimetabolites and even consider stopping MMF and continuing on tacrolimus and steroid
DVT prophylaxis
if no improvement then considers bronchoscopy and BAL fluid assessment for cytology galactomannan and cmv pcr, PJP Q pcr
the possibility of CMV reactivation is high if the Donor is positive, the recipient negative, and if confirmed CMV pneumonia then needs ganciclovir IV 5 mg/kg BID for 3 weeks
CMV co-infection increased the risk of PJP and needs prompt diagnosis by bronchoscopy and BAL q PCR for PJP if confirmed then the drug of choice as first-line TMP-SMX low dose is still effective with better tolerance and compliance with lower side effects and lower cost and even lower mortality (3). but in case of side effects or intolerance still, we can use second-line therapy like dapsone, pentamidine, and atovaquone. combination of clindamycin and primaquine.
This patient needs prolonged long-term chemoprophylaxis to prevent latent reactivation
References
1. Week 5 lecture
2. van Delden C, Stampf S, Hirsch HH, Manuel O, Meylan P, Cusini A, Hirzel C, Khanna N, Weisser M, Garzoni C, Boggian K, Berger C, Nadal D, Koller M, Saccilotto R, Mueller NJ; Swiss Transplant Cohort Study. Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study. Clin Infect Dis. 2020 Oct 23;71(7):e159-e169. doi: 10.1093/cid/ciz1113. PMID: 31915816; PMCID: PMC7583409.
3. ReviewTrimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization
in Pneumocystis jirovecii Pneumonia (PCP) Management:
A Systematic Review, JC 3, week 5.
With this hypoxia if diagnosed as PCP ( though early) treatment should be more aggressive.
totally agree with you Prog dawlat and we are doing the same use a high dose of IVcotrimoxazole 15-20mg /kg TID for 21 days with close monitoring for intolerance and side effects
You can not expect a culture for PCJ.
How about PCR.
SURE
Differential Diagnosis;
Aspiration pneumonia
· Pneumocystis Jirovecii
· Bacterial Pneumonia
· CMV pneumonitis
· COVID-19 Pneumonia
Management;
CBC, LDH, CRP, ABG.Sputum for gm stain c/s,fungal stain and c/s, PCR.
BAL
Treatment
· Oxygen inhalation as required
· Reduction in IS particularly antimetabolites in presence of active infection and increase steroids to 20-40mg/day.
· TMP-SMX 20mg/kg iv in divided doses 3 time daily
·
What other drugs that can be used and under which circumstances?
This patient has developed a pneumonia 11 days post cadaveric transplantation. The CXR shows perihilar infiltrates and the CT scan shows ground glass opacities with honeycombing. It would be important to know if the patient was on PJP prophylaxis and what the CMV status was prior to transplantation and if she was on CMV prophylaxis
The differential diagnosis includes:
The management will involve:
1.Further work up:
2.Treatment:
What other drugs used in PJP.
The other drugs used in PJP apart from septrin include:
Clindamycin plus primaquine
Atovaquone
Pentamidine
Trimethoprim plus dapsone
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.
What about TMP-SMX resistant cases!
Atovaquone is a second-line agent. although it is used only for mild-to-moderate
PJP.
or Clindamycin plus Primaquine.
or IV pentamidine is but it is also highly toxic.
and LDH.
treatment
TMP-SMX I.V every 6 to 8 hours dose 15 to 20 mg/kg/day.
corticosteroid if o2 sat less than 92%
alternative therapy if allergic, SE, or not respond in such severe disease
clindamycin plus primaquine.
I.V pentamidine 4mg/kg/day.
duration of therapy is 21 days with lifelong prophylaxis.
MMF holds it and decreases the TAC level to 7-8( risk of rejection)
prednisone 60 mg daily
monitor the KFT and this early transplant period as high risk of rejection
Reference
lecture prof Gammal saadi
uptodate
Are you sure this dose of TMP-SMX I.V 15 to 20 mg/kg/day will be good enough for treatment of PCP (PJP)?
👉 The current case with old age , intense immunosupression and diabetic so may be early onset PCP in the first month.
👉 Diffrential diagnosis :
_PCP (parahilar infiltration with subpleural sparing and honey combing).
_COVID 19 (has subpleural affection).
_CMV pneumonitis.
_Aspegillosis.
👉 Management:
⭐Investigations:
_CBC, CRP ,Blood and sputum culture is feasible.
_BAL with PCR for PCP.
_CMV and COVID 19 PCR.
⭐Treatment:
_Oxygen therapy guided by SPO2.
_Follow up ABG for hypoxemia and for fear of respiratory failure and failed compensation.
_Ensure adequate hydration.
_Once suspect PCP, start IV SMT_TMP.
_Steroids can be used to improve oxygenation in case of hypoxemia.
_If CMP PCR is postitive, IV ganciclovir will be started .
_ Decrease IS as decrease dose of MMF and keep CNI on lower therapeutic window around 7_8.
_FU LDH level as prognostic marker.
_Close follow up of graft function as risk of rejection in early period post transplant.
_ life long secondary prophylaxis for PCP is indicated
I suggest:
Thanks dear professor
I don’t know when it is indicated to just decrease dose of MMF and when to stop it
What is the differential diagnosis?
1. SARS-Covid-2 infection
2. Antimicrobial –resistant pathogens (MRSA, VRE)
3. Bacterial pneumonia
4. Fungal infection (pneumocystic, nocardia)
5. CMV and EBV
6. Pulmonary tuberculosis
Although rare immediately after transplantation, the diagnosis may be Pneumocystis Jirovecii Pneumonia as
1. Symptoms of dry cough, dyspnea, and low grade temperature
2. very few physical findings on chest examination
3. and radiological features of chest x-ray (bilateral perihilar infiltrates)and CT chest (ground glass appearance)
How do you manage this case?
Diagnosis:
o Complete history and clinical examination
o CBC, e GFR, electrolytes, CRP, s. albumin, liver enzymes, blood culture, urine culture and line cultures
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 Treat the underlying cause
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:
§ O2 therapy (maintain 0xygen > 92%)
§ Duration of antimicrobial treatment is for at least 14days (21 days in severe infection)
§ This is severe pneumocystis Jirovecii Pneumonia needs intravenous antimicrobial
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.
IV Pentamidine ?
I mean to ask pentamidine by IV route?
This post kidney transplant patient developed fever and acute respiratory symptoms in 11 days post transplant CXR showed perihilar infiltrate and CT chest showed ground glass appearance .
Differential diagnosis is:
-PCP or other fungal pneumonia
-Bacterial pneumonia
-Viral pneumonia like CMV or covid 19
How do you manage this case?
Management :
-Hospital admission with start of Supportive treatment oxygen antipyretic and hemodynamic stabilization.
Invitations :
-Full blood count , graft function ,liver function test urine analysis and urine PCR
-Induced sputum by BAL for cytology culture and PCR for PCP
-Plasma PCR for CMV .
-Blood culture .
Specific treatment directed towards most likely cause PCP:
Reduction of immunosuppression : stop the antimetabolites increase the steroid dose 40-60 mg for 5 days then tapering till baseline dose over 21 days of treatment .
Antibiotic of choice is Trimethoprim-Sulfamethoxazole- TMP-SMX (15 to 20 mg/kg/day of the trimethoprim component) IV given in three or four divided doses for 21 days .
Other alternatives :
-If patients show worse course or have severe adverse effects including elevated serum creatinine or potassium level, cytopenia, and gastrointestinal disorder, alternative agents like pentamidine which is the second line (4 mg/kg IV once daily ), dapsone (100 mg orally once per day) , and atovaquone (750 mg orally twice daily ) should be considered.
-prophylaxis : for this patient after cure with TMP-SMX for 6 month
– If CMV infection id detected treatment with iv gancyclovir
-Other bacterial infection the choice of antibiotic is according to culture and sensitivity but in such critical situation you will start empirically while waiting for the culture .
reference :
1.Clin Transplant. 2019 Sep; 33(9): e13545. Published online 2019 Apr 23. doi: 10.1111/ctr.13545
2 -Uptodate ;Treatment and prevention of Pneumocystis pneumonia in HIV-uninfected patients Authors:Charles F Thomas, Jr, MD Andrew H Limper, MD
3.-Child Kidney Dis > Volume 24(1); 2020 > Published online: April 30,/ 2020 DOI: https://doi.org/10.3339/jkspn.2020.24.1.47
IV Pentamidine ?
I mean to ask pentamidine by IV route?
Thank you prof Ajay Sharma .
I mentioned pentamidine as therapeutic second line for treatment of PCP as recommended by CDC to be given iv in a dose of 3-4mg/kg/day iv for 14-21days , with close monitoring because of side effect hypotension and prolong QT interval .also with cautions in case of renal impairment .
.
If used as prophylaxis : Root is nebulization in a dose of 300 mg administered via the Respirgard(R) II nebulizer every 4 weeks.
Referrence :
Pentamidine also can be used IM but there is risk of sterile abscess .
nebulized pentamidine may also be used as therapeutic treatment .
History
====================================================================
This picture Early post-transplant infection (Pneumonia)
====================================================================
Early Post-Transplant Infection (0-30 Days Post-Transplant)
1- Nosocomial InfectionS:-
2- Donor – Derived Infections
3-Recipient -Derived Infections
====================================================================
How do you manage this case?
IF sulfa allergies and mild to moderate disease include:
Alternative treatments for moderate to severe cases include:
====================================================================
Reference
IV Pentamidine ?
I mean to ask pentamidine by IV route?
Many thanks Prof.Sharma
=============================================================
Reference
Day 11 post kidney transplant, tacrolimus based triple immunosuppressive medications.
Tachypnea, dry cough, low grade fever, and crepitation to auscultation, and hpoxemia of 8 kPa.
CXR= bilateral perihilar infiltrates, ground glass appearance by chest CT.
What is the differential diagnosis?
Pneumonia hospital acquired, pseudomonas, kliebsella, streptococcus,
Atypical infections, legionella, mycoplasma,..etc
Viral infections, CMV, HSV, Parvovirus,corona viruses… etc
Fungal infections,PJP, Aspergillus, cryptoccocus,…etc
Pulmonary embolism
How do you manage this case?
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- raise the suspicion of PJP.
CT Scan- honeycombing, ground glass opacities, subpleural sparing, reticulation, stipes, and pneumatic cysts- PJP should be put on DDx.
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 for PJP.
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 (15-20 mg/kg/day in 3-4 devided doses) is the drug of choice, if allergic to sulfa drugs then: Atovaquone (1500 mg qd), pentamidine (IV 4 mg/kg/day loading then 2-3 mg/kg/day), dapson (15-30 mg/kg once daily)+ TMP-SMX, or a combination of clindamycin+pyrimethamine, and pentamidine.
Steroid stress dose (high dose) especially when PJP is the diagnosis, with marked hypoxemia.
Stopping MMF it in hemodynamically unstable patients, but continue on CNI.
Adoptive immunotherapy could be used, but of un proven benefit.
It is supposed that the patient is on CMV, and PJP prophylaxis 6 months post transplant.
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.
We never had to do lung biopsy, an early BAL is the key to prompt diagnosis
What is your differential diagnosis?
1- Pneumocystitis carenii pneumonia (PCP).
2- Bacterial pneumonia
3- Viral infections including influenza and Covid
4- CMV pneumonitis
5- Fungal pneumonia (aspirgillosis)
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 in case of severe infection
B- Antimicrobial therapy
Thankyou you are right that 11 days is a bit early!
True it can not be cultured.
You need to ellaborate more on TREATMENT, resistance to TMP-SMX,
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
Early post kidney transplant pneumonia.
Differential diagnosis:
1] Bacterial bronchopneumonia:
a] Nosocomial pneumonia.
b] Gram negative bacteria, including, E. coli, pseudomonas and klebsiella pneumonia.
c] Gram positive pneumonia, mainly Staph. aureus.
2] Pulmonary thromboembolism.
3] Exacerbation of underlying bronchiectasis.
4] Adult respiratory distress syndrome.
5] Congestive cardiac failure with pulmonary edema.
6] Vasculitic process
Management:
Blood culture.
Induced sputum culture.
Bronchoscopy if no improvement reported.
Trans-esophageal echo to roll out right sided valvular heart disease.
Plan:
Start broad spectrum Antibiotic, to cover underlying gram negative and nosocomial pneumonia.
Stop anti-metabolites temporarily.
refences:
1] Daniel E. Dulek, 1 Nicolas J. Muelle.Pneumonia in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.2019 Sep; 33(9)
DDx
Case of early posttransplant pneumonia
Causative organism
Pneumocystis jirovecii Pneumonia PJP
Aspergillosis
CMV
Varicella pneumonia
Covid 19
Influenza
Hospital acquired infection (nosocomial) seek local microbiology help for the common local hospital organism
How to manage
Isolation in ICU negative pressure room till results of screening
Monitoring and Support hemodynamics as appropriate (help of ICU team) ABG 12 hourly
Oxygen supply to keep SPO2 >94%
Rebreathing bags and Calcium iv if needed
CBC, chemistry (LFT, KFT and electrolytes) LDH, PT, INR, APTT, Ionized calcium Total calcium
Sputum CS (BAL or tracheal tube aspiration for better yield)
Blood CS
Seek missiology help
Review her medication for starting the prophylaxis regimen for PJ
Review the serology of donor and recipient
Start empirical antimicrobial including TMP/SUL every 6 hours: Co-trimoxazole 120mg/kg (sulphamethoxazole 100mg + trimethoprim 20mg)/day (usually four divided doses) for 14 days.
Sensitivity to co-trimoxazole
Sensitivity to co-trimoxazole (sulphamethoxazole > trimethoprim) is common. Alternative treatments include: dapsone + trimethoprim, atovaquone, clindamycin + primaquine, and nebulized pentamidine
Change according to the results of culture and sensitivity
Modification of immunosuppressive with observation of kidney function
Prophylaxis for 6-12 months according to risk assessment
Thankyou but:
PCJ can not be cultured exvivo so no sensitivity can be judged.
You have to judge by the clinical picture, radiology,BAL, TBL, even to lung biopsy,PCR.
In this case you TREAT first and later refer to PROPHYLAXIS.
the early infection(0-30 days) : viral, bacterial ,fungal,..etc
How do you manage this case
further work ups for reaching diagnosis
co-ordination with microbiologist and pulmonologist
Thankyou for attempting to answer but it has to be more precise ie in the given scenario.
what are the radiology findings.
sure lab findings.
lines of treatment.
-What is the differential diagnosis?
This is a recent transplant with manifestations of acute respiratory infection on day 11 post transplant.
Diabetes may put her at more risk of infection
This time line is very important for the formulation of the differential diagnosis.
The differential diagnosis of respiratory infection < one months post-transplantation are ;
-How do you manage this case?
Management is MDT as usual but this case is tricky due to diagnostic challenges and the management will the depend on the specific cause.
Source:
Nephrology secrets ,chapter 60, posttransplant infections by Beje Thomas and Metthew R. Weir
A discussion about this patient would not wait for a weekly MDT. In such a critically ill patient, I would go to the on-call radiologist straightaway in his (or her) department.
Yes, prof , I would the same, MDT here we meant consulting every one immediately.
The patient is in respiratory distress, recommended to be in high dependency unit with chest and ID consultation
The chest CT showed a bilateral cystic lesion with an air bronchogram(highly suspicious of PCP)
He needs high-flow O2 or BIPAP to keep the AO2 above 94% and to decrease the RR, or the patient will need to be ventilated from respiratory exhaustion.
It is essential to investigate the patient’s past inoculation history as well as their travel history.
Diagnostic approach:
A blood count that also includes the differential
Creatinine, as well as the electrolytes and blood urea nitrogen,CRP ,and LDH
Blood cultures (minimum of two sets, with at least one peripheral set and one set from any indwelling catheter)
The inspection and cultivation of the urine sediment
Sputum is to be stained with Gram stain, cultured and examined for fungal smears
Imaging of any symptomatic location as well as imaging of the lungs (chest radiography or, if feasible, chest computed tomographic scanning) (eg, abdomen)
Examination of the patient’s skin, searching for signs of a metastatic infection
CMV quantitative molecular testing is often helpful, along with other viral polymerase chain reaction (PCR) tests that are tailored to the specific patient (adenovirus, parvovirus B19, severe acute respiratory syndrome coronavirus 2)
Consideration should be given to the collection of samples for the use of diagnostic tools that are not based on cultures, such as specific molecular and antigen tests (such as Aspergillus or Pneumocystis PCR, cryptococcal antigen), Aspergillus galactomannan, beta-1,3-glucan, and whole genome sequencing.
To increase the sensitivity of the test, BAL samples should be paired with microbiologic tests (such as cultures, polymerase chain reaction, and Aspergillus galactomannan antigen).
Quntiferon test for TB
Treatment:
Patients with PCP of any severity should be treated with trimethoprim-sulfamethoxazole (TMP-SMX), which is the medication that we propose as the therapy of choice.
When TMP-SMX cannot be used to treat PCP, other treatments, such as clindamycin with primaquine, trimethoprim plus dapsone, atovaquone, and pentamidine, may be used instead. The severity of the patient’s condition is a factor that should be considered while selecting an alternative treatment plan for patients who are unable to take TMP-SMX.
Check the serum level of creatinine and the CNI trough regularly.
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. The usual duration of therapy is 21 days.
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.
Wieruszewski, P. M., Barreto, J. N., Frazee, E., Daniels, C. E., Tosh, P. K., Dierkhising, R. A., … & Limper, A. H. (2018). Early corticosteroids for Pneumocystis pneumonia in adults without HIV are not associated with better outcomes. Chest, 154(3), 636-644.
Please use bold or underline for headings or sub-headings to make it easier to read.
Differential Diagnosis;
Based on clinical scenario and Radiological findings the D/Ds are:
· Pneumocystis Jirovecii
· Bacterial Pneumonia
· CMV pneumonitis
· COVID-19 Pneumonia
Management;
Initial investigation CBC, LDH, CRP, ABGS, RFTS. S Electrolytes Sputum staining, B D- glucan and PCP PCR.
BAL for PCP staining .
Treatment
· Oxygen inhalation NIV.
· Reduction in IS particularly antimetabolites in presence of active infection and increase steroids to 20-40mg/day.
· TMP-SMX 20mg/kg iv in divided doses 3-4(dosing is based on TMP component) maintin iv dosing until PaO2 is >60mmHg or RR<25).
· Allergic patients can be desensitized but not for sever allergy like Stevens-johnson.
Alternative agents;
Agents used for mild disease are;
1. Atovaquone; 750mg bid with food.
2. Clindamycin plus primaquine; clinda 900mg iv TDS and Primaquine 30mg OD.
3. TMP plus dapsone; dapsone 100mg daily and TMP 5mg/kg orally TDS.
Moderate disease;
1. Clindamycin plus primaquine ( doses as above)
2. TMP plus dapsone
Severe disease;
1. Clindamycin plus primaquine , primaquine is only oral.
2. IV pentamidine ; preferred agents are clinda plus primaquine because it is less toxic than iv pentamidine.
Reference; Topic 1393 Vesrsion 47.0 UpToDate
IV Pentamidine ?
I mean to ask pentamidine by IV route?
Yes professor, intravenous route
as far it is 11 days post RTX it is primary infection
firstly we need to secure his oxygenation probably he will need BIPAP
then need to reduce immunosuppression medication will start by antiproliferative mesures.
THis is severe chest infection evident by respiratory alkalosis due to hyperventalation and hypoxia
for that he need to take iv medications first line for severe infection is sulfamethoxazole and TMP.
there are other medications which can be used as well
Typing whole sentence in bold or capitals equals to shouting !
Please use bold or underline for headings or sub-headings to make it easier to read.
Please quote references.
Differential Diagnosis
65 yr old diabetic
Post Cadaveric Tx
Apparantly good kidney function though RFTS not mentioned
Day 11
Dry cough
Low grade fever
Few crackles
increqsed respiratory rate
CXR Perihilar infiltrates
CT chest ground glass haze
This all is suggestive of
PCP pneumonia reactivation
Bacterial pneumonia
Atypical pneumonia
less likely TB
Fungal ?
Management
It will depend on confirmation of diagnosis and initiation of targeted treatment at the same time.
will do
BLOOD CP CRP
RFTS
ELECTROLYTES
LDH
B D GLUCAN
SPUTUM FOR GRAM STAIN CULTURE AND STAINING FOR PCP AND AFB
PCP PCR
BAL SPECIALLY FOR PCP
Treatment
Maintain oxygenation , will consider BiPAP
Reduction of immunosuppressants preferably anti metabolites initially if clinical condition deteriorates we can stop CNI as well
Increase dose of steroids
Ensure concomitant valganciclovir
Start therapeutic dose of sulfamethoxazole and TMP.
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.
For patients with allergy to TMP-SMX, desensitization should ideally be performed since TMP-SMX is the most effective regimen. However, if the patient has a history of a severe allergy (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis), TMP-SMX should be avoided and desensitization should not be performed.(up to date)
The choice of regimen in patients who cannot take TMP-SMX depends in part upon the severity of disease.
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 atovaquonein 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. (up to date)
About use of Iv pentamidine
IV pentamidine is not often used because it is associated with substantial toxicity (eg, hypotension, hypoglycemia, nephrotoxicity, and pancreatitis) and must be administered parenterally. In a randomized trial of 50 patients with PCP, IV pentamidine (4 mg/kg once daily) was as effective as TMP-SMX
IV Pentamidine ?
I mean to ask pentamidine by IV route?
Yes sir it is mentioned in up to date but the reference article is of 1978🤔
Differential diagnosis
– Pneumocystosis – Reactivation most probably
– Mycobacteria (especially Tuberculosis)
– Histoplasmosis
– invasive aspergillosis
– COVID 19 + CAPA
– Cryptogenic pneumonia (BOOP)
– atypical pneumonia
Management
1. Diagnosis
Non-contrast-enhanced computed tomography (in the case of Pneumocystosis, heterogeneous bilateral interstitial lesion with clinical-radiological dissociation). As there is a suspicion of invasive Aspergillosis, consider the introduction of contrast
Sputum test
Bronchoalveolar lavage with investigation for BAAR, Gene Xpert for Tuberculosis, RT PCR for Pneumocystosis, Culture for aerobes, fungi, Ziehl Neelsen, Galactomannan, RT PCR COVID-19
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
Urinary and serum antigen for Histoplasmosis (higher sensitivity and specificity in SOT)
2. Clinical management
Define the need for corticosteroids and their progressive withdrawal during treatment. (In case of BOOP and Pneumocystosis)
Low-dose corticosteroids (Dexamethasone 6mg/day) associated with Remdesivir in case of COVID-19
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 tacrolimus, due to the high interaction with Sulfas (Evaluate its exchange for another immunosuppressant)
Investigate and treat CMV reactivation
If the patient is allergic to Sulfa, there are alternative treatments with
3. Post-treatment care
In this specific case, I would undergo computed tomography with contrast because it is related to angioinvasive aspergillosis because it presents a lesion suggestive of a cavitated nodule. In this case, the BAL galactomannan helps a lot in the diagnosis and would change the treatment based on Sulfa to Isavuconazole.
Thank you, Professor
The CXR shows bilateral in-homogenous opacity with reticulonodular infiltrates
The chest CT scan shows a bilateral perihilar ground glass appearance and honeycombing, but with sparing of subpleural area.
Differential diagnosis
Although PJP and CMV infection is uncommon in the first-month post kidney transplantation if prophylaxis TMP-SMX is used. Before further investigations, detailed history of adherence to PJP and CMV prophylaxis will be obtained
Also the history of D/R CMV status
Investigation
-Gomori methanamine Silver polychrome stain
-Immunofluorescence.
Treatment
This is a severe respiratory infection as evidenced by compensated respiratory alkalosis likely from hyperventilation from severe hypoxia
Other alternative medication if allergic to sulfur for 4 weeks
If not yet started, primary prophylaxis will be commenced after recovery at single doses ( 480mg)TMP-SMX will be considered for the patient for 6 -12 months.
Also, CMV prophylaxis (Valganciclovir 900mg daily oral) will be given for 200 days
References
Thank you for your reply
You mentioned IV pentamidine as a treatment for PCP. Please explain to us the different routes of administration
Thank you prof for the response,
SORRY, it was an error, I retract that statement of I.V pentamidine, I meant to write Inhalational pentamidine.
Thank you, well done,
What is your differential diagnosis?
The Chest X-ray picture showing bilateral diffuse hazy pulmonary reticular interstitial infiltrates with hilar opacity and hazy ground glass changes
CT are extensive ground-glass opacities (central distribution & sparing the periphery)
DD:
1- Pneumocystis jirovecii (PJP), Fungal pneumonia==> Most likely diagnosis
2- Other Viral (Influenza, COVID-19)infections
3- Bacterial Infection
4- PTB
5- CMV
6- Aspergillosis
How do you manage this case?
Diagnosis is challenging due to:
1- Nonspecific presenting signs and symptoms , need high clinical suspicion
2- Inadequate conventional diagnostic methods
Diagnostic tests:
1- Sputum (BAL)Gomori methenamine silver (GMS) staining on samples (sputum or
bronchoalveolar lavage fluid, and tissue( Staining for Trophozoite or cysts)
2- Serum β-D-glucan (BDG) test: Widely used method, PPV 96 % NPV 60%
3- ABGs, LDH
3- PCR testing: PJP PCR
•Fast & more sensitive than GMS staining.
•Not widely used in clinical practice
•Variable cut values in different studies.
4.Metagenomic next-generation sequencing (mNGS):
•Is a new diagnostic method.
•Both sputum and serum can be used.
•Can help detect a large amount of complex and rare pathogens quickly & accurately.
5. CT scan will showing ground glass appearance, honeycombing, and cystic lesions.
Treatment of PJP:
All Post Solid organ Transplant with signs and symptoms of infections, feeling unwell==> should be admitted to acute ward or ICU according to severity (ABCD support) and for viral, septic, radiology screening , beside the routine blood work (LDH) and stabilization the general conditions (IV Fluids, Empirical Ab, decrease IS accord. to severity and you assessment ).
Sever PJP will use IV Bactrim or Pentamidine +_ Steroids (14 to 21 days )
1. Inhaled pentamidine. 300 mg nebulizer monthly or IV Pentamidine (Initially 4
mg/kg/day over 1–2 h)
2.Dapsone. 50-100 mg po daily
3.Atovaquone 1500 mg po daily,
4.Primaquine combined with clindamycin po or iv .
5.Combined dapsone and trimethoprim
6.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.
CMV Pneumonia : 14 to 21 days
Ganciclovir intravenously for CMV 5mg/kg /12 HR accord to Cr CL .
Factors Associated with poor outcomes:
Complications:
References :
Thank you for your reply
You mentioned IV pentamidine as a treatment for PCP. Please explain to us the different route of administration
Pentamidine can be given intravenously or inhaled as an aerosol for P. jirovecii pneumonia. It can be given by deep intramuscular injection for leishmaniasis or trypanosomiasis.
Administer by slow IV infusion over a period of at least 60–120 minutes at a final concentration of administration not to exceed 2 mg/ml. Maintain patient lying down during infusion. Rapid infusion causes hypotension. If hypotension occurs, increase infusion time to 2–3 hours
·What is the differential diagnosis?
Acute causes include:
Pneumocystis pneumonia:
CMV:
COVID-19:
Pulmonary embolism:
Pulmonary edema:
Alveolar hemorrhage:
==========================
·How do you manage this case?
Treat the underlying cause accordingly:
Treatment of PJP:
Anticoagulation for pulmonary embolism
Ganciclovir intravenously for CMV
References
1.Matos MJR, Rosa MEE, Brito VM, Amaral LTW, Beraldo GL, et al., Differential diagnoses of acute ground-glass opacity in chest computed tomography: pictorial essay. Einstein (Sao Paulo). 2021 Mar 15;19:eRW5772. doi: 10.31744/ Einstein_journal/2021RW5772. PMID: 33729289; PMCID: PMC7935089.
2. Lecture by Prof Gamal Saadi
Thank you for your reply
You mentioned IV pentamidine as a treatment for PCP. Please explain to us the different route of administration
Thank you, dear Prof Halawa
Pentamidine aerosols (300 mg every 3–4 weeks) is effective prophylaxis, with fewer & less severe adverse effects than those occurring with systemic regimens, while IV Pentamidine is use as a second line therapy.
CXR showed bilateral pulmonary infiltration in cadaveric renal allograft recipient c/o fever and dry cough , together with hypoxia, CT showed ground glass appearance
DD:
1- viral pneumonia like CMV, COVID infection
2- bacterial pneumonia
3-fungal pneumonia like PCP, aspergillus infection
management:
1- hospitalization and oxygen therapy
2-lab investigations CBC, LDH (non-specific)
3-PCR for CMV
4-PCR for PCP
5-BAL which is a sample of choice or induced sputum as it is simple and cost effective , for microbiological diagnosis
6- blood culture
7- detection of the β-d-glucan antigen in blood samples facilitates detection of PCP.
8-presence of dry cough and hypoxia with this picture of CXR and CT suggest a diagnosis of PCP which can be treated as follow:
1- Trimethoprim-Sulfamethoxazole (TMP-SMX) which is the first-line agent for the treatment of mild to severe PCP in both HIV and non-HIV-infected patients and in SOT, The recommended daily dose is TMP 15–20 mg/kg plus SMX 75–100 mg/kg, preferably by IV administration for severe PCP for 14-21 days.
2-Intravenous pentamidine remains probably the best second-line agent after TMP-SMX for SOT recipients.
3-Atovaquone, clindamycin-primaquine, or dapsone-TMP.
4-clindamycin-primaquine combination seems to be the most effective regimen, particularly in cases where TMP-SMX has failed.
5-In HIV-negative patients with moderate-to-severe PCP, the use of adjunctive glucocorticoids remains questionable and is highly controversial.
6-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)
7-Corticosteroids should be administered with antimicrobial therapies, ideally within 72 h of initiating the antimicrobial therapy to obtain the maximum benefits
8-American Society of Transplantation guidelines suggest that 40–60 mg of prednisone is administered per oral twice daily and tapered after 5–7 days over a period of 1–2 weeks
9-Reduction in Immunosuppressive Medications
10-CMV prophylaxis by valganciclovir should be given and needs renal dose adjustment.
references:
1-Xavier Iriart, Marine Le Bouar, Nassim Kamar, Antoine Berry.Pneumocystis Pneumonia in Solid-Organ Transplant Recipients. J Fungi (Basel). 2015 Dec; 1(3): 293–331.2-Dominykas Varnas, 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.
Thank you for your reply
What is the differential diagnosis?
Viral or bacterial pneumonia
Tuberculosis
Legionella pneumonia
Mycoplasma infections
COVID-19 pneumonia
ARDS
How do you manage this case?
Decrease MMF dose by half,totally stop if condition deteriorating
TMP 15 to 20 mg/kg/day and SMX 75-100 mg/kg/day are given intravenously (IV) every 6 to 8 hours with a switch to oral when the patient shows clinical improvement.
TMP 15 to 20 mg/kg/day and SMX 75 to 100 mg/kg/day, given orally in 3 or 4 divided doses or TMP-SMX DS, two tablets three times per day.
Total 21 days treatment.
Alternative drug regimens for the treatment of PCP in those with 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.
Once acute episode is treated then prophylaxis for 6 months-
First-line prophylaxis treatment is trimethoprim-sulfamethoxazole, one double-strength tablet by mouth daily or one single-strength tablet by mouth daily.
For those with sulfa allergies, recommended prophylaxis includes:
Dapsone 100 mg by mouth daily or 50 mg by mouth twice each day
Dapsone 50 mg by mouth daily plus pyrimethamine 50 mg plus leucovorin 25 mg by mouth weekly
Dapsone 200 mg plus pyrimethamine 75 mg plus leucovorin 25 mg by mouth weekly
Atovaquone 1500 mg by mouth daily
Atovaquone 1500 mg plus pyrimethamine 25 mg plus leucovorin 10 mg by mouth daily
Aerosolized pentamidine 300 mg monthly via Respigard II nebulizer.
It is uncommon to have PCP infection 11 days post-transplantation. Will you explain what happened here in the index case?
Receiving induction therapy with ATG
Not receiving PCP prophylaxis due to high creatinine
exposure to a common hospital environment reservoir
non compliance to prophylaxis
intensified immunosuppression
sulfonamide resistance related to mutation of dihydropterate synthase
What is the role of steroids in the treatment of PCP?
Corticosteroids also may be recommended in patients with PCP due to the potential for high mortality and fulminant course of illness, but data are limited on whether there are benefits or a decrease in in-hospital mortality.
Dosing for prednisone should be started as soon as possible or within 72 hours of starting treatment for PCP and is as follows:
40 mg by mouth twice per day on days 1 through 5,
40 mg by mouth daily on days 6 through 10,
20 mg orally daily on days 11 through 21.
IV methylprednisone can be given at 75% of the prednisone dose if oral therapy cannot be tolerated.
Pneumocystis Jirovecii Pneumonia
Justina Truong
Pneumocystis Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after Transplantation: A Case Report and Literature Review
Dominykas Varnas et al
Pneumocystis carinii Pneumonia Among Renal Transplant
Recipients Despite Antibiotic Prophylaxis
Sze-Kit Yuen et al