5. A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
Detailed evaluation ( history of UTI before Tx, any voiding difficulty, exclusion any obstruction by doing USG of KUB with PVR, urodynamic study/cystoscopyif indicated)
Maintain personal hygeine, avoid constipaion, bladder evacuation frequently, use cranberry juice, use post coital pill if needed. Long term prophylactic antibiotic (monthly rotation of TMP/SMX, Nitrofurantoin, cefalaxin..) may be ne necessary in this pt.
How would you manage this patient?
· UTI is a very common infection following kidney transplantation and it ranges from asymptomatic bacteriuria to cystitis or pyelonephritis.
· Recurrent UTI is associated with an increased risk of graft and patient loss. It is defined as ≥ 2 episodes within 6 months or ≥ 3 episodes within 1 year.
· Risk factors for recurrent UTI:
o Old age
o female gender
o post-surgical complications like urine leak, lymphocele or infected hematoma, infected peri-nephric collection
o prolonged catheterization, or DJ stent complications
o low bladder capacity,
o Anatomical abnormality including low bladder capacity, vesico ureteric reflux or neurogenic bladder.
o History of DM
o Immunosuppression medication increases the risk of infection
o Compliance to the use of prophylactic antibiotics · Workup
Urine culture and sensitivity to isolate the offending pathogen to guide for the suitable antibiotic.
Determine the source of UTI whether it is native or the allograft
Urological evaluation to exclude structural or anatomical abnormalities using US, CT KUB ,flexible cystoscopy ,urodynamic studies and post-voiding residual volume
Revise immunosuppression protocol.
gynecology to rule out any local cause of recurrent UTI
Treatment of recurrent UTI (directed by urine C/S):
o Initial treatment: TMP-SMX for 7-14 days or quinolones for 7 days o Complicated UTI: IV 3rd generation cephalosporin IV o ESBL cases: Carbapenems (imipenem or meropenem) can be used. o Consider nephrectomy of the native kidney if in recurrent UTI resistant to treatment
Strategies to prevent recurrent UTI:
o Prophylaxis treatment with TMP-SMX for at least 6-12 months. If SMX-TMP is contraindicated, use nitrofurantoin 100 mg twice daily provided GFR > 30 ml/min or cephalexin 500 mg twice daily. o Screen for asymptomatic bacteruria. o General measures like encourage for adequate hydration, frequent voiding, wiping from front to back of the perineum in females References:
Rubenstein JN, Schaeffer AJ. Managing complicated urinary tract infections: the urologic view. Infect Dis Clin North Am 2003 Jun;17(2):333-51.
post-op – forgotten stent; sexual exposure; prophylactic antibiotics.
Immunological history – donor sister, probably well-matched. DSA not mentioned, probably negative — low immunological risk.
Immunosuppression: No mention about Induction; Tac and MMF dose to be assessed as per body weight – may need to reduce immunosuppression.
h/o rejection? use of high dose steroid ? NODAT ? – sugar control
Antibiotics used, with duration.
To get fresh Urine Cultures and sensitivity; Urine for AFB; Candida (KOH / fungal culture) Drug level
– Tacrolimus and MMF level
– CMV, BKV PCR quantitative analysis. Urological evaluation:
· Uroflowmetry and PVRU
· Any neurological illness (PIVD),
· Imaging of transplant and native kidneys: CECT-KUB with IVU; look for forgotten stent, stone, obstruction. Gynaecological check-up / pelvic exam– cystocele or prolapse; atrophic vaginitis; urethral caruncle.
· May need Cystoscopy – (stent removal, if done yet)
Treatment:
· Course of Antibiotic as per sensitivity – adequate dose, 2-3 weeks.
· Followed by Prophylactic antibiotics x 3-6months
o Cotrimoxazole (SEPTRAN-DS) shall cover PCP as well as Asymptomatic Bacturia.
o Ciprofloxacin 500mg OD bed time is alternative.
o Nitrofurantoin or Fosfomycin can be used if Cotrimoxazole / Ciprofloxacin resistant.
Ø Personal hygiene
Ø Plenty of liquids to drink – 1 glass every hour; void urine every 2-3 hours
Ø Avoid sexual intercourse or next 1 year; if at to participate, wash perinium and genitalia before sex; pass urine immediately after sexual intercourse.
Ø Additional antibiotic dose after intercourse – post-exposure prophylaxis
· Atrophic vaginitis à Premarin (Estrogen) vaginal cream application
· Candidiasis à Candid vaginal gel LA bed time + oral Fluconazole
· Correction of Cystocele and prolapse
· If voiding difficulty à Cystoscopy + urethral dilation
2. Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9): e13507. Available at: https://pubmed.ncbi.nlm.nih.gov/30793386/
3. Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
Aydın S, Patil A, Desai M, Simforoosh N. Five compelling UTI questions after kidney transplant. World J Urol. 2020 Nov;38(11):2733-2742. doi 10.1007/s00345-020-03173-4. Epub 2020 Apr 7. PMID: 32266510.
This patient has recurrent UTI post- transplantation. Complete history about UTI before TX, remaining DJ, use of co-trimoxazole or not and physical examination are necessary. Ultrasonography of native kidneys and transplanted kidney with measurement of residual urine after void could be informative.
Further imaging with non-contrast CT scan to determine stone or cysts and VCUG to determine VUR is indicated. Urodynamic study including cytometry and uroflometery are necessary for bladder dysfunction or dyssynergia (DSD) with sphincter if there is high residue.
Urology consultation and cystoscopy should be performed as well.
The patient should continue co-trimoxazole to prevent UTI. Stent removal if indicated, should be done. Frequent and double voiding, wiping from front to back in females and drinking enough water are recommended. Treatment of UTI depends on its severity and recurrence and anatomical abnormalities. For example, treatment of infected cysts should be lasted for 4-6 weeks, but cystitis needs shorter courses of proper antibiotic therapy. In case of pyelonephritis, IV broad spectrum antibiotics are administered in hospital for 10-14 days and then switch to oral antibiotics or prophylaxis.
· How would you manage this patient?
Recurrent UTI 3months post transplant in female patient.
Careful history of recurrent UTI, obstructive uropathy, stone, stent removal, sexual history and use of prophylactic antibiotics.
Immunological history to assess risk of rejection, as we need to reduce immunosuppression specially if she is low risk of rejection.
Imaging of transplant and native kidneys, to see any stent, obstruction, stone.
Cultures and antibiotics used and their duration.
To consider prophylactic antibiotics if recurrent UTI.
Personal hygiene care and advice of cleaning of the perineal area and voiding of urine after intercourse.
Sometimes prophylactic antibiotics after intercourse may be used.
Proper management always starts by proper history taking :
-pre transplant history of recurrent UTI’s or stones .
-Family history
-Any history suggestive of neurogenic bladder .
-symptoms suggestive of vaginal infection .
-Drug history and proper assessment regarding the medications .
-Post surgical stent removal .
Investigations entailing:
-CBC
-CRP with titer
-FK level
-MMF level
-CMV , BKV PCR quantitative analysis .
-PAUS with assessment of the residual kidney volume .
-KUB
-CTUT without contrast accordingly .
Treatment of the cause , proper hydration , antibiotics accordingly , and long antibiotics prophylaxis may be needed.
Treatment of UTI in renal transplant patients should be according to the general guidelines for treatment of complicated UTI, but in the first 3 months after transplantation empirical treatment with the combination of amoxicillin and ciprofloxacin is recommended.
No recommendation can be made about changing immunosuppressive drugs from one class to another to prevent a recurrence of UTI.
In the choice of antibiotics for treatment of recurrent UTI the increased risk for ESBL-related infections should be considered. Therefore, earlier culture results and fluoroquinolone use in the last < 30 days have to be checked.
Removal of the urinary catheter should be done as soon as appropriate.
In case of a UTI the JJ stent should be removed if possible and the urine must be cultured.
In patients with recurrent UTI further investigations for anatomical abnormalities, bladder dysfunction or infection of the native kidneys should be initiated.
It is important to note that several antimicrobial agents can interact with immunosuppressants, especially with calcineurine-inhibitors. Therefore, interactions have to be checked.
Recurrent urinary tract infections (UTI) are a common clinical problem in kidney transplant recipients.
Due to the complex urological anatomy derived from the implantation of the kidney graft, the spectrum of the disease and the broad underlying pathophysiological mechanisms.
Recurrent UTI worsen the quality of life, decrease the graft survival and increase the costs of kidney transplantation.
Urinary tract infections (UTIs) are common among kidney transplant recipients in the first year after transplantation.
The reported incidence varies from 11.7% to 67.5% .
risk factors include :
older age, female gender, diabetes, history of acute rejection , delayed graft function, deceased donor kidney transplantation, longer duration of dialysis , and urological abnormalities .
Timing of stent removal and the use of antibiotic prophylaxis are important modifying factors.
UTIs similar are classified as follows: (1)Asymptomatic bacteriuria: >105 colony-forming unit (cfu)/mL (2)Simple (uncomplicated) UTI: positive urine culture in addition to any urinary symptoms such as dysuria, urgency, frequency, or suprapubic pain (3)Complicated UTI: positive urine culture in addition to systemic symptoms such as fever, chills, and flank/allograft pain (4)Complicated UTI with bacteremia (5)Recurrent UTI: more than one UTI in the first 6 months. Management management of recurrent urinary tract infections in transplant patients requires a diagnosis of the underlying risk factor. -It is recommended to Treat asymptomatic UTI in the first 6 months after transplantation, especially if the urinary stent is still in place. – treat simple UTIs for one week, Quinolones 2nd and 3rd generation cephalosporin for 5-7 days are suggested for mild cases and for patients without risk of MDR -treat more complex UTIs (especially MDRO) for more prolonged durations (two weeks with Ceftriaxone, piperacillin-tazobactam or cefepime or at least one week plus subsequent suppressive antibiotic therapy such as nitrofurantoin or fosfomycin in the case of susceptible organism). -current prophylaxis protocol consists of Bactrim SS for 6 months which is conjunctly used as prophylaxis for Pneumocystis carinii pneumonia .
Reference Ziad Arabi,1,2,3Khalefa Al Thiab,2,4Abdulrahman Altheaby.Urinary Tract Infections in the First 6 Months after Renal Transplantation. Volume 2021.
Recurrent UTI is a common situation after transplantation and may be related to the etiology of the underlying disease that led to chronic kidney disease, such as polycystic kidneys, and the persistence of this native kidney after transplantation. Or another example is how much the bladder becomes atrophied by disuse.
Or the recurrent UTI may have its pathophysiology related to a post-transplantation event, requiring investigation regarding the patient’s hygiene habits, habits of the type of sexual intercourse, anatomical alterations, retention mechanisms, etc. And they should be investigated with USG of the urinary system, uroflowmetry and others.
Targeted antibiotic treatments will be prioritized and followed by prophylactic antibiotic options to try to decrease the number of recurrences.
Physical examination and Lab Tests for CBC, Tac level, DIC profile, CRP, RFTs, Blood cultures and microbiological analysis of urine culture are done.
the first line of management will be antibiotic treatment with fluoroquinolone and specific antibiotics (cephalosporin, nitrofurantoin, meropenem, piperacillin-tazobactam) against the identified causative agent post-identification.
Recurrent UTI is a common problem after renal transplantation
I would like to assess the patient with history and examination…. We need to assess the history of recurrent UTI pre transplant…Detailed history with relation to voiding pre transplant should be elicited…As the pre transplant this patient had bilateral small kidneys..There is no mention about the bladder pathology or PVR pre transplant….
If there are no such history we should do a detailed examination and investigation..
as she is 47 years there is no factor like post menopausal predisposing to recurrent UTI
We need to get USG KUB with post void residue…Uroflowmetry ..If there is significant PVR there could be urethral stricture….there could be history of recurrent Foley catheterization which could have lead to urethral stricture….urodynamic study is indicated if the uroflow patttern is indicative of underactive bladder…If there is significant PVR we should also rule out reflux by MCU under the cover of antibiotics….
Treatment of UTI with IV 3rd generation cephalosporins/IV meropenem/IV piperacillin tazobactum is needed to eradicate the infection
The duration of antibiotic needs to be emphasized…If ESBL bug is found it is imperative to continue IV for 14 days….
Antibiotic prophylaxiss is indicated for recurrent UTI post transplant… TMP SMX is used universally for all transplant recipients for PCP prophylaxis’s..It is supposed to work for UTI as well…If there is breakthrough UTI despite TMP SMX, we need to change the prophylaxsis…Tab nitrofurantoin 100mg at night, Tabh cephalexin 250mg at night are other alternatives….
It is important to screen for asymptomatic bacteriuria in the first 2 months after renal transplant as it has been found to be associated with increased incidence of graft pyelonephritis…. more than 2 months after transplant, there is no indication to treat ASB.
other general measures like toilet training like frequent voiding, double voiding in case of bladder dysfunction, perineal hygiene, avoidance of constipation, voiding after sexual intercourse, use of cranberry supplements maybe encouraged…
If there is recurrent symptomatic UTI impairing graft function we need to change or reduce the dose of antimetabolite namely MMF and change to AZA if required
UTI post kidney transplantation is a very common problem, and the classical symptoms of UTI such as frequency,urgency are abscent due to the state of IS and the surgical denervation of kidney and bladder .
For assessment of this pt. We need detailed history of the attacks of UTI before the development of ESRD, proper information about the anatomical and functional structure of the urinary system by doing US, VCUG, non-contrast CT scan , urodynamic study , cystoscope for any bladder or urethral problems, in edition to the usual screen for UTI by GUE and urine cultures, PCR for BK and CMV which may cause hematuria and urethral strictures .
Treatment start by empirical AB till optain the result of C/s
Make sure from removal of any stent within 4 weeks post transplant, removal of urinary catheters within the first week post transplantation.
Use of prophylactic septrin for 3-6 months or many use for long period.
In kidney transplant recipients, urinary tract infections are prevalent. In immunocompromised people, the cause of UTI is multifaceted. So, how should we handle our patient? -A thorough history of UTI episodes prior to developing ESRD is required, and if the septic focus is on the native kidneys, nephrectomy will be recommended. Infectious diseases consultant should be onboard for the optimal antibiotic therapy.
If an infection is diagnosed in immunocompromised patients, a treatment period of up to 21 days may be necessary. Some specialists recommend preventative antibiotics for 3 to 6 months, or even for life.
-The structure of the kidneys and urinary tract must be evaluated, specifically the post-voiding residual volume, because ESRD patients develop an atonic bladder after prolonged anuria.
-Functional and anatomical abnormalities may necessitate urodynamic studies for a more precise evaluation.
-Due to their effect on the tubules and ureter, which frequently manifests clinically as recurrent UTI, certain viral infections, in particular BK, should be evaluated as potential cause of hematuria/active urinary sediment.
Good hx from pt to est whether she had recurrent UTIs pre transplant.
Do baseline tests and others to find out the cause and other antecedent complications;
FHG
UECS
Urinalysis
Tac levels
Hba1c
Urine cultures.
Blood cultures.
Evaluate for other common viral infections post transplant ;BK and CMV PCR.
Native and graft ultrasound to evaluate for pyelonephritis.
Non contrast CT scan of urinary tract to check out for any hydro nephrosis, strictures or stones.
VCUG to assess for any VUR.
Cystoscopy to check for any anatomical anomalies in bladder and urethra.
Bladder urodynamic studies to assess bladder pressures, emptying and if we get abnormal manometry results we involve both the urologist and medical team.
After the above ,we start treatment and adopt other measures to decrease UTI frequancy;
Start antibiotics as we await culture results, Amoxicillin + ciprofloxacin for symptomatic cystitis in the 1st 3 /12 post kidney transplant. For severe UTI +pyelonephritis ;carbapenems ,Piptaz and 3rd generation cephalosporins recommended.
Septrin prophylaxis for PCP prophylaxis in 1st 6/12 post transplant .
Stent removal within 4/52 post transplant.
Ensure we don’t have indwelling urethral catheters beyond 1 week.
Adequate hydration at least 2l in 24 hrs, increase urination frequency and do post coital urination to decrease frequency of UTIs. Proper hygiene and vaginal wiping from front to back should be practiced to decrease UTI frequency.
Vaccination; E coli, Proteus, Klebsiella, E faecalis.
Topical estrogen in post menopausal women has been found to decrease UTI.
Trial of metheneamine hippurate 1g BD +/- ascorbic acid has been found to decrease UTI frequency in some studies and also decrease the antibiotics duration.
REF;
Prof Salah lecture on UTI post transplant.
Mitra et al;Recurrent UTI in KTR.Current infectious disease.13,579-587.
Goldman et al.UTI in SOT recipients;Guidelines from AST IDSA.Clin Transplant.2019 sep ;33(a);e13502
How would you manage this patient?Recurrent UTI is 2 attack in 6 month or 3 attacks in one year
Need to know all risk facotrs that could precipitate recurrent UTI Plain XR to exclude missed stent or stone · Ultrasonography pre- and post-voiding · Risk factors for UTI post transplantation: female, age, recurrent UTI pre-transplant
need to check the status of the patient BK virus status as it can leads to severe hemorrhagic cystitis and uratheral strictuers .
need to do US to check for any risk factors or strictuers , she will need urine culture specific antibiotics and also prophylaxis Abnormal bladder also need to be ruled out by history and examination
5. A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
– common organisms: gram negative uropathogens – E. coli,
Pseudomonas, Klebsiella, Enterobacter
– imaging:
· ultrasound to assess the graft kidney, native kidneys, postvoid residual volume
· non-contrast CT scan of the urinary tract for patients with recurrent UTIs and a normal ultrasound – to assess for strictures, stones, complex cysts
· if CT scan is unrevealing, rule out bladder dysfunction and outflow tract obstruction by measuring urine flow rate and performing urodynamic studies
· flexible cystoscopy to detect abnormalities in the urethra or bladder
· PET CT scan for ADPKD patients with suspected infected cysts in the native kidneys
– differential diagnosis: acute graft rejection
– rising serum creatinine, new onset or worsening proteinuria and hypertension are suggestive of graft rejection for which a kidney biopsy is usually performed
– fever and graft tenderness are suggestive of UTI
– Prevention: antimicrobial prophylaxis, early ureteral stent removal, monitoring for ASB
· Antimicrobial prophylaxis:
– TMP-SMX prophylaxis (prevents PCP and UTIs) for 6-12months posttransplant or
– Nitrofurantoin 100mg BD (eGFR >30) for one month or
– Cephalexin 500mg BD for one month
– Nitrofurantoin and cephalexin are alternative for UTI prophylaxis in patients allergic to TMP-SMX (for PCP prophylaxis the alternative is Atovaquone)
– avoid fluoroquinolones for prophylaxis due to development of resistance
· early ureteral stent removal:
– remove within 4 weeks to help prevent UTI posttransplant
· monitoring for ASB:
– can be performed in the first 1-2 months posttransplant, a 2nd
urine culture should be done to confirm persistent bacteriuria with the same pathogen before treatment decisions are made
– if positive (i.e., 2 consecutive urine cultures yielding >10⁵ CFU/ml of the same pathogen), treat with antibiotics for 5days as guided by the sensitivity pattern
– if the 2nd culture is negative or grows another organism do not give antibiotics
– do not treat asymptomatic candiduria unless the patient is at risk for complications or infection progression e.g., neutropenic patients, patients undergoing a urologic procedure
– no need to monitor for ASB 2months posttransplant since screening and treatment beyond this point is not associated with prevention of symptomatic UTI, pyelonephritis, bloodstream infection, graft rejection – it can lead to antibiotic misuse
– Management of symptomatic infections: obtain urine sample for m/c/s, then start with empiric therapy awaiting definitive therapy as guided by the sensitivity patterns
· simple cystitis: empiric therapy with
– a fluoroquinolone (ciprofloxacin 250mg BD, levofloxacin 500mg OD), or
– a 3rd generation cephalosporin (cefpodoxime 100mg BD, cefdinir 300mg BD) or
– amoxicillin-clavulanate 500mg BD or
– nitrofurantoin 100mg BD if eGFR >30
– duration of therapy 10-14days if the simple cystitis occurs earlier than 6 months posttransplant and 5-7days if it occurs 6 months posttransplant
· complicated UTI: empiric therapy with
– piperacillin-tazobactam 4.5g IV QID or
– meropenem 1g IV TID or
– a combination of vancomycin plus cefepime 1g IV TID
– treat for 14-21days, can switch to oral medications once the patient is symptom free and the antibiotic sensitivity patterns are known
· recurrent UTI: approach to treatment is similar to a case of initial UTI i.e.,
– evaluate for anatomic and functional abnormalities,
– counsel on behavioural modifications i.e., increased fluid intake, frequent voiding, postcoital voiding, contraception modification, wiping from front to back in females
– decision to give antibiotics should be individualised
· recurrent UTI is associated with an increased risk of graft loss and death
· fosfomycin is limited to patients with multidrug-resistant cystitis
· there is increased resistance to ciprofloxacin and TMP-SMX due to widespread use of antibiotic prophylaxis
References
1. Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clinical transplantation. 2005 Apr;19(2):230-5. PubMed PMID: 15740560. Epub 2005/03/03. eng.
2. Senger SS, Arslan H, Azap OK, Timurkaynak F, Cağir U, Haberal M. Urinary tract infections in renal transplant recipients. Transplantation proceedings. 2007 May;39(4):1016-7. PubMed PMID: 17524879. Epub 2007/05/26. eng.
3. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Current infectious disease reports. 2011 Dec;13(6):579-87. PubMed PMID: 21870039. Epub 2011/08/27. eng.
4. Singh R, Bemelman FJ, Hodiamont CJ, Idu MM, Ten Berge IJ, Geerlings SE. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis. 2016 Feb 25;16:90. PubMed PMID: 26912326. Pubmed Central PMCID: PMC4766656. Epub 2016/02/26. eng.
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI. How would you manage this pt?
Good hx from pt to est whether she had recurrent UTIs pre transplant.
Do baseline tests and others to find out the cause and other antecedent complications;
FHG
UECS
Urinalysis
Tac levels
Hba1c
Urine cultures.
Blood cultures.
Evaluate for other common viral infections post transplant ;BK and CMV PCR.
Native and graft ultrasound to evaluate for pyelonephritis.
Non contrast CT scan of urinary tract to check out for any hydro nephrosis, strictures or stones.
VCUG to assess for any VUR.
Cystoscopy to check for any anatomical anomalies in bladder and urethra.
Bladder urodynamic studies to assess bladder pressures, emptying and if we get abnormal manometry results we involve both the urologist and medical team.
After the above ,we start treatment and adopt other measures to decrease UTI frequancy;
Start antibiotics as we await culture results, Amoxicillin + ciprofloxacin for symptomatic cystitis in the 1st 3 /12 post kidney transplant. For severe UTI +pyelonephritis ;carbapenems ,Piptaz and 3rd generation cephalosporins recommended.
Septrin prophylaxis for PCP prophylaxis in 1st 6/12 post transplant .
Stent removal within 4/52 post transplant.
Ensure we don’t have indwelling urethral catheters beyond 1 week.
Adequate hydration at least 2l in 24 hrs, increase urination frequency and do post coital urination to decrease frequency of UTIs. Proper hygiene and vaginal wiping from front to back should be practiced to decrease UTI frequency.
Vaccination; E coli, Proteus, Klebsiella, E faecalis.
Topical estrogen in post menopausal women has been found to decrease UTI.
Trial of metheneamine hippurate 1g BD +/- ascorbic acid has been found to decrease UTI frequency in some studies and also decrease the antibiotics duration.
REF;
Prof Salah lecture on UTI post transplant.
Mitra et al;Recurrent UTI in KTR.Current infectious disease.13,579-587.
Goldman et al.UTI in SOT recipients;Guidelines from AST IDSA.Clin Transplant.2019 sep ;33(a);e13502
· The primary disease could be reflux and recurrent UTI
· Plain XR to exclude missed stent or stone
· Ultrasonography pre- and post-voiding
· Risk factors for UTI post transplantation: female, age, recurrent UTI pre-transplant, DM, UT abnormalities, length of dialysis, Duplicated ureter, ureteral stent, catheter, ATG, MMF.
· Exclude BK virus infection, then treat according to culture for at least 2 weeks up to 4 weeks.
· Prophylaxis of recurrent UTI:
1) TMP/SMZ 160/800 mg
2) Vaccination with inactivated E. coli, Morganella morganii, proteus, klebsiella, Enterrococcus faecalis
3) High water intake to excrete > 2l urine per day
4) Genital hygiene wiping after urination: vaginal>anal
5) Urine PH 5.8-6.5 ( vit C , methionine)
6) Vaginal oetrogen/Lactobacillus
7) Cranberry products
A lecture of Post Renal Transplantation Urinary Tract Infection By Prof. Mohamed Salah EldinZaki, Dean of National Institute of Urology and Nephrology
· How would you manage this patient?– Ensure that stent was removed- Urine analysis, culture & sensitivity.- CRP, cbc- Exclude for CMV & BK virus- US KUB, plain CT on the graft & native kidneys – Post voiding assessment & exclusion of urinary tract abnormalities – Treat as per culture results.- Patient mostly is on prophylaxis TMP/SMX – Patient education regarding good hydration , self-hygiene , frequent emptying of the bladder & to avoid constipation – consider lowering dose of MMF if recurrent UTI(2 or more in 6 months , or 3 or more in 1 year ) plus chronic suppressive AB therapy
UTI is common in female in general
more so after IS
one has to understand her risk of UTI prior to transplant
post of UTI is to be ruled out by USG KUB and detailed history like use of DJ in surgery , collection and urine leak
she will need urine culture specific antibiotics and also prophylaxis
Abnormal bladder also need to be ruled out by history and examination
How would you manage this patient Definition of recurrent UTI means more than 2 episodes /6months or 3 episodes /year Causes
· Relapse because of insufficient duration or inappropriate antibiotics
· Septic focus
· Anatomical abnormalities. How to manage
–good history taking about episodes of UTI before reaching ESRD and if the septic focus is native kidneys nephrectomy will be indicated
–Refer to ID team for best antibiotic management and prolonged duration maybe needed up to 21 days in immunocompromised patients. Some experts use antibiotics prophylactic for 3-6 months or even lifelong.
–Evaluation of anatomy by US especially post voiding residual volume because ESRD patients after long period of being anuric they develop atonic bladder.
–if US normal CT or even urodynamics maybe needed for better assessment of functional and anatomical abnormalities -Some viral infections especially BK should be excluded becbecause of its effect on tubules and ureter which usually presents clinically with recurrent UTI References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
How would you manage this patient Definition of recurrent UTI means more than 2 episodes /6months or 3 episodes /year Causes ·Relapse because of insufficient duration or inappropriate antibiotics ·Septic focus ·Anatomical abnormalities. How to manage -good history taking about episodes of UTI before reaching ESRD and if the septic focus is native kidneys nephrectomy will be indicated
–Refer to ID team for best antibiotic management and prolonged duration maybe needed up to 21 days in immunocompromised patients. Some experts use antibiotics prophylactic for 3-6 months or even lifelong.
–Evaluation of anatomy by US especially post voiding residual volume because ESRD patients after long period of being anuric they develop atonic bladder. -if US normal CT or even urodynamics maybe needed for better assessment of functional and anatomical abnormalities -Some viral infections especially BK should be excluded becbecause of its effect on tubules and ureter which usually presents clinically with recurrent UTI References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
Recurrent UTI post kidney transplantation in female 3-month post-transplant (assuming ureteral stent has been removed.
Management
Reduction of immunosuppression
During the acute setting arrange for a graft ultrasound to look at any graft collection, calculi or pyelonephritis. Infective markers (WCC, CRP and procalcitonin) as well as to look for evidence of bacteremia that may require prolonged intravenous antibiotics. Urine culture and blood culture. Following empirical therapy, the treatment should be based on culture and sensitivity.
Prophylaxis antibiotic with Bactrim.
Investigations to rule out anatomical and functional abnormalities (ie: urinary calculi, VUR, bladder outlet obstruction and urethral stricture)
Ultrasound KUB and the allograft- Calculi, Cyst, residual volume
Abdominal and pelvic ultrasound – look at gynaecological mass or abnormalities that potentially leading to obstruction
Cystoscopy – to assess bladder
Cystourethrogram – To diagnosed VUR
Urodynamic study – Neurogenic bladder
Educate on hygiene and safe sex (after sexual intercourse, post-coital voiding and limiting used of spermicide ) and double voiding.
Post-coital antibiotic prophylaxis
Non-pharmacological therapy with cranberry juice and plenty of water.
References
1.Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship? J Clin Med. 2021 Dec 31;11(1):226. doi: 10.3390/jcm11010226. PMID: 35011966; PMCID: PMC8745876. 2.Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21. PMID: 30092153.
Post transplant patient with recurrent uti should be thoroughly evaluated including detailed history of anatomical urinary tract abnormalities like bladder diverticlui,past history of nephrolithaisis,previous history of recurrent uti before transplant and also history of whether stent post transplant has been removed or still there etc,followed by examination and then investigations like Ultrasonography with pre and post void residual volume ,then plain ct scan KUB plain or contrast study only if creatinine normal ,urodynamic studies which will help in bladder dysfunction or outflow tract problem.Cystoscopy in certain cases if above no cause found.
For recurrent uti treatment-first strategy should be to address all the risk factors and patient should be counselled to take plenty of fluids ,maintaining hygiene(wiping from front to back),frequent voiding and also post costal voiding.Empirically antibiotic I.e., fluoroquinolones for simple cystitis and broad spectrum antibiotic I.e., antipseudomonal penicillin or cabapenem or third generation cephalosporin for pyelonephritis and then tailoring the antibiotic according to culture and sensitivity.Frequent monitoring of graft function and tacrolimus level should be maintained around 5-7ng/ml and antimetabolite should be stopped.Surgical correction should be done if cause is anatomical problem in the urinary tract..In case of recurrent uti as in above case,patient should be given long term prophylactic treatment with trimethoprim-sulfamethoxazole .Drug drug interaction with the immunosuppressive should be bear in mind while prescribing antibiotic.
REFERENCES:
1-Chacon-Mora N., Diaz J. and Matia E. Urinary tract infection in kidney transplant recipients. Enferm Infecc Microbiol Clin, 2017;35(4):255-259
2-Kidney transplant handbook 6th edition
Post transplant UTI associated with increased risk of acute graft dysfunction.
Incidence of MDR strain of urinary pathogens is increased worldwide, & this increased incidence associated with increased mortality, graft loss & favor the recurrence of UTI.
Risk factors o recurrent UTI in post transplant:
Advance age
Female gender
DM
Urinary tract abnormalities.
Previous history of UTI
Deceased donor kidney transplant
Re-transplantation.
Neurological bladder dysfunction
VUR
Prolonged DJ stent & indwelling urinary catheter
Exclude diabetes mellitus
Thorough investigation to role out anatomical & functional abnormalities of urinary tract, e.g. urinary tract obstruction, stricture, VUR, renal calculi, neurogenic bladder or complex cyst.
Investigations may include cystoscopy, cystogram, uroflowmetry & other urodynamic studies if necessary.
Knowing the causative micro-organism of previous UTI to guide selection of empiric antibiotics.
Prophylaxis selection depends on culture results.
Non pharmacological antimicrobial prophylaxis as cranberry extract or L-Methionine.
References:
Chacon-Mora N., Diaz J. and Matia E. Urinary tract infection in kidney transplant recipients. Enferm Infecc Microbiol Clin, 2017;35(4):255-259.
Velioglu A., Guneri G., Arikan H., Asicioglu E., Tigen E., et al. Incidence and risk factors for urinary tract infections in the first year after renal transplantation. LoS One, 2021;16(5).
· How would you manage this patient?
Recurrent UTI after kidney transplantation is common specially in female patients and risk factors include DM , female sex , abnormal urinary tract .
Indication for treatment are : 1-Symptomatic UTI with fever , urological symptoms such as dysurea , frequency or tender graft suggesting pyelonephritis.2-Detriorating graft function For this patient , as she has symptomatic UTI , so further evaluation is required with
1- CBC , ESR, CRP ,procalcitonin
2- Complete urine analysis and C&S.
3- Excluding BK nephropatrhy with BKV PCR and decoy cells in urine.
4- Evaluting graft function and albuminuria level
5- Monitor trough level of IS.
6- Non contrast CT : for diagnosis of pyelonephritis, nephrenophthesis .
– Treatment :- Start antibiotic therapy based on C&S . start empirical therapy with fluroquinolones ,and if suspected MDR gram negative infection consider antipseudomonal carbapenem, piperacillin-tazobactam or cefepime
· How would you manage this patient?
Recurrent UTI after kidney transplantation is common specially in female patients and risk factors for recurrent UTI include
female patients, DM ,urinary tract abnormalities . Indication for treatment are : 1-Symptomatic UTI with fever , urological symptoms such as dysurea , frequency or tender graft suggesting pyelonephritis.2-Detriorating graft function For this patient , as she has symptomatic UTI , so further evaluation is required with1- CBC , ESR, CRP ,procalcitonin 2- Complete urine analysis and C&S.3- Excluding BK nephropatrhy with BKV PCR and decoy cells in urine.4- Evaluting graft function and albuminuria level5- Monitor trough level of IS.6- Non contrast CT : for diagnosis of pyelonephritis, nephrenophthesis .- Treatment :- Start antibiotic therapy based on C&S . start empirical therapy with fluroquinolones ,and if suspected MDR gram negative infection consider antipseudomonal carbapenem, piperacillin-tazobactam or cefepime
How would you manage this patient?Recurrent UTI 3 months post-transplant.
Management should begin with a detailed history looking to identify risk factors for UTI.
Risk factors can be grouped into three categories that are:
Pre-operative factors include female sex, diabetes mellitus and the presence of urological abnormalities.
Intra-operative factors of note include kidney transplantation from a deceased donor, the use of ureteric stents and prolonged indwelling bladder catheterisation.
Post-operative factors of note include acute allograft dysfunction and rejection as well as excessive immunosuppression as a result of rejection episodes
This patient risk factors include female gender, she is 3 months post-transplant period of time where is high immunosuppression, chances are in the peri-operative period she had an indwelling catheter and also had a ureteral stent.
To confirm a diagnosis of UTI there should be clinical symptoms plus the growth CFU >105.
The presence of UTI in this kidney transplant recipient this makes it a complicated UTI.
Hence she should be on empirical antibiotic therapy as a waits culture and sensitivity results.
A midstream early morning urine sample should be taken for dipstick, culture and sensitivity.
Next should be to do any imaging to rule out any urological abnormalities like a forgotten ureteral stent.
Imaging of the native kidney should also be done to rule out any abnormalities- nephrocalcinosis.
Cystoscopy and urodynamic studies can be done to rule out urological abnormalities
Once the culture results are out then the antibiotics should be tailored to the sensitivity and culture results.
This patient with recurrent UTI it is prudent to look for other factors that make her susceptible like DM.
Also the patient should be on UTI prophylaxis TMP/SMX for at least 6 months and the patient should be taught on genital hygiene.
References
Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship?Jens Strohaeker, Victoria Aschke, Alfred Koenigsrainer, Silvio Nadalin and Robert Bachmann Prof Salah Zaki lecture
Risk factors for UTI in recipient classified in three categories:
Preoperative factors:
Advanced age
female gender
diabetes mellitus
immunosuppressive treatment
pre-transplant UTI
urinary tract abnormalities
prolonged dialysis
Intraoperative factors:
Use of double-J ureteral stent
duplex ureters
prolonged urinary catheterization transplantation with deceased donor compared to living donor
re-transplantation.
Postoperative factors:
Graft dysfunction and rejection
excessive immunosuppression
infection of native urinary tract
invasive urological procedures
Management :
requires a proper investigation for the source of infection
identification of structural or functional urological abnormalities should be prioritised
FBC, urinalysis ,blood and urine culture ,tacrolimus level
Imaging studies of the genitourinary tract should be considered to rule out structural changes-usg or CT
Cystoscopy, cystogram, uroflowmetry and other urodynamic studies when anatomical and/or functional changes are suspected such as vesico-ureteric reflux, functional bladder dysfunction or obstruction.
Empiric antibiotic treatment based on local epidemiological data and the patient’s history of previous resistant organisms and previous antibiotic therapies prescribed in previous months.
Quinolones 2nd and 3rd generation cephalosporin for 5-7 days are generally suggested for mild cases and for patients without risk of MDR .
Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days is suggested in case of moderately severe UTI, including acute pyelonephritis.
Carbapenem plus vancomycin are considered for patients present with severe sepsis and septic shock
Systemic antifungals for fungal cystitis or pyelonephritis.
Specific antibiotics depend on the result of C/S .
Surgical or interventional radiologist in case of complicated UTI with abscess formation or in case emphysematous pyelonephritis or removal of DJ stent .
Scenario:
47F, ESRD secondary to unknown cause (atrophic native kidneys), living donor renal transplant 3 months ago, on triple immunosuppression with excellent graft function. Recurrent presentations (number not specified) with symptoms of urinary tract infection (UTI)
Key considerations from the scenario:
· The patient is only 3 months out from her transplant operation so she is in a period of maximum immunosuppression and is likely to have had interventions during this time such as urinary catheter removal and ureteric stent removal which could have increased her incidence of UTI. The highest incidence of UTI is in the first 3-6 months post-transplantation [1]
· She has excellent allograft function so it is likely she has good fluid balance status but we do not have confirmation of her recent urine output volumes or know whether she is staying well hydrated
· We do not know the original cause of her ESRD (reflux nephropathy is in the differential) – important to remember the source of infection could be her native kidneys or her renal allograft – does she have any known underlying structural abnormality of her renal tract?
· We do not know whether she was dialysis-dependent prior to transplantation (i.e. did she have residual urine output or not prior to transplantation). This is potentially relevant as this might affect patient behaviours/highlight need for patient intervention regarding self-care measures to avoid UTI. Additionally, prolonged dialysis duration and anuria (leading to bladder atony) are risk factors for post-transplant UTI
· We know she had ‘symptoms’ of UTI but we need to confirm what these symptoms were and whether there was associated evidence of systemic infection or confirmed infection on urine culture
· The patient is on triple immunosuppression so she may experience more severe clinical course if she does get an infection- similarly if she is having repeated admissions with ?sepsis necessitating temporary suspension of her anti-metabolite this could be putting her at unacceptable risk of rejection and approaches such as prophylaxis may need to be considered Management: 1. History and basic examination including assessing UTI risk factors Questions I would wish to confirm on taking history from patient:
· Describe the symptoms she is getting
· How many separate episodes have there been? What is their relationship to any procedures on the urinary tract e.g. when was her urinary catheter removed? Has she had a ureteric stent removal?
· Has she had any antibiotic treatment?
· Have the UTIs been proven on urine culture and were they sensitive to the antibiotics given? (‘recurrent’ infection could also be same infection with ineffective treatment)?
· Did she have any symptoms of systemic infection e.g. fever? Any pain over her allograft?
· Any symptoms of pyelonephritis such as vomiting, ascending pain?
· What is her fluid intake like? How much urine is she passing?
· Any issues with incontinence or voiding difficulties?
· Did she experience recurrent UTIs prior to her transplant?
· Was she on dialysis prior to transplant and if so for how long?
· Any history of diabetes or renal stones (factors that would increase her risk of developing UTI alongside her female gender)?
· Consider whether sexual history/STI screen is indicated as chlamydia, gonorrhoea and genital herpes can be alternative causes of dysuria
2. Initial investigations:
· Bedside observations including temperature, blood pressure and heart rate
· Urinalysis (assess pyuria)
· Mid-stream urine for culture and sensitivity
· Ultrasound renal tract (any evidence of obstruction, abscess)
· Blood tests including capillary blood glucose (steroids being part of her triple immunosuppression) and full blood count, renal function and c-reactive protein. Consider testing for CMV and BK levels
· Blood cultures if symptoms or signs of pyelonephritis
Simple cystitis
· For simple cystitis this would usually be a 5-7 day course of oral antibiotics as per local microbiology guidelines (pending sensitivity results) although there is some guidance to suggest that in the early post-transplant period (as with this patient) this should be 7-10 days [1]
· This may be followed by watch and wait approach to see how many further episodes occur (having implemented patient education measures etc)
Pyelonephritis/signs of systemic infection
· Intravenous antibiotics may be required whilst awaiting confirmation of sensitivities. Total duration of antibiotic course 2-3 weeks
· The patient’s immunosuppression will need to be reviewed and anti-metabolite may be temporarily suspended
· Further imaging may be required to exclude nephrolithiasis, abscess etc.
Longer term prophylaxis:
· If confirmed recurrent UTI (see below) a discussion with the local microbiology team might be relevant to consider a single daily low-dose antibiotic (alternating every 2 weeks) as prophylaxis or a post-coital antibiotic if the infections are related to sexual intercourse – this must be balanced against the risks of developing drug-resistance, c.difficile diarrhoea and other potential side effects of specific antibiotics e.g. nitrofurantoin and pulmonary toxicity [1]
Defining recurrent UTI in the renal transplant patient
· 2 or more confirmed urinary tract infections within 6 months
· 3 or more confirmed urinary traxt infections within 1 year
Alongside the above described patient education measures and pharmacological interventions, a diagnosis of recurrent UTIs in a renal transplant patient should prompt evaluation for any anatomical or functional abnormalities [1].
· Post-void residual ultrasound scan to exclude structural abnormality
· If no structural abnormality – proceed to voiding cystourethrography to evaluate for vesicoureteral reflux
· If no vesicoureteral reflux identified consider urodynamic study to evaluate for any bladder or outflow obstruction
Reference: 1. Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. Available at: https://pubmed.ncbi.nlm.nih.gov/30793386/
How would you manage this patient? Definition of Recurrent UTI; -Two or more episodes of UTI in six months, or three or more episodes of UTI in one year. Diagnostic Evaluation; -Ultrasonography of the urinary system with measurement of a postvoid residual is a reasonable first step for most patients, given its ease and lack of side effects. -In patients with recurrent UTI who have unrevealing ultrasonography, we perform a noncontrast computed tomography (CT) scan of the urinary tract. -Although the absence of contrast reduces the sensitivity of the CT scan, we avoid contrast to prevent nephrotoxicity. -These imaging studies can identify urinary tract strictures, stones, and complex cysts. -If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction, -In consultation with urology; flexible cystoscopy may be required to detect abnormalities in the urethra or bladder. Approach to prevention; -In kidney transplant recipients with recurrent UTI, we take the following approach to prevention: -All patients should be evaluated for anatomic or functional abnormalities of the urinary tract, which may increase the risk of infection. -All patients should be counseled on the risk factors for recurrent UTI and behavioral changes that might reduce the risk. -Such behavioral changes are similar to those for nontransplant patients with recurrent UTI and include increased fluid intake, frequent voiding, postcoital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females). -Some experts administer prophylactic antibiotics to selected patients with recurrent UTI, the decision to administer long-term antibiotic prophylaxis should be individualized. -Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the TMP component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant; some experts continue TMP-SMX prophylaxis indefinitely. -For postmenopausal females, topical estrogen may prevent recurrence of UTIs. -Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI. -Do not routinely use strategies such as cranberry juice or probiotics due to the lack of clear data supporting their use in transplant recipients. Treatment of recurrent episodes; -Each episode of simple cystitis or complicated UTI should be treated with an appropriate duration of antibiotic therapy. -In some situations, a longer course may be necessary for patients with persistent/recurrent UTI with the same organism. -As an example, recurrent UTIs associated with an indwelling source (such as infected cysts in native kidneys) can require up to four to six weeks of therapy. -In other situations, therapy for recurrent UTIs can be discontinued after a shorter period, and the patient can be transitioned to prophylactic antibiotics. Early ureteral stent removal; -Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation. -One analysis found that the risk of UTI could be reduced with early (within two weeks) stent removal compared with late stent removal, particularly if a bladder indwelling stent was used. References; –Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758. –Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063. –Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579. –Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261. –Thompson ER, Hosgood SA, Nicholson ML, Wilson CH. Early versus late ureteric stent removal after kidney transplantation. Cochrane Database Syst Rev 2018; 1:CD011455.
How would you manage this patient? Symptomatic UTI after KTX is defined as a ‘complicated’ UTI, as are all UTIs after surgery of the urinary tract. Furthermore, other criteria defining ‘complicated’ UTI, such as occurrence in an immunodeficient patient, are fulfilled in the situation after KTX
Treatment of recurrent episodes — Each episode of simple complicated UTI should be treated with an appropriate duration of antibiotic therapy a longer course may be necessary for patients with persistent/recurrent UTI with the same organism. As an example, recurrent UTIs associated with an indwelling source (such as infected cysts in native kidneys) can require up to four to six weeks of therapy. In other situations, therapy for recurrent UTIs can be discontinued after a shorter period, and the patient can be transitioned to prophylactic antibiotics.
Prevention of UTI after kidney transplantation
management of structural and functional urinary tract abnormalities in the pre-transplant period, which sometimes even justifies nephrectomy of the native kidneys, especially in patients with recurrent UTI in patients with VUR to their native kidneys
The patients should be educated for basic preventive measures like hydration and frequent voiding.
Radiological studies should be implicated to rule out the anatomical defects, obstruction, calculi and retained foreign bodies.
Diagnosis
urine analysis (dipstick/sediment) and always a urinary culture.
BK and/or CMV infection should be excluded.
(C-reactive protein, leucocytes) might help in differentiating between infection and rejection in a dysfunctional graft
The level of immunosuppression must be reevaluated to exclude over-immunosuppression.
Imaging (ultrasonography) should exclude postrenal causes of infection (urolithiasis, urinary tract obstruction, ‘forgotten’ ureteric stent, etc.)
TREATMENT
Complicated UTI
treat with intravenous (IV) antibiotics that cover both gram-negative and gram-positive bacteria initially, unless signs and symptoms are mild enough such that outpatient oral antibiotics with high bioavailability can be started. If the urine culture reveals candiduria, treatment should be tailored according to the identified Candida species
Antibiotic selection – Empiric antibiotics should have adequate coverage against P. aeruginosa, enteric gram-negative organisms, and Enterococcus species. Commonly prescribed treatment regimens include •Piperacillin-tazobactam 4.5 g IV every six hours, or •Meropenem 1 g IV every eight hours, or •Combination therapy with vancomycin plus cefepime 1 g IV every eight hours.
Antibiotic dosing must be adjusted according to kidney function. ●Duration of therapy – complicated UTI with 14 to 21 days of antibiotic therapy
Oral agents may be substituted for IV therapy once the patient is free of symptoms and antibiotic susceptibilities are known.
Fluoroquinolone-calcineurin inhibitor drug interactions, should be anticipated,especially with the higher dose of ciprofloxacin typically used for treatment of pyelonephritis, and dose reduction of the calcineurin inhibitor is often necessary to prevent calcineurin inhibitor toxicity.
Surgical therapy of recurrent UTI after KTX must aim at long-term optimization of urinary drainage. • This includes (besides early removal of ureteric stents and bladder catheters)
Treatment of obstructed transplant ureters, urolithiasis,
The causes of bladder outlet obstruction include:
Scar tissue in your urethra.-Bladder stones.Tumors in your rectum.
Procedures for stress urinary incontinence (SUI) surgery.-Non-cancerous (benign) lesions or cysts.
Urethra, vaginal or cervical cancer.–Urethral scarring (stricture) disease.
Tumors in your uterus or cervix.
Bladder or uterus falling down into your vaginal area (pelvic organ prolapse).
Severe constipation or impaction of stool.
reflux is common and appears in >80% of cases . Nephrectomy of native kidneys has been used successfully in refluxive kidneys to reduce recurrent UTI
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
For postmenopausal females, topical estrogen may prevent recurrence of UTIs
neurogenic bladder or incmplete voidingureteric refluxpoor hygine like wiping from back to frontB) Donnor related
infected graft with resistnat or uncommon organsim like TBC) surgery related
poor anastomotic siteD) Others like BK virus infection or heavy immunosupression
****Steps:
look for urine MC&S, is it the same organsim every time or different organsimsare we ttt with the appropritat Abx type and durationScan like simple US scan, cystoscope to urodynamic studieslook BK virus PCRConsider prophylactic AbxConsider cutting down immunosupression with risk of rejection in mind
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI. Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation. Urinary tract infections (UTI) are defined as the growth of 105 colony forming units on a proper urine sample) in the presence of symptoms such as dysuria, urinary frequency or localized pain(the incidence of a UTI ranges from 4–80%. Recurrent UTI is defined as ≥ 2 episodes within 6 months or ≥ 3 episodes within 1 year.
Recurrent UTI is associated with an increased risk of graft and patient loss. Risk factors of UTIs after kidney transplantation include:
Female gender
Advanced age
Pre-transplant UTIs
Prolonged period of haemodialysis before transplantation
Immunosuppression Management of the Recurrent UTI in kidney transplant recipients
Exclude functional or anatomical structural abnormality.
Determine the source of UTI, (native or allograft kidney).
Details history.
Immunosuppressants regimen intensity.
Workup of the current episode of the UTI:
Detailed family history, personal history of recurrent UTI since childhood and pre-transplantation (some female patient has increased susceptibility /receptivity for adherence of micro-organism
Detailed history of the recurrent UTI, diabetes mellitus, urinary tract anomalies, and the waiting time before KTX. History of vesicoureteral reflux, History of polycystic kidney disease The details of previous urine culture and sensitivity results and any history of drug resistance, if available.
Details history, Gynecological history by pelvic examination to check for cystoceles, vaginitis, vaginal atrophy, and prolapse of pelvic organs.
Details history of constipation, neurological diseases, any association with sexual activity, hygiene, hydration status and menopause (vaginal mucosal quality) The presenting symptoms, for example painful voiding, urgency, frequency, pain of the lower abdomen, hematuria, and fever.
Physical examination, including tenderness of the graft & the presence of urinary catheters.
Prophylactic antibiotic use, for example TMP-SMZ for PJP. Genital hygiene (method of wiping after urination), proper hygiene / perineal sweeping from anterior to posterior Double kidney transplant history, leading to an increase in JJ stents. Urinalysis (dipstick/sediment) & urinary culture.
Exclude BKV and CMV infection by blood PCR.
CBC, Lytes, creatinine CRP, septic screen
Exclude over-immunosuppression: review levels of IS medications.
Ultrasonography of the native urinary system and the graft to exclude post-renal causes (stones, obstruction, ‘forgotten’ ureteric stent, etc.).
CT-KUB, Cystoscopy, +/- Urodynamic study to r/o any anatomical or functional abnormalities.
The most common findings include.
Ureteral reflux.
Strictures at the ureterovesical junction.
Neurogenic bladder, and sub vesical obstruction, especially in men aged over 60 years, clean intermittent catheterization might be required.
Measures to prevent UTI in Kidney Transplant. A single shot antibiotic is administered prior to incision.
Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis.
To remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection to remove biofilms.
Use of TMP at 160 mg & SMZ at 800 mg for 6 months, especially in high-risk patients (e.g., urinary reflux, &/or voiding disorders), is recommended.
Good Hydration; 2 L urine out/day
Treatment Of Constipation
Proper Hygiene / Perineal Sweeping from Anterior to Posterior
Post Coital Voiding
If Dry Vaginal Local Estrogen Therapy
Prophylaxis Ab:
Chronic Suppressive Low Dose Ab.
Post Coital Single Dose Ab.
Empirical Short Course (3-5days) Ab. Prophylactic antibiotic regimens: Use of TMP at 160 mg + SMZ at 800 mg for 6 months, especially in high-risk patients (e.g., urinary reflux, &/or voiding disorders), is recommended. Ciprofloxacin was later reserved for treatment rather than prophylaxis. The 2019 FDA warning against the use of fluoroquinolones in KT recipients.
Fosfomycin showed preventative efficacy.
TMP-SMX is the best studied drug.
Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to.
TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients. Class of antibiotics used to treat UTI in the post-transplant period. Penicillin’s (49%), Cephalosporins (36%), Fluoroquinolones (16%), Carbapenems (4%).
Common Practice Medications. Outpatient with uncomplicated UTI, quinolones for 7 days are recommended as empirical treatment till the culture results or TMP-SMX for 7-14 days.
Complicated and hospitalized patients, 3rd generation cephalosporin IV, till the culture results.
ESBL cases the carbapenems (imipenem or meropenem) are advised till culture results. Native kidney as a source of recurrent UTI: Consider nephrectomy if resistant to treatment and there is a risk of graft dysfunction. Follow up:
Urine Culture for screening for ASB.
Prophylaxis treatment with TMP-SMX for at least 6 months with monitoring bacteriuria assessment, and culture guided. References
UpToDate
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011 Mar 1;52(5): e103-e120.
Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21. PMID: 30092153. Markus Giessing, Urinary tract infection in renal transplantation, Arab Journal of Urology (Official Journal of the Arab Association of Urology) doi: 10.1016/j.aju.2012. 01.005 Olenski S, Scuderi C, Choo A, Bhagat Singh AK, Way M, Jeyaseelan L, John G. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrol. 2019 Dec 27;20(1):479. doi: 10.1186/s12882-019-1666-6. PMID: 318818
Major risk factors of early recurrent UTI infection in post renal -transplant are;
· Female gender
· Old age
· Prolonged catheterization, or stent complication
· Post-surgical complications like urine leak, lymphocele or infected hematoma, infected peri nephric collection.
· Duration of HD with NO residual renal function which leads to low bladder capacity,
· Previous history of recurrent UTI prior to transplantation.
· Kidney stone, pyelonephritis or dysfunctional UB.
· Anatomical abnormality including low capacity UB or UV reflux
· DM and neurogenic bladder
· Immunosuppression increased the risk of infection. This patient should be evaluate for recurrent urinary tract infection if she has more than three Infections in the first post-transplantation year
1. Urological review and assessment for dysfunctional Urinary Bladder by urodynamic studies and post-voiding residual volume.
2. Anatomical anomalies abdo and pelvic U/S including native kidneys for any obstructive or structural abnormalities, collection,
3. urine culture and identify MDR microorganism choice should be according to the culture and sensitivity and be given for appropriate duration especially for MDR microorganism,
4. In female patient particularly post-menopausal should be referred to gynecology consult.
Empiric antibiotic treatment depends on clinical presentation and must be based on local epidemiological data and the patient’s history of previous resistant organisms and previous antibiotic therapies prescribed in previous months. later after culture and sensitivity the antibiotic may be changed.
Antibiotics
Low-tract UTI (cystitis); Fosfomycin, ciprofloxacin, amoxicillin/clavulanate or 2nd/3rd generation oral cephalosporins for 5-7 days.
Moderately severe UTI, including acute pyelonephritis; Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days.
Severe infection and/or septic shock, carbapenem plus vancomycin considered, completing 14-21 days.
To find the cause of recurrent UTI Check for USG Post micturating residual urine volume and to rule out the structural abnormality need to do CT KUB CT KUB -Structure abnormalities- corrective measure/surgery -No structure abnormalities-voiding cystourethrogram Voiding cystourethrogram -Vesicoureteral reflux-corrective measure /surgery
-No Vescio ureteral- then do urodynamics Urodynamics
-Presence of bladder dysfunction need (medical management), -Presence of outflow obstruction need (surgical management) Prevention Behavioral changes (increased fluid intake, holding urine, wiping technique in female, frequent voiding, postcoital voiding) Continuous Intermittent self-catheterization- for residual urine Urine dipstick at home for monitoring uti For postmenopausal females, topical estrogen TMP-SMX prophylaxis to prevent recurrent UTI (reflux, transplantation, voiding disorder)
Reference Post renal transplant UTI Lecture, Prof Mohamed Salah Eldin Zaki
Marta Bodro, Laura Linares, Diana Chiang, Asuncion Moreno & Carlos Cervera (2018): Managing recurrent urinary tract infections in kidney transplant patients, Expert Review of Anti-infective Therapy, DOI: 10.1080/14787210.2018.1509708
In such a patient, I need to check for VUR, which can be estimated by mega ureters, etc. Can be missed on USG as the kidneys are functioning, but we need to sterilize the urine (antibiotics according to culture) , followed by voiding cystography to explore reflux to native and or transplanted kidneys. Teflon injection is not very successful but can be the first step, followed by neoureterotomy in case VUR is diagnosed.
Recurrent UTI means that she has at least two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
In such case we need to rule out any STRUCTURAL OR FUNCTIONAL ABNORMALITY We have to perform an ultrasound of the kidney allograft, native kidney, and postvoid bladder . In patients with recurrent UTI who have unrevealing ultrasonography, we need to perform a non contrast computed tomography (CT) scan of the urinary tract.
These imaging studies can identify urinary tract strictures, stones, and complex cysts. If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction, in consultation with urology.
Flexible cystoscopy may be required to detect abnormalities in the urethra or bladder
• Complicated UTI – For transplant recipients with a complicated UTI, we suggest empiric therapy with piperacillin-tazobactam, meropenem, or combination therapy with vancomycin plus cefepime rather than other agents used in nontransplant patients (up to date)
All patients should be counseled on the risk factors for recurrent UTI and behavioral changes that might reduce the risk.
Such behavioral changes are similar to those for nontransplant patients with recurrent UTI and include increased fluid intake, frequent voiding, postcoital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females).
PROPHYLACTIC ANTIBIOTICS CAN BE INDIVIDUALIZED
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
Intraoperative factors: Use of double-J ureteral stent, duplex ureters, prolonged urinary catheterization transplantation with deceased donor compared to living donor and retransplantation.
Postoperative factors: Graft dysfunction and rejection,excessive immunosuppression, infection of native urinary tract and invasive urological procedures can be postoperative factors related to UTI.
Management :
*The management of recurrent urinary tract infections in kidney transplant patients requires a proper diagnosis of the underlying mechanism.
*Early identification of structural or functional urological abnormalities is important for successful management.
CBC ,urinalysis and culture ,blood culture ,U&E ,tacrolimus level
Imaging studies of the genitourinary tract should be considered (ultrasound examination or CT) to rule out structural changes .
Cystoscopy, cystogram, uroflowmetry and other urodynamic studies when anatomical and/or functional changes are suspected such as vesico-ureteric reflux, functional bladder dysfunction or obstruction.
Empiric antibiotic treatment depends on clinical presentation and must be based on local epidemiological data and the patient’s history of previous resistant organisms and previous antibiotic therapies prescribed in previous months.
Quinolones 2nd and 3rd generation cephalosporin for 5-7 days are generally suggested for mild cases and for patients without risk of MDR .
Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days is suggested in case of moderately-severe UTI, including acute pyelonephritis.
Carbapenem plus vancomycin are considered for patients present with severe sepsis and septic shock
Systemic antifungals for fungal cystitis or pyelonephritis.
Specific antibiotics depend on the result of C/S .
Surgical or interventional radiologist in case of complicated UTI with abscess formation or in case emphysematous pyelonephritis or removal of DJ stent .
Reference :
1. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21
⭐⭐⭐Management of recurrent UTI after kidney transplantation involves the management of any modifiable risk factors:
_ exclusion of any anatomical problems as VUR on native kidney or the allograft (diagnosed by MCUG and ttt by surgical ureteric reimplantation) , neglected stone (diagnosed by US or CT and removed by ESWL or cystoscopy according to the size of the stones), missed or forgotten DJ stent (diagnosed by US /KUB and must be removed by ureteroscopy) , dysfunctional voiding (diagnosed by increased PVR and urodynamic studies, and treated by frequent and timed voiding plus or minus CIC).
_Exclude gynecological causes of UTI and ensure good hygiene (wiping from front to back)
_start treatment with empirical antibiotics (ciprofloxacin or ceftrixaone ) till the result of culture and sensitivity …then shift to culture based antibiotics.
_ Consider multidrug resistant organism.
_consider SMX-TMP prophylaxis for aat least 6 months after treatment of the current infection to decrease the risk of recurrence.
_general measures to decrease UTI as increase water intake, frequent voiding.
_check for diabetes (random glucose and HBA1C) and also for over immunosuppression (check trough level of CNI and MMF).
This female recipient with early recurrent UTI (3 months) after kidney transplantation with no clear cause of primary disease.
UTI is a very common infection after kidney transplantation and it’s in the range of asymptomatic bacteriuria, cystitis pyelonephritis (1), risk factors of early recurrent UTI infection include female gender, old age, prolonged catheterization, or DJ stent complication like migration or missed piece,post-surgical complications like urine leak, lymphocele or infected hematoma, infected perinephric collection also the duration on HD with risk of low bladder capacity, and previous history of recurrent UTI prior to transplantation, or kidney stone, pyelonephritis or dysfunctional UB, or anatomical abnormality including low capacity UB or Ureterovesical reflux, in addition, history of DM and the control and possible neurogenic bladder, immunosuppression medication and CNI trough level as intense IS can affect the immune response and increased the risk of infection, use of prophylaxis AB and compliance. So this patient if have more than 3 episodes of UTI in the first year post-transplantation fit the definition of recurrent UTI and needs to be evaluated including urological review and assessment for dysfunctional UB by urodynamic studies and post-voiding residual volume, abd, and pelvic US including native kidneys for any obstructive or anatomical or structural abnormalities, collection, urine culture and identify MDR microorganism and the AB choice should be according to the culture and sensitivity and be given for appropriate duration especially for MDR microorganism, being a female should also be referred to gynecology to rule out any local cause of recurrent UTI.
References
1. Transplantation Proceedings Volume 45, Issue 4, May 2013, Pages 1590-1592
2. Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
3 Aydın S, Patil A, Desai M, Simforoosh N. Five compelling UTI questions after kidney transplant. World J Urol. 2020 Nov;38(11):2733-2742. doi 10.1007/s00345-020-03173-4. Epub 2020 Apr 7. PMID: 32266510.
4. Kidney transplant handbook 6th edition.
Detailed history of the recurrent UTI, diabetes mellitus, & urinary tract anomalies, & the waiting time before KTX.
The details of previous urine culture & sensitivity results, & any history of drug resistance, if available.
After appropriately treating the current episode of UTI guided by the results of cultures & reversing any underlying functional & structural abnormalities that might appear during the workup, I will consider the use of prophylactic antibiotics.
Prophylactic measures include assessing the voiding situation & complete bladder emptying, occasionally clean intermittent catheterization might be required.
Use of TMP at 160 mg & SMZ at 800 mg for 6 months, especially in high-risk patients (e.g., urinary reflux, &/or voiding disorders), is recommended.
References
Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21. PMID: 30092153.
Markus Giessing, Urinary tract infection in renal transplantation, Arab Journal of Urology (Official Journal of the Arab Association of Urology) doi: 10.1016/j.aju.2012. 01.005
Management of the Recurrent UTI in kidney transplant recipients
Exclude functional or anatomical restructure.
Determine the source of UTI, (native or allograft kidney).
Review the past history.
Immunuosppressants regimen.
Workup
Culture for pathogen isolate, and sensitivity.
US +/- CT KUB
The most common findings include;
Ureteral reflux.
Strictures at the ureterovesical junction.
Neurogenic bladder, and sub vesical obstruction, especially in men aged over 60 years.
Medication
In outpatient with uncomplicated UTI, quinolones for 7 days are recommended as empirical treatment till the culture results or TMP-SMX for 7-14 days
In complicated and hospitalized patients, 3rd generation cephalosporin IV, till the culture results.
In ESBL cases the carbapenems (imipenem or meropenem) are advised till culture results.
Native kidney as a source of recurrent UTI
Consider nephrectomy if resistant to treatment and there is a risk of graft dysfunction.
Follow up
Screening for ASB.
Prophylaxis treatment with TMP-SMX for at least 6 months with monitoring bacteriuria assessment, and culture guided.
References
Rubenstein JN, Schaeffer AJ. Managing complicated urinary tract infections: the urologic view. Infect Dis Clin North Am 2003 Jun;17(2):333-51.
2 – Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am 2003 Jun;17(2):303-32.
3 – Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011 Mar 1;52(5):e103-e120.
4 – Lutters M, Vogt-Ferrier NB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008;(3):CD001535.
Management of recurrent UTI in the post-transplant period
1. Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation.
2. UTIs are defined as the growth of 105 colony forming units on a proper urine sample) in the presence of symptoms such as dysuria, urinary frequency or localized pain(the incidence of a UTI ranges from 4–80%)(1).
3. To diagnose UTI in the post-transplant period, the followings are required:
a) Urinalysis, CBC, RFT and CRP.
b) Urine for culture and sensitivity panel.
c) USS of the native urinary system and the graft.
4. Measures to prevent UTI in KTR(1):
a) A single shot antibiotic is administered prior to incision.
b) Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis.
c) To remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection in order to remove biofilms.
d) Prophylactic antibiotic regimens:
· Ciprofloxacin was later reserved for treatment rather than prophylaxis. The 2019 FDA warning against the use of fluoroquinolones in KT recipients.
· Fosfomycin showed preventative efficacy.
· TMP-SMX is the best studied drug.
· Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to.
5. TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients(1).
6. Class of antibiotics used to treat UTI in the post-transplant period(2):
· Penicillins (49%). · Cephalosporins (36%). · Fluoroquinolones (16%). · Carbapenems (4%). References 1. Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship? J Clin Med. 2021 Dec 31;11(1):226. doi: 10.3390/jcm11010226. PMID: 35011966; PMCID: PMC8745876. 2. Olenski S, Scuderi C, Choo A, Bhagat Singh AK, Way M, Jeyaseelan L, John G. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrol. 2019 Dec 27;20(1):479. doi: 10.1186/s12882-019-1666-6. PMID: 31881863; PMCID: PMC6935183.
Thank you for your input. You concentrated on Antibiotic treatment with different options. You do not need to explore the reasons behind the recurrence of UTI in this patient? significant residual urine, urodynamics, vesicoureteric reflux, multiple stones in the native kidneys etc.
A case of recurrent UTI :Two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
UTIs are associated with significant morbidity among transplant recipients, especially if they occur early after transplantation. History (cause of original disease, stone former, recurrent UTI, and other co-morbidities).
Urine analysis , Urine culture and sensitivity.
We perform an ultrasound of the kidney allograft, native kidney, and post-void bladder for patients with recurrent UTI. we perform a non-contrast computed tomography (CT) scan of the urinary tract which can identify urinary tract strictures, stones, and complex cysts.
If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction, if any abnormalities detected Urologist should be involved.
Flexible cystoscopy may be required to detect abnormalities in the urethra or bladder.
Treatment of UTI according to culture result and some require up to four to six weeks of therapy Antimicrobial prophylaxis. Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the trimethoprim component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant.
Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation. Behavioral changes such as behavioral changes are similar to those for non-transplant patients with recurrent UTI and include increased fluid intake, frequent voiding, post-coital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females).
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI. Adjusting the immunosuppression medications. References:
1-Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13507.
2-Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis. 2019;21(3):e13063. doi:10.1111/tid.13063.
3-Urinary tract infection in kidney transplant recipients, UpToDate 2023.
Thank you. Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the trimethoprim component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant.
Do you think this patient is not already on TMP-SMX for 6 month already for PJP prophylaxis?
Thanks prof .
I thought she was already taking MP-SMX for PJP prophylaxis. my point that generally using this group also have prophylactic role in UTI and looking for a predisposing factor in this scenario is the main point.
2 documented infection /6 month or 3 documented infection/ year
either re infection (different micro-organism ) or persistent infection (same micro-organism ) which is due to either untreated properly previous infection or presence of a nidus of infection such as FB,stone,..etc
WORK UP:
proper family history (her mother) and personal history of recurrent UTI since childhood and pre-transplantation (some female patient has increased susceptibility /receptivity for adherence of micro organism
any history of constipation, neurological diseases, any association with sexual activity, hygiene, hydration status and menopause (vaginal mucosal quality )
require work up for any anatomical or functional abnormalities : isolated urine cultures from bladder +/- both native ureters & transplanted ureter , US,CT-KUB ,cystoscopy ,+/- Urodynamic study
Management:
general measures:
good hydration
treatment of constipation
proper hygiene / perineal sweeping from anterior to posterior
post coital voiding
if dry vagina…..local estrogen therapy
2.specific treatment according to any anatomical or functional abnormality will found
Recurrent UTI is defined as ≥ 2 episodes within 6 months or ≥ 3 episodes within 1 year
Recurrent UTI is associated with an increased risk of graft and patient loss (1).
Evaluation should be done to exclude structural or anatomical abnormalities and this includes
Primary US assessment
If US is normal, non-contrast CT scan is indicated to exclude the presence of strictures or stones
If CT is normal, we can perform urodynamic studies to exclude bladder dysfunction or urinary tract outflow obstruction.
Lastly if the cause is not clear flexible cystoscopy may be indicated to detect abnormalities in the urethra or bladder. (2)
Treatment of symptomatic recurrent UTI is the same as ordinary symptomatic UTI but
The treatment duration may be extended in some patients if the same organism is isolated, and if the recurrence is caused by an indwelling source such as infected cysts in the native kidneys in which treatment may be given for up to four to six weeks of therapy.
Post successful treatment strategies to prevent recurrence should be implemented
Strategies to prevent recurrence of UTI
Behavioral therapy including increasing oral fluid intake, frequent voiding, post coital voiding, wiping from front to back in females
For premenopausal women, modification of contraception may be advised while in post-menopausal females, topical estrogen may decrease he frequency of recurrent UTI
Use of prolonged prophylactic antibiotics, the most important regimen is the use of SMX-TMP for 6-12 months which was associated with reduction of UTI episodes and severity. (3, 4). Some experts continue TMP-SMX prophylaxis indefinitely (5).If SMX-TMP is contraindicated, some recommends the use of nitrofurantoin 100 mg twice daily provided GFR > 30 ml/min or cephalexin 500 mg twice daily.
Methenamine hippurate (1000 mg twice daily) can be used for prevention of recurrent UTI, which was found that it is associated with 45 % reduction in the frequency of UTI, 42 % reduction in the duration of antibiotic use for the treatment of UTI, and 59 % reduction in hospitalization due to UTI (6).
Probiotics are not recommended to be used in transplant recipients, as they are immunocompromised and data regarding its benefit is not clear.
Cranberry juice although the evidence is limited but because of its high safety, the patient can use it if she wants
References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
4- imaging study KUB, u/s abdomen and pelvis, non contrast CT to exclude or diagnose and structural abnormalities or obstruction or missed stent, stones.
5- trough level of tacrolimus to avoid over immunosuppression
6-confirmation of diagnosis and early treatment is very important to prevent pyelonephritis of the graft and endanger the life due to sepsis
7-Fosfomycin for 2-4 weeks
8- renal dose adjustment needed
9- interaction between immunosuppression CNI and gentamycin or TMP-SMZ, may increase the toxicity
UTI is the most common infection in early period post KT. It may lead to significant morbidity with recurrent hospitalization, acute T cell-mediated rejection, impaired allograft function, and allograft loss. Recurrent UTI defined as : Two or more episodes of UTI in six months, or three or more episodes of UTI in one year. Risk factors includes: female sex, advanced age, recurrent UTI prior to transplant, urinary tract anomalies, VUR, urethral catheterization, ureteral stent placement, DD kidney transplant, ADPKD, DGF and immunosuppressed state. Evaluation of recurrent UTI: The index case has ESRD and bilateral atrophic kidneys with recurrent UTI, VUR should be considered. -History:
Nature of recurrent UTI (cystitis or complicated UTI) and the current symptoms.
pre-transplant recurrent UTI, voiding habits, constipation.
use of CIC, ask about ureteral stent (removed or not)
compliance to TMP-SMX
Management: A .Identify the reason for recurrent UTI
-Aim to rule out existence of anatomical or functional changes such as VUR, neurogenic bladder and stenosis of the ureterovesical junction or sub-vesical obstruction (especially in male).
-Urology team and transplant surgeon involvement.
– KUB US evaluate both allograft and native kidneys; UT dilatation, stone, stent, post void residual , complicated cysts, ureterocele.
– non-contrast CT for detailed evaluation if US was inconclusive; can identify urinary tract strictures, stones, and complex cysts
– VCUG: to rule out VUR.
– Uroflowmetry and urodynamic considered in case of clinical suspicion of bladder dysfunction or outflow tract obstruction
– Cystoscopy may be required.
-Evaluate for prostatitis in male
B. Active infection:
-For each episode evaluate the patient clinically; severity of symptoms, assess the needs for hospitalization
-Urine analysis (dipstick/sediment) and always a urinary culture.
-Evaluate kidney function (any change from baseline)
– CBC, CPR, Blood culture.
– BK and CMV infection should be excluded.
-Treatment of acute episodes should always be based on the local epidemiology of antibacterial resistance.
– Must consider interaction with immunosuppression drug; nephrotoxicity of TMP-SMZ and gentamicin in recipients taking CNI.
– Empiric therapy should be started taking into account previous antibiotic therapies prescribed in previous months.
– low-tract UTI (cystitis); Fosfomycin, ciprofloxacin, amoxicillin/clavulanate or 2nd/3rd generation oral cephalosporins for 5-7 days.
– Moderately-severe UTI, including acute pyelonephritis; Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days.
– Severe infection and/or septic shock, carbapenem plus vancomycin considered, completing 14-21 days.
– Once culture susceptibility results are available, tailor the antimicrobial therapy according to the result.
– Progression to renal or perinephric abscess or emphysematous pyelonephritis requires a MDT approach.
– Removal of indwelling urinary catheter and/or ureteric stents ( if present) should be considered in KTR with UTI.
C. Prevention: – Correct conditions amenable to surgical management.
-Avoid prolong use of catherization if not necessary, strategies such as chlorhexidine and antibiotic coated stents to prevent biofilm formation may be considered.
– Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation.
– Monitoring for asymptomatic bacteriuria in the first 2 months post-Tx.
– Behavioral changes (increased fluid intake, frequent voiding, postcoital voiding, contraception modification) – For postmenopausal females, topical estrogen may prevent recurrence of UTI
– Antibiotic prophylaxis: KDIGO recommended TMP-SMX to prevent PCP for 6 months post transplantation; this is also effective at preventing UTIs, risk of resistance.
References:
-Nicola Petrosillo, Guido Granata, Breida Boyle, Maeve M. Doyle, Biagio Pinchera, Fabrizio Taglietti. (2020) Preventing sepsis development in complicated urinary tract infections. Expert Review of Anti-infective Therapy 18:1, pages 47-61.
Marta Bodro, Laura Linares, Diana Chiang, Asuncion Moreno & Carlos Cervera
(2018): Managing recurrent urinary tract infections in kidney transplant patients, Expert Review of
Anti-infective Therapy, DOI: 10.1080/14787210.2018.1509708 Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. doi: 10.1111/ctr.13507. Epub 2019 Mar 28. PMID: 30793386.
5. A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI. ===================================================================
Urinary tract infections (UTIs) are the most common infectious complication after kidney transplantation (KT).
Recurrent UTIs after KT can contribute to increased morbidity and may also be associated with graft loss and mortality.
Urinary tract infections (UTIs) are the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%.
A recurrence is termed reinfection if the interval between two episodesis greater than 2 weeks, if a different strain of uropathogen is documented or if a sterile culture (with the patient off antibiotics) was documented between two UTI episodes.
If the interval between the two episodes is less than two weeks, it is defined as a relapse.
Relapsing infections often require additional evaluation with urological imaging.
Pyelonephritis is still a frequent infection after renal transplantation, especially in the first six months post-transplantation and among female transplant recipients.
Pyelonephritis may increase the risk of graft loss, sepsis and mortality emphasizing the importance of preventive measures as well as early detection and treatment of UTI in RTx recipients.
==================================================================== How would you manage this patient?
A complete history and physical are necessary
Women with recurrent UTIs should have a pelvic examination to check for cystoceles, vaginitis, vaginal atrophy, and prolapse of pelvic organs.
Potential risk factors involved in the development of UTIs after kidney transplantation include:
Female gender
Advanced age
Pre-transplant UTIs
Prolonged period of haemodialysis before transplantation
Immunosuppression
Double kidney transplant history, leading to an increase in DJ stents
Acute rejection episodes
Impaired graft function
Bladder catheter postoperatively
Technical complications associated with ureteral anastomosis
Intraperative ureteral stents
Surgical manipulation of the graft (allograft trauma)
A history of stone passage; or repeated isolation of Proteus from the urine, which is often associated with renal stones.
Preferred imaging modalities include renal ultrasonography or, ideally, a CT scan of the abdomen and pelvis.
If post-transplant UTI relapses or recurs immediate investigations have to be performed including imaging studies including CT of the kidneys (stones, complex cysts), CT-PET (cyst infection?) and urological investigations like cystoscopy, urodynamics and micturating cystogram (reflux, bladderdysfunction) before a prolonged course of antibiotic therapy.
Prevention of UTI after kidney transplantation also needs athorough management of structural and functional urinary tract abnormalities in the pre-transplant period, which sometimes even justifies nephrectomy of the native kidneys, especially in patients with recurrent UTI in polycystic kidney disease and in patients with VUR to their native kidneys
Treatment
The patients should be educated for basic preventive measures like hydration and frequent voiding.
Treatment of UTI in renal transplant patients should be according to the general guidelines for treatment of complicated UTI, but in the first 3 months after transplantation empirical treatment with the combination of amoxicillin and ciprofloxacin is recommended.
In the choice of antibiotics for treatment of recurrent UTI the increased risk for ESBL-related infections should be considered.
Therefore, earlier culture results and fluoroquinolone use in the last < 30 days have to be checked.
Removal of the urinary catheter should be done as soon as appropriate.
In case of a UTI the JJ stent should be removed if possible and the urine must be cultured.
In patients with recurrent UTI further investigations for anatomical abnormalities, bladder dysfunction or infection of the native kidneys should be initiated.
It is important to note that several antimicrobial agents can interact with immunosuppressants, especially with calcineurine-inhibitors. Therefore, interactions have to be checked.
Prophylaxis of UTI in Transplant Recipients
Early removal of foreign material (catheter)
TMP 160 mg/SMZ 800∗ especially in high-risk patients: (Reflux Re-transplantation Voiding disorder).
Vaccination (Inactivated species of E. coli, Morganella morganii, Proteus, Klebsiella, Enterococcus faecalis).
General behaviour Excretion minimum > 2 L/day ,Urine dipsticks at home, ‘home treatment on demand’ ,Genital hygiene (wiping after urination: vaginal ⩾ anal) Urine pH 5.8–6.5 (vitamin C, methionine) Vaginal oestrogen/lactobacillus, Intermittent self-catheterization for residual urine ,Cranberry products (juice/tablets).
Liu P, Hamilton KW, O’Donnnell JA. Urinary Tract Infection. Cunha CB. Schlosberg Clinical Infectious Disease. Third. Oxford University Press; 2022. 423-429.
[Guideline] Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar. 52(5):e103-20.
Alangaden GJ, Thyagarajan R, Gruber SA, et al. Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transplant. 2006;20:401–9. doi
Aydin A, Ahmed K, Zaman I, Khan MS, Dasgupta P. Recurrent urinary tract infections in women. Int Urogynecol J. 2015 Jun;26(6):795-804.
Post Renal Transplantation Urinary Tract Infection By Prof. Mohamed Salah Eldin Zaki Dean of National Institute of Urology and Nephrology
The risk factors of recurrent UTI include female gander as in the case, surgical, anatomical, recipient, and graft-related factors, Vesico-ureteric reflux (VUR) increases the pyelonephritis risk, also temporary ureteric stent enhances VUR, abolishing peristalsis and dilating the vesico-ureteric junction, ureteric stents and urinary catheter particularly if left for a long period enhance UITI risk also immunosuppressive drugs as ATG, Azathioprine and MMF increase UTI risk.
Investigations include
Urine analysis and urine culture are indicated if UTI is suspected, and blood cultures should be collected in case of severe systemic symptoms
Renal ultrasound or non-contrast computed tomography (CT) scan should be considered to assess complications such as obstruction and abscess also Non-contrast CT scan is useful to identify nephrolithiasis, complex cyst, and other anatomical urinary abnormalities
Cystourethrography, cystoscopy ,urodynamic studies can be needed for VUR Treatment
Empirical treatment with the combination of amoxicillin and ciprofloxacin is recommended.
No recommendation can be made about changing immunosuppressive drugs from one class to another to prevent a recurrence of UTI.
In the choice of antibiotics for treatment of recurrent UTI with the increased risk for ESBL-related infections should be considered.
Antibiotic selection should be guided by the results of microbiology tests and culture due to emergence of drug-resistant uropathogens. The duration of antimicrobial therapy in recurrent UTIs is not well defined, but some authors recommend longer durations of treatment (4–6 weeks or even longer)
Multiple antibiotics can interact with immunosuppressants, especially with calcinurine-inhibitors. Therefore, interactions have to be checked.
Removal of the urinary catheter should be done as soon as appropriate.
In case of a UTI the JJ stent should be removed if possible.
Effect of reoperation of refluxive transplanted kidney is not clear as in spite of antirefluxive urtetic implanation reflux is still common.
Nephrectomy of native kidneys with reflux can successfully low recurrent UTI risk meanwhile it is the last option.
Behavioural education can decrease recurrent UTI risk as hydration , frequent voiding and sanitation
Antibiotic prophylaxis for the prevention of recurrent UTI has not been well evaluated.
Topical estrogen has been used in perimenopausal and postmenopausal females and a combination of hyaluronic acid and chondroitin sulphate instilled intravesically.
It was lately published that bacterial vaccines reduced the incidence of recurrent UTI in a small case series of KT patients without eliciting any safety concerns. Reference
-Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship?. J Clin Med. 2021;11(1):226. Published 2021 Dec 31.
– Suárez Fernández, M.L.; Ridao Cano, N.; Álvarez Santamarta, L.; Gago Fraile, M.; Blake, O.; Díaz Corte, C. A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients. Diagnostics 2021, 11, 1456
How would you manage this patient?Recurrent UTIs are associated with higher morbidity and graft loss. The cause of recurrent UTIs have to be explored.
First step is detailed history. The primary kidney disease have to explored. History will include frequency of episodes , voiding LUTS, status of immune suppression, medical conditions, fluid habits constipation, sense of incomplete bladder emptying. Inquiry about removal of DJ stent See the culprit organism in urine cultures USS KUB with post void CT scan to see any stones, kinks in Ureter, hydronephrosis or any other structural abnormality. If any concern about VUR then a MCUG can be arranged. If there is any abnormality in bladder then a flexible cystoscopy should be done BK virus infection also needs to be ruled out
Management It will depend upon any pathology detected. General life style measures to be advised. These will include care of hydration, timed and double voiding , hygienic measures , avoidance of constipation. In case of atrophic vaginitis, topical estrogens can be used Use of prophylactic antibiotics
Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732.
How would you manage this patient?
In the management of the index patient, it will be prudent to identify the possible risk or aetiological factors responsible for the recurrent UTI post-kidney transplantation. It is good to note that the most common site of infection after a kidney transplant is the urinary bladder in >95% of cases, then pyelonephritis in the rest.
Female gender
History of recurrent UTI prior to kidney transplant
History of DM
History of urinary tract abnormality like reflux, bladder dysfunction
Length of stay on hemodialysis
History of foreign material in the recipient e.g. ureteral stent, bladder catheter
Immunosuppressive regimen
History of glomerulonephritis ?? atrophy kidney in the recipient
History of a double kidney transplant, thus increasing the number of DJ stents
The following investigations will be done after obtaining the above information
Imaging tests like urinary bladder ultrasonography to rule out urolithiasis (though plan CT is better), urinary tract obstruction, or any forgotten DJ stent
Voiding cystourethrography
Urine analysis/ culture
BKV and CMV PCR, both needed to be excluded before treatment of the UTI
Tacrolimus trough level
FBC + Differential
CRP
Treatment
This will depend on the isolated aetiological cause
Empirical combination therapy of Amoxicillin plus ciprofloxacin has been advised in the first three months of kidney transplant for recurrent UTI
Removal of the urethral catheter in 5-7 days KTP
Removal of double J stent in < 4 weeks
Health education on proper hydration and voiding should be done for the patient
Avoid intense immunosuppression
Watch out for antibiotics – CNIs interaction
Close kidney function monitoring
References
Post Renal Transplantation Urinary Tract Infection Lecture by Prof. Mohamed Salah Eldin Saki
Simon OLENSKI, Carla SCUDERI, Alex CHOO, Aneesha Kaur BHAGAT SINGH, et al. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrology. 2019; 20: 479
The patient is on triple immunosuppression and is getting recurrent UTIs
Recurrent UTIs are a common clinical problem in kidney transplant recipients. Recurrent UTIs:
Worsen the quality of life
Decrease the graft survival
Increase the costs
Management:
Get a detailed history regarding the UTIs – the frequency, what investigations were done, whether culture and sensitivity was done, what treatments were given, duration of treatments, history of pre-transplant UTI
Get a urine culture and sensitivity
A KUB US with post-void residual volume – to assess for significant post-void residual volume and any structural abnormality
If there is a structural abnormality – refer to urology team for corrective surgery
If there is no structural abnormality – to get a voiding cystourethrography
If there is presence of vesicoureteic reflux – refer to urology team for surgery
If there is no VUR – refer for urodynamic flow studies
If there is presence of bladder outflow obstruction – refer for surgery
If there is presence of bladder dysfunction – medical management
If there is an active infection, the patient should be started on empiric therapy – risk of ESBL organisms should be assessed – treatment with a fluoroquinolone in the previous 30 days need to be assessed. If the risk of ESBL is low – she can be started on a fluoroquinolone or a third generation cephalosporin or amoxicillin/clavulunate whilst awaiting culture results
If the risk of ESBL is high, then the antibiotics chosen should cover for ESBL organisms, which are normally carbapenems or tazobactum/piperacillin
The DJ stents if present should be removed
The patient should be taught basic preventive measures including:
Adequate hydration
Frequent voiding
Cleaning from front to back
Voiding after sexual intercourse
The use of cranberry supplements is controversial and the data does not support the use of cranberry supplements for prevention of UTIs
The patient may need antimicrobial prophylaxis with with either septrin, nitrofurantoin or cephalexin. Nitrofurantoin is not recommended for long term prophylaxis due to the risk of interstitial lung disease
Some transplant programs use metheneamine hippurate 1 gm twice daily with or without ascorbic acid for prevention of recurrent UTI. A retrospective study of 38 kidney transplant recipients found that the use of metheneamine alone reduced the frequency of UTI by 45%, reduced the length of antibiotic use for treatment by 42% and reduced hospitalization for the UTI by 59%
Bodro M et al. Experts Review of Anti-infective Therapy. 2018;16:9, 723-732 Hollyer I et al. Transpl Infect Dis. 2019;21(3)
-How would you manage this patient?-Unfortunately , this is one of the difficult conditions and may be associated with increased morbidity, allograft loss and mortality
-Its usually requires a very exhaustive investigations and management
-It may be important to follow a structured approach for this kind of problems e.g.
-History of recurrent UTI in the native kidney before transplantation
-Make sure that her double J stent was removed as per protocol; sometimes this may be forgotten and creates a problem. If it was not remove, the organize for its urgent removal and send it for microbiology, culture & sensitivity.
-Role out BK virus; this is a differential for pyelonephritis as a tubulo-interstitial disease and it may cause ureteric stricture and surgical issues
-Check for post-void residual US/CT and evaluate for structural abnormalities
A. Presence of structural abnormalities: Corrective measures/surgery
B. Absence of structural abnormalities: Voiding cystourethrography
Thankyou for starting with HISTORY as this can answer a lot of questions.
Forgoten stents are always a surprise!
New post TX UTI have are a diff. options BK is among them.
work-up
Some individuals with UTIs may need imaging to rule out correctable anatomical or functional urinary tract abnormalities. Patients who:
Are one-month post-transplant or
Nephrolithiasis history
Having recurrent UTI (2 incidents in six months or 3 episodes in one year) or
Continuously elevated serum creatinine.
Most patients start with urinary system ultrasonography with postvoid residual measurement due to its convenience and absence of adverse effects.
We do a non-contrast urinary tract CT scan in recurrent UTI patients with unrevealing ultrasonography. Avoiding contrast to minimize nephrotoxicity limits CT scan sensitivity. Imaging may detect urinary tract strictures, stones, and complicated cysts. Urology may undertake urine flow rate and urodynamic investigations to determine bladder dysfunction or outflow tract blockage if the CT is unrevealing. Flexible cystoscopy may identify urethral or bladder problems.
prevention and treatment:
Antibiotic prophylaxis – Early post-transplant UTIs cause severe morbidity. Early posttransplant prophylactic antibiotics reduce UTIs in kidney transplant patients.
Early ureteral stent removal: early ureteral stent removal within four weeks of transplant may help prevent UTI after kidney transplantation.
Recurrent UTI risk factors and behavioral changes should be discussed with all patients. Increased fluid intake, frequent voiding, postcoital voiding, contraceptive adjustment (in sexually active patients), and wiping from front to back (in females) are comparable to nontransplant patients with recurrent UTIs.
Some specialists give recurrent UTI patients preventive antibiotics. Individualize long-term antibiotic prophylaxis. For postmenopausal females, topical estrogen may prevent the recurrence of UTIs.
Several transplant programs utilize methenamine hippurate (1000 mg twice a day) with or without ascorbic acid to avoid recurrent UTIs.
Recurrent episodes—Each episode of simple cystitis or severe UTI should be treated with an adequate period of antibiotic medication.
Patients with persistent/recurrent UTIs with the same organism may need a longer course. Infected kidney cysts may cause recurrent UTIs that need four to six weeks of treatment.
Recurrent UTI treatment may be terminated after a shorter time and switched to preventive antibiotics in other cases.
Reference: Mitra, S., & Alangaden, G. J. (2011). Recurrent urinary tract infections in kidney transplant recipients. Current infectious disease reports, 13, 579-587.
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI. How would you manage this patient? From the scenario female with unknown etiology of ESRD and found to have bilateral small kidneys, raise the possibility of reflux nephropathy.
From historymake sure that she underwent double J stent removal, hygiene, and adequate water intake, and sexual history.
Laboratory: CBC, BUN, creatinine, CRP, urinalysis and urine culture is a must, blood culture, consider PCR for BK virus and CMV.
The management of this patient consists of: 1. Culture based antibiotic treatment. 2. Anatomical evaluation of kidneys and urinary tract. 3. Prevention of recurrence. 4. Reduction/ stoppage of immunosuppressive medications.
Culture based antibiotic treatment:every patient presents with UTI post-transplant, should have urine culture done.
In symptomatic cystitis empirical antibiotics to use are: oral fluoroquinolone, amoxicillin-clavulanate, or an oral third-generation cephalosporin, nitrofurantoin can be used.
In severe UTI and pyelonephritis empirical antibiotics recommended are: carbapenems, cefepime, and pipracillin/tazobactams.
Anatomical evaluation of urinary tract:
First by pre and post void ultrasound or voiding CT scan– if any corrective lesions should be done, or obstructive stones or evidence of ureteric stenosis..etc.
Second if the post void image normal the MCUG (Micturition cystouretherography)– if reflux is identified either medical prophylactic tx/ endoscopic injections or surgical intervention as needed.
Third if the MCUG normal then consider urodynamic studies– if bladder dysfunction medical treatment accordingly, and if outflow obstruction surgical intervention is warranted.
Prevention of recurrence:
By life style modification and better genital hygiene, and maintaining at least 2l/day UOP, standby post coital antibiotic prophylaxis.
If post menopause then topical estrogen therapy may be beneficial, and keeping alkaline urine may also prevent recurrence by use of vitamin C, cranberry
Antibiotic secondary prophylaxis of recurrent UTI in KT recipients, usually not recommended unless for selected patients who have severe episodes of recurrent UTIs such as pyelonephritis (Weak, Low). References: (1) Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. doi: 10.1111/ctr.13507. Epub 2019 Mar 28. PMID: 30793386. (2) Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi: 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
How would you manage this patient?o Recurrent UTIs after KT are defined as ≥ 2UTI episodes in a 6-month period or ≥3UTI episodes within 1 year (occur in 3 to 27% of cases)
o Gram-negative organisms account for the majority of recurrent UTIs (E.coli remains the most common cause)
Risk factors:
1. female gender (strongest risk factor), immunosuppression, hyperglycemia, prostatitis, concomitant CMV, and re-transplantation
2. anatomical abnormalities [vesicoureteral reflux (the most important), renal calculi, bladder dysfunction, urethral abnormalities, and complex cysts]
Diagnosis:
o Blood tests (C-reactive protein, leucocytes)
o BK and/or CMV infection should be excluded
o Ultrasonography to exclude postrenal causes of infection (urolithiasis, urinary tract obstruction, ‘forgotten’ ureteric stent, etc.)
o Prostatitis should be considered as an important differential diagnosis in men who present with recurrent post-transplant UTI.
o Radiography, CT even CT-PET, cystoscopy, cystourethrography (vesicoureteral reflux), and urodynamic studies
Treatment:
o Antibiotic selection should be guided by the results of microbiology tests (because of the emergence of drug-resistant uropathogens)
o The duration of treatment is not well defined, but some authors recommend longer durations of treatment (4–6 weeks or even longer)
o Correction of structural and functional urinary tract abnormalities (for example obstructed transplant ureters, urolithiasis, and BOO from causes like BPH)
o Nephrectomy may be indicated in recurrent UTI with reflux or APKD
o Interaction with immunosuppression must be considered, such as increased nephrotoxicity of TMP-SMZ and gentamicin in recipients taking calcineurin inhibitors
Prevention:
1. Behavioral education (hydration, frequent voiding, and intimate hygiene, especially for females after a sexual intercourse)
2. Antibiotic prophylaxis has not been well studied. The potential benefits of extended antibiotic prophylaxis should be carefully weighed against the risks of promoting bacterial resistance, Clostridium difficile infection, and other adverse events associated with antibiotics. Antimicrobial prophylaxis might be appropriate for selected patients who have severe episodes of recurrent UTIs such as pyelonephritis
1 and 2 if no structural abnormalities
3. Nonantimicrobial therapies have been tried in patients with recurrent UTI most of all in the non-transplant population. It has been described that (cranberry juice, topical estrogen, and a combination of hyaluronic acid and chondroitin sulphate instilled intravesically
4. Other therapies (methenamine and probiotics)
5. Bacterial vaccines: in a small case series of KT patients without eliciting any safety concerns
References
1. Suárez Fernández ML, Ridao Cano N, Álvarez Santamarta L, Gago Fraile M, Blake O, Díaz Corte C. A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients. Diagnostics (Basel). 2021 Aug 12;11(8):1456. doi: 10.3390/diagnostics11081456. PMID: 34441390; PMCID: PMC8392421.
2. Oxford handbook of Nephrology and Hypertension, 2nd edition, 2014.
3. A lecture of Post Renal Transplantation Urinary Tract Infection By Prof. Mohamed Salah EldinZaki, Dean of National Institute of Urology and Nephrology
Thank you prof.
A post voiding residual urine of 254cc is high and is a leading cause of recurrent UTI The most common causes are:
1. Bladder outlet obstruction (BPH) Bladder neck contracture
2. Urethral stricture
3. Detrusor underactivity
4. Bladder tumours Diagnosed by ultrasonography, urodynamic testing, and cystoscopy Treat the underlying cause (transurethral prostatectomy for BPH)
The plan of management divided into
1- treatment of the current symptomatic urinary tract infection
2 – evaluating the cause of this recurrent UTI
3- prophylactic management
1–Treatment: Cystitis
○It can be treated with oral antibiotic on most occasions.
○Empiric antibiotic treatment should be initiated pending results of urine culture.
○Cotrimoxazole is not an adequate empirical treatment for those solid organ transplant recipients receiving prophylaxis with this antibiotic.
○quinolones, oral cephalosporins and fosfomycin that do not interact with immunosuppressive drugs.
○ Most experts recommend therapy for10-14 days.
○Eradication of the organism should be confirmed by a follow-up culture of an after-treatment urine sample.
Pyelonephritis
■blood and urine samples have been collected.
[CBC- CREA- CRP ….Urine sample test and culture]
■In febrile patient with abrupt deterioration of renal function, treatment with empirical parenteral antibiotic therapy
■aimed at Gram negative bacilli, including Pseudomonas aeruginosa, and enterococci
■Hospitalization may be considered.
■Active antibiotics against Pseudomonas aeruginosa include piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, cefepime, imipenem, meropenem and doripenem.
■aminoglycoside may be considered in patients with multiresistant Gram negative bacteria.
■Alternative antibiotics for those patients reporting an allergic phenomenon to β-lactams are fluoroquinolones and aztreonam for Gram negative bacteria, and vancomycin for enterococci.
■For those patients in whom vancomycin-resistant enterococci is a concern, linezolid, daptomycin and quinupristin/dalfopristin can be an alternative.
■pyelonephritis should receive therapy for 14 days.
■Step-down from intravenous to oral therapy is appropriate when the patient has clinically improved and is afebrile for at least 48 hours.
■Longer treatments may be necessary for those with renal or perirenal abscesses.
2– evaluating the cause of this recurrent UTI
●We should ask about the period before transplantation. Is there a history of recurrent urinary tract infections?
●Ultrasound should be performed to functional or anatomic abnormalities must be exclude (e.g., stone, obstructive uropathy, poorly functioning bladder) by testing the native kidneys and renal graft then studying the post-void residual.
●If the former was negative, we should initiate the second step of investigation, VCUG.
If there was a VUR ==> may be need surgery or only observation
If it was negative (no VUR) ==> urodynamic may be recommended
3– PROPHYLAXIS
●For renal transplant recipients without anatomical abnormality who suffer more than three recurrences per year, a prolonged antibiotic prophylaxis can be considered.
●Antibiotics that have proved to be useful in this setting are
– bactrim (trimetoprim 80 mg plus
– sulfamethoxazole 400 mg)
– or a quinolone (200-250 mg) every other day.
●Cephalexin, fosfomycin or nitrofurantoin could be alternative options.
●KDIGO (Kidney Disease: Improving global outcomes) recommend the use of this antibiotic as prophylaxis for UTI and Pneumocystis jiroveci pneumonia during, at least, the first 6 months after renal transplantation.
●All patients should be counseled on behavioral changes that might reduce the risk. (Increased fluid intake, frequent voiding, postcoital voiding, contraception modification )
●For postmenopausal females, topical estrogen may prevent recurrence of UTIs
●We do not routinely use strategies such as cranberry juice or probiotics due to the lack of clear data supporting
●Evidence in support of antimicrobial prophylaxis to prevent UTI is provided by a meta-analysis of six randomized trials in 545 kidney transplant recipients, which demonstrated that antibiotic prophylaxis (mostly with TMP-SMX) reduced the risk of sepsis and bloodstream infection (relative risk [RR] 0.13, 95% CI 0.2-0.7) and bacteriuria (RR 0.41, 95% CI 0.31-0.56) . Prophylaxis did not reduce graft loss or mortality, and effects on the risk of symptomatic UTI or pyelonephritis were not reported.
REFERENCES
1–Urinary Tract Infections in Transplant Recipients. Francisco López-Medrano
2–Urinary tract infection in kidney transplant recipients (UpToDate)
3–Managing recurrent urinary tract infections in kidney transplant patientsMarta Bodro et al.
4–Post Renal Transplantation Urinary TractInfection By Prof. Mohamed Salah EldinZaki
Thank you professor. In the center where I work stent has been removed 6 weeks after transplantation. That is why I didn’t mentioned this issue. But it is an important point
Detailed evaluation ( history of UTI before Tx, any voiding difficulty, exclusion any obstruction by doing USG of KUB with PVR, urodynamic study/cystoscopyif indicated)
Maintain personal hygeine, avoid constipaion, bladder evacuation frequently, use cranberry juice, use post coital pill if needed. Long term prophylactic antibiotic (monthly rotation of TMP/SMX, Nitrofurantoin, cefalaxin..) may be ne necessary in this pt.
Recurrent UTI means > or =2 times in 6 months or >or = 3 times per 1 year
Risk factors:
Anatomical abnormalities in urinary tract
Sexual intercourse
NODAT
Immunosuppression
Female
OLd age
DJ stent
Treatment:
SMX-TMA 7-14 days or quinolones for 7 days
if complicated IV cephalosporins
If ESBL:carbabenemes
Nephrectomy,DJ stent removal if resistent UTI
How would you manage this patient?
· UTI is a very common infection following kidney transplantation and it ranges from asymptomatic bacteriuria to cystitis or pyelonephritis.
· Recurrent UTI is associated with an increased risk of graft and patient loss. It is defined as ≥ 2 episodes within 6 months or ≥ 3 episodes within 1 year.
· Risk factors for recurrent UTI:
o Old age
o female gender
o post-surgical complications like urine leak, lymphocele or infected hematoma, infected peri-nephric collection
o prolonged catheterization, or DJ stent complications
o low bladder capacity,
o Anatomical abnormality including low bladder capacity, vesico ureteric reflux or neurogenic bladder.
o History of DM
o Immunosuppression medication increases the risk of infection
o Compliance to the use of prophylactic antibiotics
· Workup
o Initial treatment: TMP-SMX for 7-14 days or quinolones for 7 days
o Complicated UTI: IV 3rd generation cephalosporin IV
o ESBL cases: Carbapenems (imipenem or meropenem) can be used.
o Consider nephrectomy of the native kidney if in recurrent UTI resistant to treatment
o Prophylaxis treatment with TMP-SMX for at least 6-12 months. If SMX-TMP is contraindicated, use nitrofurantoin 100 mg twice daily provided GFR > 30 ml/min or cephalexin 500 mg twice daily.
o Screen for asymptomatic bacteruria.
o General measures like encourage for adequate hydration, frequent voiding, wiping from front to back of the perineum in females
References:
How would you manage this patient?
Recurrent UTI 3months post-transplant in female patient.
Elicit history:
pre-operative UTI, obstructed voiding, stone disease,
Bilateral native kidney shrunken kidney (?CGN) – non-obstructed system.
post-op – forgotten stent; sexual exposure; prophylactic antibiotics.
Immunological history – donor sister, probably well-matched. DSA not mentioned, probably negative — low immunological risk.
Immunosuppression: No mention about Induction; Tac and MMF dose to be assessed as per body weight – may need to reduce immunosuppression.
h/o rejection? use of high dose steroid ?
NODAT ? – sugar control
Antibiotics used, with duration.
To get fresh Urine Cultures and sensitivity; Urine for AFB; Candida (KOH / fungal culture)
Drug level
– Tacrolimus and MMF level
– CMV, BKV PCR quantitative analysis.
Urological evaluation:
· Uroflowmetry and PVRU
· Any neurological illness (PIVD),
· Imaging of transplant and native kidneys: CECT-KUB with IVU; look for forgotten stent, stone, obstruction.
Gynaecological check-up / pelvic exam– cystocele or prolapse; atrophic vaginitis; urethral caruncle.
· May need Cystoscopy – (stent removal, if done yet)
Treatment:
· Course of Antibiotic as per sensitivity – adequate dose, 2-3 weeks.
· Followed by Prophylactic antibiotics x 3-6months
o Cotrimoxazole (SEPTRAN-DS) shall cover PCP as well as Asymptomatic Bacturia.
o Ciprofloxacin 500mg OD bed time is alternative.
o Nitrofurantoin or Fosfomycin can be used if Cotrimoxazole / Ciprofloxacin resistant.
Ø Personal hygiene
Ø Plenty of liquids to drink – 1 glass every hour; void urine every 2-3 hours
Ø Avoid sexual intercourse or next 1 year; if at to participate, wash perinium and genitalia before sex; pass urine immediately after sexual intercourse.
Ø Additional antibiotic dose after intercourse – post-exposure prophylaxis
· Atrophic vaginitis à Premarin (Estrogen) vaginal cream application
· Candidiasis à Candid vaginal gel LA bed time + oral Fluconazole
· Correction of Cystocele and prolapse
· If voiding difficulty à Cystoscopy + urethral dilation
References:
1. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
2. Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9): e13507. Available at: https://pubmed.ncbi.nlm.nih.gov/30793386/
3. Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
Aydın S, Patil A, Desai M, Simforoosh N. Five compelling UTI questions after kidney transplant. World J Urol. 2020 Nov;38(11):2733-2742. doi 10.1007/s00345-020-03173-4. Epub 2020 Apr 7. PMID: 32266510.
This patient has recurrent UTI post- transplantation. Complete history about UTI before TX, remaining DJ, use of co-trimoxazole or not and physical examination are necessary. Ultrasonography of native kidneys and transplanted kidney with measurement of residual urine after void could be informative.
Further imaging with non-contrast CT scan to determine stone or cysts and VCUG to determine VUR is indicated. Urodynamic study including cytometry and uroflometery are necessary for bladder dysfunction or dyssynergia (DSD) with sphincter if there is high residue.
Urology consultation and cystoscopy should be performed as well.
The patient should continue co-trimoxazole to prevent UTI. Stent removal if indicated, should be done. Frequent and double voiding, wiping from front to back in females and drinking enough water are recommended. Treatment of UTI depends on its severity and recurrence and anatomical abnormalities. For example, treatment of infected cysts should be lasted for 4-6 weeks, but cystitis needs shorter courses of proper antibiotic therapy. In case of pyelonephritis, IV broad spectrum antibiotics are administered in hospital for 10-14 days and then switch to oral antibiotics or prophylaxis.
· How would you manage this patient?
Recurrent UTI 3months post transplant in female patient.
Careful history of recurrent UTI, obstructive uropathy, stone, stent removal, sexual history and use of prophylactic antibiotics.
Immunological history to assess risk of rejection, as we need to reduce immunosuppression specially if she is low risk of rejection.
Imaging of transplant and native kidneys, to see any stent, obstruction, stone.
Cultures and antibiotics used and their duration.
To consider prophylactic antibiotics if recurrent UTI.
Personal hygiene care and advice of cleaning of the perineal area and voiding of urine after intercourse.
Sometimes prophylactic antibiotics after intercourse may be used.
Proper management always starts by proper history taking :
-pre transplant history of recurrent UTI’s or stones .
-Family history
-Any history suggestive of neurogenic bladder .
-symptoms suggestive of vaginal infection .
-Drug history and proper assessment regarding the medications .
-Post surgical stent removal .
Investigations entailing:
-CBC
-CRP with titer
-FK level
-MMF level
-CMV , BKV PCR quantitative analysis .
-PAUS with assessment of the residual kidney volume .
-KUB
-CTUT without contrast accordingly .
Treatment of the cause , proper hydration , antibiotics accordingly , and long antibiotics prophylaxis may be needed.
Treatment of UTI in renal transplant patients should be according to the general guidelines for treatment of complicated UTI, but in the first 3 months after transplantation empirical treatment with the combination of amoxicillin and ciprofloxacin is recommended.
No recommendation can be made about changing immunosuppressive drugs from one class to another to prevent a recurrence of UTI.
In the choice of antibiotics for treatment of recurrent UTI the increased risk for ESBL-related infections should be considered. Therefore, earlier culture results and fluoroquinolone use in the last < 30 days have to be checked.
Removal of the urinary catheter should be done as soon as appropriate.
In case of a UTI the JJ stent should be removed if possible and the urine must be cultured.
In patients with recurrent UTI further investigations for anatomical abnormalities, bladder dysfunction or infection of the native kidneys should be initiated.
It is important to note that several antimicrobial agents can interact with immunosuppressants, especially with calcineurine-inhibitors. Therefore, interactions have to be checked.
https://richtlijnendatabase.nl/en/richtlijn/antimicrobial_therapy_of_uti_in_adults/uti_in_patients_with_a_renal_transplantation.html#:~:text=Treatment%20of%20UTI%20in%20renal%20transplant%20patients%20should,the%20combination%20of%20amoxicillin%20and%20ciprofloxacin%20is%20recommended.
Recurrent urinary tract infections (UTI) are a common clinical problem in kidney transplant recipients.
Due to the complex urological anatomy derived from the implantation of the kidney graft, the spectrum of the disease and the broad underlying pathophysiological mechanisms.
Recurrent UTI worsen the quality of life, decrease the graft survival and increase the costs of kidney transplantation.
Urinary tract infections (UTIs) are common among kidney transplant recipients in the first year after transplantation.
The reported incidence varies from 11.7% to 67.5% .
risk factors include :
older age, female gender, diabetes, history of acute rejection , delayed graft function, deceased donor kidney transplantation, longer duration of dialysis , and urological abnormalities .
Timing of stent removal and the use of antibiotic prophylaxis are important modifying factors.
UTIs similar are classified as follows:
(1)Asymptomatic bacteriuria: >105 colony-forming unit (cfu)/mL
(2)Simple (uncomplicated) UTI: positive urine culture in addition to any urinary symptoms such as dysuria, urgency, frequency, or suprapubic pain
(3)Complicated UTI: positive urine culture in addition to systemic symptoms such as fever, chills, and flank/allograft pain
(4)Complicated UTI with bacteremia
(5)Recurrent UTI: more than one UTI in the first 6 months.
Management
management of recurrent urinary tract infections in transplant patients requires a diagnosis of the underlying risk factor.
-It is recommended to Treat asymptomatic UTI in the first 6 months after transplantation, especially if the urinary stent is still in place.
– treat simple UTIs for one week, Quinolones 2nd and 3rd generation cephalosporin for 5-7 days are suggested for mild cases and for patients without risk of MDR
-treat more complex UTIs (especially MDRO) for more prolonged durations (two weeks with Ceftriaxone, piperacillin-tazobactam or cefepime or at least one week plus subsequent suppressive antibiotic therapy such as nitrofurantoin or fosfomycin in the case of susceptible organism).
-current prophylaxis protocol consists of Bactrim SS for 6 months which is conjunctly used as prophylaxis for Pneumocystis carinii pneumonia .
Reference
Ziad Arabi,1,2,3Khalefa Al Thiab,2,4Abdulrahman Altheaby.Urinary Tract Infections in the First 6 Months after Renal Transplantation. Volume 2021.
· How would you manage this patient?
Recurrent UTI is a common situation after transplantation and may be related to the etiology of the underlying disease that led to chronic kidney disease, such as polycystic kidneys, and the persistence of this native kidney after transplantation. Or another example is how much the bladder becomes atrophied by disuse.
Or the recurrent UTI may have its pathophysiology related to a post-transplantation event, requiring investigation regarding the patient’s hygiene habits, habits of the type of sexual intercourse, anatomical alterations, retention mechanisms, etc. And they should be investigated with USG of the urinary system, uroflowmetry and others.
Targeted antibiotic treatments will be prioritized and followed by prophylactic antibiotic options to try to decrease the number of recurrences.
How would you manage this patient?
Physical examination and Lab Tests for CBC, Tac level, DIC profile, CRP, RFTs, Blood cultures and microbiological analysis of urine culture are done.
the first line of management will be antibiotic treatment with fluoroquinolone and specific antibiotics (cephalosporin, nitrofurantoin, meropenem, piperacillin-tazobactam) against the identified causative agent post-identification.
Recurrent UTI is a common problem after renal transplantation
I would like to assess the patient with history and examination…. We need to assess the history of recurrent UTI pre transplant…Detailed history with relation to voiding pre transplant should be elicited…As the pre transplant this patient had bilateral small kidneys..There is no mention about the bladder pathology or PVR pre transplant….
If there are no such history we should do a detailed examination and investigation..
as she is 47 years there is no factor like post menopausal predisposing to recurrent UTI
We need to get USG KUB with post void residue…Uroflowmetry ..If there is significant PVR there could be urethral stricture….there could be history of recurrent Foley catheterization which could have lead to urethral stricture….urodynamic study is indicated if the uroflow patttern is indicative of underactive bladder…If there is significant PVR we should also rule out reflux by MCU under the cover of antibiotics….
Treatment of UTI with IV 3rd generation cephalosporins/IV meropenem/IV piperacillin tazobactum is needed to eradicate the infection
The duration of antibiotic needs to be emphasized…If ESBL bug is found it is imperative to continue IV for 14 days….
Antibiotic prophylaxiss is indicated for recurrent UTI post transplant… TMP SMX is used universally for all transplant recipients for PCP prophylaxis’s..It is supposed to work for UTI as well…If there is breakthrough UTI despite TMP SMX, we need to change the prophylaxsis…Tab nitrofurantoin 100mg at night, Tabh cephalexin 250mg at night are other alternatives….
It is important to screen for asymptomatic bacteriuria in the first 2 months after renal transplant as it has been found to be associated with increased incidence of graft pyelonephritis…. more than 2 months after transplant, there is no indication to treat ASB.
other general measures like toilet training like frequent voiding, double voiding in case of bladder dysfunction, perineal hygiene, avoidance of constipation, voiding after sexual intercourse, use of cranberry supplements maybe encouraged…
If there is recurrent symptomatic UTI impairing graft function we need to change or reduce the dose of antimetabolite namely MMF and change to AZA if required
How would you manage this pt?
UTI post kidney transplantation is a very common problem, and the classical symptoms of UTI such as frequency,urgency are abscent due to the state of IS and the surgical denervation of kidney and bladder .
For assessment of this pt. We need detailed history of the attacks of UTI before the development of ESRD, proper information about the anatomical and functional structure of the urinary system by doing US, VCUG, non-contrast CT scan , urodynamic study , cystoscope for any bladder or urethral problems, in edition to the usual screen for UTI by GUE and urine cultures, PCR for BK and CMV which may cause hematuria and urethral strictures .
Treatment start by empirical AB till optain the result of C/s
Make sure from removal of any stent within 4 weeks post transplant, removal of urinary catheters within the first week post transplantation.
Use of prophylactic septrin for 3-6 months or many use for long period.
In kidney transplant recipients, urinary tract infections are prevalent. In immunocompromised people, the cause of UTI is multifaceted. So, how should we handle our patient? -A thorough history of UTI episodes prior to developing ESRD is required, and if the septic focus is on the native kidneys, nephrectomy will be recommended. Infectious diseases consultant should be onboard for the optimal antibiotic therapy.
If an infection is diagnosed in immunocompromised patients, a treatment period of up to 21 days may be necessary. Some specialists recommend preventative antibiotics for 3 to 6 months, or even for life.
-The structure of the kidneys and urinary tract must be evaluated, specifically the post-voiding residual volume, because ESRD patients develop an atonic bladder after prolonged anuria.
-Functional and anatomical abnormalities may necessitate urodynamic studies for a more precise evaluation.
-Due to their effect on the tubules and ureter, which frequently manifests clinically as recurrent UTI, certain viral infections, in particular BK, should be evaluated as potential cause of hematuria/active urinary sediment.
How would you manage this pt?
REF;
How would you manage this patient?Recurrent UTI is 2 attack in 6 month or 3 attacks in one year
Need to know all risk facotrs that could precipitate recurrent UTI
Plain XR to exclude missed stent or stone
· Ultrasonography pre- and post-voiding
· Risk factors for UTI post transplantation: female, age, recurrent UTI pre-transplant
need to check the status of the patient BK virus status as it can leads to severe hemorrhagic cystitis and uratheral strictuers .
need to do US to check for any risk factors or strictuers , she will need urine culture specific antibiotics and also prophylaxis
Abnormal bladder also need to be ruled out by history and examination
5. A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
Issues/ concerns
– 47yo female, primary kidney disease unknown, KTx 3 months ago, donor sister
– medication: tacrolimus-based triple immunosuppression
– excellent kidney function
– symptoms of recurrent UTI
How would you manage this patient? (1-4)
– detailed history and thorough physical examination
– assess for risk factors: female sex, advanced age, recurrent UTI prior to transplant, VUR, urethral catheterization, ureteral stent placement, deceased donor kidney transplant, history of ADPKD, DGF
– multidisciplinary approach: infectious disease specialist
– baseline investigations: urine dipstick, urine m/c/s, blood cultures, CBC, ESR, CRP, UECs, LFTs, tacrolimus trough levels
– common organisms: gram negative uropathogens – E. coli,
Pseudomonas, Klebsiella, Enterobacter
– imaging:
· ultrasound to assess the graft kidney, native kidneys, postvoid residual volume
· non-contrast CT scan of the urinary tract for patients with recurrent UTIs and a normal ultrasound – to assess for strictures, stones, complex cysts
· if CT scan is unrevealing, rule out bladder dysfunction and outflow tract obstruction by measuring urine flow rate and performing urodynamic studies
· flexible cystoscopy to detect abnormalities in the urethra or bladder
· PET CT scan for ADPKD patients with suspected infected cysts in the native kidneys
– differential diagnosis: acute graft rejection
– rising serum creatinine, new onset or worsening proteinuria and hypertension are suggestive of graft rejection for which a kidney biopsy is usually performed
– fever and graft tenderness are suggestive of UTI
– Prevention: antimicrobial prophylaxis, early ureteral stent removal, monitoring for ASB
· Antimicrobial prophylaxis:
– TMP-SMX prophylaxis (prevents PCP and UTIs) for 6-12months posttransplant or
– Nitrofurantoin 100mg BD (eGFR >30) for one month or
– Cephalexin 500mg BD for one month
– Nitrofurantoin and cephalexin are alternative for UTI prophylaxis in patients allergic to TMP-SMX (for PCP prophylaxis the alternative is Atovaquone)
– avoid fluoroquinolones for prophylaxis due to development of resistance
· early ureteral stent removal:
– remove within 4 weeks to help prevent UTI posttransplant
· monitoring for ASB:
– can be performed in the first 1-2 months posttransplant, a 2nd
urine culture should be done to confirm persistent bacteriuria with the same pathogen before treatment decisions are made
– if positive (i.e., 2 consecutive urine cultures yielding >10⁵ CFU/ml of the same pathogen), treat with antibiotics for 5days as guided by the sensitivity pattern
– if the 2nd culture is negative or grows another organism do not give antibiotics
– do not treat asymptomatic candiduria unless the patient is at risk for complications or infection progression e.g., neutropenic patients, patients undergoing a urologic procedure
– no need to monitor for ASB 2months posttransplant since screening and treatment beyond this point is not associated with prevention of symptomatic UTI, pyelonephritis, bloodstream infection, graft rejection – it can lead to antibiotic misuse
– Management of symptomatic infections: obtain urine sample for m/c/s, then start with empiric therapy awaiting definitive therapy as guided by the sensitivity patterns
· simple cystitis: empiric therapy with
– a fluoroquinolone (ciprofloxacin 250mg BD, levofloxacin 500mg OD), or
– a 3rd generation cephalosporin (cefpodoxime 100mg BD, cefdinir 300mg BD) or
– amoxicillin-clavulanate 500mg BD or
– nitrofurantoin 100mg BD if eGFR >30
– duration of therapy 10-14days if the simple cystitis occurs earlier than 6 months posttransplant and 5-7days if it occurs 6 months posttransplant
· complicated UTI: empiric therapy with
– piperacillin-tazobactam 4.5g IV QID or
– meropenem 1g IV TID or
– a combination of vancomycin plus cefepime 1g IV TID
– treat for 14-21days, can switch to oral medications once the patient is symptom free and the antibiotic sensitivity patterns are known
· recurrent UTI: approach to treatment is similar to a case of initial UTI i.e.,
– evaluate for anatomic and functional abnormalities,
– counsel on behavioural modifications i.e., increased fluid intake, frequent voiding, postcoital voiding, contraception modification, wiping from front to back in females
– decision to give antibiotics should be individualised
· recurrent UTI is associated with an increased risk of graft loss and death
· fosfomycin is limited to patients with multidrug-resistant cystitis
· there is increased resistance to ciprofloxacin and TMP-SMX due to widespread use of antibiotic prophylaxis
References
1. Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clinical transplantation. 2005 Apr;19(2):230-5. PubMed PMID: 15740560. Epub 2005/03/03. eng.
2. Senger SS, Arslan H, Azap OK, Timurkaynak F, Cağir U, Haberal M. Urinary tract infections in renal transplant recipients. Transplantation proceedings. 2007 May;39(4):1016-7. PubMed PMID: 17524879. Epub 2007/05/26. eng.
3. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Current infectious disease reports. 2011 Dec;13(6):579-87. PubMed PMID: 21870039. Epub 2011/08/27. eng.
4. Singh R, Bemelman FJ, Hodiamont CJ, Idu MM, Ten Berge IJ, Geerlings SE. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis. 2016 Feb 25;16:90. PubMed PMID: 26912326. Pubmed Central PMCID: PMC4766656. Epub 2016/02/26. eng.
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
How would you manage this pt?
REF;
· The primary disease could be reflux and recurrent UTI
· Plain XR to exclude missed stent or stone
· Ultrasonography pre- and post-voiding
· Risk factors for UTI post transplantation: female, age, recurrent UTI pre-transplant, DM, UT abnormalities, length of dialysis, Duplicated ureter, ureteral stent, catheter, ATG, MMF.
· Exclude BK virus infection, then treat according to culture for at least 2 weeks up to 4 weeks.
· Prophylaxis of recurrent UTI:
1) TMP/SMZ 160/800 mg
2) Vaccination with inactivated E. coli, Morganella morganii, proteus, klebsiella, Enterrococcus faecalis
3) High water intake to excrete > 2l urine per day
4) Genital hygiene wiping after urination: vaginal>anal
5) Urine PH 5.8-6.5 ( vit C , methionine)
6) Vaginal oetrogen/Lactobacillus
7) Cranberry products
A lecture of Post Renal Transplantation Urinary Tract Infection By Prof. Mohamed Salah EldinZaki, Dean of National Institute of Urology and Nephrology
· How would you manage this patient?– Ensure that stent was removed- Urine analysis, culture & sensitivity.- CRP, cbc- Exclude for CMV & BK virus- US KUB, plain CT on the graft & native kidneys – Post voiding assessment & exclusion of urinary tract abnormalities – Treat as per culture results.- Patient mostly is on prophylaxis TMP/SMX – Patient education regarding good hydration , self-hygiene , frequent emptying of the bladder & to avoid constipation – consider lowering dose of MMF if recurrent UTI(2 or more in 6 months , or 3 or more in 1 year ) plus chronic suppressive AB therapy
UTI is common in female in general
more so after IS
one has to understand her risk of UTI prior to transplant
post of UTI is to be ruled out by USG KUB and detailed history like use of DJ in surgery , collection and urine leak
she will need urine culture specific antibiotics and also prophylaxis
Abnormal bladder also need to be ruled out by history and examination
How would you manage this patient
Definition of recurrent UTI means more than 2 episodes /6months or 3 episodes /year
Causes
· Relapse because of insufficient duration or inappropriate antibiotics
· Septic focus
· Anatomical abnormalities.
How to manage
–good history taking about episodes of UTI before reaching ESRD and if the septic focus is native kidneys nephrectomy will be indicated
–Refer to ID team for best antibiotic management and prolonged duration maybe needed up to 21 days in immunocompromised patients. Some experts use antibiotics prophylactic for 3-6 months or even lifelong.
–Evaluation of anatomy by US especially post voiding residual volume because ESRD patients after long period of being anuric they develop atonic bladder.
–if US normal CT or even urodynamics maybe needed for better assessment of functional and anatomical abnormalities
-Some viral infections especially BK should be excluded becbecause of its effect on tubules and ureter which usually presents clinically with recurrent UTI
References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
How would you manage this patient
Definition of recurrent UTI means more than 2 episodes /6months or 3 episodes /year
Causes
· Relapse because of insufficient duration or inappropriate antibiotics
· Septic focus
· Anatomical abnormalities.
How to manage
-good history taking about episodes of UTI before reaching ESRD and if the septic focus is native kidneys nephrectomy will be indicated
–Refer to ID team for best antibiotic management and prolonged duration maybe needed up to 21 days in immunocompromised patients. Some experts use antibiotics prophylactic for 3-6 months or even lifelong.
–Evaluation of anatomy by US especially post voiding residual volume because ESRD patients after long period of being anuric they develop atonic bladder.
-if US normal CT or even urodynamics maybe needed for better assessment of functional and anatomical abnormalities
-Some viral infections especially BK should be excluded becbecause of its effect on tubules and ureter which usually presents clinically with recurrent UTI
References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
Recurrent UTI post kidney transplantation in female 3-month post-transplant (assuming ureteral stent has been removed.
Management
References
1.Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship? J Clin Med. 2021 Dec 31;11(1):226. doi: 10.3390/jcm11010226. PMID: 35011966; PMCID: PMC8745876.
2.Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21. PMID: 30092153.
Post transplant patient with recurrent uti should be thoroughly evaluated including detailed history of anatomical urinary tract abnormalities like bladder diverticlui,past history of nephrolithaisis,previous history of recurrent uti before transplant and also history of whether stent post transplant has been removed or still there etc,followed by examination and then investigations like Ultrasonography with pre and post void residual volume ,then plain ct scan KUB plain or contrast study only if creatinine normal ,urodynamic studies which will help in bladder dysfunction or outflow tract problem.Cystoscopy in certain cases if above no cause found.
For recurrent uti treatment-first strategy should be to address all the risk factors and patient should be counselled to take plenty of fluids ,maintaining hygiene(wiping from front to back),frequent voiding and also post costal voiding.Empirically antibiotic I.e., fluoroquinolones for simple cystitis and broad spectrum antibiotic I.e., antipseudomonal penicillin or cabapenem or third generation cephalosporin for pyelonephritis and then tailoring the antibiotic according to culture and sensitivity.Frequent monitoring of graft function and tacrolimus level should be maintained around 5-7ng/ml and antimetabolite should be stopped.Surgical correction should be done if cause is anatomical problem in the urinary tract..In case of recurrent uti as in above case,patient should be given long term prophylactic treatment with trimethoprim-sulfamethoxazole .Drug drug interaction with the immunosuppressive should be bear in mind while prescribing antibiotic.
REFERENCES:
1-Chacon-Mora N., Diaz J. and Matia E. Urinary tract infection in kidney transplant recipients. Enferm Infecc Microbiol Clin, 2017;35(4):255-259
2-Kidney transplant handbook 6th edition
References:
· How would you manage this patient?
Recurrent UTI after kidney transplantation is common specially in female patients and risk factors include DM , female sex , abnormal urinary tract .
Indication for treatment are : 1-Symptomatic UTI with fever , urological symptoms such as dysurea , frequency or tender graft suggesting pyelonephritis.2-Detriorating graft function For this patient , as she has symptomatic UTI , so further evaluation is required with
1- CBC , ESR, CRP ,procalcitonin
2- Complete urine analysis and C&S.
3- Excluding BK nephropatrhy with BKV PCR and decoy cells in urine.
4- Evaluting graft function and albuminuria level
5- Monitor trough level of IS.
6- Non contrast CT : for diagnosis of pyelonephritis, nephrenophthesis .
– Treatment :- Start antibiotic therapy based on C&S . start empirical therapy with fluroquinolones ,and if suspected MDR gram negative infection consider antipseudomonal carbapenem, piperacillin-tazobactam or cefepime
· How would you manage this patient?
Recurrent UTI after kidney transplantation is common specially in female patients and risk factors for recurrent UTI include
female patients, DM ,urinary tract abnormalities . Indication for treatment are : 1-Symptomatic UTI with fever , urological symptoms such as dysurea , frequency or tender graft suggesting pyelonephritis.2-Detriorating graft function For this patient , as she has symptomatic UTI , so further evaluation is required with1- CBC , ESR, CRP ,procalcitonin 2- Complete urine analysis and C&S.3- Excluding BK nephropatrhy with BKV PCR and decoy cells in urine.4- Evaluting graft function and albuminuria level5- Monitor trough level of IS.6- Non contrast CT : for diagnosis of pyelonephritis, nephrenophthesis .- Treatment :- Start antibiotic therapy based on C&S . start empirical therapy with fluroquinolones ,and if suspected MDR gram negative infection consider antipseudomonal carbapenem, piperacillin-tazobactam or cefepime
How would you manage this patient?Recurrent UTI 3 months post-transplant.
Management should begin with a detailed history looking to identify risk factors for UTI.
Risk factors can be grouped into three categories that are:
This patient risk factors include female gender, she is 3 months post-transplant period of time where is high immunosuppression, chances are in the peri-operative period she had an indwelling catheter and also had a ureteral stent.
To confirm a diagnosis of UTI there should be clinical symptoms plus the growth CFU >105.
The presence of UTI in this kidney transplant recipient this makes it a complicated UTI.
Hence she should be on empirical antibiotic therapy as a waits culture and sensitivity results.
A midstream early morning urine sample should be taken for dipstick, culture and sensitivity.
Next should be to do any imaging to rule out any urological abnormalities like a forgotten ureteral stent.
Imaging of the native kidney should also be done to rule out any abnormalities- nephrocalcinosis.
Cystoscopy and urodynamic studies can be done to rule out urological abnormalities
Once the culture results are out then the antibiotics should be tailored to the sensitivity and culture results.
This patient with recurrent UTI it is prudent to look for other factors that make her susceptible like DM.
Also the patient should be on UTI prophylaxis TMP/SMX for at least 6 months and the patient should be taught on genital hygiene.
References
Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship?Jens Strohaeker, Victoria Aschke, Alfred Koenigsrainer, Silvio Nadalin and Robert Bachmann
Prof Salah Zaki lecture
Risk factors for UTI in recipient classified in three categories:
Preoperative factors:
Intraoperative factors:
Postoperative factors:
Management :
Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
–Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
Scenario:
47F, ESRD secondary to unknown cause (atrophic native kidneys), living donor renal transplant 3 months ago, on triple immunosuppression with excellent graft function. Recurrent presentations (number not specified) with symptoms of urinary tract infection (UTI)
Key considerations from the scenario:
· The patient is only 3 months out from her transplant operation so she is in a period of maximum immunosuppression and is likely to have had interventions during this time such as urinary catheter removal and ureteric stent removal which could have increased her incidence of UTI. The highest incidence of UTI is in the first 3-6 months post-transplantation [1]
· She has excellent allograft function so it is likely she has good fluid balance status but we do not have confirmation of her recent urine output volumes or know whether she is staying well hydrated
· We do not know the original cause of her ESRD (reflux nephropathy is in the differential) – important to remember the source of infection could be her native kidneys or her renal allograft – does she have any known underlying structural abnormality of her renal tract?
· We do not know whether she was dialysis-dependent prior to transplantation (i.e. did she have residual urine output or not prior to transplantation). This is potentially relevant as this might affect patient behaviours/highlight need for patient intervention regarding self-care measures to avoid UTI. Additionally, prolonged dialysis duration and anuria (leading to bladder atony) are risk factors for post-transplant UTI
· We know she had ‘symptoms’ of UTI but we need to confirm what these symptoms were and whether there was associated evidence of systemic infection or confirmed infection on urine culture
· The patient is on triple immunosuppression so she may experience more severe clinical course if she does get an infection- similarly if she is having repeated admissions with ?sepsis necessitating temporary suspension of her anti-metabolite this could be putting her at unacceptable risk of rejection and approaches such as prophylaxis may need to be considered
Management:
1. History and basic examination including assessing UTI risk factors
Questions I would wish to confirm on taking history from patient:
· Describe the symptoms she is getting
· How many separate episodes have there been? What is their relationship to any procedures on the urinary tract e.g. when was her urinary catheter removed? Has she had a ureteric stent removal?
· Has she had any antibiotic treatment?
· Have the UTIs been proven on urine culture and were they sensitive to the antibiotics given? (‘recurrent’ infection could also be same infection with ineffective treatment)?
· Did she have any symptoms of systemic infection e.g. fever? Any pain over her allograft?
· Any symptoms of pyelonephritis such as vomiting, ascending pain?
· What is her fluid intake like? How much urine is she passing?
· Any issues with incontinence or voiding difficulties?
· Did she experience recurrent UTIs prior to her transplant?
· Was she on dialysis prior to transplant and if so for how long?
· Any history of diabetes or renal stones (factors that would increase her risk of developing UTI alongside her female gender)?
· Consider whether sexual history/STI screen is indicated as chlamydia, gonorrhoea and genital herpes can be alternative causes of dysuria
2. Initial investigations:
· Bedside observations including temperature, blood pressure and heart rate
· Urinalysis (assess pyuria)
· Mid-stream urine for culture and sensitivity
· Ultrasound renal tract (any evidence of obstruction, abscess)
· Blood tests including capillary blood glucose (steroids being part of her triple immunosuppression) and full blood count, renal function and c-reactive protein. Consider testing for CMV and BK levels
· Blood cultures if symptoms or signs of pyelonephritis
3. Treatment options
A. Non-pharmacological measures
Patient education:
· Advice on preventative measures
– Frequent voiding
– Ensuring complete bladder emptying
– Staying well hydrated
– Post-coital voiding
– Hygiene measures (wiping front-back)
B. Pharmacological measures
Simple cystitis
· For simple cystitis this would usually be a 5-7 day course of oral antibiotics as per local microbiology guidelines (pending sensitivity results) although there is some guidance to suggest that in the early post-transplant period (as with this patient) this should be 7-10 days [1]
· This may be followed by watch and wait approach to see how many further episodes occur (having implemented patient education measures etc)
Pyelonephritis/signs of systemic infection
· Intravenous antibiotics may be required whilst awaiting confirmation of sensitivities. Total duration of antibiotic course 2-3 weeks
· The patient’s immunosuppression will need to be reviewed and anti-metabolite may be temporarily suspended
· Further imaging may be required to exclude nephrolithiasis, abscess etc.
Longer term prophylaxis:
· If confirmed recurrent UTI (see below) a discussion with the local microbiology team might be relevant to consider a single daily low-dose antibiotic (alternating every 2 weeks) as prophylaxis or a post-coital antibiotic if the infections are related to sexual intercourse – this must be balanced against the risks of developing drug-resistance, c.difficile diarrhoea and other potential side effects of specific antibiotics e.g. nitrofurantoin and pulmonary toxicity [1]
Defining recurrent UTI in the renal transplant patient
· 2 or more confirmed urinary tract infections within 6 months
· 3 or more confirmed urinary traxt infections within 1 year
Alongside the above described patient education measures and pharmacological interventions, a diagnosis of recurrent UTIs in a renal transplant patient should prompt evaluation for any anatomical or functional abnormalities [1].
· Post-void residual ultrasound scan to exclude structural abnormality
· If no structural abnormality – proceed to voiding cystourethrography to evaluate for vesicoureteral reflux
· If no vesicoureteral reflux identified consider urodynamic study to evaluate for any bladder or outflow obstruction
Reference:
1. Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. Available at: https://pubmed.ncbi.nlm.nih.gov/30793386/
How would you manage this patient?
Definition of Recurrent UTI;
-Two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
Diagnostic Evaluation;
-Ultrasonography of the urinary system with measurement of a postvoid residual is a reasonable first step for most patients, given its ease and lack of side effects.
-In patients with recurrent UTI who have unrevealing ultrasonography, we perform a noncontrast computed tomography (CT) scan of the urinary tract.
-Although the absence of contrast reduces the sensitivity of the CT scan, we avoid contrast to prevent nephrotoxicity.
-These imaging studies can identify urinary tract strictures, stones, and complex cysts.
-If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction,
-In consultation with urology; flexible cystoscopy may be required to detect abnormalities in the urethra or bladder.
Approach to prevention;
-In kidney transplant recipients with recurrent UTI, we take the following approach to prevention:
-All patients should be evaluated for anatomic or functional abnormalities of the urinary tract, which may increase the risk of infection.
-All patients should be counseled on the risk factors for recurrent UTI and behavioral changes that might reduce the risk.
-Such behavioral changes are similar to those for nontransplant patients with recurrent UTI and include increased fluid intake, frequent voiding, postcoital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females).
-Some experts administer prophylactic antibiotics to selected patients with recurrent UTI, the decision to administer long-term antibiotic prophylaxis should be individualized.
-Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the TMP component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant; some experts continue TMP-SMX prophylaxis indefinitely.
-For postmenopausal females, topical estrogen may prevent recurrence of UTIs.
-Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
-Do not routinely use strategies such as cranberry juice or probiotics due to the lack of clear data supporting their use in transplant recipients.
Treatment of recurrent episodes;
-Each episode of simple cystitis or complicated UTI should be treated with an appropriate duration of antibiotic therapy.
-In some situations, a longer course may be necessary for patients with persistent/recurrent UTI with the same organism.
-As an example, recurrent UTIs associated with an indwelling source (such as infected cysts in native kidneys) can require up to four to six weeks of therapy.
-In other situations, therapy for recurrent UTIs can be discontinued after a shorter period, and the patient can be transitioned to prophylactic antibiotics.
Early ureteral stent removal;
-Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation.
-One analysis found that the risk of UTI could be reduced with early (within two weeks) stent removal compared with late stent removal, particularly if a bladder indwelling stent was used.
References;
–Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
–Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
–Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
–Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
–Thompson ER, Hosgood SA, Nicholson ML, Wilson CH. Early versus late ureteric stent removal after kidney transplantation. Cochrane Database Syst Rev 2018; 1:CD011455.
How would you manage this patient?
Symptomatic UTI after KTX is defined as a ‘complicated’ UTI, as are all UTIs after surgery of the urinary tract. Furthermore, other criteria defining ‘complicated’ UTI, such as occurrence in an immunodeficient patient, are fulfilled in the situation after KTX
Treatment of recurrent episodes — Each episode of simple complicated UTI should be treated with an appropriate duration of antibiotic therapy
a longer course may be necessary for patients with persistent/recurrent UTI with the same organism. As an example, recurrent UTIs associated with an indwelling source (such as infected cysts in native kidneys) can require up to four to six weeks of therapy. In other situations, therapy for recurrent UTIs can be discontinued after a shorter period, and the patient can be transitioned to prophylactic antibiotics.
Prevention of UTI after kidney transplantation
management of structural and functional urinary tract abnormalities in the pre-transplant period, which sometimes even justifies nephrectomy of the native kidneys, especially in patients with recurrent UTI in patients with VUR to their native kidneys
The patients should be educated for basic preventive measures like hydration and frequent voiding.
Radiological studies should be implicated to rule out the anatomical defects, obstruction, calculi and retained foreign bodies.
Diagnosis
urine analysis (dipstick/sediment) and always a urinary culture.
BK and/or CMV infection should be excluded.
(C-reactive protein, leucocytes) might help in differentiating between infection and rejection in a dysfunctional graft
The level of immunosuppression must be reevaluated to exclude over-immunosuppression.
Imaging (ultrasonography) should exclude postrenal causes of infection (urolithiasis, urinary tract obstruction, ‘forgotten’ ureteric stent, etc.)
TREATMENT
Complicated UTI
treat with intravenous (IV) antibiotics that cover both gram-negative and gram-positive bacteria initially, unless signs and symptoms are mild enough such that outpatient oral antibiotics with high bioavailability can be started. If the urine culture reveals candiduria, treatment should be tailored according to the identified Candida species
Antibiotic selection – Empiric antibiotics should have adequate coverage against P. aeruginosa, enteric gram-negative organisms, and Enterococcus species. Commonly prescribed treatment regimens include
•Piperacillin-tazobactam 4.5 g IV every six hours, or
•Meropenem 1 g IV every eight hours, or
•Combination therapy with vancomycin plus cefepime 1 g IV every eight hours.
Antibiotic dosing must be adjusted according to kidney function.
●Duration of therapy – complicated UTI with 14 to 21 days of antibiotic therapy
Oral agents may be substituted for IV therapy once the patient is free of symptoms and antibiotic susceptibilities are known.
Fluoroquinolone-calcineurin inhibitor drug interactions, should be anticipated,especially with the higher dose of ciprofloxacin typically used for treatment of pyelonephritis, and dose reduction of the calcineurin inhibitor is often necessary to prevent calcineurin inhibitor toxicity.
Surgical therapy of recurrent UTI after KTX must aim at long-term optimization of urinary drainage. • This includes (besides early removal of ureteric stents and bladder catheters)
Treatment of obstructed transplant ureters, urolithiasis,
The causes of bladder outlet obstruction include:
reflux is common and appears in >80% of cases . Nephrectomy of native kidneys has been used successfully in refluxive kidneys to reduce recurrent UTI
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
For postmenopausal females, topical estrogen may prevent recurrence of UTIs
recurrent UTI early post transplant
A) Recipient related:
neurogenic bladder or incmplete voidingureteric refluxpoor hygine like wiping from back to frontB) Donnor related
infected graft with resistnat or uncommon organsim like TBC) surgery related
poor anastomotic siteD) Others like BK virus infection or heavy immunosupression
****Steps:
look for urine MC&S, is it the same organsim every time or different organsimsare we ttt with the appropritat Abx type and durationScan like simple US scan, cystoscope to urodynamic studieslook BK virus PCRConsider prophylactic AbxConsider cutting down immunosupression with risk of rejection in mind
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation.
Urinary tract infections (UTI) are defined as the growth of 105 colony forming units on a proper urine sample) in the presence of symptoms such as dysuria, urinary frequency or localized pain(the incidence of a UTI ranges from 4–80%.
Recurrent UTI is defined as ≥ 2 episodes within 6 months or ≥ 3 episodes within 1 year.
Recurrent UTI is associated with an increased risk of graft and patient loss.
Risk factors of UTIs after kidney transplantation include:
Female gender
Advanced age
Pre-transplant UTIs
Prolonged period of haemodialysis before transplantation
Immunosuppression
Management of the Recurrent UTI in kidney transplant recipients
Exclude functional or anatomical structural abnormality.
Determine the source of UTI, (native or allograft kidney).
Details history.
Immunosuppressants regimen intensity.
Workup of the current episode of the UTI:
Detailed family history, personal history of recurrent UTI since childhood and pre-transplantation (some female patient has increased susceptibility /receptivity for adherence of micro-organism
Detailed history of the recurrent UTI, diabetes mellitus, urinary tract anomalies, and the waiting time before KTX. History of vesicoureteral reflux, History of polycystic kidney disease
The details of previous urine culture and sensitivity results and any history of drug resistance, if available.
Details history, Gynecological history by pelvic examination to check for cystoceles, vaginitis, vaginal atrophy, and prolapse of pelvic organs.
Details history of constipation, neurological diseases, any association with sexual activity, hygiene, hydration status and menopause (vaginal mucosal quality)
The presenting symptoms, for example painful voiding, urgency, frequency, pain of the lower abdomen, hematuria, and fever.
Physical examination, including tenderness of the graft & the presence of urinary catheters.
Prophylactic antibiotic use, for example TMP-SMZ for PJP.
Genital hygiene (method of wiping after urination), proper hygiene / perineal sweeping from anterior to posterior
Double kidney transplant history, leading to an increase in JJ stents.
Urinalysis (dipstick/sediment) & urinary culture.
Exclude BKV and CMV infection by blood PCR.
CBC, Lytes, creatinine CRP, septic screen
Exclude over-immunosuppression: review levels of IS medications.
Ultrasonography of the native urinary system and the graft to exclude post-renal causes (stones, obstruction, ‘forgotten’ ureteric stent, etc.).
CT-KUB, Cystoscopy, +/- Urodynamic study to r/o any anatomical or functional abnormalities.
The most common findings include.
Ureteral reflux.
Strictures at the ureterovesical junction.
Neurogenic bladder, and sub vesical obstruction, especially in men aged over 60 years, clean intermittent catheterization might be required.
Measures to prevent UTI in Kidney Transplant.
A single shot antibiotic is administered prior to incision.
Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis.
To remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection to remove biofilms.
Use of TMP at 160 mg & SMZ at 800 mg for 6 months, especially in high-risk patients (e.g., urinary reflux, &/or voiding disorders), is recommended.
Good Hydration; 2 L urine out/day
Treatment Of Constipation
Proper Hygiene / Perineal Sweeping from Anterior to Posterior
Post Coital Voiding
If Dry Vaginal Local Estrogen Therapy
Prophylaxis Ab:
Chronic Suppressive Low Dose Ab.
Post Coital Single Dose Ab.
Empirical Short Course (3-5days) Ab.
Prophylactic antibiotic regimens:
Use of TMP at 160 mg + SMZ at 800 mg for 6 months, especially in high-risk patients (e.g., urinary reflux, &/or voiding disorders), is recommended.
Ciprofloxacin was later reserved for treatment rather than prophylaxis. The 2019 FDA warning against the use of fluoroquinolones in KT recipients.
Fosfomycin showed preventative efficacy.
TMP-SMX is the best studied drug.
Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to.
TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Class of antibiotics used to treat UTI in the post-transplant period.
Penicillin’s (49%), Cephalosporins (36%), Fluoroquinolones (16%), Carbapenems (4%).
Common Practice Medications.
Outpatient with uncomplicated UTI, quinolones for 7 days are recommended as empirical treatment till the culture results or TMP-SMX for 7-14 days.
Complicated and hospitalized patients, 3rd generation cephalosporin IV, till the culture results.
ESBL cases the carbapenems (imipenem or meropenem) are advised till culture results.
Native kidney as a source of recurrent UTI:
Consider nephrectomy if resistant to treatment and there is a risk of graft dysfunction.
Follow up:
Urine Culture for screening for ASB.
Prophylaxis treatment with TMP-SMX for at least 6 months with monitoring bacteriuria assessment, and culture guided.
References
UpToDate
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011 Mar 1;52(5): e103-e120.
Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21. PMID: 30092153.
Markus Giessing, Urinary tract infection in renal transplantation, Arab Journal of Urology (Official Journal of the Arab Association of Urology) doi: 10.1016/j.aju.2012. 01.005
Olenski S, Scuderi C, Choo A, Bhagat Singh AK, Way M, Jeyaseelan L, John G. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrol. 2019 Dec 27;20(1):479. doi: 10.1186/s12882-019-1666-6. PMID: 318818
Urinary Tract Infection is a very common in kidney transplantation and it can present as
· Asymptomatic bacteriuria,
· Cystitis
· Pyelonephritis
Major risk factors of early recurrent UTI infection in post renal -transplant are;
· Female gender
· Old age
· Prolonged catheterization, or stent complication
· Post-surgical complications like urine leak, lymphocele or infected hematoma, infected peri nephric collection.
· Duration of HD with NO residual renal function which leads to low bladder capacity,
· Previous history of recurrent UTI prior to transplantation.
· Kidney stone, pyelonephritis or dysfunctional UB.
· Anatomical abnormality including low capacity UB or UV reflux
· DM and neurogenic bladder
· Immunosuppression increased the risk of infection.
This patient should be evaluate for recurrent urinary tract infection if she has more than three Infections in the first post-transplantation year
1. Urological review and assessment for dysfunctional Urinary Bladder by urodynamic studies and post-voiding residual volume.
2. Anatomical anomalies abdo and pelvic U/S including native kidneys for any obstructive or structural abnormalities, collection,
3. urine culture and identify MDR microorganism choice should be according to the culture and sensitivity and be given for appropriate duration especially for MDR microorganism,
4. In female patient particularly post-menopausal should be referred to gynecology consult.
The management of recurrent urinary tract infections in kidney transplant patients requires a proper diagnosis of the underlying etiology.
Investigation
Preliminary test -Urine c/s, cbc, rft, blood c/s, tacrolimus level
Empiric antibiotic treatment depends on clinical presentation and must be based on local epidemiological data and the patient’s history of previous resistant organisms and previous antibiotic therapies prescribed in previous months. later after culture and sensitivity the antibiotic may be changed.
Antibiotics
Low-tract UTI (cystitis); Fosfomycin, ciprofloxacin, amoxicillin/clavulanate or 2nd/3rd generation oral cephalosporins for 5-7 days.
Moderately severe UTI, including acute pyelonephritis; Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days.
Severe infection and/or septic shock, carbapenem plus vancomycin considered, completing 14-21 days.
To find the cause of recurrent UTI
Check for USG Post micturating residual urine volume and to rule out the structural abnormality need to do CT KUB
CT KUB
-Structure abnormalities- corrective measure/surgery
-No structure abnormalities-voiding cystourethrogram
Voiding cystourethrogram
-Vesicoureteral reflux-corrective measure /surgery
-No Vescio ureteral- then do urodynamics
Urodynamics
-Presence of bladder dysfunction need (medical management),
-Presence of outflow obstruction need (surgical management)
Prevention
Behavioral changes (increased fluid intake, holding urine, wiping technique in female, frequent voiding, postcoital voiding)
Continuous Intermittent self-catheterization- for residual urine
Urine dipstick at home for monitoring uti
For postmenopausal females, topical estrogen
TMP-SMX prophylaxis to prevent recurrent UTI (reflux, transplantation, voiding disorder)
Reference
Post renal transplant UTI Lecture, Prof Mohamed Salah Eldin Zaki
Marta Bodro, Laura Linares, Diana Chiang, Asuncion Moreno & Carlos Cervera
(2018): Managing recurrent urinary tract infections in kidney transplant patients, Expert Review of Anti-infective Therapy, DOI: 10.1080/14787210.2018.1509708
In such a patient, I need to check for VUR, which can be estimated by mega ureters, etc. Can be missed on USG as the kidneys are functioning, but we need to sterilize the urine (antibiotics according to culture) , followed by voiding cystography to explore reflux to native and or transplanted kidneys. Teflon injection is not very successful but can be the first step, followed by neoureterotomy in case VUR is diagnosed.
Recurrent UTI means that she has at least two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
In such case we need to rule out any
STRUCTURAL OR FUNCTIONAL ABNORMALITY
We have to perform an ultrasound of the kidney allograft, native kidney, and postvoid bladder
.
In patients with recurrent UTI who have unrevealing ultrasonography, we need to perform a non contrast computed tomography (CT) scan of the urinary tract.
These imaging studies can identify urinary tract strictures, stones, and complex cysts. If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction, in consultation with urology.
Flexible cystoscopy may be required to detect abnormalities in the urethra or bladder
•
Complicated UTI – For transplant recipients with a complicated UTI, we suggest empiric therapy with piperacillin-tazobactam, meropenem, or combination therapy with vancomycin plus cefepime rather than other agents used in nontransplant patients (up to date)
All patients should be counseled on the risk factors for recurrent UTI and behavioral changes that might reduce the risk.
Such behavioral changes are similar to those for nontransplant patients with recurrent UTI and include increased fluid intake, frequent voiding, postcoital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females).
PROPHYLACTIC ANTIBIOTICS CAN BE INDIVIDUALIZED
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
Risk factors for UTI in KTR can be classified in three main categories:
Management :
*The management of recurrent urinary tract infections in kidney transplant patients requires a proper diagnosis of the underlying mechanism.
*Early identification of structural or functional urological abnormalities is important for successful management.
Reference :
1. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732. doi: 10.1080/14787210.2018.1509708. Epub 2018 Aug 21
2. Recurrent Urinary Tract Infections in Kidney Transplant RecipientsSubhashis Mitra & George John Alangaden Current Infectious Disease Reports 13, pages 579–587 (2011)
Thankyou well done
Thank you Prof Dawlat
⭐⭐⭐Management of recurrent UTI after kidney transplantation involves the management of any modifiable risk factors:
_ exclusion of any anatomical problems as VUR on native kidney or the allograft (diagnosed by MCUG and ttt by surgical ureteric reimplantation) , neglected stone (diagnosed by US or CT and removed by ESWL or cystoscopy according to the size of the stones), missed or forgotten DJ stent (diagnosed by US /KUB and must be removed by ureteroscopy) , dysfunctional voiding (diagnosed by increased PVR and urodynamic studies, and treated by frequent and timed voiding plus or minus CIC).
_Exclude gynecological causes of UTI and ensure good hygiene (wiping from front to back)
_start treatment with empirical antibiotics (ciprofloxacin or ceftrixaone ) till the result of culture and sensitivity …then shift to culture based antibiotics.
_ Consider multidrug resistant organism.
_consider SMX-TMP prophylaxis for aat least 6 months after treatment of the current infection to decrease the risk of recurrence.
_general measures to decrease UTI as increase water intake, frequent voiding.
_check for diabetes (random glucose and HBA1C) and also for over immunosuppression (check trough level of CNI and MMF).
Yes, exclusion of anatomic abnormalities.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Thanks dear professor
How would you manage this patient?
This female recipient with early recurrent UTI (3 months) after kidney transplantation with no clear cause of primary disease.
UTI is a very common infection after kidney transplantation and it’s in the range of asymptomatic bacteriuria, cystitis pyelonephritis (1), risk factors of early recurrent UTI infection include female gender, old age, prolonged catheterization, or DJ stent complication like migration or missed piece,post-surgical complications like urine leak, lymphocele or infected hematoma, infected perinephric collection also the duration on HD with risk of low bladder capacity, and previous history of recurrent UTI prior to transplantation, or kidney stone, pyelonephritis or dysfunctional UB, or anatomical abnormality including low capacity UB or Ureterovesical reflux, in addition, history of DM and the control and possible neurogenic bladder, immunosuppression medication and CNI trough level as intense IS can affect the immune response and increased the risk of infection, use of prophylaxis AB and compliance. So this patient if have more than 3 episodes of UTI in the first year post-transplantation fit the definition of recurrent UTI and needs to be evaluated including urological review and assessment for dysfunctional UB by urodynamic studies and post-voiding residual volume, abd, and pelvic US including native kidneys for any obstructive or anatomical or structural abnormalities, collection, urine culture and identify MDR microorganism and the AB choice should be according to the culture and sensitivity and be given for appropriate duration especially for MDR microorganism, being a female should also be referred to gynecology to rule out any local cause of recurrent UTI.
References
1. Transplantation Proceedings Volume 45, Issue 4, May 2013, Pages 1590-1592
2. Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
3 Aydın S, Patil A, Desai M, Simforoosh N. Five compelling UTI questions after kidney transplant. World J Urol. 2020 Nov;38(11):2733-2742. doi 10.1007/s00345-020-03173-4. Epub 2020 Apr 7. PMID: 32266510.
4. Kidney transplant handbook 6th edition.
I appreciate your well-referenced reply.
Please use headings and sub-headings to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
How would you manage this patient?
To manage this case, I will consider the following points:
Workup of the current episode of the UTI:
Review the details of the previous episodes:
References
I appreciate your well-referenced reply.
Management of the Recurrent UTI in kidney transplant recipients
Workup
The most common findings include;
Medication
Native kidney as a source of recurrent UTI
Follow up
References
I appreciate your well-referenced reply.
Management of recurrent UTI in the post-transplant period
1. Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation.
2. UTIs are defined as the growth of 105 colony forming units on a proper urine sample) in the presence of symptoms such as dysuria, urinary frequency or localized pain(the incidence of a UTI ranges from 4–80%)(1).
3. To diagnose UTI in the post-transplant period, the followings are required:
a) Urinalysis, CBC, RFT and CRP.
b) Urine for culture and sensitivity panel.
c) USS of the native urinary system and the graft.
4. Measures to prevent UTI in KTR(1):
a) A single shot antibiotic is administered prior to incision.
b) Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis.
c) To remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection in order to remove biofilms.
d) Prophylactic antibiotic regimens:
· Ciprofloxacin was later reserved for treatment rather than prophylaxis. The 2019 FDA warning against the use of fluoroquinolones in KT recipients.
· Fosfomycin showed preventative efficacy.
· TMP-SMX is the best studied drug.
· Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to.
5. TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients(1).
6. Class of antibiotics used to treat UTI in the post-transplant period(2):
· Penicillins (49%).
· Cephalosporins (36%).
· Fluoroquinolones (16%).
· Carbapenems (4%).
References
1. Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship? J Clin Med. 2021 Dec 31;11(1):226. doi: 10.3390/jcm11010226. PMID: 35011966; PMCID: PMC8745876.
2. Olenski S, Scuderi C, Choo A, Bhagat Singh AK, Way M, Jeyaseelan L, John G. Urinary tract infections in renal transplant recipients at a quaternary care centre in Australia. BMC Nephrol. 2019 Dec 27;20(1):479. doi: 10.1186/s12882-019-1666-6. PMID: 31881863; PMCID: PMC6935183.
Thank you for your input. You concentrated on Antibiotic treatment with different options. You do not need to explore the reasons behind the recurrence of UTI in this patient? significant residual urine, urodynamics, vesicoureteric reflux, multiple stones in the native kidneys etc.
A case of recurrent UTI :Two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
UTIs are associated with significant morbidity among transplant recipients, especially if they occur early after transplantation.
History (cause of original disease, stone former, recurrent UTI, and other co-morbidities).
Urine analysis , Urine culture and sensitivity.
We perform an ultrasound of the kidney allograft, native kidney, and post-void bladder for patients with recurrent UTI.
we perform a non-contrast computed tomography (CT) scan of the urinary tract which can identify urinary tract strictures, stones, and complex cysts.
If the CT is also unrevealing, measurement of urine flow rate and urodynamic studies can be performed to identify bladder dysfunction or outflow tract obstruction, if any abnormalities detected Urologist should be involved.
Flexible cystoscopy may be required to detect abnormalities in the urethra or bladder.
Treatment of UTI according to culture result and some require up to four to six weeks of therapy
Antimicrobial prophylaxis.
Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the trimethoprim component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant.
Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation.
Behavioral changes such as behavioral changes are similar to those for non-transplant patients with recurrent UTI and include increased fluid intake, frequent voiding, post-coital voiding, contraception modification (in sexually active patients), and wiping from front to back (in females).
Some transplant programs use methenamine hippurate (1000 mg twice daily) with or without ascorbic acid (1000 mg twice daily) for prevention of recurrent UTI.
Adjusting the immunosuppression medications.
References:
1-Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13507.
2-Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis. 2019;21(3):e13063. doi:10.1111/tid.13063.
3-Urinary tract infection in kidney transplant recipients, UpToDate 2023.
Thank you. Prophylaxis with TMP-SMX can be administered as one double-strength tablet (160 mg of the trimethoprim component) daily or three times per week or one single-strength tablet daily and continued for six months to one year post-transplant.
Do you think this patient is not already on TMP-SMX for 6 month already for PJP prophylaxis?
Thanks prof .
I thought she was already taking MP-SMX for PJP prophylaxis. my point that generally using this group also have prophylactic role in UTI and looking for a predisposing factor in this scenario is the main point.
Recurrent UTI
WORK UP:
Management:
2.specific treatment according to any anatomical or functional abnormality will found
3.three approaches:
Evaluation should be done to exclude structural or anatomical abnormalities and this includes
Treatment of symptomatic recurrent UTI is the same as ordinary symptomatic UTI but
Strategies to prevent recurrence of UTI
References
1. Britt NS, Hagopian JC, Brennan DC, et al. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant 2017; 32:1758.
2. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep 2011; 13:579.
3. Green H, Rahamimov R, Gafter U, et al. Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 2011; 13:441.
4. Singh R, Bemelman FJ, Hodiamont CJ, et al. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among renal allograft recipients: a retrospective before-after study. BMC Infect Dis 2016; 16:90.
5. Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transpl Infect Dis 2014; 16:261.
6. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis 2019; 21:e13063.
management:
1- urine analysis and culture
2-BK and CMV should be excluded
3-CRP, CBC, graft function
4- imaging study KUB, u/s abdomen and pelvis, non contrast CT to exclude or diagnose and structural abnormalities or obstruction or missed stent, stones.
5- trough level of tacrolimus to avoid over immunosuppression
6-confirmation of diagnosis and early treatment is very important to prevent pyelonephritis of the graft and endanger the life due to sepsis
7-Fosfomycin for 2-4 weeks
8- renal dose adjustment needed
9- interaction between immunosuppression CNI and gentamycin or TMP-SMZ, may increase the toxicity
10-surgical treatment of obstruction
11-remove urinary cath, or stent
Dr Mohamed Salah lecture
UTI is the most common infection in early period post KT. It may lead to significant morbidity with recurrent hospitalization, acute T cell-mediated rejection, impaired allograft function, and allograft loss.
Recurrent UTI defined as : Two or more episodes of UTI in six months, or three or more episodes of UTI in one year.
Risk factors includes: female sex, advanced age, recurrent UTI prior to transplant, urinary tract anomalies, VUR, urethral catheterization, ureteral stent placement, DD kidney transplant, ADPKD, DGF and immunosuppressed state.
Evaluation of recurrent UTI:
The index case has ESRD and bilateral atrophic kidneys with recurrent UTI, VUR should be considered.
-History:
Nature of recurrent UTI (cystitis or complicated UTI) and the current symptoms.
pre-transplant recurrent UTI, voiding habits, constipation.
use of CIC, ask about ureteral stent (removed or not)
compliance to TMP-SMX
Management:
A .Identify the reason for recurrent UTI
-Aim to rule out existence of anatomical or functional changes such as VUR, neurogenic bladder and stenosis of the ureterovesical junction or sub-vesical obstruction (especially in male).
-Urology team and transplant surgeon involvement.
– KUB US evaluate both allograft and native kidneys; UT dilatation, stone, stent, post void residual , complicated cysts, ureterocele.
– non-contrast CT for detailed evaluation if US was inconclusive; can identify urinary tract strictures, stones, and complex cysts
– VCUG: to rule out VUR.
– Uroflowmetry and urodynamic considered in case of clinical suspicion of bladder dysfunction or outflow tract obstruction
– Cystoscopy may be required.
-Evaluate for prostatitis in male
B. Active infection:
-For each episode evaluate the patient clinically; severity of symptoms, assess the needs for hospitalization
-Urine analysis (dipstick/sediment) and always a urinary culture.
-Evaluate kidney function (any change from baseline)
– CBC, CPR, Blood culture.
– BK and CMV infection should be excluded.
-Treatment of acute episodes should always be based on the local epidemiology of antibacterial resistance.
– Must consider interaction with immunosuppression drug; nephrotoxicity of TMP-SMZ and gentamicin in recipients taking CNI.
– Empiric therapy should be started taking into account previous antibiotic therapies prescribed in previous months.
– low-tract UTI (cystitis); Fosfomycin, ciprofloxacin, amoxicillin/clavulanate or 2nd/3rd generation oral cephalosporins for 5-7 days.
– Moderately-severe UTI, including acute pyelonephritis; Ceftriaxone, piperacillin-tazobactam or cefepime for 14 days.
– Severe infection and/or septic shock, carbapenem plus vancomycin considered, completing 14-21 days.
– Once culture susceptibility results are available, tailor the antimicrobial therapy according to the result.
– Progression to renal or perinephric abscess or emphysematous pyelonephritis requires a MDT approach.
– Removal of indwelling urinary catheter and/or ureteric stents ( if present) should be considered in KTR with UTI.
C. Prevention:
– Correct conditions amenable to surgical management.
-Avoid prolong use of catherization if not necessary, strategies such as chlorhexidine and antibiotic coated stents to prevent biofilm formation may be considered.
– Early ureteral stent removal within four weeks of transplant may help to prevent UTI after kidney transplantation.
– Monitoring for asymptomatic bacteriuria in the first 2 months post-Tx.
– Behavioral changes (increased fluid intake, frequent voiding, postcoital voiding, contraception modification)
– For postmenopausal females, topical estrogen may prevent recurrence of UTI
– Antibiotic prophylaxis: KDIGO recommended TMP-SMX to prevent PCP for 6 months post transplantation; this is also effective at preventing UTIs, risk of resistance.
References:
-Nicola Petrosillo, Guido Granata, Breida Boyle, Maeve M. Doyle, Biagio Pinchera, Fabrizio Taglietti. (2020) Preventing sepsis development in complicated urinary tract infections. Expert Review of Anti-infective Therapy 18:1, pages 47-61.
Marta Bodro, Laura Linares, Diana Chiang, Asuncion Moreno & Carlos Cervera
(2018): Managing recurrent urinary tract infections in kidney transplant patients, Expert Review of
Anti-infective Therapy, DOI: 10.1080/14787210.2018.1509708
Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. doi: 10.1111/ctr.13507. Epub 2019 Mar 28. PMID: 30793386.
5. A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
===================================================================
====================================================================
How would you manage this patient?
Potential risk factors involved in the development of UTIs after
kidney transplantation include:
Laboratory testing should include :–
Indications for urological imaging include
===================================================================
Treatment
Prophylaxis of UTI in Transplant Recipients
Early removal of foreign material (catheter)
====================================================================
Refernce
The risk factors of recurrent UTI include female gander as in the case, surgical, anatomical, recipient, and graft-related factors, Vesico-ureteric reflux (VUR) increases the pyelonephritis risk, also temporary ureteric stent enhances VUR, abolishing peristalsis and dilating the vesico-ureteric junction, ureteric stents and urinary catheter particularly if left for a long period enhance UITI risk also immunosuppressive drugs as ATG, Azathioprine and MMF increase UTI risk.
Investigations include
Urine analysis and urine culture are indicated if UTI is suspected, and blood cultures should be collected in case of severe systemic symptoms
Renal ultrasound or non-contrast computed tomography (CT) scan should be considered to assess complications such as obstruction and abscess also Non-contrast CT scan is useful to identify nephrolithiasis, complex cyst, and other anatomical urinary abnormalities
Cystourethrography, cystoscopy ,urodynamic studies can be needed for VUR
Treatment
Empirical treatment with the combination of amoxicillin and ciprofloxacin is recommended.
No recommendation can be made about changing immunosuppressive drugs from one class to another to prevent a recurrence of UTI.
In the choice of antibiotics for treatment of recurrent UTI with the increased risk for ESBL-related infections should be considered.
Antibiotic selection should be guided by the results of microbiology tests and culture due to emergence of drug-resistant uropathogens. The duration of antimicrobial therapy in recurrent UTIs is not well defined, but some authors recommend longer durations of treatment (4–6 weeks or even longer)
Multiple antibiotics can interact with immunosuppressants, especially with calcinurine-inhibitors. Therefore, interactions have to be checked.
Removal of the urinary catheter should be done as soon as appropriate.
In case of a UTI the JJ stent should be removed if possible.
Effect of reoperation of refluxive transplanted kidney is not clear as in spite of antirefluxive urtetic implanation reflux is still common.
Nephrectomy of native kidneys with reflux can successfully low recurrent UTI risk meanwhile it is the last option.
Behavioural education can decrease recurrent UTI risk as hydration , frequent voiding and sanitation
Antibiotic prophylaxis for the prevention of recurrent UTI has not been well evaluated.
Topical estrogen has been used in perimenopausal and postmenopausal females and a combination of hyaluronic acid and chondroitin sulphate instilled intravesically.
It was lately published that bacterial vaccines reduced the incidence of recurrent UTI in a small case series of KT patients without eliciting any safety concerns.
Reference
-Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship?. J Clin Med. 2021;11(1):226. Published 2021 Dec 31.
– Suárez Fernández, M.L.; Ridao Cano, N.; Álvarez Santamarta, L.; Gago Fraile, M.; Blake, O.; Díaz Corte, C. A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients. Diagnostics 2021, 11, 1456
How would you manage this patient?Recurrent UTIs are associated with higher morbidity and graft loss. The cause of recurrent UTIs have to be explored.
First step is detailed history. The primary kidney disease have to explored. History will include frequency of episodes , voiding LUTS, status of immune suppression, medical conditions, fluid habits constipation, sense of incomplete bladder emptying.
Inquiry about removal of DJ stent
See the culprit organism in urine cultures
USS KUB with post void
CT scan to see any stones, kinks in Ureter, hydronephrosis or any other structural abnormality.
If any concern about VUR then a MCUG can be arranged.
If there is any abnormality in bladder then a flexible cystoscopy should be done
BK virus infection also needs to be ruled out
Management
It will depend upon any pathology detected.
General life style measures to be advised. These will include care of hydration, timed and double voiding , hygienic measures , avoidance of constipation.
In case of atrophic vaginitis, topical estrogens can be used
Use of prophylactic antibiotics
Bodro M, Linares L, Chiang D, Moreno A, Cervera C. Managing recurrent urinary tract infections in kidney transplant patients. Expert Rev Anti Infect Ther. 2018 Sep;16(9):723-732.
How would you manage this patient?
In the management of the index patient, it will be prudent to identify the possible risk or aetiological factors responsible for the recurrent UTI post-kidney transplantation. It is good to note that the most common site of infection after a kidney transplant is the urinary bladder in >95% of cases, then pyelonephritis in the rest.
The following investigations will be done after obtaining the above information
Treatment
References
The patient is on triple immunosuppression and is getting recurrent UTIs
Recurrent UTIs are a common clinical problem in kidney transplant recipients. Recurrent UTIs:
Management:
The patient should be taught basic preventive measures including:
Bodro M et al. Experts Review of Anti-infective Therapy. 2018;16:9, 723-732
Hollyer I et al. Transpl Infect Dis. 2019;21(3)
-How would you manage this patient?-Unfortunately , this is one of the difficult conditions and may be associated with increased morbidity, allograft loss and mortality
-Its usually requires a very exhaustive investigations and management
-It may be important to follow a structured approach for this kind of problems e.g.
-History of recurrent UTI in the native kidney before transplantation
-Make sure that her double J stent was removed as per protocol; sometimes this may be forgotten and creates a problem. If it was not remove, the organize for its urgent removal and send it for microbiology, culture & sensitivity.
-Role out BK virus; this is a differential for pyelonephritis as a tubulo-interstitial disease and it may cause ureteric stricture and surgical issues
-Check for post-void residual US/CT and evaluate for structural abnormalities
A. Presence of structural abnormalities: Corrective measures/surgery
B. Absence of structural abnormalities: Voiding cystourethrography
C.Urodynamis:
Source,
-urinary tract infecion in renal transplantation by Simon Olenski et al.
-Prof Salah Zaki lecture
Thankyou for starting with HISTORY as this can answer a lot of questions.
Forgoten stents are always a surprise!
New post TX UTI have are a diff. options BK is among them.
Most welcome prof
work-up
Some individuals with UTIs may need imaging to rule out correctable anatomical or functional urinary tract abnormalities. Patients who:
Are one-month post-transplant or
Nephrolithiasis history
Having recurrent UTI (2 incidents in six months or 3 episodes in one year) or
Continuously elevated serum creatinine.
Most patients start with urinary system ultrasonography with postvoid residual measurement due to its convenience and absence of adverse effects.
We do a non-contrast urinary tract CT scan in recurrent UTI patients with unrevealing ultrasonography. Avoiding contrast to minimize nephrotoxicity limits CT scan sensitivity. Imaging may detect urinary tract strictures, stones, and complicated cysts. Urology may undertake urine flow rate and urodynamic investigations to determine bladder dysfunction or outflow tract blockage if the CT is unrevealing. Flexible cystoscopy may identify urethral or bladder problems.
prevention and treatment:
Antibiotic prophylaxis – Early post-transplant UTIs cause severe morbidity. Early posttransplant prophylactic antibiotics reduce UTIs in kidney transplant patients.
Early ureteral stent removal: early ureteral stent removal within four weeks of transplant may help prevent UTI after kidney transplantation.
Recurrent UTI risk factors and behavioral changes should be discussed with all patients. Increased fluid intake, frequent voiding, postcoital voiding, contraceptive adjustment (in sexually active patients), and wiping from front to back (in females) are comparable to nontransplant patients with recurrent UTIs.
Some specialists give recurrent UTI patients preventive antibiotics. Individualize long-term antibiotic prophylaxis.
For postmenopausal females, topical estrogen may prevent the recurrence of UTIs.
Several transplant programs utilize methenamine hippurate (1000 mg twice a day) with or without ascorbic acid to avoid recurrent UTIs.
Recurrent episodes—Each episode of simple cystitis or severe UTI should be treated with an adequate period of antibiotic medication.
Patients with persistent/recurrent UTIs with the same organism may need a longer course. Infected kidney cysts may cause recurrent UTIs that need four to six weeks of treatment.
Recurrent UTI treatment may be terminated after a shorter time and switched to preventive antibiotics in other cases.
Reference:
Mitra, S., & Alangaden, G. J. (2011). Recurrent urinary tract infections in kidney transplant recipients. Current infectious disease reports, 13, 579-587.
Well done.
A 47-year-old female patient received a kidney from her sister 3 months ago. The primary kidney disease is unknown as she presented with bilateral small atrophic kidneys. Currently, she is on Tacrolimus-based triple immunosuppression with excellent kidney function. She kept presenting with symptoms of recurrent UTI.
How would you manage this patient?
From the scenario female with unknown etiology of ESRD and found to have bilateral small kidneys, raise the possibility of reflux nephropathy.
From history make sure that she underwent double J stent removal, hygiene, and adequate water intake, and sexual history.
Laboratory:
CBC, BUN, creatinine, CRP, urinalysis and urine culture is a must, blood culture, consider PCR for BK virus and CMV.
The management of this patient consists of:
1. Culture based antibiotic treatment.
2. Anatomical evaluation of kidneys and urinary tract.
3. Prevention of recurrence.
4. Reduction/ stoppage of immunosuppressive medications.
Culture based antibiotic treatment: every patient presents with UTI post-transplant, should have urine culture done.
In symptomatic cystitis empirical antibiotics to use are: oral fluoroquinolone, amoxicillin-clavulanate, or an oral third-generation cephalosporin, nitrofurantoin can be used.
In severe UTI and pyelonephritis empirical antibiotics recommended are: carbapenems, cefepime, and pipracillin/tazobactams.
Anatomical evaluation of urinary tract:
First by pre and post void ultrasound or voiding CT scan– if any corrective lesions should be done, or obstructive stones or evidence of ureteric stenosis..etc.
Second if the post void image normal the MCUG (Micturition cystouretherography)– if reflux is identified either medical prophylactic tx/ endoscopic injections or surgical intervention as needed.
Third if the MCUG normal then consider urodynamic studies– if bladder dysfunction medical treatment accordingly, and if outflow obstruction surgical intervention is warranted.
Prevention of recurrence:
By life style modification and better genital hygiene, and maintaining at least 2l/day UOP, standby post coital antibiotic prophylaxis.
If post menopause then topical estrogen therapy may be beneficial, and keeping alkaline urine may also prevent recurrence by use of vitamin C, cranberry
Antibiotic secondary prophylaxis of recurrent UTI in KT recipients, usually not recommended unless for selected patients who have severe episodes of recurrent UTIs such as pyelonephritis (Weak, Low).
References:
(1) Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. doi: 10.1111/ctr.13507. Epub 2019 Mar 28. PMID: 30793386.
(2) Fiorentino M, Pesce F, Schena A, Simone S, Castellano G, Gesualdo L. Updates on urinary tract infections in kidney transplantation. J Nephrol. 2019 Oct;32(5):751-761. doi: 10.1007/s40620-019-00585-3. Epub 2019 Jan 28. PMID: 30689126.
Well done.
The history issue is important as well to rule out native kidneys as a source of persistent UTI which should have been dealt with earlier .
How would you manage this patient?o Recurrent UTIs after KT are defined as ≥ 2UTI episodes in a 6-month period or ≥3UTI episodes within 1 year (occur in 3 to 27% of cases)
o Gram-negative organisms account for the majority of recurrent UTIs (E.coli remains the most common cause)
Risk factors:
1. female gender (strongest risk factor), immunosuppression, hyperglycemia, prostatitis, concomitant CMV, and re-transplantation
2. anatomical abnormalities [vesicoureteral reflux (the most important), renal calculi, bladder dysfunction, urethral abnormalities, and complex cysts]
Diagnosis:
o Blood tests (C-reactive protein, leucocytes)
o BK and/or CMV infection should be excluded
o Ultrasonography to exclude postrenal causes of infection (urolithiasis, urinary tract obstruction, ‘forgotten’ ureteric stent, etc.)
o Prostatitis should be considered as an important differential diagnosis in men who present with recurrent post-transplant UTI.
o Radiography, CT even CT-PET, cystoscopy, cystourethrography (vesicoureteral reflux), and urodynamic studies
Treatment:
o Antibiotic selection should be guided by the results of microbiology tests (because of the emergence of drug-resistant uropathogens)
o The duration of treatment is not well defined, but some authors recommend longer durations of treatment (4–6 weeks or even longer)
o Correction of structural and functional urinary tract abnormalities (for example obstructed transplant ureters, urolithiasis, and BOO from causes like BPH)
o Nephrectomy may be indicated in recurrent UTI with reflux or APKD
o Interaction with immunosuppression must be considered, such as increased nephrotoxicity of TMP-SMZ and gentamicin in recipients taking calcineurin inhibitors
Prevention:
1. Behavioral education (hydration, frequent voiding, and intimate hygiene, especially for females after a sexual intercourse)
2. Antibiotic prophylaxis has not been well studied. The potential benefits of extended antibiotic prophylaxis should be carefully weighed against the risks of promoting bacterial resistance, Clostridium difficile infection, and other adverse events associated with antibiotics. Antimicrobial prophylaxis might be appropriate for selected patients who have severe episodes of recurrent UTIs such as pyelonephritis
1 and 2 if no structural abnormalities
3. Nonantimicrobial therapies have been tried in patients with recurrent UTI most of all in the non-transplant population. It has been described that (cranberry juice, topical estrogen, and a combination of hyaluronic acid and chondroitin sulphate instilled intravesically
4. Other therapies (methenamine and probiotics)
5. Bacterial vaccines: in a small case series of KT patients without eliciting any safety concerns
References
1. Suárez Fernández ML, Ridao Cano N, Álvarez Santamarta L, Gago Fraile M, Blake O, Díaz Corte C. A Current Review of the Etiology, Clinical Features, and Diagnosis of Urinary Tract Infection in Renal Transplant Patients. Diagnostics (Basel). 2021 Aug 12;11(8):1456. doi: 10.3390/diagnostics11081456. PMID: 34441390; PMCID: PMC8392421.
2. Oxford handbook of Nephrology and Hypertension, 2nd edition, 2014.
3. A lecture of Post Renal Transplantation Urinary Tract Infection By Prof. Mohamed Salah EldinZaki, Dean of National Institute of Urology and Nephrology
Thanks, Mohamed
Assume that USS (post-micturition) of the bladder showed residual urine of 254 cc.
Would your management differ?
Thank you prof.
A post voiding residual urine of 254cc is high and is a leading cause of recurrent UTI
The most common causes are:
1. Bladder outlet obstruction (BPH) Bladder neck contracture
2. Urethral stricture
3. Detrusor underactivity
4. Bladder tumours
Diagnosed by ultrasonography, urodynamic testing, and cystoscopy
Treat the underlying cause (transurethral prostatectomy for BPH)
The plan of management divided into
1- treatment of the current symptomatic urinary tract infection
2 – evaluating the cause of this recurrent UTI
3- prophylactic management
1–Treatment:
Cystitis
○It can be treated with oral antibiotic on most occasions.
○Empiric antibiotic treatment should be initiated pending results of urine culture.
○Cotrimoxazole is not an adequate empirical treatment for those solid organ transplant recipients receiving prophylaxis with this antibiotic.
○quinolones, oral cephalosporins and fosfomycin that do not interact with immunosuppressive drugs.
○ Most experts recommend therapy for10-14 days.
○Eradication of the organism should be confirmed by a follow-up culture of an after-treatment urine sample.
Pyelonephritis
■blood and urine samples have been collected.
[CBC- CREA- CRP ….Urine sample test and culture]
■In febrile patient with abrupt deterioration of renal function, treatment with empirical parenteral antibiotic therapy
■aimed at Gram negative bacilli, including Pseudomonas aeruginosa, and enterococci
■Hospitalization may be considered.
■Active antibiotics against Pseudomonas aeruginosa include piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, cefepime, imipenem, meropenem and doripenem.
■aminoglycoside may be considered in patients with multiresistant Gram negative bacteria.
■Alternative antibiotics for those patients reporting an allergic phenomenon to β-lactams are fluoroquinolones and aztreonam for Gram negative bacteria, and vancomycin for enterococci.
■For those patients in whom vancomycin-resistant enterococci is a concern, linezolid, daptomycin and quinupristin/dalfopristin can be an alternative.
■pyelonephritis should receive therapy for 14 days.
■Step-down from intravenous to oral therapy is appropriate when the patient has clinically improved and is afebrile for at least 48 hours.
■Longer treatments may be necessary for those with renal or perirenal abscesses.
2– evaluating the cause of this recurrent UTI
●We should ask about the period before transplantation. Is there a history of recurrent urinary tract infections?
●Ultrasound should be performed to functional or anatomic abnormalities must be exclude (e.g., stone, obstructive uropathy, poorly functioning bladder) by testing the native kidneys and renal graft then studying the post-void residual.
●If the former was negative, we should initiate the second step of investigation, VCUG.
If there was a VUR ==> may be need surgery or only observation
If it was negative (no VUR) ==> urodynamic may be recommended
3– PROPHYLAXIS
●For renal transplant recipients without anatomical abnormality who suffer more than three recurrences per year, a prolonged antibiotic prophylaxis can be considered.
●Antibiotics that have proved to be useful in this setting are
– bactrim (trimetoprim 80 mg plus
– sulfamethoxazole 400 mg)
– or a quinolone (200-250 mg) every other day.
●Cephalexin, fosfomycin or nitrofurantoin could be alternative options.
●KDIGO (Kidney Disease: Improving global outcomes) recommend the use of this antibiotic as prophylaxis for UTI and Pneumocystis jiroveci pneumonia during, at least, the first 6 months after renal transplantation.
●All patients should be counseled on behavioral changes that might reduce the risk. (Increased fluid intake, frequent voiding, postcoital voiding, contraception modification )
●For postmenopausal females, topical estrogen may prevent recurrence of UTIs
●We do not routinely use strategies such as cranberry juice or probiotics due to the lack of clear data supporting
●Evidence in support of antimicrobial prophylaxis to prevent UTI is provided by a meta-analysis of six randomized trials in 545 kidney transplant recipients, which demonstrated that antibiotic prophylaxis (mostly with TMP-SMX) reduced the risk of sepsis and bloodstream infection (relative risk [RR] 0.13, 95% CI 0.2-0.7) and bacteriuria (RR 0.41, 95% CI 0.31-0.56) . Prophylaxis did not reduce graft loss or mortality, and effects on the risk of symptomatic UTI or pyelonephritis were not reported.
REFERENCES
1–Urinary Tract Infections in Transplant Recipients. Francisco López-Medrano
2–Urinary tract infection in kidney transplant recipients (UpToDate)
3–Managing recurrent urinary tract infections in kidney transplant patientsMarta Bodro et al.
4–Post Renal Transplantation Urinary TractInfection By Prof. Mohamed Salah EldinZaki
First question that comes to my mind is: Has her stent been removed?
Thank you professor. In the center where I work stent has been removed 6 weeks after transplantation. That is why I didn’t mentioned this issue. But it is an important point
Thanks, Ghalia
USS of the bladder is important. Do you know why?