Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT).
prevention and adequate treatment of urinary tract infections in KT recipients is crucial. While there is increasing data that asymptomatic bacteriuria (ASB) does not affect graft function ،inadequate use of antibiotics certainly has the potential to do so. However, the decreased GFR in patients that underwent antibiotic treatment in our cohort should not be interpreted in a vacuum. While about 10% were treated with antibiotic doses that were above the recommended limit more than 25% of patients had a deterioration of graft function. The increasing use of extended donor allocation and overall comorbidities of the recipients adds to this complexity.
Several prophylactic antibiotic regimens have been studied. Ciprofloxacin was shown
to prevent UTIs 25 years ago, but was later reserved for treatment rather than prophylaxis .Aside from a recent randomized trial that showed the preventative efficacy of Fosfomycin the best studied drug is TMP-SMX. TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic dose for 6–12 months after KT
Empiric antibiotics should therefore always cover gram-negative enterobacteria. There was no resistance to carbapenems in our gram-negative bacteria, which makes them the most attractive choice for critically ill patients. Of the remaining antibiotics Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to, at a rate of 15%.
The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not recommended as first line therapy for urinary tract infections in transplant recipients. Nearly all isolated bacteria in our study cohort had a “weak spot” to one of these agents. These agents will grow in popularity given that they are safe and effective even against MRGN bacteria.
While symptomatic patients need to be treated empirically to avoid development ofsepticemia, we believe it is safe to wait for the final antibiotic resistance testing in ASB and use targeted therapy rather than empiric broad spectrum coverage followed by a step- down approach. This is common practice in pregnant patients but to our knowledge there is yet to be consensus for transplant recipients.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind which may vary a lot regionally.
While our MRGN rate of 10% was similar to other German KT centers it was
considerably lower than described by Tekkarismaz et al., who reported 41% MRGN urinary tract infections in their cohort in Turkey. Nevertheless 10% was considerably higher than the average of 5% described in a 2017 meta-analysis.
The global numbers are increasing and vary considerably even within states and countries.
Strengths and Limitations
We presented single center data on bacterial isolates from urine samples of over
200 kidney transplant recipients early after kidney transplantation. The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection. Still, we were able to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main
goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Please summarise this article. # Introduction:
* (UTI) are the most common infection in the early postoperative phase (PKT).
* The incidence of a UTI ranges from (4–80%).
*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.
*Asymptomatic bacteriuria (ASB) is defined as the presence of 105 colony-forming units of bacteria in the absence of symptoms.
*ASB is encountered in around 25% of KT recipients, so it is commonly screened for and treated in the
early PTK phase.
* In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression.
*The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
*Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT).
*After the recent recommendation to avoid them in these patients, however, alternative treatment strategies need to be investigated.
#The aim of the study to evaluated antibiotic prescription practice during the first 30 days PKT, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based on data provided by the hygiene department.
# The methods:
*Retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of (ASB) and (UTI) and the patients’ clinical characteristics and outcomes were evaluated.
*Immunosuppressive Protocol:
Induction therapy was Methylprednisolone as well as either Basiliximab for low immunologic risk or Anti-Thymocyte Globulin for intermediate risk or an Anti-CD56-Antibody for high risk patients. Maintenance immunosuppression consisted of steroid tapering, CNI as well as MMF.
*Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam (Ampicillin/
Sulbactam or Cefotaxime) or 3 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant
surgeons’ discretion.
*Treatment Protocols for Urinary Tract Infections Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics
#The results:
Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed
UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both, bacterial resistance was more common in the study cohort than in the control group.
#Strengths and Limitations
The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
Still, it demonstrates distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between KT recipients and the control group.
Uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data.
Therefore, multicentric comparative data will be necessary prior to generalization of our data.
# Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
What is the level of evidence provided by this article?Level 2
How do you treat recurrent UTI at your workplace?All transplanted patients receive TMP/SMX as prophylaxis for period of six months.
In reccurent UTI infections we take sample for culture and sensitivity for bacteriology lab first, and started with broad spectrum antibiotics (Ceftaxime or Meropenem) then we give the drug according to the result type of microorganism.
Nitrofurantoin can be used in small dose for 3 – 6 months following recurrent infection
Summary The impact of urinary tract infections (UTI) on kidney transplant recipients and the related consequence of antibiotic resistance. As well as requirement antibiotics stewardship in treating such patients is discussed in this article. Introduction UTI are common in the early post-transplant period, can lead to pyelonephritis sepsis, damage to graft, and even death, if left untreated. Even a single episode of urinary tract infection can impact function of the allograft. So, it is imperative that UTI in transplant recipients should be prevented, and be treated on time. Methods and results: From January 2015 to August 2020, 207 kidney transplant recipients (KTR) were studied for UTI. 68 of the 130 patients exhibited usual symptoms, clinical or laboratory evidence of UTI. 10 of 68 patients with UTI, had typical symptoms along with urinalysis abnormality, and 58 patients had growth of a urinary pathogen on urine culture. 166 (80%) of the 207 patients of kidney transplants had at least one round of antibiotic therapy (excluding preoperative and peri-interventional prophylaxis). Within the first 30 days following the transplant, 262 antibiotic treatment sessions were provided to the patient cohort. The most common pathogen, E. coli, was discovered in 49 cultures, followed by E. faecium (n = 23). Discussion Measures to prevent infection in renal transplant recipients: · Single antibiotic shot ½ hr before incision
Intraoperative gentamicin irrigation of bladder before ureteral anastomosis in order to decontaminate the bladder.
Remove ureteral stent 21 days after kidney transplant procedure. Stent can be removed earlier if there is suspicion of infection.
Ciprofloxacin can be used for prophylaxis and treatment in most cases.
Screening and Prophylaxis: During the first month following transplantation, patients are subjected to weekly screening for urine pathogens in attempt to identify ASB and UTI early. TMP-SMX is recommended for first 6months for PCP prophylaxis, which reduces incidence of UTI during this period. Lee et al. found that skipping the peri-interventional antibiotics (often Ciprofloxacin) was not hazardous, if patient was receiving TMP-SMX prophylaxis. Treatment
Asymptomatic infection can be treated using narrow spectrum antibiotics such as TMP SMX, fosfomycin, nitrofurantoin, pivmecillinam.
Antibiotic resistance testing has to be done in patients with symptomatic infection.
Treatment for symptomatic infection has to be done empirically and quickly to avoid development of septicemia, after sending samples for culture.
Ciprofloxacin, other fluoroquinolones are used for empiric treatment.
· Carbapenem is the best option for critically unwell patients, and empiric antibiotics should always cover gram-negative enterobacteria. · An oral narrow-spectrum antibiotic may be necessary following the results of the culture. · Can postpone using empiric broad spectrum antibiotics in ASB, in favour of tailored treatment while awaiting the results of the final antibiotic resistance testing. · Data on antibiotic stewardship and hospital cleanliness can be helpful, but they must be carefully watched. Conclusion UTI prevention and effective treatment are crucial in transplant recipients, in order to have long term graft function, and patient survival. Rational use of antibiotics is key to prevent development of resistance. Solid organ transplant recipients are at high risk for development of septicemia and fatal infections. Thus, adequate monitoring, quick diagnosis and effective treatment is required. Antibiotic stewardship teams are essential in the fight against antibiotic resistance and poor treatment choices. Level of evidence: Level 2 How do you treat recurrent UTI at your workplace? In our practice we insert stents in all patients, but removed it by 2-3weeks. TMP-SMX for PCP prophylaxis for 6 months, also protects from UTI.
Urine analysis weekly in the first month post-transplant, then every two week for 3 months. then monthly for one year. Abnormal Urinalysis report requires Urine culture and USG graft kidney.
We use Ciprofloxacin or cephalosporins empirically, till culture results come, after which antibiotics drug and duration is tailored according to culture sensitivity report. Routine USG graft kidney with doppler is done at 7days, at 3-4 weeks, 3months and 6months post-transplant for any abnormality, in addition to any clinical suspicion. Abnormal USG findings or severe pyelo-nephritis / high fever / recurrent UTI / persistent infection, requires CT scan of abdomen and KUB with CT IVU. VCUG is reserved for high grade reflux (hydronephrosis with graft dysfunction) which might require surgical correction.
We don’t treat ASB, rather take another culture after proper clean precautions. Recurrent ASB is investigated for forgotten stent / stone / hydronephrosis or voiding problems which are sorted out. Patients are advised to drink plenty of water, voiding every 2-3hourly, avoid use protections for sex, as well as post-coital voiding. Women are asked to wipe from front to back, use short time vaginal tampon and change frequently during menses.
This article is concerned with the impact of urinary tract infections in kidney transplant recipients and the related consequence of antibiotic resistance and required stewardship regarding the use of the aforementioned antibiotics.
Introduction
Urinary tract infections are common the early post transplant period. They can lead to sepsis and death if left untreated. It can also cause significant damage to life. Even a single episode of urinary tract infection can impact function of the allograft. Taking all these factors into consideration, it is imperative that urinary tract infections are prevented, and if not, at the very least treated in a timely manner.
Discussion
Measures to prevent infection in renal transplant recipients include the following:
Single antibiotic shot before incision.
Intraoperative gentamicin irrigation of bladder before ureteral anastomosis in order to decontaminate the bladder.
Remove ureteral stent 21 days after kidney transplant procedure. Stent can be removed earlier if there is suspicion of infection.
Ciprofloxacin can be used for prophylaxis and treatment in most cases.
TMP SMX given 6 months after kidney transplant can aid in prevention of UTI.
Treatment
Asymptomatic infection can be treated using narrow spectrum antibiotics such as TMP SMX, fosfomycin, nitrofurantoin, pivmecillinam.
Antibiotic resistance testing has to be done in patients with symptomatic infection.
Treatment for symptomatic infection has to be done empirically and quickly to avoid development of septicemia.
Ciprofloxacin and fluoroquinolones are used for treatment.
Conclusion
Prevention and effective treatment are crucial with regards to urinary tract infections. Rational use of antibiotics is key to prevention of resistance. Solid organ transplant recipients are at high risk for development of septicemia and fatal infections. Thus adequate monitoring and quick diagnosis and treatment is to be done. Antibiotic stewardship teams are essential in the fight against antibiotic resistance and poor treatment choices.
This study revealed single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation. It also emphasizes the necessity for antibiotic stewardship in kidney transplant recipients. The most significant information in this text is that early posttransplant screening and treatment for asymptomatic bacteriuria (ASB) is common, and that UTI is assumed to be lower in living donor kidney transplantation due to shorter waiting times, higher volume urine output, and early onset graft function. Due to their broad availability, oral and intravenous formulations, and good urinary tract penetration, fluoroquinolones are among the most often used antibiotics in the treatment of urinary tract infections in KT users.
From January 2015 to August 2020, 207 kidney transplant patients (KT) were the subject of this study, which focused on their clinical characteristics.
68 of the 130 UTI patients exhibited the usual symptoms and/or clinical or laboratory evidence of inflammation.
Ten of these 68 individuals had typical symptoms along with laboratory and urine chemistry results compatible with UTI, and 58 of these patients had growth of a urinary pathogen on urine culture.
166 (80%) of the 207 patients of kidney transplants had at least one round of antibiotic therapy (excluding preoperative and periinterventional prophylaxis).
Within the first 30 days following the transplant, 262 antibiotic treatment sessions were provided to the patient cohort. The most common pathogen, E. coli, was discovered in 49 cultures, followed by E. faecium (n = 23).
For the first month following transplantation, patients are subjected to weekly screening for urine pathogens in attempt to identify ASB and UTI early.
TMP-SMX is recommended for use for 6–12 months following KT in order to avoid Pneumocystis jiroveci pneumonia. After KT, TMP-SMX decreased UTIs after six months.
In cases when the patient was receiving TMP-SMX prophylaxis, Lee et al. discovered that skipping the periinterventional antibiotics (often Ciprofloxacin) was not hazardous.
· Carbapenem is the best option for critically unwell patients, and empiric antibiotics should always cover gram-negative enterobacteria. An oral narrow-spectrum antibiotic may be necessary following the results of the culture.
can postpone using empiric broad spectrum antibiotics in favor of tailored treatment while awaiting the results of the final ASB antibiotic resistance testing.
Data on antibiotic stewardship and hospital cleanliness can be helpful, but they must be carefully watched.
Summary
· This article discusses the need for antibiotic stewardship in kidney transplant recipients.
· This study presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
· The most important details in this text are that asymptomatic bacteriuria (ASB) is commonly screened for and treated in the early posttransplant phase, and that UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
· Fluoroquinolones are among the most common antibiotics in the treatment of urinary tract infections in KT recipients due to their widespread availability, intravenous and oral formulations, and excellent penetration into the urinary tract.
· This study examined the clinical characteristics of 207 kidney transplant recipients (KT) from January 2015 to August 2020.
· Of 130 patients with a UTI, 68 had typical symptoms and/or clinical/laboratory signs of inflammation.
· In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded, and ten patients found typical symptoms accompanied by laboratory and urine chemistry findings consistent with UTI.
· Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis).
· 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant.
· E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
· The most commonly isolated gram-positive bacteria was E. faecalis
· In this cohort, urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
· Prevention and adequate treatment of urinary tract infections in KT recipients is crucial, and several measures have been proposed to prevent infections.
· In order to detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant.
· TMP-SMX is prescribed for 6–12 months after KT to prevent Pneumocystis jirovecii pneumonia. TMP-SMX reduced UTIs for 6 months after KT.
· For ureteral stent removal, Lee et al. found that omitting periinterventional antibiotics (usually Ciprofloxacin) was not harmful if the patient was on TMP-SMX prophylaxis.
· Empiric antibiotics should always cover gram-negative enterobacteria. , carbapenem is the best choice for critically ill patients. After culture result , an oral narrow-spectrum antibiotic may be appropriate.
· can wait for the final antibiotic resistance testing in ASB and use targeted therapy instead of empiric broad spectrum .
· Antibiotic stewardship and hospital hygiene data can be useful but must be monitored and updated. Level of evidence
· Level 2, retrospective cohort study Our practice:
– Supportive measures.
– IV AB, carbapenem , tazocin , or depending on last previous positive culture if recurrent.
– Chronic suppressive therapy with ciprofloxacin low dose , TMP/SMX , Fosfomycin or nitrofurantoin.
Urinary tract infections (UTIs) are a common occurrence in the early postoperative phase after kidney transplantation (KT). The incidence of UTI after KT ranges from 4-80%, and is defined as the growth of 105 colony forming units of bacteria in the presence of symptoms such as dysuria, urinary frequency or localized pain. Asymptomatic bacteriuria (ASB) is also frequently encountered in KT recipients and is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms. Fluoroquinolones were commonly used to treat UTIs in KT recipients due to their good coverage of uropathogenic bacteria, including Pseudomonas species, and their excellent penetration into the urinary tract. However, the FDA’s warning in 2019 regarding the use of fluoroquinolones in KT recipients has forced clinicians to re-evaluate their empiric antibiotic choice.
This study evaluated the antibiotic prescription practice, incidence of ASB and UTIs, and antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients compared to the local population. The study was performed on a consecutive database of adult patients (age ≥ 16 years) who underwent KT at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany between January 2015 and August 2020. The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation.
Per protocol, all episodes of UTIs and ASB were treated with antibiotics. The recommended empiric treatment for UTIs was Ciprofloxacin with a dose equivalent of 250 mg twice daily for 5 days with dose adjustments according to the glomerular filtration rate (GFR). After the recommendation to avoid fluoroquinolones, Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR was the recommended empiric antibiotic. For critically ill patients, Meropenem 1000 mg 3×/day was the recommended substance and dose.
Urinary cultures were routinely taken every Monday until discharge. Perioperative antibiotics consisted of a Single-Dose Beta-Lactam or 3 × 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant surgeons’ discretion. Urinary catheters were placed preoperatively and removed on postoperative day 5 in patients with retained diuresis prior to transplant. Ureterocystoneostomy was performed according to Lich-Gregoir. Intraoperatively a Double-J-ureteral stent was placed which was removed on postoperative day 21 per protocol (or earlier if urinary tract infection was detected).
Multi-resistant gram-negative bacteria were defined as those resistant to three out of four of the following substance classes: acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, and carbapenems. Bacterial strains resistant to all four substance classes were classified as 4-MRGN.
Comparison between groups was carried out using the Chi-Square test or Fisher’s exact test for nominal variables and the Mann–Whitney U-test for continuous variables. The statistical analysis was carried out using IBM SPSS Statistics for Windows, Version 26.0.
The study analyzed the medical records of 207 consecutive adult kidney transplant recipients who underwent transplantation at the University Hospital Tuebingen, Germany, from January 2015 to August 2020. Urine samples were collected every Monday and based on postoperative labs and clinical course. During the first 30 days after their transplant, 63% of patients were suspected to have a urinary tract infection, with 68 patients fulfilling the criteria of a UTI.
The most common isolates were gram-negative enterobacteriaceae and enterococcus species, with E. coli being the leading pathogen. Of the 207 patients, 80% underwent at least one course of antibiotic treatment, with fluoroquinolones being the most commonly prescribed antibiotic. Nine patients presented with multiresistant gram-negative bacteria, and Ciprofloxacin was the most prescribed antibiotic, with E. coli being resistant to fluoroquinolones in 45%.
The resistance rates to different empiric treatment options were high, with resistance to Ampicillin/Sulbactam being present in 76 of the 135 strains. Overall, the results suggest that antibiotic resistance is a significant concern in kidney transplant recipients, and more efforts are needed to optimize antibiotic use in this population.
UTIs are the most common infection in the early postoperative, incidence of 4-80%.
UTI -10^5 CFU on proper urine sample, early morning sample, or from a sterile catheter associated with upper or lower urinary tract symptoms, (dysuria, frequency, or localized pain).
Asymptomatic bacteriuria – presence of > or more 10^5CFU of bacteria without symptoms, occurs in around 25% of KTR
KTR- threshold of ASB treatment is lower due to increased risk of septicemia or atypical presentation
Multi-resistant gram-negative bacteria (MRGN) = bacteria resistant to three or more of the following antibiotics (acyl ureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems)
The most common pathogen kidney transplant – Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae.
UTI incidence is lower in living donor KTRs because: shorter waiting time, higher volume UOP prior, during transplantation & early onset graft function.
Peri-operative antibiotic prophylaxis is a standard in kidney transplant.
EAU guidelines recommend a single shot antibiotic prophylaxis.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KTRs, but after FDA warning in 2019 re-evaluation of empiric antibiotic is considered.
The observational longitudinal cohort study evaluated antibiotic prescription practice in first 30 days post-transplant and incidence of ASB and UTI
The study also compared antibiotic susceptibility of isolated urinary tract bacteria from KTR to local population.
The study analyzed the charts of all consecutive adult kidney transplant recipients from January 2015 to August 2020 at the University Hospital Tuebingen, Tuebingen, Germany.
During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection. In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded.
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.Ureaplasma (1%) was excluded from this analysis.
The most common indication for antibiotic treatment in kidney transplant recipients was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-
Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria were E. coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
UTI is associated with lower graft function and so prevention and early and proper treatment is highly recommended.
Screening for ASB using urine culture or urine analysis with subsequent culture in suspicious patients is recommended during the first month after transplantation, and treatment should be given upon confirmation of the ASB.
UTI usually occurs due to infection with gram negative organism, so the use of empiric antibiotics with gram negative coverage is recommended.
It is recommended to treat UTI using empiric IV antibiotic according to the local drug resistance, then switching to an oral antibiotic after culture and sensitivity result
ASB should be treated only in the first month after transplantation using narrow spectrum antibiotics or waiting till culture result.
Carbapenems is the drug of choice in the treatment of UTI in critically ill patients.
Antibiotic stewardship programs are essential to reduce the number of antibiotics prescribed to solid organ transplant recipients.
Peri-transplant surgery, one dose of perioperative antibiotic is recommended, (Cefazolin or Vancomycin).
Screening of UTI by either urine culture or urine analysis (and culture taken if urine analysis is suspicious for UTI) every week in the first month after transplantation, some recommends screening for 3 months after transplantation, but this is debatable since after the first month the incidence of ASB decrease to 4%.
Removal of urinary catheter as soon as possible after transplantation
Removal of stents as soon as possible at 3 weeks after transplantation and may be before if there is bacteriuria.
Prolonged antibiotic prophylaxis, the most important regimen is the use of SMX-TMP used already for PCP prophylaxis for 6-12 m which was associated with reduction of UTI episodes and severity.
Antibiotic prophylaxis using ciprofloxacin during the period of stent removal, but it is not needed if the patient is already on SMX-TMP prophylaxis.
Cohort study -The level 2 of evidence
How do you treat recurrent UTI at your workplace?
In our centre, we tend to treat ASB with augmentin and unasyn, some might prefer cefuroxime. We usually send C n S whle treating. Recurrent ASB will be investigated for ? stone by doing CTU
Lifestyle changes such drinking plenty of water, frequent voiding, post coital voiding, wiping from front to back in females will be advised
● Urinary tract infections (UTI) are the most common infection in the early postoper-ative phase after KTx
● The incidence of a UTI 4–80%
● A symptomatic bacteriuria (ASB) is defined as the presence of ≥10^5 colony-forming units of bacteria in the absence of symptoms 25% of KT recipients
● Threshold for treatment in KTx is lower due to the increased risk of septicemia or atypical presentation due to IS
● The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function
● The most common pathogens after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae
● Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci.
◇ Materials and Methods
● Data Acquisition
☆ A retrospectively study included All adult patients (age ≥ 16 years) who underwent KT at one center between January 2015 and August 2020
☆ Patients with simultaneous pancreas or
liver transplantation were excluded.
☆ Intra- and perioperative microbiological cultures within 30 days after KTx were screened for all patients
☆ The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients.
● Immunosuppressive Protocol
☆ Induction therapy was MP and Basiliximab for low immunologic risk
or ATG with 3 doses for intermediate risk or an Anti-CD56-Antibody (Alemtuzumab 20 mg) for high risk patients (without MMF until lymphocytes have regenerated).
☆ Maintenance immunosuppression consisted of steroid tapering, CNi, MMF
● Perioperative Antibiotic Prophylaxis
☆ TMP-SMX 960 mg 3× per week.
☆ Bladder irrigation with Gentamicin Prior to ureteral anastomosis
● Treatment Protocols for Urinary Tract Infections
☆ When clinical suspicion for a UTI arose empiric antibiotics were initiated.
☆ After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days
with dose adjustments according to GFR.
☆ For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
● Urinary Catheter and Double-J-Stent Management
☆ Urinary catheters were placed pre-operatively and removed on (POD) 5 in patients with retained diuresis prior to transplant.
☆ In patients with reduced urine output prior to transplantation the urinary catheter was scheduled to be removed on POD.
☆ Ureterocystoneostomy was performed according to Lich-Gregoir.
☆ Double-J-ureteral stent was placed which was removed on POD 21 (or earlier
if urinary tract infection was detected).
● Postoperative Follow-Up
☆ Blood workup three times per week and urinary sampling (chemistry and culture) every Monday or whenever clinical or laboratory signs of inflammation/infection were present.
☆ All patients had at least two ultrasounds per week to evaluate graft perfusion, rule out ureteral stenosis and perirenal fluid collections.
☆ Renal biopsies were taken according
to the Banff classification.
● Clinical Definitions
☆ A symptomatic bacteriuria: Asymptomatic patients without systemic signs of infection and >10^5 colony
☆ Uncomplicated UTI :
When symptoms were present
☆ Complicated UTI :
When signs of septicemia were present.
☆ Multi-resistant gram-negative bacteria:
when bacteria were resistant to three out of four of the following substance classes (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems)
◇ Discussion
● Aside from progression to septicemia, recent data has suggested a negative impact of even single episodes of (complicated) urinary tract infections on allograft function
● Urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT.
● The increasing use of extended donor allocation and overall comorbidities of the
recipients adds to this complexity.
● Measures to prevent infections in KTRs:
☆ A single shot antibiotic is administered prior to incision
☆ Prolonged antibiotics have not proven
beneficiary for the prevention of urinary tract or surgical site infection
☆ Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis
☆ The best studied drug is TMP-SMX for prophylaxis isTMP-SMX for 6–12 months after KT
☆ UTI rate was significantly lower in patients that were on TMP-SMX.
☆ Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly gram-negative bacteria.
☆ Gram-negative bacteria were more frequently associated with infections, while gram-positive were more common in bacteriuria.
☆ Due to low resistance to carbapenems it is the best choice for critically ill patients.
☆ Resistance to Ciprofloxacin was as high as (29%).
☆ Tesistance to aminopenicillins in over 50% and a resistance to cephalosporins of nearly 20%
☆ It is recommended to treat urinary tract infections after Kidney Transplantation
with empiric intravenous antibiotics according to local resistance patterns.
☆ Most transplant centers treat ASB within the first month after KT so further screening is likely unnecessary.
☆ There are no difference in progression to UTI when treated ASBs during first month after TRx or left untreated
☆ TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
☆ 40% were resistant to TMP-SMX.
☆ Resistance to antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
● Strength points :
☆ Study demonstrated distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
● Limitations :
☆ A retrospective study
☆ It was difficult to distinguish between colonization/bacteriuria and urinary tract infection as it retrospective study
☆ As it a single center study we need a multicentric comparative data prior to generalization this data.
☆ Statistical comparisons were limited to exploratory data due to uneven sample sizes between the study and control group
● Conclusions
☆ Prevention of infections after surgery as well as rational use of antibiotics is a main
goal of antibiotic stewardship programs.
☆ Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
● Level : 2
● In our practice we use TMP-SMX for PCP protection for 6 months which also offers UTi protection
● Urine analysis weekly first month after transplantation then every two week for 3 month then monthly for one year
● If there is abnormalities in Urine analysis we do Urine culture
● We treat empirically with cephalosporins until culture results were available
● USS for transplant kidney and other investigations as VCUG and renogram if the patient has recurrent UTI or transplant kidney hydronephrosis with urolog consult
1- Introduction
Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation (KT) [1,2]. The incidence of a UTI ranges from 4–80%. UTIs are defined as the growth of 105 colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria is encountered in around 25% of KT recipients
The incidence of UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
A perioperative antibiotic prophylaxis is standard in KT.
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae.
Fluoroquinolones were among the most common antibiotics in the treatment of urinary tract infections in KT recipients. 2. Materials and Methods
Retrospectively all patients who underwent kidney transplantation at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany. between January 2015 and August 2020 were included in the final analysis. 3- results:
E. coli was the most commonly isolated gram-negative bacteria.
UTI is suspected so treatment with antibiotic is indicated such as fluoroquinolones. 4- discussion:
Urinary tract infections are the most common infecti9*on in the early postoperative phase after kidney transplantation They can lead to sepsis and are a potential threat to life.
Preoperative: antibiotic is indicated to prevent infections in KT recipients.
prophylactic antibiotic regimens have been studied, including Ciprofloxacin, Fosfomycin, and TMP-SMX.99
Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly gram-negative bacteria.
To detect ASB and UTI early, our patients unde9rgo weekly screening for urinary pathogens for the first month post-trans*9plant
The treatment of asymptomatic bacteriuria is the n9iche for narrow-spectrum antibiotics such as TMP-9SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not r*9ecommended as first line therapy for urinary tract infections in tra9nsplant recipients. 5- conclusion:
Preve9ntion of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Level of evidence is II
How do you treat recurrent UTI at your workplace?
First treat the predisposing factors
Do culture and sensitivity
Renal US and CT KUB
Involve the urologist
IV. Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
Summarise this article
Introduction
– UTIs are the most common infections in the early postoperative period following kidney transplantation, incidence ranges from 4-80%
– UTI is defined as growth of 10⁵ CFU on a proper urine sample i.e., morning urine, puncture urine, urine from sterile single catheterization in the presence of symptoms like dysuria, frequency, localized pain
– asymptomatic bacteriuria (ASB) is defined as presence of ≥10⁵ CFU of bacteria in the absence of symptoms
– 25% of KTRs experience ASB
– in as much as the impact of UTI and ASB on patient and graft outcomes is still controversial, ASB is commonly screened for and treated in the early posttransplant period
– clinicians should have a low threshold to treat UTI and ASB in KTRs due to the risk of septicemia, urosepsis, potential threat to the graft and atypical presentation due to immunosuppression
– incidence of UTIs is thought to be lower in LDKT due to the shorter waiting time, higher volume urine output before and during kidney transplantation, early onset graft function
– perioperative antibiotic prophylaxis is standard practice in kidney transplantation- common uropathogens in kidney transplantation include E. coli, enterococcus faecalis, klebsiella pneumoniae
– gram negative bacteria are more pathogenic than gram positive enterococci
– fluoroquinolones were commonly used in management of UTI in KTRs given that they are readily available, have oral and IV formulations, have excellent penetration into the urinary tract, cover most uropathogenic bacteria including pseudomonas
– in 2019 there was an FDA warning regarding use of fluoroquinolones both in general and KTRs in particular, forcing clinicians to reevaluate their empiric antibiotic choice
– this study evaluated the antibiotic prescription practice in the 1st 30 days post kidney transplant, the incidence of ASB and UTIs, compared the antibiotic susceptibility patterns of the isolated urinary tract bacteria from KTRs to those isolated from the local population
Materials and methods
– retrospective chart review of 207 consecutive adult kidney transplantations
– all charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and UTIs
– patients clinical characteristics and outcomes were then evaluated
– induction therapy: methylprednisolone 500mg, Basiliximab 20mg IV day 0 and day 4 for low immunologic risk patients or ATG 1.5mg/kg/d on day 0-1 for intermediate risk patients and Alemtuzumab 20mg for high-risk patients
– maintenance therapy: steroid tapered dose, CNI (tacrolimus 0.1mg/kg/day as well as mycophenolic acid 1g BD
– perioperative antibiotics: single dose beta lactam (ampicillin/ sulbactam or cefotaxime) or 3 doses of ampicillin/ sulbactam 3g at Q0h, 12h,24h); TMP-SMX 960mg 3*/week for PCP prophylaxis, bladder irrigation with gentamicin prior to ureteral anastomosis
– treatment protocols for UTI: all episodes of UTI and ASB were to be treated with antibiotics (per protocol), empiric treatment entailed use of ciprofloxacin 250mg BD for 5 days (dose adjusted according to renal function), following the recommendation to avoid fluoroquinolones, there was a switch to piperacillin/ tazobactam 4.5g TID for 5 days (dose adjusted according to renal function), meropenem 1g TID was recommended in the critically ill patients
– antibiotics were deescalated according to the urine culture results and antibiotic resistance testing was recommended
– urine catheter and double-J-stent management: urine catheter was placed preoperatively and removed on the 5th POD in patients with retained diuresis prior to transplant and removed on the POD in patients with reduced urine output prior to transplant, DJ stent was placed intraoperatively and removed on POD21 per protocol or earlier if a UTI was detected
– postoperative follow-up: blood works thrice weekly (per protocol); routine urine sampling (m/c/s) every Monday or whenever clinical or laboratory signs of infection were present; twice weekly ultrasounds to assess for graft perfusion, ureteral stenosis, perirenal fluid collections; indication kidney biopsies which were assessed using the Banff classification; patients were reviewed 1 week after discharge for blood and urine investigations, clinical and sonographic examination
– clinical definitions: UTI (presence of ≥10⁵ CFU of bacteria plus symptoms); ASB (presence of ≥10⁵ CFU of bacteria in the absence of symptoms); multi-resistant gram-negative bacteria (MRGN) refers to bacteria resistant to 3 out of 4 of the following drug class i.e., carbapenems, fluoroquinolones, 3rd generation cephalosporins, acylureidopenicillin; 3-MRGN refers to bacterial strains resistant to 3 out of 4 drug classes, 4-MRGN refers to bacterial strains resistant to all 4 drug classes
– microbiological culture, identification of strains and resistance testing: urine cultures were done every Monday and when there was suspicion for UTI, antimicrobial susceptibility testing was also done
Results
Clinical characteristics
– 207 patients met the inclusion criteria; 35% (73 patients) underwent LDKT, 57% (119 patients) were male, median age was 55±14 years
– during the first 30 days posttransplant, 63% (130 patients) were suspected to have UTI
– 68 out of these 130 patients fulfilled the criteria for UTI; 58/68 patients had growth of a urine pathogen on m/c/s while 10 patients were unable to culture the pathogen
Microbiological results
– most common isolates were gram-negative Enterobacteriaceae and enterococcus species i.e., E. coli (n=49), E. faecium (n=23), E. faecalis (n=23), Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=6)
– 62 uropathogenic bacteria were cultured during ASBs
– in total 135 bacterial isolates were cultured, 88 (65%) were gram negative, 46 (34%) were gram positive, ureaplasma (1%) was excluded
– 56 of the 88 gram-negative bacteria isolates were recorded during a UTI while 32 (36%) were found in ASB
– 30 out of the 46 gram-positive isolates were recorded during ASB while 16 (35%) were found during an episode of UTI
Antibiotic prescription
– 80% (166 patients) received at least a single course of antibiotic treatment
– median duration of antibiotic treatment was 5±4 days
– 262 courses of antibiotic treatments were prescribed within the first 30 days posttransplant
– (suspected) UTI was the most common indication for antibiotic treatment, 2.4% (5 patients) had urosepsis, 127 patients had suspected UTI
– of these 127 patients, 85 patients received a single course of antibiotics, 33 patients received 2 courses, 7 received 3 courses and 2 patients received 4 courses of antibiotics
– patients who received a single course of antibiotics had a significantly worse GFR at discharge
– most commonly prescribed antibiotics were ciprofloxacin (n=101), piperacillin/ tazobactam (n=17), linezolid (n=17), meropenem (n=8), amoxiclav (n=6), TMP-SMX (n=5), cefuroxime (n=4), fosfomycin (n=4), nitrofurantoin (n=1)
Antibiotic resistance
– 9 patients had 3-MRGN, with a relevant percentage being resistant to piperacillin/ tazobactam, 3rd generation cephalosporin, ciprofloxacin
– none of the patients had carbapenem-resistant gram-negative bacteria
– E. coli was the most commonly isolated gram-negative bacteria whereas E. faecalis was the most commonly isolated gram positive
– E. coli was resistant to ampicillin/ sulbactam in 73% of KTRs, TMP-SMX in 67% of KTRs, fluoroquinolones in 45% of KTRs
– E. faecalis was resistant to fluoroquinolones in 87% of the KTRs
Bacterial resistance to empiric antibiotic treatment options
– resistance was highest in ampicillin/ sulbactam (56%), 3rd generation cephalosporins (46%), fluoroquinolones (39%), piperacillin/ tazobactam (26%), carbapenems (17%)
Discussion
– UTIs are the most common infection in the early posttransplant period and can lead to sepsis
– complicated UTIs have a negative impact on graft function therefore prevention and proper treatment of UTIs in KTRs is crucial
– ASB does not directly affect graft function but inadequate antibiotic use does
– patients who developed UTI had worse graft function at discharge and at 12 months follow-up
– most commonly prescribed antibiotics were ciprofloxacin and piperacillin/tazobactam
– bacterial resistance was more common in the study group compared to the control group hence the need for antibiotic stewardship teams
– measures taken to prevent infection in KTRs include:
·antibiotic stat dose prior to incision
·intraoperative bladder irrigation with gentamicin prior to ureteral anastomosis so as to decontaminate the bladder
·remove the ureteral stent 21 days posttransplant or earlier if there is suspicion for bacteriuria or infection so as to remove the biofilms (presence of indwelling catheters i.e., ureteral stents, foley’s catheters, is an independent risk factor for UTIs)
– ciprofloxacin was previously used for prophylaxis but is now reserved for treatment
– fosfomycin has been shown to have preventative efficacy
– TMP-SMX is now considered the best drug for prophylaxis
– previously patients would get peri-interventional antibiotics (usually ciprofloxacin) for ureteral stent removal, this is no longer the case as long as the patient is on TMP-SMX prophylaxis
– gram-negative bacteria were associated with infections whereas gram-positive bacteria were common in bacteriuria
– UTIs in KTRs require empiric antibiotics against gram-negative bacteria
– carbapenems are preferred in the critically ill patients since there was no resistance to the gram-negative bacteria
– piperacillin-tazobactam had the least gram-negative bacteria
– in this cohort there was a high bacterial resistance to ciprofloxacin
– there was over 50% resistance to aminopenicillins and almost 20% resistance to cephalosporins hence the recommendation to treat UTIs post kidney transplantation with empiric IV antibiotics then de-escalate to oral narrow-spectrum antibiotics once the bacterial strain has been identified
– however, for ASB, it is safe to wait for the final antibiotic resistance testing and use targeted therapy rather than empiric broad-spectrum antibiotic treatment followed by a step-down approach
– to detect ASB and UTI early, weekly screening for urinary pathogens can be done for the first month posttransplant
– treat ASB within the first month
– treatment of ASB after the 1st month has not been found to be beneficial, the prevalence of ASB decreases beyond the 1st month
– narrow-spectrum antibiotics e.g., TMP-SMX, nitrofurantoin, fosfomycin, pivmecilinam are used in the treatment of ASB
– these agents are safe and effective against MRGN bacteria
– the choice of antibiotics for empiric treatment for UTIs should be guided by the local antibiogram which should be updated regularly
– resistance to commonly used antibiotics seems to be greater in patients on dialysis and KTRs then in their healthy counterparts
– antibiotic stewardship data for SOT recipients and transplant programs is scarce
Study strengths
– ability to demonstrate different resistance patterns to antibiotics commonly used in UTIs between the KTRs and the control group
Study limitations
– retrospective study hence it was slightly difficult to distinguish between colonization/ bacteriuria and UTI
– single center study
– statistical comparisons were limited to exploratory data due to the uneven sample sizes between the study and control group – hence the need for multicentric comparative data prior to generalization of this data
Conclusion
– antibiotic stewardship programs should aim at preventing of postoperative infections as well as rational antibiotic use
– SOT recipients are at increased risk of fatal infections hence the low threshold for initiating antibiotics when an infection is suspected
– there is need to reduce antibiotic use by applying the different preventive measures to avoid infections
Level of evidence provided by this article
– Level II
How do you treat recurrent UTI at your workplace?
– all kidney transplant recipients are initiated on TMP-SMX prophylaxis posttransplant for 9-12 months
– we do not routinely do weekly urine cultures in the 1st month however we do weekly urine dipstick tests
– if there are features suggestive of UTI on the urine dipstick or if the patient is symptomatic, we request for urine cultures (m/c/s)
– empiric antibiotic therapy is initiated:
~ for outpatient treatment we commonly prescribe nitrofurantoin, amoxicillin-clavulanic acid or 2nd generation cephalosporins
~ for inpatient management we usually prescribe 3rd generation cephalosporins unless the patient has sepsis in which case we prescribe piperacillin-tazobactam or meropenem
– the antibiotic prescription is then adjusted according to the sensitivity pattern
– foley’s catheter is usually removed on the 5th POD unless the patient is still very polyuric
– ureteral stents are routinely removed at week 6 unless there are complications warranting early removal
– for recurrent UTIs we exclude other causes e.g., TB, structural and functional abnormalities by doing cystoscopy, uroflow dynamics, graft ultrasound, further imaging as is deemed appropriate
Aim of the study
Authors looked at antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of asymptomatic bacteriuria (ASB) and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those from local community.
Study design: Observational longitudinal cohort study. Inclusion criteria: adutls16 years who had kidney transplantation between January 2015 and August 2020. Exclusion criteria: combined Tx
All patient had the standard immunosuppressive therapy, induction with basiliximab, ATG and alemtuzumab, and MMF, CNIN+ prednisolone maintenance. Perioperative antibiotic prophylaxis used is Beta-Lactam or Ampicillin/Sulbactam, with TMP-SMX 960 mg 3×/week for Pneumocystis prophylaxis, and gentamycin bladder irrigation before ureter anastomosis.
Results
total inclusion 207
63% were suspected to have UTI and halve of them fulfilled the criteria for UTI with 6/7 had positive culture. Most common organisms were E.coli, klebsiella and E.faecalium.
166 of all participants received antibiotic course with median duration was 5 days and clinical indication was suspected UTI.
Fluoroquinolones were the most commonly prescribed.
9 patients had multi-resistant gram negative bacteria.
Discussion
UTI are the most common infections in the early post-transplant period.
Studies have shown that even one episode of UTI negatively impacts the allograft function. ASB doesn’t affect the allograft function however the inappropriate use of antibiotics does.Indwelling catheters are an independent risk factor.
prevention of UTIs.
Prior to the incision, a single shot of an antibiotic is given
In individuals with recurrent UTIs, gentamicin irrigation of the bladder prior to ureteral anastomosis has shown promise.
Ureteral stents & Foley catheters are standalone risk factor for UTIs. It is optimal to remove the ureteral stent 21 days following KTX
Gram negative bacilli: most common UTI, emperic Abx should cover
Gram positve bacilli: mainly ASB
Strenght -Demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group. 2-Clearly demonstrate the role of prophylactic antibiotics and prevalence of resistance. Weakness. 1-Difficult to distinguish between colonization/bacteriuria and urinary tract infection. 2-Single center study. 3-Small sample size.
4- Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data
Urinary tract infections (UTI) are the most common infection in the early postoper- ative phase after kidney transplantation (KT). In this article Jens Strohaeker and colleagues have tried to look into impact of UTI on graft outcome and importance of appropriate antibiotic management.
UTIs are defined as the growth of 10-5colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
In contrast to UTIs asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
Materials and Methods
They retrospectively screened their hospital information system for all patients who underwent kidney transplantation at the department of General, Visceral and Transplan- tation Surgery of the University Hospital of Tuebingen, Germany.
All adult patients (age ≥ 16 years) who underwent KT at their center between January 2015 and August 2020 were included in the final analysis.
Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) or 3 × 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant surgeons’ discretion.
Treatment Protocols for Urinary Tract Infections
Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics.
Recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR. For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
Urinary catheters we’re removed on day 5 and meticulous follow up was ensured.
RESULTS
During the study period, 207 patients met the inclusion criteria.
Of these 207 patients 73 patients underwent living donation kidney transplantation (35%)
134 received a kidney from a deceased donor (65%).
Overall 119 (57%) of patients were male compared to 88 (43%) females.
The median age during KT was 55 years with a standard deviation (SD) of ±14 years.
During the first 30 days after their transplant 130 patients (63%) were suspected to have a urinary tract infection.
The most common isolates from urinary cultures were gram-negative enterobacteri- aceae as well as enterococcus species.
E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23).
Antibiotic Prescription
Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis). The median duration of antibiotic treatment was 5 days with a SD of ±4 days.
Antibiotic Resistance
Overall nine patients presented with multiresistant gram-negative bacteria (MRGN). All nine were 3-mrgn (E. coli n = 7, Enterobacter cloacae n = 1, Citrobacter koseri, n = 1). Of the gram-negative bacteria a relevant percentage was resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
Strengths and Limitations
The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data. Therefore, multicentric comparative data will be necessary prior to generalization of our data.
Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
In this cohort between 207 patients 262 courses of antibiotics were prescribed. Of these, 180 were prescribed antibiotics for suspected urinary tract infection. Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
LEVEL OF EVIDENCE
2
We at our center treat recurrent UTI
according to culture results and usually use Meropenem and try to find out an obvious reason for recurrent UTI. We usually keep such patients on Nitrofurantoin prophylaxis.
We keep all patients on TMP/SMX for six months
Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship? Summarise.
Introduction;
UTI incidence post KT is estimated to be 4-80% and is lower in living as compared to dead donation.
Commonest organisms post KT are E.coli,E.feacalis and K.pneumoniae with gram -VE being more pathogenic in comparison to gram +VE.
Quinolones were previously the most used in early transplant periods for UTI.
This study evaluated antibiotics susceptibility of isolated urine bacteria from KTR in comparison to those from the general population.
Materials and methods.
Data acquisition.
Retrospective study in KTR at department of General Visceral and Transplantation sx of University hospital of Tuebingen, Germany.
Inclusion criteria;
Pts . 16 yrs at above centre; Jan 2015-Aug 2020
Exclusion criteria;
Simultaneous pancreas, kidney transplantation.
The above was compared to the control group-General population screened for the same as inpatient and outpatient.
Immunosuppressive protocol;
Induction ; Solumedrol 500mg iv+basiliximab/ATG/Anti CD 56.
Maintanance;Steroids+CNI + MMF
Peri op antibiotic prophylaxis;
Single dose beta lactam/3x3g of ampicillin/sulbactam.
Pre 2018-leucocyte depleted agents use- septrin for PCP prophylaxis.
Post 2018- All pts put on PCP prophylaxis.
Pre Ureteral anastomosis-Bladder irrigation with gentamicin.
Tx protocols for UTI;
Empiric tx once UTI suspected until neg cultures or alternative dx made.
Previously; cipro 250mg bd x 5/7 and renal dosed.
Post Cipro recommendations ;Piptazo 4.5g 3x/day-5/7 with eGFR adjustments with meropenem 1g TDS for critically ill.
Urinary catheter and double J stent mgt;
Urinary catheter removed on day 5.
Double J stent removed on day 21/7 as per protocol.
Post op follow up;
Blood works done x3/week per protocol until discharge.
Graft ultrasound done x2/week.
Renal biopsies done as indicated.
1 week post discharge- blood + urine workups and ultrasound done.
Clinical definitions;
UTI defined as per CDC.
MRGN- Bacteria resistant to 3/4 drugs(Acylureidopenicillin,3rd generation cephalosporin, quinolones, carbapenems)
Microbiological culture, identification of strains and resistance testing.
Urine samples taken to microbiology dept, cultured and antimicrobial resistance defined as per EU-CAST thresholds and MIC measured.
Statistics;
CHI square or FISCHER test used for continuous variables as indicated with P value <0.05 being considered significant.
Results;
Clinical xtics; 207pts studied,73 living donation,134 deceased donation,68 pts had UTI,58 had +VE urine cultute,10% had typical symptoms +lab +urine chem supporting UTI with negative cultures.
Microbiological results; Ecoli and K pneumonia account for most of infections;49 and 14 Pts respectively.
Antibiotics prescription;80% of pts had an antibiotic tx,2.4% were tx for urosepsis.Pts with single course of antibiotics had a worsened eGFR at discharge,3/12 and 12/12 follow up.In suspected UTI,quinolones(102) followed by Piptazo(17) were the most common prescribed meds.
Antibiotics resistance;9 pts had MRGN.None had carbapenem resisitance.In transplant popn,Ecoli resistance-73% ampicillin/sulbactam,14% piptazo,16% 3rd gen cephalosporin,45% quinolones,0%carbapenem While in control group,37% ampicillin /sulbactam,5% piptazo,9% 3rd gen cephalosporin and 17% quinolones.
Discussion;
UTI has a poor prognosis post transplant with worse creatinine at 1 yr making prevention and adequate tx important.
Some preventive measures worth considering; Antibiotics pre op, intra op gentamicin bladder irrigation in those with recurrent UTI before ureteral anastomosis and avoiding unnecessarily long indwelling ureteral stents and urinary catheters. Septrin for PCP has mixed outcomes in treating UTI and further studies needed.
Empiric antibiotics should cover gram neg enterobacteria with carbapenems being reserved for the critically ill.
More studies needed on when to screen and how to treat ASB post transplant.
Targeted antibiotics with a step down approach advised on symptomatic UTI and choice made with centre specific results pathogens in mind.
Limitations;
Single centre study.
Retrospective this difficult to tell apart colonization/bacteria/UTI.
Uneven sample size thus comparison btn transplant and control group limited to exploratory data.
Conclusion;
Prevention of UTI with rational antibiotics use should be practiced post transplant with low threshold for treatment being adopted to improve our outcome.
LEVEL OF EVIDENCE;2
OUR CENTRE PRACTICE;
6/12 Septrin for PCP Prophylaxis.
3rd generation cephalosporin for inpatient cases.
Quinolones for outpatient cases.
Tx tailored with culture results,
We do weekly screening with urinalysis in 1st 1/12 post transplant.
Post renal transplant UTI is by the most common recognized infection worldwide with incidence ranging from 4–80%.The growth of (10)5 colony forming units on a proper urine sample is significant when accompanied by symptoms in the form of dysuria, urinary frequency or even localized pain. While asymptomatic bacteriuria (ASB) is characterized by the presence of (10)5 colony-forming units of bacteria in the absence of any symptom. Astonishingly, it was estimated by 25% of renal transplant recipients. This mandated the necessary screening and proper treatment consequently.
This raised the question for the need for antimicrobial administration to avoid the occurrence of urosepsis or other atypical presentation owing to immunosuppression and renal denervation or the posing the patients to worse long-term graft survival. This came out clear in 2018 after the European Association of Urology Guidelines recommended the administration of a single shot antibiotic prophylaxis.
Most cultures revealed that the common pathogens were detected are Escherichia coli, Enterococcus and Klebsiella species. Thus, Fluoroquinolones were considered the best line due to their widespread availability, intravenous and oral formulations and excellent penetration into the urinary tract up to the detection of pseudomonas species which required different approach then.
So, our study was directed to evaluate the antibiotic prescription practice during the first month post operatively after renal transplantation, the incidence of ASB and UTIs besides comparing the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those of the local population.
Materials and Methods
The study was retrospective for renal transplant recipients at University Hospital of Tuebingen, Germany. It included adult patients who were exceeding 16 years from January 2015 till August 2020. Patients with Simultaneous pancreas or liver transplantation were excluded.
Perioperative antibiotics consisted of a Beta-Lactam and Trimethoprim-Sulfametoxazole (TMP-SMX). Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
Before the recommendation to avoid fluoroquinolones the proposed empiric treatment was Ciprofloxacin. Piperacillin/Tazobactam and Meropenem have been suggested then.
Urinary catheters were removed on the fifth postoperative day while the Double-J-ureteral stent was removed after 21 days postoperatively according to the centre protocol.
Statistics were performed by the Chi-Square test (X2), Fisher’s exact test (FET) and the Mann–Whitney U-test (MWU). P-values less than 0.05 was considered to be statistically significant.
Results
The study included 207 patients; 73 patients underwent living donation kidney transplantation (35%) 134 received a kidney from a deceased donor (65%).study population involved 119 (57%) male patients and 88 female patients (43%). The median age was 55 years with a standard deviation (SD) of 14 years.
A total of 130 patients (63%) were suspected to have a urinary tract infection during the first 30 days postoperatively. Only 68 patients fulfilled the criteria of a UTI among them 58 patients showed growth of a urinary pathogen on urine culture while only ten patients were unable to culture the pathogen.
E. coli was the leading pathogen as it was detected in 49 cultures followed by enterococcus species. It was found that 73 uropathogenic bacteria were cultured from the whole 68 cultures. Mixed cultures of two uropathogenic organisms were detected in 5 cultures as well. One patient only experienced four individual episodes of UTI with four different bacteria being recorded. The presence of ASB was detected in 59 individuals.
Data of culture results of UTI compared to asymptomatic bacteriuria is totally different. A total of 135 bacterial isolates were cultured; 88 (65%) were gram-negative and 46 (34%) were gram positive. Regarding the 88 gram negative; UTI patients were 56, while 32 patients were ASB.
Concerning the 46 cultures of gram-positive isolates; 30 patients (65%) had ASB and only 16 patients (35%) had UTI with (p = 0.001).
The need of further antibiotic prescription was 262 courses to the whole patient cohort within the first 30 days posttransplant. Five patients had urosepsis (2.4%). A total of 127 patients were treated for suspected UTI who required 180 courses of antibiotics. Among the 127 patients; 85 patients received a single course of antibiotics, 33 patients received two courses, 7 received three courses and two patients received four courses of antibiotics. About 25% of these patients had showed a rise in creatinine.
Antibiotic Resistance was encountered in nine patients presented with multiresistant gram-negative bacteria (MRGN). Fortunately, none of them showed carbapenem resistant gram-negative bacteria. E. coli being the most common isolate have been resistant to fluoroquinolones in 45%.
Data from the control group revealed that E. coli was resistant to Ampicillin / Sulbactam in 37%, to Piperacillin/Tazobactam in 5%, to 3rd generation cephalosporins in 9%, to fluoroquinolones in 17%, to TMP-SMX in 20%. In our renal transplant recipients E- coli was found to be resistant to Ampicillin/Sulbactam in 73%, to Piperacillin/Tazobactam in 14%, to 3rd generation cephalosporins in 16%, to fluoroquinolones in 45%, to TMP-SMX in 67%.
The most commonly isolated gram-positive bacteria was E. faecalis which was resistant in our renal transplant recipients to Fluoroquinolones in 87% and carbapenems in 4% while in the control group E. faecalis was resistant to only fluoroquinolones in 10% .
Among both gram-negative and gram-positive bacteria in both UTI and ASB the overall bacterial resistance was actually high. Resistance to Ampicillin/Sulbactam was detected in 76 of the 135 strains (56%), to Piperacillin/Tazobactam in 35 strains (26%), to 3rd generation cephalosporins in 62 strains (46%), to fluoroquinolones in 52 strains (39%) and even to carbapenems in 23 strains (17%).
The resistance to Piperacillin/Tazobactam and carbapenems can be explained by the prevalence of Enterococcus species.
Discussion
The conflict of UTI and ASB was aroused only after recent data has suggested the negative impact of even a single episodes of complicated urinary tract infections on allograft function.
According to this study, UTI can be accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT. This highlights the crucial role of prevention and proper treatment in KT recipients.
The facts of the increasing use of extended donor allocation and overall comorbidities of the recipients make the whole process more complicated particularly after revealing that 10% were treated with antibiotic doses that were above the recommended limit caused more than 25% of the patients to have more deterioration of graft function.
Some strategies were adopted according to the variable centres protocols to avoid the occurrence of UTI postoperatively as the administration of single shot antibiotic prior to incision, intraoperative Gentamicin irrigation of the bladder also prior to ureteral anastomosis and removal of urinary catheters as well ureteric stents without delay per protocol.
The Mayo clinic study declared that there is a reduction in UTIs after TMP-SMX was used for 6 months after KT. Horwedel et al. also confirmed that as our study did. Oppositely, Singh et al. had different data against the decline of incidence of UTIs and ASB in patients adopted the pneumocystis prophylaxis in their cohort.
Lee et al. raised another concern regarding the omission of extra peri-interventional antibiotics didn’t seem to be disadvantageous provided that our patient was on TMP-SMX prophylaxis at the time of stent removal.
The most attractive choice for critically ill patients is carbapenems owing to its zero resistance in the common gram-negative bacteria. Followed by the Piperacillin/ Tazobactam that had the least gram-negative resistance estimated by a rate of 15%.
The study also adopted a weekly screening strategy to ensure early detection of ASB and UTI variable urinary pathogens in the first month post-transplant.
A meta-analysis from Spain recommended not to treat ASB after the first month post KT, whereas Origuën et al. and Coussement et al. both confirmed no extra benefits concerning treating ASB two months after kidney transplant. This can be explained by the after that time the prevalence of ASB was generally reported to be decreasing to below 4% of patients. Bohn et al. reported on a small cohort of ASBs during the first month post-transplant that no difference in progression to UTI both when treated or left untreated conflicting this principle.
This study believes that it is safe to wait for the final antibiotic resistance testing in ASB and use targeted therapy rather than empiric broad spectrum coverage. This is attributed to the fact that the resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy population. So, the next challenge is to adopt the idea of prevention of the development of resistant strains in dialysis patients for antibiotic stewardship teams worldwide. The barrier that is faced now is the scarce data for Antibiotic stewardship of solid organ transplant recipients and transplant programs.
This study stated that the MRGN rate of 10% that was found to be similar to other German KT centers. Fortunately, it was lower than what Tekkarismaz et al. reported to be 41% MRGN urinary tract infections in their cohort in Turkey. However,10% was considerably higher than the average of 5% described in a 2017 meta-analysis reflecting that the global numbers are increasing.
Strengths and Limitations
Limitations are mainly being only single center data, 200 kidney transplant recipients only, for limited time early after kidney transplantation and the fact that uneven sample sizes between the study and control group might affect statistical comparisons data.
Strengths are essentially the ability to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between recipients and the control group based on urinary cultures ordered at a massive tertiary university hospital.
Conclusions
Solid organ transplant recipients are at higher risk of fatal infection. Low threshold for initiating antibiotic treatment when infection is suspected can therefore be justified.
Multicentric comparative data are required besides the collaboration of efforts of transplant surgeons, physicians and antibiotic stewardship teams should be coordinated to face this serious infection impacts.
Level of evidenceis II.
Our centre protocolinclude perioperative antibiotic prophylaxis, urinary catheter insertion occurs in the operation, monitoring the patient by ultrasound postoperatively. After discharge weekly screening for UTI and ASB for the first month.
TMP-SMX prophylaxis for the first 6 months post renal transplantation is a must. Management of both UTI and ASB is only culture based.
Cases of recurrent UTI after being assessed by ultrasound, the urology team is consulted for the co-management in addition to urine flow metric studies are considered.
Summary
· This article discusses the need for antibiotic stewardship in kidney transplant recipients.
· This study presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
· The most important details in this text are that asymptomatic bacteriuria (ASB) is commonly screened for and treated in the early posttransplant phase, and that UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
· Fluoroquinolones are among the most common antibiotics in the treatment of urinary tract infections in KT recipients due to their widespread availability, intravenous and oral formulations, and excellent penetration into the urinary tract.
· This study examined the clinical characteristics of 207 kidney transplant recipients (KT) from January 2015 to August 2020.
· Of 130 patients with a UTI, 68 had typical symptoms and/or clinical/laboratory signs of inflammation.
· In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded, and ten patients found typical symptoms accompanied by laboratory and urine chemistry findings consistent with UTI.
· Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis).
· 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant.
· E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
· The most commonly isolated gram-positive bacteria was E. faecalis
· In this cohort, urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
· Prevention and adequate treatment of urinary tract infections in KT recipients is crucial, and several measures have been proposed to prevent infections.
· In order to detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant.
· TMP-SMX is prescribed for 6–12 months after KT to prevent Pneumocystis jirovecii pneumonia. TMP-SMX reduced UTIs for 6 months after KT.
· For ureteral stent removal, Lee et al. found that omitting periinterventional antibiotics (usually Ciprofloxacin) was not harmful if the patient was on TMP-SMX prophylaxis.
· Empiric antibiotics should always cover gram-negative enterobacteria. , carbapenem is the best choice for critically ill patients. After culture result , an oral narrow-spectrum antibiotic may be appropriate.
· can wait for the final antibiotic resistance testing in ASB and use targeted therapy instead of empiric broad spectrum .
· Antibiotic stewardship and hospital hygiene data can be useful but must be monitored and updated. Level of evidence
· Level 2, retrospective cohort study Our practice:
– Supportive measures.
– IV AB, carbapenem , tazocin , or depending on last previous positive culture if recurrent.
– Chronic suppressive therapy with ciprofloxacin low dose , TMP/SMX , Fosfomycin or nitrofurantoin.
Urinary tract infections (UTI) are the most common infection in the early postoperative
phase after kidney transplantation (KT) .
The incidence of a UTI ranges from 4–80% .
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 .
asymptomatic bacteriuria (ASB) is defined as the presence of105 colony-forming units of bacteria in the absence of symptoms .
Asymptomatic bacteriuria is encountered in around 25% of KT recipients .
Thus, ASB is commonly screened for and treated in the early posttransplant phase , even though there is ongoing controversy about the impact of ASB and UTI on the overall patient and graft outcome .
In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression.
The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function .
A perioperative antibiotic prophylaxis is standard in KT.
But the regimens is heterogenous .
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae . Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci .
Fluoroquinolones are among the most commonly used antibiotics.
After the FDA warning in 2019 regarding the use of fluoroquinolones both in general and KT recipients in particular.
AIM OF STUDY:
To evaluated our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based on data provided by our hygiene department
Methods:
retrospectively analysis of the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated.
Results:
Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed
UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both,
bacterial resistance was more common in the study cohort than in the control group.
Discussion
Urinary tract infections are the most common infection in the early postoperative phase
after kidney transplantation .
They can lead to sepsis and are a potential threat to life.
It has a negative impact on allograft function .
UTI associated with worse creatinine clearance both at the end of our study and one year after KT.
prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
that asymptomatic bacteriuria (ASB) does not affect graft function but
inadequate use of antibiotics certainly has the potential to do so .
Several measures have been proposed to prevent infections in KT recipients.
1- A single shot antibiotic is administered prior to incision.
2- Prolonged antibiotics have not proven beneficiary for the prevention of UTI or surgical site infection .
3- intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, is proven promising .
The presence of indwelling catheters, mainly ureteral stents and Foley catheters
is an independent risk factor of urinary tract infections .
the ideal timing of stent removal is three weeks post-transplant .
Ciprofloxacin was shown to prevent UTIs 25 years ago, but was later reserved for treatment rather than prophylaxis.
a recent randomized trial that showed the preventative efficacy of Fosfomycin .
TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic
dose for 6–12 months after KT.
The Mayo clinic group reported a reduction in UTIs when TMP-SMX was prescribed for 6 months after KT .
There is a report of , a lower rate of septicemia while patients were on TMP-SMX prophylaxis .
In contrast, Singh et al. reported no difference in the incidence of urinary tract infections
and asymptomatic bacteriuria in patients that underwent Pneumocystis prophylaxis in their
cohort .
At our center the UTI rate was significantly lower in patients that were on TMP-SMX.
Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly
gram-negative bacteria.
In this dtudy 89 gram-negative strains of bacteria were isolated compared to 46 gram-positive ones.
Gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria.
Empiric antibiotics should therefore always cover gram-negative enterobacteria.
There was no resistance to carbapenems in our gram-negative bacteria, which makes them the
most attractive choice for critically ill patients.
Of the remaining antibiotics Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to, at a rate of 15%.
In this study there is high bacterial resistance to Ciprofloxacin was in our cohort (29%).
With a resistance to aminopenicillins in over 50% and a resistance to cephalosporins of nearly
20% we strongly recommend treating urinary tract infections after Kidney Transplantation
with empiric intravenous antibiotics according to local resistance patterns. This study report 59 episodes of ASB (29%) is comparable to other reports .
A meta-analysis from Spain recommended not to treat ASB after the
first month post KT .
This practice has been backed by two randomized controlled multicenter trials report that no benefits in treating ASB two months after kidney transplant .
Unfortunately, there are no randomized controlled trials on the treatment of ASB within the first month after KT.
The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics
such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not
recommended as first line therapy for urinary tract infections in transplant recipients.
In this study , not a single strain of E. coli was resistant to Fosfomycin or Nitrofurantoin, while over 40% were resistant to TMP-SMX.
The author strongly advocate against the use of fluoroquinolones in ASB.
While symptomatic patients need to be treated empirically to avoid development of
septicemia, we believe it is safe to wait for the final antibiotic resistance testing in ASB and
use targeted therapy rather than empiric broad spectrum coverage followed by a step- down
approach.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind which may vary a lot regionally.
More specifically, the resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
Strengths and Limitations
1- We presented single center data on bacterial isolates from urine samples of over200 kidney transplant recipients early after kidney transplantation.
2- The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
3- Still, we were able to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
4- Given the uneven sample sizes between the study and control group statistical omparisons were limited to exploratory data.
5- Therefore, multicentric comparative data will be necessary prior to generalization of our data.
5. Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection.
This leads to a low threshold for initiating antibiotic treatment when infection is suspected. In our cohort between 207 patients 262 courses of antibiotics were prescribed. Of these, 180 were prescribed antibiotics for suspected urinary tract infection. Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
Q2- What is the level of evidence provided by this article?
Level of evidence 2
Q3- How do you treat recurrent UTI at your workplace?
Exclude any structural abnormalties.
Patient usually treated depending on the result of C/S .
Treat and control other medical disease DM ,
Education of female patient regarding preventive measures.
Please summarise this article.1) A retrospective study looking at 207 kidney transplantation at a single centre between January 2015 and August 2020
2) The cohort was divided into No UTI (139 patients) vs UTI (68 patients) (asymptomatic bacteriuria, UTI)
3) The outcome was graft functions upon discharge and 12 months. Patients with UTI were associated with poorer graft outcomes. The most commonly prescribed antibiotics were ciprofloxacin and piperacillin/tazobactam
What is the level of evidence provided by this article?Level 2: Cohort study
How do you treat recurrent UTIs at your workplace?1) Asymptomatic vs symptomatic
2) Serum creatinine to look at concomitant raises in serum creatinine
3) Urine culture
4) If symptomatic treat empirically, and if asymptomatic to wait and evaluate the culture
5) Reduction of immunosuppression in recurrent UTI
6) Further investigations in recurrent UTI ie: ultrasound, cystoscopy and cystourethrogram
UTIs are defined as the growth of 105 colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
Controversy about the impact of ASB and UTI on the overall patient and graft outcome
The incidence of UTI is assumed to be lower in living donation kidney transplantation.
The most common pathogens found in urine samples after KT are Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae
This study evaluated our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based
Methodology
Theyretrospectively analyzed the charts of adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
As protocol all KT recipients had urine samples sent for culture every Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. Simultaneous pancreas or liver transplantation were excluded.
Results
Of the 207 patients included, 73 underwent living donation , and 134 received deceased donor kidney transplantation
The median length of stay was 20 days (range 10–53)
During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection.
In 58 of these 68 patients, growth of a urinary pathogen on urine culture
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.
The most common indication for antibiotic treatment was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria was E.coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high,with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
Discussion
In this study urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
Prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
Prolonged antibiotics for the prevention of urinary tract or surgical site infection may not be benificial
To decontaminate the bladder, intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, shown promising in patients with recurrent UTIs.
The presence of indwelling catheters is an independent risk factor of urinary tract infections.
For reduction rate of UTI after KTx, early removal of the ureteral stent is suggested.
A meta-analysis from Spain recommended not to treat ASB after the first month post KT.
The treatment of asymptomatic bacteriuria with narrow-spectrum antibiotics such as TMP-SMX/ Fosfomycin/ Nitrofurantoin/ Pivmecillinam are not recommended as first line therapy for urinary tract infections in transplant recipients.
Limitation
Single center data.
Retrospective analysis of data
Uneven sample size between study & control group statistical comparison limited to exploratory data.
Strength
Demonstration of distinct different resistant pattern to commonly used antibiotics in UTI between KTR & control group.
.
Conclusion
Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Level of evidence: 2 Cohort study
How do you treat recurrent UTI at your workplace?
Empiric oral antibiotic according to susceptible patten of bacteria.
Then treatment as urine c/s report- oral or iv
Prophylactic antibiotic TMB-SMX or nitrofurantoin (at prophylactic dose) for 3-6 months.
Exclusion of any structural or functional causes do as needed U/S KUB, MCUG, CT KUB ,Urodynamics
Urinary tract infections (UTIs) are common infection in the early postoperative phase of kidney transplantation, with an incidence of 4-80%.
Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients, and ASB is commonly screened for and treated in the early posttransplant phase.
In living donation kidney transplantation, the incidence of UTI is lower due to shorter waiting time, higher volume urine output, and early onset graft function.
The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis, and Klebsiella pneumonia.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KT recipients.
Materials and Methods
· Retrospectively, the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral, and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020 have been analyzed. Results
· The most common indication for antibiotic treatment was suspected urinary tract infection, with fluoroquinolones being the most commonly prescribed antibiotic.
· E. coli was the most commonly isolated gram-negative bacteria. Discussion
Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation, leading to sepsis and a potential threat to life.
To prevent infections, several measures have been proposed, such as a single-shot antibiotic administered prior to incision, Gentamicin irrigation of the bladder prior to the ureteral anastomosis, and removal of indwelling catheters.
Prophylactic antibiotic regimens have been studied, including Ciprofloxacin, Fosfomycin, and TMP-SMX.
Empiric antibiotic coverage of gram-negative enterobacteria was found to be the most attractive choice for critically ill patients.
Narrow-spectrum antibiotics such as TMP-Sulphamethoxazole / Fosfomycin / Nitrofurantoin / Pivmecillinam are safe and effective in treating asymptomatic bacteriuria but should not be used as first-line therapy.
Conclusions
Antibiotic stewardship programs aim to prevent infections after surgery and rationally use antibiotics. Solid organ transplant recipients are at increased risk of fatal infection, leading to a low threshold for initiating antibiotic treatment. To reduce this number, a team effort of transplant surgeons and physicians and antibiotic stewardship teams is needed. ========================== Level of Evidence II ========================== How do you treat recurrent UTI at your workplace? Recurrent UTI after limited workup including (Ultrasound, MCUG, Urine culture, and sensitivity) to manage any structural abnormalities, and foreign bodies, then start them with proper empirical and culture-based antibiotics promptly.
Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship? Introduction.
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 and if no symptoms considered asymptomatic bacteriuria which is encountered in around 25% of KT recipients, risk of UTI is less in LKTX than cadaveric TX, and still short – long term graft effect is controversial.
Prophylactic pre-operative antibiotics is decreasing incidence of UTI, because gram negative bacteria is the most common cause of UTI in KTX recipient as well as in general population thus fluoroquinolones is considered the most common used medications for treating UTI. Aim of the work:
1-To evaluate antibiotic prescription practice during the first 30 days after kidney transplant.
2-To detect the incidence of ASB and UTIs.
3-To compare the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population. Materials and Methods.
A retrospective study that screened our hospital information system for all patients who
underwent kidney transplantation at the department of General, Visceral and Transplantation
Surgery of the University Hospital of Tuebingen, Germany. All adult patients who underwent KT at our center between January 2015 and August 2020 which are 207 patients. Results:
1-During the first 30 days after their transplant ,130 patients (63%) were suspected
to have a urinary tract infection, 68 patients of 130 patients fulfilled the criteria of a UTI (typical symptoms and/or clinical/laboratory signs of inflammation) In 58 of these 68 patients growth of a urinary pathogen on urine culture was recorded.
2-The most common isolates from urinary cultures were gram-negative enterobacteriaceae
as well as enterococcus species and E-coli was the most common one.
3-Of the 180 suspected UTIs, fluoroquinolones were the most commonly prescribed
antibiotic followed by Piperacillin/Tazobactam), aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporin, Fosfomycin, Pivmecillinam, Nitrofurantoin , Linezolid, and others.
4-Resistance to Ampicillin / Sulbactam, fluoroquinolones and Trimethoprim-Sulfamethoxazole (TMP–SMX) is substantially higher in the Kidney Transplant cohort.
5-Urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT. Discussion.
Prevention is so much important to prevent UTI, starting from single dose pre-operative antibiotics, intra-operative antibiotic irrigation, early removal of Foleys catheter as well as ureteric stent, now trimethoprim-Sulfamethoxazole (TMP–SMX) prophylaxis against PJP has a prophylactic role in UTI prevention and empiric antibiotics therapy has preventive effect of UTI progression till C/S result released and chosen antibiotics mainly depends on hospital local policy with microbiologist guidance (antibiotic stewardship teams) according to most common isolation organism and the common resistant antibiotics. Strength.
1-Demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group.
2-Clearly demonstrate the role of prophylactic antibiotics and prevalence of resistance. Weakness.
1-Difficult to distinguish between colonization/bacteriuria and urinary tract infection.
2-Single center study.
3-Small sample size. Conclusion.
UTI is a common complication post kidney transplant and prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Using prophylactic antibiotics and empirical use of high sensitive antibiotics according to local institution survey of organism resistance and prevalence of infection can decrease rate of complicated UIT in PKTX which can affect graft and patient survival. A retrospective cohort study (level of evidence III). How do you treat recurrent UTI at your workplace?
We are treating UTI on culture base.
Fine tuning of immunosuppression.
Treat predisposing factors (uncontrolled DM for example ), behavior management.
KUB.USG, up to CT KUB.
Urodynamic and involve the urologist.
Introduction:
-Urinary tract infections (UTI) are the most common infections after kidney transplantation.
-The incidence of a UTI ranges from 4–80% in the early postoperative phase after kidney transplantation (KT) , a symptomatic bacteriuria is encountered in around 25% of KT recipients
-Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low.
-The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
-The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumonia. Aim:
-This study evaluated the effect of antibiotic during the first 30 days after kidney transplant , and the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population. Methodology:
-Theyretrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
-As protocol all KT recipients had urine samples sent for culture every Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
-The median length of stay was 20 days (range 10–53).
-Patients that underwent simultaneous pancreas or liver transplantation were excluded.
-All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. Results:
-Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up.
-The most common isolates from urinary cultures were gram-negative enterobacteriaceae as well as enterococcus species , E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
-The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam.
-To both, bacterial resistance was more common in the study cohort than in the control group. Discussion;
-In this cohort urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
-Thus, prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
-Prolonged antibiotics have not proven beneficiary for the prevention of urinary tract or surgical site infection.
-In order to decontaminate the bladder they perform intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, which has been proven promising in patients with recurrent UTIs.
-The presence of indwelling catheters, mainly ureteral stents and Foley catheters is an independent risk factor of urinary tract infections.
-So, for reduction rate of UTI after KTx, it require removal the ureteral stent at 21 days after KT or earlier if there is suspicion for bacteriuria or infection in order to remove biofilms & TMP-SMX was prescribed for 6 months after KT .
-Following the 2019 FDA warning against the use of fluoroquinolones in KT recipients, this has slowly led to a decrease in Ciprofloxacin use.
-Recently, more data is becoming available on the treatment of ASB early after transplantation.
-A meta-analysis from Spain recommended not to treat ASB after the first month post KT.
-The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not recommended as first line therapy for urinary tract infections in transplant recipients. Limitations;
-They presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
-The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
-Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data.
-Therefore, multicentric comparative data will be necessary prior to generalization of this data. Conclusion:
-Urinary tract infections appear to be linked to worse graft functions.
-Thus, prevention and treatment should be accompanied by antibiotic stewardship teams.
-This Article is Cohort study with ( LOE 2b ).
-How do you treat recurrent UTI at your workplace? -According the severity of UTI; Admission and start him IVF. -Strat empiric antibiotic if patient has symptomatic dysuria and urine analysis suggestive for UTI.
-Usually we start broad spectrum antibiotic Piperacillin/Tazobactam or meropenem then switch according to the culture result for 2 weeks.
-Prophylactic TMB-SMX for 3-6 months. -In recurrent UTI we usually exclude any structural or functional causes, do U/S KUB & MCUG, and urology review. -Patients especially females should be educated about self hygiene.
Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
1. Please summarise this article. 2. What is the level of evidence provided by this article? 3. How do you treat recurrent UTI at your workplace?
Please summarise this article.
Introduction The Urinary tract infections (UTIs) are the most common infection in the early postoperative with an incidence of 4-80%.
UTI defined as growth of 10^5 CFU on proper urine sample, early morning sample, or from a sterile catheter associated with upper or lower urinary tract symptoms, (dysuria, frequency, or localized pain).
Asymptomatic bacteriuria (ASB) defined as presence of > or more 10^5CFU of bacteria without symptoms, it occurs in around 25% of KTR. ASB frequently screened and treated in post-transplant period.
In transplant recipient’s threshold of ASB treatment is lower due to increased risk of septicemia or atypical presentation.
Multi-resistant gram-negative bacteria (MRGN) = bacteria resistant to three or more of the following antibiotics (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems). The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae.
UTI incidence is lower in living donor kidney transplant recipients because: shorter waiting time, higher volume UOP prior, during transplantation & early onset graft function.
Peri-operative antibiotic prophylaxis is a standard in kidney transplant.
EAU guidelines recommend a single shot antibiotic prophylaxis.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in kidney transplant recipients, but after FDA warning in 2019 re-evaluation of empiric antibiotic is considered. Aims of the study:
Evaluation of antibiotic prescription practice in first 30 days post-transplant. Evaluation of ASB and UTI incidence Compare antibiotic susceptibility of isolated urinary tract bacteria from KTR to isolated bacteria from local population. Materials and Methods:
Observational longitudinal cohort study.
Inclusion criteria: Patients above 16 years who underwent kidney transplantation between January 2015 and August 2020.
Exclusion criteria: Patients who underwent simultaneous liver and pancreas transplant.
Data acquisition was conducted for all patients who underwent kidney transplantation at the University Hospital of Tuebingen, Germany between January 2015 and August 2020. Medical reports were screened for intra- and perioperative microbiological cultures,and the control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene.
Immunosuppressive protocols included 500 mg of iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
Perioperative antibiotics included Single-Dose Beta-Lactam, Ampicillin/Sulbactam, or 3 3 g of Ampicillin/Sulbactam.
Treatment protocols for Urinary Tract Infections included iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
The protocol recommended empiric antibiotics for urinary tract infections and asymptomatic bacteriuria.
Urinary catheters were placed preoperatively and removed on postoperative day (POD) 5 in patients with retained diuresis.
Ureterocystoneostomy was performed according to Lich-Gregoir.
Intraoperatively, a Double-J-ureteral stent was placed and removed on POD 21.
Postoperative follow-up included blood workup, urine sampling, ultrasounds, and renal biopsies.
Patients were seen at the outpatient clinic for blood and urine workup, clinical and sonographic follow-up.
Results:
Clinical Characteristics:
The study analyzed the charts of all consecutive adult kidney transplant recipients from January 2015 to August 2020 at the University Hospital Tuebingen, Tuebingen, Germany.
207 patients met the inclusion criteria, 73 underwent living donation kidney transplantation, and 134 received a kidney from a deceased donor. During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection. In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded.
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures. 135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive. Ureaplasma (1%) was excluded from this analysis. The most common indication for antibiotic treatment in kidney transplant recipients was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria was E.coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high,with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%). Discussion:
Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation and can lead to sepsis and a potential threat to life. Recent data suggests a negative impact of even single episodes of (complicated)urinary tract infections on allograft function.
To prevent infections in KT recipients, several measures have been proposed, such as a single shot antibioticadministered prior to incision, Gentamicin irrigation of the bladder prior to ureteral anastomosis, and removal of indwelling catheters.
Prophylactic antibiotic regimens have been studied, with Ciprofloxacin being the beststudied drug.
TMP-SMX is recommended for the prevention of Pneumocystis jiroveciipneumonia and is usually administered in a prophylactic dose for 6-12 months after kidney transplant. TMP-SMX prophylaxis was initiated in 2018 in all KTX recipients, and the UTI rate was significantly lower in patients on TMP-SMX.
Gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria.
There was no resistance to carbapenems in the gram-negative bacteria, and Piperacillin / Tazobactam was the least gram-negative resistant substance.
Oral treatment alternatives for empiric treatment of UTIs are highly sought after but did not exist in this study.
Patients undergo weekly screening for urinary pathogens for the first month post-transplant. Recently, more data is becoming available on the treatment of ASB early after transplantation. A potential alternative to screening cultures could be reflex urinary cultures triggered by positive urinary nitrite or a threshold urinary white blood count. Narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients. Fluoroquinolones should not be used in ASB.
The choice of antibiotic for empiric treatment of UTIs must be made with thecenters’ urinary tract infection’s spectrum and antibiotic resistance in mind.
Resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
Prevention of the development of resistant strains in dialysis patients will be anupcoming challenge for antibiotic stewardship teams worldwide.
The MRGN rate of 10% was like other German KTX centers but was higher than the average of 5% in a 2017 meta-analysis. Strengths and Limitations:
Single center data showed distinct differences in resistance to commonly used antibiotics in urinary tract infections between kidney transplant recipients and a control group.
All urinary cultures done at tertiary university hospital.
Multi-centric comparative data is needed for generalization. Limitation:
Single center data.
Retrospective analysis of data (poor > Prospective)
Uneven sample size between study & control group statistical comparison limited to exploratory data. Conclusions: UTI is associated with lower graft function and so prevention and early and proper treatment is highly recommended.
Screening for ASB using urine culture or urine analysis with subsequent culture in suspicious patients is recommended during the first month after transplantation, and treatment should be given upon confirmation of the ASB.
UTI usually occurs due to infection with gram negative organism, so the use of empiric antibiotics with gram negative coverage is recommended.
It is recommended to treat UTI using empiric IV antibiotic according to the local drug resistance, then switching to an oral antibiotic after culture and sensitivity result ASB should be treated only in the first month after transplantation using narrow spectrum antibiotics or waiting till culture result.
Carbapenems is the drug of choice in the treatment of UTI in critically ill patients. Antibiotic stewardship programs are essential to reduce the number of antibiotics prescribed to solid organ transplant recipients. Prevention of UTI:
Peri-transplant surgery, one dose of perioperative antibiotic is recommended, (Cefazolin or Vancomycin).
Screening of UTI by either urine culture or urine analysis (and culture taken if urine analysis is suspicious for UTI) every week in the first month after transplantation, some recommends screening for 3 months after transplantation, but this is debatable since after the first month the incidence of ASB decrease to 4%.
Removal of urinary catheter as soon as possible after transplantation Removal of stents as soon as possible at 3 weeks after transplantation and may be before if there is bacteriuria.
Prolonged antibiotic prophylaxis, the most important regimen is the use of SMX-TMP used already for PCP prophylaxis for 6-12 m which was associated with reduction of UTI episodes and severity.
Antibiotic prophylaxis using ciprofloxacin during the period of stent removal, but it is not needed if the patient is already on SMX-TMP prophylaxis. What is the level of evidence provided by this article? Cohort study ==> The level of evidence is II. How do you treat recurrent UTI at your workplace?
Prolonged Ab prophylaxis, the most common regimens TMP-SMX is used to treat recurrent UTI in renal transplant patients for 3 months, Dose of SMX-TMP DS tablet Q MWF 3 times weekly or SS tablet daily or nitrofurantoin 100 mg once daily for 6-12 months.
Lifestyle changes, including drinking plenty of water, frequent voiding, post coital voiding, wiping from front to back in females.
For premenopausal women, modification of contraception may be advised such as removal of IUD and Vaginal Estrogen twice weekly cream or tablets. We can use cranberry juice and d- mannose.
Do not forget, KUB Imaging to rule out any urological abnormality and cystoscopy.
Introduction
In the early postoperative phase after kidney transplantation, urinary tract infections (UTIs) are a common infection. UTIs are defined as the growth of 10^5 colony forming units on a proper urine sample in the presence of symptoms such as dysuria, urinary frequency or localized pain. Asymptomatic bacteriuria (ASB) is defined as the presence of ≥ 10^5 colony-forming units of bacteria in the absence of symptoms. ASB is common in kidney transplant recipients.
In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression. The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
The most commonly found pathogens in the urine of kidney transplant recipients are: E. coli, E. faecalis and K. pneumoniae. Common antibiotics used for the treatment of UTIs in kidney transplant recipients initially were fluoroquinolones. However, their use had to be reevaluated due to the recent FDA warnings.
The aim of this study was to evaluate antibiotic prescription practice the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population.
Materials and methods
Adult patients who underwent kidney transplantation at the hospital between January 2015 and August 2020 were included in the study. The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation.
The immune suppression protocol included 500 mg of IV Methylprednisolone as well as either Basiliximab or Anti-Thymocyte Globulin for intermediate risk or an Anti-CD56-Antibody for high risk patients.
Maintenance immunosuppression consisted of steroids in a tapering dose, calcineurin inhibitor and mycofenolic acid. Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam or Ampicillin/Sulbactam.
From 2018 all patients received Pneumocystis prophylaxis with TMP-SMX. Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
As per the protocol, all episodes of urinary tract infections and asymptomatic bacteriuria were treated with antibiotics. The initial emperic treatment was Ciprofloxacin, but after the recommendation to avoid fluoroquinolones, it was changed to Piperacillin/Tazobactam. For patients who were critically ill, Meropenem was used. Urinary catheters were placed preoperatively and removed on postoperative day 5. Until discharge all patients received blood workup three times per week as per the protocol. They also underwent routine urinary sampling (chemistry and culture) every Monday and when clinical or laboratory signs of inflammation/infection were present. l patients had at least two ultrasounds per week to evaluate graft perfusion, rule out ureteral stenosis and perirenal fluid collections. After discharge, the patients were reviewed after one week in outpatient clinic.
Results
207 patients met the inclusion criteria. Out of these patients 73 patients underwent living donation kidney transplantation, 134 underwent deceased donor transplantation. 119 patients were male, 88 were female. The median age of transplantation was 55 years. During the first 30 days after their transplant 130 patients (63%) were suspected to have a urinary tract infection, out of which 68 patients fulfilled the criteria of a UTI.
The most common isolates from urinary cultures were gram-negative enterobacteriaceae as well as enterococcus species. E. coli was the most common pathogen and was found in 49 cultures, followed by E. faecalis. The culture results during urinary tract infections compared to asymptomatic bacteriuria is distinctly different. In total, 135 bacterial isolates were cultured. Of these, 88 (65%) were gram-negative and 46 (34%) were gram-positive. Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment. This was excluding perioperative and periinterventional prophylaxis. Overall, 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant. Suspected UTI was the most common indication for antibiotic treatment. 5 patients were treated for urosepsis. The patients that used at least one course of antibiotics during the initial hospital admission has significantly worse GFR at discharge.
9 patients presented with multiresistant gram-negative bacteria. A significant percentage of gram negative bacteria was resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin. None of the patients had carbapenem resistant gram-negative bacteria. It was noted that Ciprofloxacin was the most prescribed antibiotic, and E. coli, the common isolate, was resistant to fluoroquinolones in 45%. They study attempted to specifically compare resistance patterns in the bacteria grown from urinary samples of KT recipients and the general population, and the resistance patterns were distinctly different. Resistance to Ampicillin/Sulbactam was present in 76 of the 135 strains (56%), to Piperacillin/Tazobactam in 35 strains (26%), to 3rd generation cephalosporins in 62 strains (46%), to fluoroquinolones in 52 strains (39%) and to carbapenems in 23 strains (17%). It was thought that a large proportion of the resistance to Piperacillin/Tazobactam and carbapenems may be due to the prevalence of Enterococcus species.
Discussion
UTIs are a common infection in the early postoperative phase after kidney transplantation and can lead to sepsis. Recent data has also suggested that UTIs may have a negative impact on allograft function. In this study, UTIs were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after transplantation. Therefore, the prevention and treatment of UTIs in kidney transplant recipients is important. Inadequate use of antibiotics in asymptomatic bacteriuria may also affect the allograft function. The overall status and comorbidities of the patient may also add to the complications. Intraoperstive Gentamicin irrigation of the bladder prior to ureteral anastomosis has proved promising in patients with recurrent UTIs. The presence of indwelling catheters, mainly ureteral stents and Foley catheters is an independent risk factor of urinary tract infections.
UTIs in patients who have received kidney transplants require empiric antibiotic coverage of mainly gram-negative bacteria. This study showed that gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria. There was no resistance to carbapenem by the gram-negative bacteria, which makes them an apt choice for critically ill patients. The strength of the study is its ability to demonstrate distinctly different resistance patterns to commonly used antibiotics. The limitations include the retrospective nature of the study and that it was conducted a single center.
Conclusion
Kidney transplant recipients are at an increased risk of infection, and some may be fatal. This leads to a low threshold for initiating antibiotic treatment when infection is suspected. It is important to lower the numbers of patients receiving antibiotics, and it requires a multidisciplinary approach between the transplant surgeons, physicians and antibiotic stewardship teams.
Study Limitations
Retrospective study
Single center data
Due to the uneven sample sizes between the study and the control group, statistical comparisons were limited to exploratory data
Level of Evidence:
This is a retrospective study, therefore the LOE is II
Local Practice
In my center, we treat ASB and UTIs. The preferred drugs are second generation or third generation cephalosporins for outpatient treatment. For in-patient treatment, we use tazobactum/piperacillin then tailor the antibiotic based on the culture and sensitivity results
We routinely give TMP/SMX to all our patients for six months
UTI is the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%. Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients. Fluoroquinolones are the most common antibiotics for treatment.
Materials and Methods:
The study retrospectively screened the hospital information system for all adult patients who underwent kidney transplantation at the University Hospital of Tuebingen between January 2015 and August 2020. The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation. The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients. Immunosuppressive protocol consisted of 500 mg of iv Methylprednisolone and either Basiliximab or Anti-Thymocyte Globulin. Maintenance immunosuppression consisted of steroid tapering, calcineurin inhibitor, tacrolimus 0.1 mg/kg/day starting day 1, and mycofenolic acid. Urinary catheters and double-J-ureteral stents were placed preoperatively and removed on postoperative day 5 in patients with retained diuresis and reduced urine output prior to transplantation, followed by postoperative follow-up. Multi-resistant gram-negative bacteria were defined as 3-MRGN, 4-MRGN and 5-MRGN according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) thresholds and minimal inhibitory concentrations.
Results:
The study found that 207 patients met the inclusion criteria for kidney transplantation at the University Hospital Tuebingen, with 207 receiving living donation kidney transplantation and 134 receiving a deceased donor from a deceased donor.
Microbiological Results: The most common isolates from urinary cultures were gram-negative enterobacteriaceae and enterococcus species, with E. coli being the leading pathogen. The culture results during urinary tract infections compared to asymptomatic bacteriuria are different, with 56 gram-negative isolates recorded during a UTI compared to 32 gram-positive isolates. The most commonly prescribed antibiotics were fluoroquinolones, followed by aminopenicillins, cephalosporins, and others. The most commonly isolated gram-negative bacteria was E. coli, which was resistant to Ampicillin/Sulbactam, Piperacillin/Tazobactam, fluoroquinolones, carbapenems, Fosfomycin, and Nitrofurantoin. Bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam, Piperacillin/Tazobactam, fluoroquinolones, and carbapenems due to Enterococcus species. Strength : Different patterns of resistance among study groups are identified to commonly used antibiotics in urinary tract infections. Limitation : This is a single center prospective study, the different sample sizes between the study and control groups .
Conclusions:
Antibiotic stewardship programs are essential to reduce the risk of fatal infection in solid organ transplant recipients.
What is the level of evidence provided by this article?
level 2
How do you treat recurrent UTI at your workplace?
In recurrent UTI we usually exclude any structural or functional causes,take C/S and check for other predisposing medical problems like DM ,prophylaxis TMB-SMX for 3-6 months and patient education about self hygiene especially females
· Urinary tract infections (UTIs) are the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%.
· Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients, and ASB is commonly screened for and treated in the early posttransplant phase.
· In living donation kidney transplantation, the incidence of UTI is lower due to shorter waiting time, higher volume urine output, and early onset graft function.
· The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis, and Klebsiella pneumonia.
· Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KT recipients.
Materials and Methods
· Retrospectively, the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral, and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020 have been analyzed.
· All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patient’s clinical characteristics and outcomes were evaluated.
Results
· The most common indication for antibiotic treatment was suspected urinary tract infection, with fluoroquinolones being the most commonly prescribed antibiotic.
· E. coli was the most commonly isolated gram-negative bacteria.
Discussion
· Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation, leading to sepsis and a potential threat to life.
· To prevent infections, several measures have been proposed, such as a single-shot antibiotic administered prior to incision, Gentamicin irrigation of the bladder prior to the ureteral anastomosis, and removal of indwelling catheters.
· Prophylactic antibiotic regimens have been studied, including Ciprofloxacin, Fosfomycin, and TMP-SMX.
· Empiric antibiotic coverage of gram-negative enterobacteria was found to be the most attractive choice for critically ill patients.
·Narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are safe and effective in treating asymptomatic bacteriuria, but should not be used as first-line therapy.
Conclusions
· Antibiotic stewardship programs aim to prevent infections after surgery and rationally use antibiotics.
· Solid organ transplant recipients are at increased risk of fatal infection, leading to a low threshold for initiating antibiotic treatment.
· To reduce this number, a team effort of transplant surgeons and physicians and antibiotic stewardship teams is needed.
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Level of Evidence II
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How do you treat recurrent UTI at your workplace?recurrent UTI passes through some workups including (Ultrasound, MCUG, Urine culture, and sensitivity) to manage any structural abnormalities, and foreign bodies, and to start the proper empirical or culture-based antibiotics promptly.
UTI …most common infection in the early post transplantation period (4-80%)
UTI : increased risk of urosepsis and graft failure
asymptomatic bacteriuria ASB : equal or more than 10 log 5 CFU in absence of symptoms
ASB ….25%
there is lower threshold for treatment of UTI in transplant patients because of fear the risk of urosepsis and sometimes atypical presentation as a result of immunossupresions.
the incidence of UTI lower in Linving donor in compare to deceased donor
peri-op AB prophylaxis is highly recommended
as much as possible prevention and proper treatment were essential
a single dose AB administration prior to incision is a standard
intra OP. gentamicin irrigation of bladder prior to ureteral anastomosis also effective especially in those with recurrent UTI
the ureteral stent and foleys catheter were undependable risk factors for UTI
In our center also we removed JJ stent at 3 weeks ,same as the article
in our center also giving bacteria for 6 months for prophylaxis of pneumocystis
1.Please summarise this article. Introduction
The most frequent (the incidence is 4–80%.) infections after KTX are urinary tract infections (UTI). UTIs are characterized as the presence of symptoms (dysuria, frequency, or localized pain) along with the growth of 105 CFUs on an appropriate urine sample.
Asymptomatic bacteriuria (ASB) is defined as the presence of =/>105 CFUs of bacteria in the absence of symptoms. Asymptomatic bacteriuria is seen in around 25% of KTX recipients. Even though there is ongoing debate regarding how ASB & UTI affect the overall patient & graft outcome, ASB is frequently detected & treated in the early post-TX phase.
The threshold for using broad spectrum antibiotics to treat UTI & asymptomatic bacteriuria is low due to the possibility of urosepsis & probable danger to the graft. Previously, in individuals who received KTX fluoroquinolones were the preferred prescription medication. However, other therapeutic approaches need to be researched after the new advice to avoid them in these individuals. The study
Asymptomatic bacteriuria (ASB) & UTI, as well as the patients’ clinical features & outcomes, were retrospectively analyzed in 207 consecutive adult KTX done between January 2015 & August 2020 at the University Hospital of Tuebingen.
Induction therapy was Methylprednisolone as well as either Basiliximab for low immunologic risk or ATG for intermediate risk or Alemtuzumab for high-risk patients (without MMF until lymphocytes have regenerated).
At the option of the transplant surgeons, perioperative antibiotics were either a Single-Dose Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) or 3X3 g of Ampicillin/Sulbactam (Q0h/12h/24h).
According to protocol, antibiotics were to be used to treat any bouts of urinary tract infections & asymptomatic bacteriuria.
In patients who had retained diuresis before TX, urinary catheters were removed on POD 5. Patients with decreased urine output had their catheters removed on POD. A DJ-ureteral stent was implanted intra-operatively & removed on POD 21.
Urinary samples were sent for urinary culture once weekly & once there was suspicion for UTIs. Results
130 patients (63%) were suspected to have a UTI.
68/130 patients fulfilled the criteria of a UTI (typical symptoms &/or clinical/laboratory signs of inflammation) In 58/68 patients, growth of a urinary pathogen on urine culture was recorded.
Enterococcus species & gram-negative enterobacteriaceae were the most typical isolates from urine cultures. E. coli was the most prevalent pathogen, followed by E. faecium & E. faecalis.
Overall, 9 patients presented with multi-resistant gram-negative bacteria.
Patients who developed UTI had worse graft function at discharge & at the 12 months follow-up.
Ciprofloxacin and Piperacillin/Tazobactam were the most often recommended antibiotics.
Resistance to Ampicillin/Sulbactam was present in 56% of the strains, to Piperacillin/Tazobactam in 26%, to 3rd generation cephalosporins in 46%, to fluoroquinolones in 39% & to carbapenems in 17% of the strains.
To both, bacterial resistance was more common in the study cohort than in the control group. Discussion
In this cohort, UTIs were associated with significantly poorer creatinine clearance. Therefore, it’s essential for KTX recipients to avoid & manage UTIs appropriately.
Although there is growing evidence that ASB does not influence graft function, improper antibiotic administration undoubtedly can do so.
A number of strategies have been suggested to prevent UTIs. Prior to the incision, a single shot of an antibiotic is given. Long-term antibiotic use has not been found to be helpful. In individuals with recurrent UTIs, gentamicin irrigation of the bladder prior to ureteral anastomosis has shown promise. Ureteral stents & Foley catheters are standalone risk factor for UTIs. It is optimal to remove the ureteral stent 21 days following KTX (Visser et al.). Limitations
The study’s retrospective design.
Sample sizes between the study & control groups are not equal. Comparative statistics were limited to exploratory data.
Prior to generalizing the study data, a multicentric comparison analysis will be required. Conclusions:
It seems that worse graft functioning is related to UTIs. Thus, teams of antibiotic stewards should be present along with prevention and treatment. ====================== 2.What is the level of evidence provided by this article?
Level II ====================== 3.How do you treat recurrent UTI at your workplace?
After sending a suitable urine sample for bacteriological culture, we provide a broad range antibiotic while we wait for the results. The two antibiotics that are most frequently used in our facility are carbapenems, such meropenem, or third generation cephalosporins like ceftazidime.
We use TMP-SMX for 6 months in all our KTX patients.
After the first six months following transplantation, we also utilize low doses of nitrofurantoin for three to six months after treating the confirmed infection for recurrent UTIs.
Summary Introduction
UTI are common infections in the early post-transplant period.
UTIs are defined as the growth of colony plus the presence of symptoms, while asymptomatic bacteriuria lack symptoms.
Most common organisms attributed are E.coli, klebsiella, and enterobacter faecalis.
Aim of the study
They examined the antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those from local community.
Methodology Study design: Observational longitudinal cohort study. Inclusion criteria: Patients above 16 years who underwent kidney transplantation between January 2015 and August 2020. Exclusion criteria: Patients who underwent simultaneous liver and pancreas transplant.
Results
Of the 207 patients included, 130 (63%) were suspected to have UTI.
68 of the 130 fulfilled the criteria for UTI.
58 of the 68 had a positive culture growth.
Most common organisms were E.coli, klebsiella and E.faecalium.
The organisms isolated in ASB were distinctly different from those of UTI.
166 of all participants received antibiotic course with median duration was 5 days and clinical indication was suspected UTI.
Fluoroquinolones were the most commonly prescribed.
9 patients had multi-resistant gram negative bacteria.
Discussion
UTI are the most common infections in the early post-transplant period.
Studies have shown that even one episode of UTI negatively impacts the allograft function.
ASB doesn’t affect the allograft function however the inappropriate use of antibiotics does.
Several measures have been proposed to prevent UTI in recipients:
Bladder irrigation with gentamicin prior to ureteral anastomosis.
Single shot of antibiotic prior to incision.
Removal ureteral stent after 21 days or when there is suspicion of bacteriuria.
Prolonged antibiotic use have not been shown to prevent infection.
Indwelling catheters are an independent risk factor.
TMP-SMX is the best studied prophylaxis that is given for 6-12 months.
Empiric antibiotic cover should always cover GNB since there are the most common of UTI while GPB are mainly seen in ASB.
TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for UTI in transplant recipients.
Strengths
They were able to demonstrate distinctly different resistance patterns to commonly used antibiotics.
Limitations.
The retrospective nature of the analysis complicates distinguishing between colonization /bacteriuria and urinary tract infection.
There was uneven sample sizes between the study and control group, hence statistical comparisons were limited to exploratory data.
Level of evidence: 2, this was an observational longitudinal cohort study
How do you treat recurrent UTI at your workplace?
All recipients receive TMP/SMX prophylaxis for 6 months.
Antibiotics guided by culture and sensitivity panel.
Imaging to rule out any urological abnormality.
Definition of UTI and asymptomatic bacteruria (ASB)
UTI is defined as the presence of > 105 CFU in a proper urine sample (early morning sample, or from a sterile catheter) associated with upper or lower urinary tract symptoms, on the other hand if the patient is asymptomatic the condition is termed ASB.
Incidence
UTI is the most common early post-transplant infection; the incidence is variable ranging from 4–80%, while around one fourth of transplant recipients have asymptomatic bacteruria
The incidence is lower in living compared to deceased donor transplantation due to shorter waiting time and higher UOP observed in living donor transplantation due to lower incidence of DGF.
Causative organism
The most common organisms found after transplantation are either gram negative (E coli, Klebsiella) or gram positive (Enterococcus faecalis)
Gram negative pathogens are more aggressive than gram positive ones
Prevention of UTI
Just before doing kidney transplant operation, one dose of perioperative antibiotic is recommended
Decontamination of the bladder by performing intraoperative gentamicin irrigation before ureteral anastomosis
Screening of UTI by either urine culture or urine analysis (and culture taken if urine analysis is suspicious for UTI) every week in the first month after transplantation, some recommends screening for 3 months after transplantation but this is debatable since after the first month the incidence of ASB decrease to 4%.
Removal of urinary catheter as soon as possible after transplantation
Removal of stents as soon as possible at 3 weeks after transplantation, and may be before if there is bacteriuria
Prolonged antibiotic prophylaxis, the most important regimen is the use of SMX-TMP used already for PCP prophylaxis for 6-12 m which was associated with reduction of UTI episodes and severity.
Antibiotic prophylaxis using ciprofloxacin during the period of stent removal, but it is not needed if the patient is already on SMX-TMP prophylaxis
Treatment of UTI and ASB
All patients with UTI should be treated
Treatment asymptomatic bacteria is recommended although there is no strong evidence, in early post-transplant period (first month after transplantation) due to the higher incidence of progression to septicemia, immunosuppression may mask the symptoms, but some recommends treatment for up to 3 months after transplantation.
The most commonly used antibiotic for UTI was flouroquinolones, but there is a FDA warning in 2019 about its use, so an alternative should be given. It is recommended to use broad spectrum IV antibiotic till culture result then step down therapy should be according to the culture result
For ASB, it is recommended to use narrow-spectrum antibiotics such as Fosfomycin , Nitrofurantoin, or SMX-TMP or wait till culture result.
The current study is a retrospective study (level of evidence III) evaluating 207 adult kidney transplantation performed in the University Hospital of Tuebingen from 2015 till 2020 regarding the incidence of UTI and ASB , center specific antibiotic prescription in the first month of transplantation and the antibiotic susceptibility of the organisms isolated in renal transplant recipients and compare it to the general population
Results
The incidence of UTI was 32%, while the incidence of ASB was 29% in the first month.
The occurrence of UTI was associated with lower graft function at discharge and after 1 year
Gram negative organisms were isolated more commonly than gram positive ones (2: 1 ratio)
Gram negative organisms were associated with UTI while gram positive bacteria were assocated with ASB
The most common antibiotics used for treatment of UTI was ciprofloxacin and piperacillin/Tazobactam.
The incidence of isolation of drug resistant bacteria was more common in transplant recipients compared to general population
In patietns with UTI, No resistance to carbapenems was found in the current study, while 15% and 29% of cases were resistant to piperacillin/Tazobactam and ciprofloxacin, respectively. Penicillin and cephalosporins were resistant in > 50% and 20 % of cases, respectively.
In patients with ASB, no resistance was found to Fosfomycin or Nitrofurantoin but > 40% of cases were resistant to SMX-TMP
Conclusions:
UTI is associated with lower graft function and so prevention and early and proper treatment is highly recommended
Screening for ASB using urine culture or urine analysis with subsequent culture in suspicious patients is recommended during the first month after transplantation, and treatment should be given upon confirmation of the ASB.
UTI usually occurs due to infection with gram negative organism, so the use of empiric antibiotics with gram negative coverage is recommended
It is recommended to treat UTI using empiric IV antibiotic according to the local drug resistance, then switching to an oral antibiotic after culture and sensitivity result
ASB should be treated only in the first month after transplantation using narrow spectrum antibiotics or waiting till culture result.
Carbapenems is the drug of choice in the treatment of UTI in critically ill patients
How do you treat recurrent UTI at your workplace?
In my work place, I first treat the current UTI, and after successful treatment, I implement strategies to prevent the recurrence of UTI including :
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 such as removal of IUD for example
Use of prolonged prophylactic antibiotics, the most common regimens used are the use of SMX-TMP DS tablet 3 times weekly or SS tablet daily or nitrofurantoin 100 mg once daily for 6-12 months
We use cranberry juice due to its high safety profile, although the evidence is limited
Urinary tract infections (UTI) are the most prevalent infection, post kidney transplants, with incidence range between 4-80%. Asymptomatic bacteriuria (ASB), which is frequently detected and treated, affects 25% of KT recipients. Fluoroquinolones are the most frequently prescribed prophylactic antibiotic due to their widespread availability, oral and intravenous formulations, and excellent urinary tract penetration. Study design:
A retrospective study screened all adult patients who underwent kidney transplantation at the University Hospital of Tuebingen between January 2015 and August 2020. Urinary cultures were sent at the surgeon’s discretion and the control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology. All patient had the standard immunosuppressive therapy, induction with basiliximab, ATG and alemtuzumab, and MMF, CNIN+ prednisolone maintenance. Perioperative antibiotic prophylaxis used is Beta-Lactam or Ampicillin/Sulbactam, with TMP-SMX 960 mg 3×/week for Pneumocystis prophylaxis, and gentamycin bladder irrigation before ureter anastomosis. Empiric treatment with Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR was the protocol, and deescalation of treatment according to urinary culture/antbiotic resistance results. Urinary catheter removed in 5th day post op., and on the post op. day to those recipients with minimal urine output. Ureterocystoneostomy was performed according to Lich-Gregoir, and DJ removed in the 21st day post-op. Post-operative follow-up:
Patients received blood and urinalysis and culture, twice weekly ultrasound, renal biopsies when needed. Definitions:
Urinary tract infections were defined according to CDC guidelines.
Asymptomatic bacteriuria (ASB) = patients with no symptoms, signs of infection with bacterial growth in culture >105cfu on a proper urinary sample.
Multi-resistant gram-negative bacteria (MRGN) = bacteria resistant to three or more of the following antibiotics (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems).
Results:
During the first 30 days post transplant 63% patients suspected to have UTI, almost half of them have full clinical and laboratory evidence of UTI. The most common culture isolates were E.coli (gram negative bacteria), followed by enterococcus (gram positive bacteria), and rarely mixed cultures. 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days posttransplant, for suspected UTI, ciprofloxacin the most commonly prescribed antibiotic, followed by Piperacillin/Tazobactam, aminopenicillins, Amoxicillin/Clavulanic acid, and Meropenem. Nine patients presented with multi resistant gram-negative bacteria (MRGN). Of these, a relevant percentage was resistant to Piperacillin/Tazobactam,3rd generation cephalosporins and Ciprofloxacin, but no resistance to meropenem were seen. Strength: urinary cultures ordered, identify different patterns of resistance among study groups to commonly used antibiotics in urinary tract infections. Limitations: single center prospective study, the different sample sizes between the study and control groups. Conclusions: Antibiotic stewardship programs are essential to reduce the risk of fatal infection in solid organ transplant recipients.
What is the level of evidence provided by this article? Level of evidence III – retrospective study. How do you treat recurrent UTI at your workplace? At our center in case of recurrent UTI:
We perform an ultrasound to r/o any urological problem, with pre and post void residue, and make sure no DJ, or foreign body is there.
We perform a urine analysis and culture, and ask for the inflammatory markers/CRP, and start empirical antibiotic with meropenem, and deescalated according to urine and blood culture result and sensitivity.
Instructions about preventive measures given to the patient, in the form of keeping urine output > 2l/day, vitamin c ingestion and cranberry.
If failed then will consider prophylactic antibiotic, according to the last cultures results.
In few cases I found a weekly sequential cyclical antibiotic (using three antibiotics) beneficial… no data support this among renal transplant patients.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages. Why level 3 evidence for this article?
Do you mean prophylactic rotating antibiotics once a day to be changed every month and then repeating the cycle after 3 months and so on?
Thank you Prof. Ajay
you are right, it is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2.
Do you mean prophylactic rotating antibiotics once a day to be changed every month and then repeating the cycle after 3 months and so on? Yes, absolutely
1- Summary
This article discusses the issue of urinary tract infections (UTIs) in kidney transplant recipients and the potential role of antibiotic stewardship in their management.
The author highlights the prevalence and impact of UTIs in this
population, which can lead to serious complications such as pyelonephritis,
graft dysfunction, and even graft loss. The author argues that while
antibiotics are often necessary to treat UTIs in kidney transplant recipients,
indiscriminate use can contribute to the development of antibiotic resistance,
which poses a threat to patient outcomes and public health.
In this article the authors analysed retrospectively 207 adult patients
with kidney transplantations that were performed at the University Hospital of
Tuebingen, Germany, between January 2015 and August 2020.
The analysis included screening for all patients with a diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. Results: Of the 207 patients, 68 patients suffered from urinary tract infections and had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
As Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics empirically. After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR. For critically ill patients Meropenem 1000 mg 3×/day was the recommended Rx. Whenever possible de-escalation of treatment according to urinary culture results and antibiotic resistance testing was recommended.
The most common isolates from urinary cultures were gram-negative enterobacteria and enterococcus species. E. coli was the leading pathogen. Fifty-nine individual episodes of ASB were recorded.
Overall, 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post-transplant. Overall, nine patients presented with multi-resistant gram-negative bacteria (MRGN).
In general, the Conclusions are:
· There is increasing data that asymptomatic bacteriuria (ASB) does not affect graft function.
· Empiric antibiotics should therefore always cover gram-negative enterobacteria.
· A meta-analysis from Spain recommended not to treat ASB after the first month post KT. This practice has been backed by two randomized controlled multicenter trials by Origuën et al. and Coussement et al. which both reported no benefits in treating ASB two months after kidney transplant.
· Symptomatic patients need to be treated empirically to avoid development of septicemia,
· For asymptomatic bacteriuria (ASB) it is safe to wait for the final antibiotic resistance testing and use targeted therapy rather than empiric broad spectrum coverage followed by a step- down approach.
· Overall, the article highlights the importance of addressing the issue of UTIs in kidney transplant recipients and the potential role of antibiotic stewardship in improving patient outcomes while minimizing the risk of antibiotic resistance.
2- Level 3 evidence, retrospective analysis
3- In our centre we treat all episodes of UTI (symptomatic and asymptomatic), particularly in the first month post-transplant.
Only those asymptomatic with indwelling catheters we don’t treat unless became symptomatic.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages. Why level 3 evidence for this article?
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.
Summary Introduction
UTIs are the most prevalent early postoperative infection following kidney transplantation (KT). UTIs are 4–80%. In the presence of dysuria, urinary frequency, or localized discomfort, 105 colony-forming units on a suitable urine sample (morning pee, puncture urine, or sterile single catheterization) indicate a UTI.
Asymptomatic bacteriuria (ASB) is the presence of 105 colony-forming units of bacteria without symptoms, unlike UTIs. 25% of KT recipients had asymptomatic bacteriuria.
Consequently, ASB is widely tested for and treated in the early posttransplant period, despite continued disagreement concerning the effects of ASB and UTI on patient and graft outcomes.
Infections and inadequate long-term transplant function have been studied.
Aim:
This research examined our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs, and the antibiotic susceptibility of isolated urinary tract bacteria from KT recipients and the surrounding community.
Material and Techniques:
We retrospectively reviewed our hospital information system for all kidney transplantation patients at the University Hospital of Tuebingen, Germany’s General, Visceral, and Transplantation Surgery department.
Results:
Urinary cultures often yield gram-negative Enterobacteriaceae and various forms of enterococcus were the most prevalent types of bacterial isolates. The most prevalent disease-causing organism was E. coli, followed by E. faecium and E. faecalis.
Five different cultures showed evidence of mixed cultures consisting of two uropathogenic cultures.
135 different bacterial isolates were cultivated, with gram-negative bacteria making up 65% of the total and gram-positive bacteria making up 34%.
This study did not include ureaplasma, which made up 1% of the sample.
Antibiotic Prescription
The most prevalent reason for administering antibiotic medication to kidney transplant patients was the clinical suspicion of having an infection in the urinary system.
Fluoroquinolones were the most commonly prescribed antibiotics for the 180 suspected cases of urinary tract infections (UTIs).
This was followed by piperacillin/tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and a variety of other antibiotics.
Multiresistant gram-negative bacteria (MRGN) were found in nine individuals, all of which were resistant to piperacillin/tazobactam, third-generation cephalosporins, and ciprofloxacin.
In this particular research, E. coli did not exhibit any resistance to fosfomycin or nitrofurantoin; nevertheless, there was a 40% rate of resistance to TMP-SMX.
limitations
single-center and retrospective data.
Making the distinction between colonization, bacteriuria, and a UTI becomes somewhat more difficult.
strength:
were able to identify unique resistance patterns to antibiotics that are often used in the treatment of UTIs.
conclusion:
Antibiotic stewardship initiatives aim to prevent post-surgery infections and rationally manage antibiotics. Infections kill solid organ transplant patients. This lowers the infection threshold for antibiotic therapy. 207 individuals received 262 antibiotic treatments. 180 received medication for suspected UTIs.
Level of evidence: 2b, cohort study
How do you treat recurrent UTIs at your workplace?
We start by doing an Ultrasound of the graft, if normal, we are proceeding with MCUG
We check the previous sensitivity and maintain the patient on the long-term prophylactic antibiotic.
The most common infection in early post kidney transplant phase is UTI.
Post kidney transplant UTI incidence is 4-80%.
UTI defined as growth of 10^5 CFU on proper urine sample with clinical symptoms(dysuria, frequency, or localized pain).
Asymptomatic bacteruria(ASB) defined as presence of > or more 10^5CFU of bacteria without symptoms, it occurs in around 25% of KTR.
ASB frequently screened & treated in post transplant period.
In transplant recipients threshold of ASB treatment is lower due to increase risk of septicemia or atypical presentation.
UTI incidence is lower in living donor kidney transplant recipients because: shorter waiting time, higher volume UOP prior & during transplantation & early onset graft function.
Peri-operative antibiotic prophylaxis is a standard in kidney transplant.
EAU guidelines recommend a single shot antibiotic prophylaxis.
Fluoroquinolone widely used in treatment of UTI in KTR, but after FDA warning in 2019 re-evaluation of empiric antibiotic is considered.
Aims of the study:
Evaluation of antibiotic prescription practice in first 30 days post transplant.
Evaluation of ASB & UTI incidence
Compare antibiotic susceptibility of isolated urinary tract bacteria from KTR to isolated bacteria from local population.
Materials & method:
All adults(>18 years) receive kidney transplant between Jan,2015 & August 2020.
Patients with simultaneous pancreas or liver transplantation were excluded.
Urinary culture was done every week until discharge.
Control group were all urinary tract bacterial isolates cultured from outpatients & inpatients.
Induction was according to immunological risk(basiliximab, ATG & Alemtuzumab) & patients maintained on tampering steroid, CNI & MMF.
Peri=operative antibiotic was either single dose of Ampicillin/Sulbactam or cefotaxime or 3*3g of Ampicillin/Sulbactam.
Before 2018 the patients receive ATG prophylaxis of PCP was TMP-SMX 960mg 3*/week & after 2018 TMP-SMX 960mg 3 per week.
Bladder irrigation with gentamicin done before ureteric anastomosis
All symptomatic &ASB treated empirically.
After recommendation to avoid ciprofloxacine, pipracilin/tazobactam used & for critical ill patient meropenem used.
DJ stent removed 21 POD
Result & discussion:
Single episode of complicated UTI associated with negative impact on graft function.
This study show that UTI associated with significant worse creatinine clearance at the end of the study period & 1 year after kidney transplant so prevention & adequate treatment is crucial.
Increase use of ECD & overall co-morbidities of recipients associated with risk of graft function deterioration.
Genamicine irrigation before ureteric anastomosis reduce recurrent UTI rate.
Early removal of folly catheter & DJ stent reduce risk of UTI.
It was found that gram negative associated with infection & gram positive were more common in bacteruria .
No resistance against meropnem, lower rate of resistance was against pipracilline/tazobactam & high resistance rate against ciprofloxacine.
ASB incidence was 29% in this cohort in first post transplant month(reduced to 4% after 1 month).
In this study E. coli show no resistance to Fosfomycin or nitrofurantoin , but resistance to TMP-SMX was 40%.
E.coli resistance in dialysis & KTR was twice higher than regional public.
MRGN rate was 10% which is similar to other center in Germany but lower than centers in Turkey(41%:
Limitation:
Single center data.
Retrospective analysis of data
Uneven sample size between study & control group statistical comparison limited to exploratory data.
Strength :
Demonstration of distinct different resistant pattern to commonly used antibiotics in UTI between KTR & control group.
All urinary cultures done at tertiary university hospital
UTI is one of the most common infections in the early postoperative after kidney transplantation and ranges from 4-80%.
Define as the growth of 10)5 CFU in the presence of symptoms (dysuria, frequency, or pain).
Asymptomatic bacteriuria is defined as >/10)5 CFU without symptoms, counted about 25% of KTR and recommended to be screened and treated.
UTI is lower in incidence in living donations as they underwent shorter waiting times, higher volume of UOP, and early onset graft function.
A perioperative antibiotic is standard in KT (single shot according to EAUG), and the most common pathogens are; E.coli and Klebsiella pneumonia.
Fluoroquinolones were commonly used for their good penetration to the urinary tract and uropathogenic coverage.
Discussion
UTI can lead to sepsis, septicemia, and a potential threat to life.
ASB and improper use of antibiotics can affect graft survival.
Measures to prevent infection
a) A single shot antibiotic prior to incision. b) Intraoperative gentamicin irrigation to the bladder prior to anastomosis in recurrent UTI. c) Early removal of ureteral stent 21 days after KT or earlier if there is a suspicion of bacteriuria of infection in order to remove biofilms. Prophylaxis
Earlier, ciprofloxacin is considered the best antibiotic used for urinary prophylaxis.
Later based on a recent RCT; fosfomycin has a preventive efficacy.
TMP-SMX
a) The best studied and recommended for prevention of PJP and given for 6-12 months after KT. b) Myoclinic reported a reduction of UTI in KT by TMP-SMX was prescribed for 6 months. c) Horwedel et al; describe a lower rate of septicemia with TMP-SMX prophylaxis. d) In the center that published this article, showed a significant reduction of UTI in patients on TMP-SMX. e) Lee at al; reported that the omission of peri interventional antibiotics on patients already on TMP-SMX does not disadvantageous.
UTI in KT requires an empiric antibiotic coverage of mainly G-ve bacteria which is the main cause of UTI while G+ve bacteria are mainly associated with bacteriuria.
Carbapenems showed no resistance to G-ve bacteria and are widely selected as an empiric antibiotic in critically ill patients.
Piperacillin/Tazobactam show the least G-ve resistance about 15%.
Surprisingly, ciprofloxacin shows a higher rate of resistance, 29% (recently 2019 FDA warning use against fluoroquinolones in KT recipients), but still highly used.
ASB and UTI detection post-transplantation
In this cohort, weekly screening for urinary pathogens for the first-month post-Tx.
59 episodes of ASB (29%) were identified.
Most transplant centers treat ASB within the first month after Tx, as we do (lack of RCT), while others are treated for 3 months post-Tx.
In a meta-analysis, Spain recommended not to treat ASB after 1st month after Tx.
Origuen et al; and Coussement et al; both recommended not to treat ASB after 2 months post-Tx.
Bohn et al; report on a small cohort that is no difference in treating or left untreated ASB for progression to UTI.
ASB (when treated) is by TMP-SMX, Fosfomycin, Nitrofurantoin, and Pivmecillin which are currently not recommended as the first-line therapy for UTI inKTR.
No single strain of E.coli was resistant to fosfomycin or nitrofurantoin, while 40% was resistant to TMP-SMX.
In symptomatic UTIs, we suggest safety to waiting for the last ASB antibiotic-resistant testing and using the targeted therapy rather than empiric antibiotics.
E.faecalis was resistant to ciprofloxacin in only 10% in general population, but the percentage is higher in the KTR (90%).
Strengths and limitations
Single center data.
Slightly complicates distinguishing between colonization/bacteruria/ and UTI.
Still we were able to distinct different resistance patterns to commonly used antibiotics in UTI.
Conclusion
Prevention of infections after surgery and as well as rational use of antibiotics is a main goal of antibiotic stewartdship programs.
SOT are at increasing risk of fatal infection.
This lead to lower the threshold of initiation antibiotics when infection is suspected.
An again this lead to decrease of the infection incidence.
Level of incidence Level ((III)) retrospective study. In our local place;
Workup for underline urological abnormality.
prophylactic TMP-SMX mostly used.
Culture based treatment coarse for specific pathogen.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP? Why level 3 evidence for this article?
Thank you, Prof Ajay
A retrospective study compared the use of TMP-SMX in recurrent UTI in kidney transplants during 3 and 6 months.
They concluded that; there is a higher rate of UTI among those who receive a 3 months course. But the treatment I think should always be individualized according to the;
The severity of the UTI.
Anatomical background.
Immunosuupressant regimen.
treatment response.
Culture results.
Level III because it is a retrospective study
Martin SI, Fishman JA the AST Infectious Diseases Community of Practice. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant. 2013;13:272–79. – PubMed
Radisic M, Lattes R, Chapman JF, et al. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: A case-control study. Transpl Infect Dis. 2004;5:84–93. – PubMed
Gordon SM, LaRosa SP, Kalmadi S, et al. Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued? Clin Infect Dis. 1999;28:240–46. – PubMed
Does not matter, retrospective or prospective, all the cohort studies are level 2. Case control would be level 3. Of course, retrospective are poorer than prospective one.
Summary of the article Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
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%).
3. Asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms(encountered in around 25% of KT recipients).
4. UTI can lead to sepsis and are a potential threat to life. Recent data has suggested a negative impact of even single episodes of (complicated) urinary tract infections on allograft function.
5. Fluoroquinolones offer decent coverage of most uropathogenic bacteria, including Pseudomonas species.
· After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic are Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR.
· For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
6. Measures to prevent UTI in KTR:
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.
7. TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Strengths and Limitations 1. The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection. 2. Statistical comparisons were limited to exploratory data(multicentric comparative data will be necessary prior to generalization of data.).
What is the level of evidence provided by this article?
This is a retrospective study with level of evidence grade 3.
How do you treat recurrent UTI at your workplace? 1. Treatment according to culture and sensitivity panel. 2. Cystoscopy may be required for recurrent cases to rule out bladder pathology. 3. Use of prophylactic antibiotic, based on the C&S beside the estimated GFR. TMP-SMX is commonly prescribed for prophylaxis.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
IV. Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship? ====================================================================
Please summarise this article.
Introduction
Urinary tract infections (UTIs) are the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%.
Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients, and is commonly screened for and treated in the early posttransplant phase.
The threshold for treatment is lower in living donation kidney transplantation due to shorter waiting time and higher volume urine output.
The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KT recipients.
After the FDA warning in 2019, clinicians were forced to reevaluate their empiric antibiotic choice.
Data acquisition was conducted for all patients who underwent kidney transplantation at the University Hospital of Tuebingen, Germany between January 2015 and August 2020.
Medical reports were screened for intra- and perioperative microbiological cultures, and the control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene.
Immunosuppressive protocols included 500 mg of iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
Perioperative antibiotics included Single-Dose Beta-Lactam, Ampicillin/Sulbactam, or 3 3 g of Ampicillin/Sulbactam.
Treatment protocols for Urinary Tract Infections included iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
The protocol recommended empiric antibiotics for urinary tract infections and asymptomatic bacteriuria.
Urinary catheters were placed preoperatively and removed on postoperative day (POD) 5 in patients with retained diuresis.
Ureterocystoneostomy was performed according to Lich-Gregoir.
Intraoperatively, a Double-J-ureteral stent was placed and removed on POD 21.
Postoperative follow-up included blood workup, urine sampling, ultrasounds, and renal biopsies.
Patients were seen at the outpatient clinic for blood and urine workup, clinical and sonographic follow-up.
The study analyzed the charts of all consecutive adult kidney transplant recipients from January 2015 to August 2020 at the University Hospital Tuebingen, Tuebingen, Germany.
207 patients met the inclusion criteria, 73 underwent living donation kidney transplantation, and 134 received a kidney from a deceased donor.
During the first 30 days after their transplant,130 patients (63%) were suspected to have a urinary tract infection. In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded.
Microbiological Results
The most common isolates from urinary cultures were gram-negative enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.
Ureaplasma (1%) was excluded from this analysis.
Antibiotic Prescription
The most common indication for antibiotic treatment in kidney transplant recipients was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most commonly prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
Ciprofloxacin was by far the most prescribed antibiotic in our department.
The most commonly isolated gram-negative bacteria was E.coli, which was resistant to fluoroquinolones in 45%.
The most commonly isolated gram-positive bacteria was E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%,Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains(56%)Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation, and can lead to sepsis and a potential threat to life.
Recent data suggests a negative impact of even single episodes of (complicated) urinary tract infections on allograft function.
To prevent infections in KT recipients, several measures have been proposed, such as a single shot antibiotic administered prior to incision, Gentamicin irrigation of the bladder prior to ureteral anastomosis, and removal of indwelling catheters.
Prophylactic antibiotic regimens have been studied, with Ciprofloxacin being the best studied drug.
TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic dose for 6-12 months after KT.
TMP-SMX prophylaxis was initiated in 2018 in all KT recipients, and the UTI rate was significantly lower in patients on TMP-SMX.
Gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria.
There was no resistance to carbapenems in the gram-negative bacteria, and Piperacillin / Tazobactam was the least gram-negative resistant substance.
Oral treatment alternatives for empiric treatment of UTIs are highly sought after, but did not exist in this study.
Patients undergo weekly screening for urinary pathogens for the first month post-transplant.
Recently, more data is becoming available on the treatment of ASB early after transplantation.
A potential alternative to screening cultures could be reflex urinary cultures triggered by positive urinary nitrite or a threshold urinary white blood count.
Narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Fluoroquinolones should not be used in ASB.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind.
Resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
Prevention of the development of resistant strains in dialysis patients will be an upcoming challenge for antibiotic stewardship teams worldwide.
The MRGN rate of 10% was similar to other German KT centers, but was higher than the average of 5% in a 2017 meta-analysis.
Single center data showed distinct differences in resistance to commonly used antibiotics in urinary tract infections between kidney transplant recipients and a control group.
Multicentric comparative data is needed for generalization.
Please summarise this article. Introduction
o UTIs are the most common infections after kidney transplantation (The incidence ranges from 4–80%)
o Asymptomatic bacteriuria (ASB) accounts for 25% of KT recipients
o Threshold for treatment is commonly low due to the increased risk of septicemia or atypical presentation due to immunosuppression
o The most common pathogens found in urine samples after KT are Escherichia coli, Enterococcus faecalis and Klebsiella pneumonia
o Fluoroquinolones were among the most common antibiotics in the treatment of UTI in KT recipients Aim of the study: evaluation of antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population
Materials and Methods
o Retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen (January 2015-August 2020)
o All charts were screened for the diagnosis and treatment of ASB and UTI and the patients’ clinical characteristics and outcomes were evaluated
o Until discharge all patients received blood workup three times per week as well as routine urinary sampling (chemistry and culture) every Monday or whenever clinical or laboratory signs of inflammation/infection were present
o All patients had at least two ultrasounds per week
Results
o 207 patients met the inclusion criteria [73 patients underwent living donation kidney transplantation (35%) and 134 received a kidney from a deceased donor (65%)]
o 119 (57%) of patients were and 88 (43%) were females
o The most common isolates from urinary cultures were gram-negative enterobacteriaceae and enterococcus species (E. coli cultures followed by E. faecium)
o Of the 207 patients, 68 patients suffered from urinary tract infections
o Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up
o The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam
o Bacterial resistance was more common in the study cohort than in the control group
Discussion
o Even single episodes of (complicated) UTIs have a negative impact of on allograft function
o UTI were accompanied by significantly worse creatinine clearance both at the end of this study period and one year after KT (prevention and adequate treatment of UTI in KT recipients is crucial)
o To detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant [59 episodes of ASB (29%) in this study]
o Treat ASB within the first month after KT
Measures to prevent infections in KT recipients:
1. single shot of antibiotic prior to incision
2. intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis
3. remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection Strengths and Limitations: Strength: samples > 200 kidney transplant recipients Limitations:
1. Reretrospective study
2. uneven sample sizes between the study and control group
Conclusions
o As SOT recipients are at increased risk of fatal infection, initiate antibiotic treatment when infection is suspected
o Urinary tract infections are linked to worse graft functions, thus, prevention and treatment should be accompanied by antibiotic stewardship teams
What is the level of evidence provided by this article?Level II (retrospective cohort study)
How do you treat recurrent UTI at your workplace?o TMP-SMX (prophylaxis)
o Nitrofurantoin for ASB
o Carbapenems (meropenem)/cephalosporins for UTI
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages. You mention and I quote from your reply, “SMX-TMP.” My question: For how long would you give prophylactic SMX-TMP?
Introduction:
-Urinary tract infections (UTI) are the most common infection in the early postoperative phase after KT -UTI is defined as; growth of 105 CFU in the presence of symptoms, while asymptomatic bacteriuria (ASB) is defined as the presence of 105 CFU of bacteria in the absence of symptoms.
-The threshold for treatment is low due to the increased risk of septicemia or uro-sepsis and negative impact on graft function.
– Overall heterogeneous regimens exist to treat UTI.
Study Aim:
-Evaluate antibiotic prescription practice during the first 30 days after KT.
-The incidence of ASB and UTIs
-Compared the antibiotic susceptibility of the isolated bacteria from KT recipients to those isolated from the local population
Materials and Methods
-Retrospective chart review of all adult (>16 year) had KT at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
– Patient with simultaneous pancreas or liver transplantation were excluded.
-The control group consisted of all urinary tract bacterial isolates cultured from both outpatients and inpatients.
– Induction therapy with IV methylprednisolone with either Basiliximab, ATG or Alemtuzumab based on the risk.
– Maintenance therapy steroid tapering, tacrolimus and MMF.
– Antibiotic prophylaxis was giver perioperatively and bladder irrigation with gentamicin.
– Urinary catheters removed on POD 5 ,and DJ-ureteral stent was removed on POD 21.
-All charts were screened for the diagnosis and treatment of ASB and UTI and the patients’ clinical characteristics and outcomes were evaluated.
Results:
– Of the 207 patients, 68 patients suffered from UTI and 59 had ASB
– E.coli was the most common isolated organism followed by E. faecium.
– Gram-negative bacteria were more frequently associated with UTI, while gram-positive bacteria were more common in ASB
-80% underwent at least a single course of antibiotic treatment with median duration of 5 days.
– Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up
-The most commonly prescribed antibiotics were Ciprofloxacin, followed by Piperacillin/Tazobactam, aminopenicillins, Meropenem and TMB-SMX.
– 9 patients presented with multi-drug resistant gram-negative bacteria.
– Resistance patterns were distinctly different between the KTR and the control group( more common in KTR)
-To both, bacterial resistance was more common in the study cohort than in the control group. (
Conclusions:
UTI prevention and treatment should be accompanied by antibiotic stewardship teams.
Level of evidence: level 2 retrospective cohort. How do you treat recurrent UTI at your workplace?
Strat empiric antibiotic when suspected clinically and UA was suggestive for UTI.
Usually we cover with broad spectrum antibiotic Piperacillin/Tazobactam or meropenum then switch according to the culture result for 2 weeks.
Prophylactic TMB-SMX for 3-6 months.
Education about the general measures to reduce UTI risk.
Introduction
Urinary tract infection (UTI) are the most common infection in the early postoperative phase after kidney transplant (KT).
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.
In contrast to UTIs asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
ASB is commonly screened for and treated in the early posttransplant phase , even though there is ongoing controversy about the impact of ASB and UTI on the overall patient and graft outcome.
The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function. Methods
We retrospectively screened our hospital information system for all patients who underwent kidney transplantation at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany.
All adult patients who underwent KT at our center between January 2015 and August 2020 were included in the final analysis.
Patients that underwent simultaneous pancreas or liver transplantation were excluded.
The medical reports of these patients were screened for intraand perioperative microbiological cultures within 30 days after transplantation.
Urinary cultures were sent at the surgeon’s discretion as well as routinely every Monday until discharge.
The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients Results
Per protocol all KT recipients had urine samples sent for culture every.
Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
One patient developed four individual episodes of urinary tract infection and grew four different bacteria (E-coli, Vancomycin sensitive E.faecium , Vancomycin-resistant E. Faecium followed by a different strain of E.coli).
Fifty-nine individual episodes of ASB were recorded.
A total of 62 uropathogenic bacteria were cultured during ASBs. Discussion
Urinary tract infection are the most common infection in the early postoperative phase after kidnet transplantation
They can lead to sepsis and are a potential threat to life.
Aside from progression to seticemia recent data has suggested a negative impact of even single episodes of urinary tract infections on allograft function.
Prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
While there is increasing data that ASB does not affect graft function, inadequate use of antibiotics certainly has the potential to do so.
While about 10% were treated with antibiotic doses that were above the recommended limit more than 25% of patients had a deterioration of graft function.
The increasing use of extended donor allocation and overall comorbidities of the recipients adds to this complexity Conclusion
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Solid organ transplant recipients are at increased risk of fatal infection.
This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
In our cohort between 207 patients 262 courses of antibiotics were prescribed.
180 were prescribed antibiotics for suspected urinary tract infection.
Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams. level of evidence: retrospective cohort (level 2) I will screen and confirm any structural and functional defect that can be curable before start any treatment
I’d like to know if switching to culture-based antibiotics would be beneficial, especially if the patient’s fever, dysuria, pus cells in the urine, and CRP are improving.
The typical antibiotics we used were: Quinolone, typically for 3–4 weeks, plus a dose of Nitrofurantoin for one week.
Based on the results of the culture, other antibiotics could be taken for a minimum of three weeks.
I will further use prophylactic tools like;
Educate people to drink at least 2.5 liters of water per day and to avoid retaining their urine for too long.
After having sex, ladies should wipe from front to back and urinate. They should also refrain from using creams that contain spermicidal agents.
-Summary Introduction
Urinary tract infections (UTI) are the most common infection in the early postoperative period after renal transplant.
UTIs is defined as the growth of 10 5 colony forming units on a proper urine sample with symptoms as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria (ASB) is the presence of ≥105 colony-forming units of bacteria in the absence of symptoms
ASB is screened and treated in the early post transplant period.
Treatment threshold is lower in transplant recipients due to the increased risk of septicemia or atypical presentation due to immunosuppression. UTI incidence is lower in living donation kidney transplantation.
In kidney transplant perioperative antibiotic prophylaxis is a standard.
Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae are the most common infectious organisms in urine samples of KT recipients.
Gram negative bacteria is more virulent than gram positive enterococcus .
Fluoroquinolones are the commonly antibiotic used which forced FDA to recommend against it’s widespread use in KT and general population. Methods
Retrospectively KT recipient data concerning ASB and UTI were analysed within nearly 5 years and 8 months at Tuebingen university hosiptal . Results
68 patients out of 207 had UTI there by had worse graft function at discharge and at the 12 months follow-up .
Ciprofloxacin and Piperacillin/Tazobactam were the most prescribed antibiotics, to which the bacterial resistance was more prevalent in patients compared to control.
A big percentage of resistance to Piperacillin/Tazobactam and carbapenems is
Rendered to prevalence of Enterococcus species. Discussion
A single episode of UTI can have negative effects on the allograft function therefore prevention and treatment is essential.
There were data which states that ASB doesnot affect graft function.
Patients used antibiotic doses above recommended limits were associated with decreased graft function, extended donor usage and comorbidities of the recipients worsen the outcome.
Prolonged antibiotic course is not preventive for UTI and surgical site infection.
Decontaminate the bladder by intraoperative Gentamicin irrigation of the bladder before ureteral anastomosis which showed efficacy in recurrent UTI.
Indwelling catheter and ureteral stents represent an important risk factor for UTI.
Ureteral stent removal 21 days after KT or earlier if bacteria is suspected is a safe practice.
Ciprofloxacin was used to prevent UTIs 25 years ago, but afterwards was used for treatment rather than prophylaxis.
TMP-SMX is usually administered in a prophylactic dose for 6–12 months after KT.
Lee et al demonstrated that at the time of stent removal, TMP-SMX prophylaxis can be enough without the need of periinterventional antibiotics
UTI in KT recipients need empirical antibiotic coverage of mainly gram-negative bacteria.
Carbapenem resistance was not detected for gram negative bacteria in the study therefore it can be used in critically ill cases .
Piperacillin/ Tazobactam had the least gram-negative resistance, Ciprofloxacin had the highest bacterial resistance.
2019 FDA warned against the fluoroquinolones use in KT recipients. Aminopenicillins resistance in >50% and to cephalosporins of nearly 20% .It is recommended to treat UTI after Kidney Transplantation with empiric intravenous antibiotics according to local resistance patterns. Oral narrow-spectrum antibiotic can be given as soon as the bacterial strain is known
Weekly screening for the first month post-transplant to detect early ASB and UTI.
Multiple studies recommended to treat ASB in the first month only.
Narrow-spectrum antibiotics as TMPSMX/Fosfomycin/Nitrofurantoin/Pivmecillinam can be used for treatment of ASB in KT being safe and effective even against MRGN bacteria.
Ecoli starin was resistant to TMP-SMX as it is used as prophylaxis against pseudomonus while there was no resistance against Fosfomycin/Nitrofurantoin
Fluoroquinolones better to be avoided in ASB .
In ASB treatment it can be safe to wait for culture results instead of starting empirical therapy.
Empirical antibiotic therapy for UTI have to be guided by the centers’ urinary tract infection’s spectrum and antibiotic resistance.
Antibiotic stewardship data for SOT recipients are limited.
Limitations are being retrospective single centered study
Strength include demonstrating variable resistance patterns Conclusions
Prevention of infections post KT and antibiotic stewardship programs is an essential practice.
-level of evidence is II
– Treatment of recurrent UTI in renal transplant by early identification of structural or functional urological abnormalities to be corrected surgically if possible . Before antibiotics use a culture have to be collected to prevent emergence of resistance and also interaction with immunosuppressives as CNI have to be watched out for.
Antibiotic used is TMP-SMX.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “And all of our cases are kept on SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
UTI in KTRs—Is There a Need for Antibiotic Stewardship?
⭐⭐⭐⭐Summary:
· UTI post kidney transplantation is common, incidence 4–80%.
· UTIs are defined as the growth of 105 CFU/ML on a proper urine sample + (presence of symptoms as frequency, urgency and dysuria).
· It carries a poor prognosis in both graft and patient outcome, even single episodes of (complicated) UTI can have negative impact on allograft function.
· Asymptomatic bacteriuria is presence of 105 CFU/ML on a proper urine sample (without any symptoms), present in ¼ cases of KTRs. It is still debatable to treat or not as the consequence on graft survival is not well defined.
· Fear of urosepsis, atypical presentation and mortality (due to use of immunosuppression) raised the question to treat asymptomatic bacteriuria. Still questionable, but most centers treat it especially in 1st month Posttransplant 9others treat it up to 2 months Posttransplant).
· Treatment of asymptomatic bacteriuria we can wait till result of culture and sensitivity which is better than starting empirical therapy with TMP-SMX/ Fosfomycin/ Nitrofurantoin/Pivmecillinam.
· While in treatment of symptomatic UTI: Empirical treatment for 3-9 days (mean 5 days), must be started till result of culture and sensitivity, was mainly fluoroquinolones (Ciprofloxacin) (available, both IV and oral, high penetration of kidney tissue, anti psudomonal activity). Then, FDA warning in 2019 against empirical use of Cipro in general and KTR s in particular. so Piperacillin/Tazobactam was used as empirical therapy and for critically ill patients Meropenem was used.
· Shift to antibiotics according to culture and sensitivity is done thereafter. Sometimes, step down using oral narrow-spectrum antibiotic is possible once the bacterial strain is identified.
· Risk factors for UTI: deceased donor (DGF and low UOP).
· Organism: G-ve as (E coli, Enterococcus faecalis and Klebsiella pneumoniae ), G +ve enterococci and staph aureus.
· Measures to decrease incidence of UTI after KT:
o Perioperative Single-Dose Antibiotic Prophylaxis: Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) and Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
o Urinary catheters were placed preoperatively and removed on postoperative day 5, Ureterocystoneostomy was performed according to Lich-Gregoir to guard against reflux in the allograft, Intraoperative a Double-J-ureteral stent (placed and then removed on POD 21) per protocol (or earlier if UTI occurs, to remove the biofilm).
o Follow up urine analysis, CBC and CRP were done weekly or when symptoms are present, to detect any evidence of UTI.
o Posttransplant antibiotic prophylaxis: was initially quinolones (but now used for treatment), so TMP-SMX which is used for PJP is now the most common prophylactic agent used for 1st 3-6 month posttransplant (decreased incidence of UTI and asymptomatic bacteriuria after KT).
o Periinterventional antibiotics (usually Ciprofloxacin) for ureteral stent removal may be used (debatable benefit).
· UTI is suspected with (symptoms, urinary dipstick showed leukocyturia or nitrite +ve).
· Multi-resistant G-ve bacteria were defined as: bacteria resistant to 3 out of 4 of the following substance classes (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems) called as 3- MRGN. Bacterial strains that were resistant to all 4 of the aforementioned substance classes were classified as 4-MRGN.
· Resistant organisms are present in dialysis and transplant patients more than in the healthy population.
· Antibiotic stewardship means putting an effort to measure and improve how antibiotics are prescribed by clinicians and used by patients (correct antibiotic choice, correct dose and duration, avoid unnecessary use) to decrease emergence of resistance.
⭐⭐⭐Level of evidence: retrospective cohort (level 2) Treatment of UTI in my work place:
· In pediatric transplantation, we usually start empirical fortum or meronam antibiotics to cover pseudomonal infection, till culture result.
· I would like to ask about shift to culture based antibiotics, mostly if the patient is improving regarding fever, symptoms as dysuria, pus cells in urine and CRP …we tend to continue on the same empirical antibiotics. Is it right or must shift to culture based one?
· And all of our cases are kept on SMX-TMP.
· Patients with lower urinary tract problems may be maintained on CIC and life-long SMX-TMP especially if positive hx of recurrent UTI.
The most common infection after kidney transplantation is urinary tract infection with an incidence rate that ranges from 4-80% and is defined as the presence of >105 CFU of sterile urine with clinical signs and symptoms in the patient. Asymptomatic UTIs are the absence of symptoms of UTI but in the presence of significant bacteriuria, and the incidence is 25% in KT.
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumonia. The Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci.
Aim of the study
to evaluate the antibiotics use in the first 30 days post-kidney transplantation
Materials and Methods
Data acquisition was obtained retrospectively from kidney transplants done between January 2015 to August 2020
Kidney and pancreas transplantation were excluded
The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients
The induction therapy used was methylprednisolone with either Basiliximab, Anti-thymocyte globulin or Alemtuximab depending on the level of immunological risk of the patient.
Maintenance therapy was TAC, MMF, and prednisolone
single dose of perioperative antibiotic prophylaxis was used
Urinary catheter and DJ stent were used and removed on days 5 and 21 respectively
Results and Discussions
The sample size was 207 patients who met the inclusion criteria.
73 patients underwent living donation kidney transplantation, 134 received a kidney from a deceased donor
. Overall 119 patients were male, and 88 were females.
The median age during KT was 55 years
Diagnosis of UTIs is made with clinical symptoms and laboratory findings of leukocytes, and nitrites, and 68 patients fulfill this criterion out of the initial 130 that were suspected
E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium, and E. faecalis.
Of the 207 kidney transplant recipients 166 underwent at least a single course of antibiotic treatment with a median duration of 5 days
Patients that underwent at least a single course of antibiotics during their initial stay had significantly worse GFR at discharge
Fluoroquinolones were the most commonly prescribed antibiotic among the 180 suspected of UTI
9 patients presented with multi-resistance gram-negative bacteria
Resistance patterns were distinctly different between the KT recipients and the control group
The most common isolated gran-positive organism in both KT and the control group is E.faecalis
UTIs were found to be significantly lower among those using TMP/SMX prophylaxis
There was no resistance of gram-negative to carbapenem in the study
Limitations of the study
It is a retrospective single-center study
Uneven sample size between the study group and the control group
Strength of the study
demonstration of distinct resistance patterns to common antibiotics used in practice
Conclusion
Antibiotics stewardship is very key in taming the proliferation of growing resistance to antibiotic. Prevntion and proper treatment of UTI in kidney transplant patient should be a team work to obtain maximum output from such programme.
The level of evidence is 3
Treatment of recurrent infection in my centre
The first thing is to investigatigate for any structural problems like:
prostate enlargement,
neurogenic bladder,
csyts or ADPKD in native kidney
Nephrolithiasis
poor glycemic control or HIV/AID
Presence of any foreign body in urinary tract
If none of the above above is present then
Urine analysis and culture
The common antibiotic we used are:
Quinolone usually for 3 -4 weeks plus one week dose of Nitrofurantoin
Other antibiotics could be used based on culture results for minimum of 3 weeks
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
What is your reason to give level 3 evidence to this study that is a retrospective cohort study. Q: We know that it is a longitudinal study. Is it a cohort study or case control study? A : Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies ( that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary). Conclusion: This is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2. Case control studies are level 3.
Article 4 Q1. Introduction
· Urinary tract infections (UTI) are the most prevalent problem immediately after kidney transplantation (KT) with incidence rate between 4 to 80%
· It is defined by the growth of 100,000 colony forming units (CFU) in the urine sample plus clinical features of infection such as burning micturition, frequency, or localized pain. The identification growth of 100,000 CFU without symptoms is called asymptomatic bacteriuria (ASB)
· ASB is seen in 25% of KT recipients
· Generally, the threshold for treatment is low for these group of patients due to elevated risk of septicemia or a typical presentation as a results of immune suppression
· Common organisms isolated are E. coli, Enterococcus faecalis, and Klebsiella pneumoniae
· The use of perioperative antibiotic prophylaxis is rout in transplant practice. There are different protocols and importantly FDA recommend against the use of fluroquinolones in these patients
· This study assessed the use of antibiotics in in the first months after KT, incidence of ASB, UTI and compared their antibiotic susceptibility to general population Methodology
· Retrospective control study at the unit of transplant surgery university of Tuebingen, Germany
· The study was conducted in the period between January 2015 and August 2020
· They included 207 transplant recipients
· All the data were examined for the diagnosis, treatment of both UTI, and ASB
· Treatment outcome were assessed Results
· Around 32% of recipients had UTI
· They had poor graft outcome at discharge and t 12 months follow up
· Ciproflaxocin or pipercillin /Tazobacam were the used to treat the UTI
· Higher antibiotic resistance in these group compared to the control from the general population Limitation
· Retrospective data
· Single center
· Relatively small sample size Strength
· They demonstrated different resistant profile to the common antibiotics utilized in treatment of UTI between KT recipients and the control group
· They acknowledged that, more multicenter studies are needed Conclusion
· Based on these results, UTI may be associated with poor allograft outcomes and therefore, it is essential to prevent and treat UTI with the help of antibiotic stewardship teams
Q.2
· Retrospective cohort study, level 3
Q.3
· Prophylaxis: Trimethoprim-Sulfamethoxazole
· Treatment: Fosfomycin for ASB, and Meropenem for UTI
What is your reason to give level 3 evidence to this study that is a retrospective cohort study. Q: We know that it is a longitudinal study. Is it a cohort study or case control study? A : Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies ( that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary). Conclusion: This is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2. Case control studies are level 3.
Urinary tract infections (UTI) are the most common infections after kidney transplantation. Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low. Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT).
prevention and adequate treatment of urinary tract infections in KT recipients is crucial. While there is increasing data that asymptomatic bacteriuria (ASB) does not affect graft function ،inadequate use of antibiotics certainly has the potential to do so. However, the decreased GFR in patients that underwent antibiotic treatment in our cohort should not be interpreted in a vacuum. While about 10% were treated with antibiotic doses that were above the recommended limit more than 25% of patients had a deterioration of graft function. The increasing use of extended donor allocation and overall comorbidities of the recipients adds to this complexity.
Several prophylactic antibiotic regimens have been studied. Ciprofloxacin was shown
to prevent UTIs 25 years ago, but was later reserved for treatment rather than prophylaxis .Aside from a recent randomized trial that showed the preventative efficacy of Fosfomycin the best studied drug is TMP-SMX. TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic dose for 6–12 months after KT
Empiric antibiotics should therefore always cover gram-negative enterobacteria. There was no resistance to carbapenems in our gram-negative bacteria, which makes them the most attractive choice for critically ill patients. Of the remaining antibiotics Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to, at a rate of 15%.
The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not recommended as first line therapy for urinary tract infections in transplant recipients. Nearly all isolated bacteria in our study cohort had a “weak spot” to one of these agents. These agents will grow in popularity given that they are safe and effective even against MRGN bacteria.
While symptomatic patients need to be treated empirically to avoid development ofsepticemia, we believe it is safe to wait for the final antibiotic resistance testing in ASB and use targeted therapy rather than empiric broad spectrum coverage followed by a step- down approach. This is common practice in pregnant patients but to our knowledge there is yet to be consensus for transplant recipients.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind which may vary a lot regionally.
While our MRGN rate of 10% was similar to other German KT centers it was
considerably lower than described by Tekkarismaz et al., who reported 41% MRGN urinary tract infections in their cohort in Turkey. Nevertheless 10% was considerably higher than the average of 5% described in a 2017 meta-analysis.
The global numbers are increasing and vary considerably even within states and countries.
Strengths and Limitations
We presented single center data on bacterial isolates from urine samples of over
200 kidney transplant recipients early after kidney transplantation. The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection. Still, we were able to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main
goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Please summarise this article.
# Introduction:
* (UTI) are the most common infection in the early postoperative phase (PKT).
* The incidence of a UTI ranges from (4–80%).
*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.
*Asymptomatic bacteriuria (ASB) is defined as the presence of 105 colony-forming units of bacteria in the absence of symptoms.
*ASB is encountered in around 25% of KT recipients, so it is commonly screened for and treated in the
early PTK phase.
* In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression.
*The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
*Historically fluoroquinolones were prescription favorites for patients that underwent kidney transplantation (KT).
*After the recent recommendation to avoid them in these patients, however, alternative treatment strategies need to be investigated.
#The aim of the study to evaluated antibiotic prescription practice during the first 30 days PKT, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based on data provided by the hygiene department.
# The methods:
*Retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of (ASB) and (UTI) and the patients’ clinical characteristics and outcomes were evaluated.
*Immunosuppressive Protocol:
Induction therapy was Methylprednisolone as well as either Basiliximab for low immunologic risk or Anti-Thymocyte Globulin for intermediate risk or an Anti-CD56-Antibody for high risk patients. Maintenance immunosuppression consisted of steroid tapering, CNI as well as MMF.
*Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam (Ampicillin/
Sulbactam or Cefotaxime) or 3 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant
surgeons’ discretion.
*Treatment Protocols for Urinary Tract Infections Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics
#The results:
Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed
UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both, bacterial resistance was more common in the study cohort than in the control group.
#Strengths and Limitations
The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
Still, it demonstrates distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between KT recipients and the control group.
Uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data.
Therefore, multicentric comparative data will be necessary prior to generalization of our data.
# Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
What is the level of evidence provided by this article?Level 2
How do you treat recurrent UTI at your workplace?All transplanted patients receive TMP/SMX as prophylaxis for period of six months.
In reccurent UTI infections we take sample for culture and sensitivity for bacteriology lab first, and started with broad spectrum antibiotics (Ceftaxime or Meropenem) then we give the drug according to the result type of microorganism.
Nitrofurantoin can be used in small dose for 3 – 6 months following recurrent infection
Summary
The impact of urinary tract infections (UTI) on kidney transplant recipients and the related consequence of antibiotic resistance. As well as requirement antibiotics stewardship in treating such patients is discussed in this article.
Introduction
UTI are common in the early post-transplant period, can lead to pyelonephritis sepsis, damage to graft, and even death, if left untreated. Even a single episode of urinary tract infection can impact function of the allograft. So, it is imperative that UTI in transplant recipients should be prevented, and be treated on time.
Methods and results:
From January 2015 to August 2020, 207 kidney transplant recipients (KTR) were studied for UTI.
68 of the 130 patients exhibited usual symptoms, clinical or laboratory evidence of UTI. 10 of 68 patients with UTI, had typical symptoms along with urinalysis abnormality, and 58 patients had growth of a urinary pathogen on urine culture.
166 (80%) of the 207 patients of kidney transplants had at least one round of antibiotic therapy (excluding preoperative and peri-interventional prophylaxis).
Within the first 30 days following the transplant, 262 antibiotic treatment sessions were provided to the patient cohort. The most common pathogen, E. coli, was discovered in 49 cultures, followed by E. faecium (n = 23).
Discussion
Measures to prevent infection in renal transplant recipients:
· Single antibiotic shot ½ hr before incision
Screening and Prophylaxis:
During the first month following transplantation, patients are subjected to weekly screening for urine pathogens in attempt to identify ASB and UTI early.
TMP-SMX is recommended for first 6months for PCP prophylaxis, which reduces incidence of UTI during this period.
Lee et al. found that skipping the peri-interventional antibiotics (often Ciprofloxacin) was not hazardous, if patient was receiving TMP-SMX prophylaxis.
Treatment
· Carbapenem is the best option for critically unwell patients, and empiric antibiotics should always cover gram-negative enterobacteria.
· An oral narrow-spectrum antibiotic may be necessary following the results of the culture.
· Can postpone using empiric broad spectrum antibiotics in ASB, in favour of tailored treatment while awaiting the results of the final antibiotic resistance testing.
· Data on antibiotic stewardship and hospital cleanliness can be helpful, but they must be carefully watched.
Conclusion
UTI prevention and effective treatment are crucial in transplant recipients, in order to have long term graft function, and patient survival.
Rational use of antibiotics is key to prevent development of resistance.
Solid organ transplant recipients are at high risk for development of septicemia and fatal infections. Thus, adequate monitoring, quick diagnosis and effective treatment is required.
Antibiotic stewardship teams are essential in the fight against antibiotic resistance and poor treatment choices.
Level of evidence: Level 2
How do you treat recurrent UTI at your workplace?
In our practice we insert stents in all patients, but removed it by 2-3weeks.
TMP-SMX for PCP prophylaxis for 6 months, also protects from UTI.
Urine analysis weekly in the first month post-transplant, then every two week for 3 months. then monthly for one year.
Abnormal Urinalysis report requires Urine culture and USG graft kidney.
We use Ciprofloxacin or cephalosporins empirically, till culture results come, after which antibiotics drug and duration is tailored according to culture sensitivity report.
Routine USG graft kidney with doppler is done at 7days, at 3-4 weeks, 3months and 6months post-transplant for any abnormality, in addition to any clinical suspicion. Abnormal USG findings or severe pyelo-nephritis / high fever / recurrent UTI / persistent infection, requires CT scan of abdomen and KUB with CT IVU. VCUG is reserved for high grade reflux (hydronephrosis with graft dysfunction) which might require surgical correction.
We don’t treat ASB, rather take another culture after proper clean precautions.
Recurrent ASB is investigated for forgotten stent / stone / hydronephrosis or voiding problems which are sorted out.
Patients are advised to drink plenty of water, voiding every 2-3hourly, avoid use protections for sex, as well as post-coital voiding. Women are asked to wipe from front to back, use short time vaginal tampon and change frequently during menses.
Summary
This article is concerned with the impact of urinary tract infections in kidney transplant recipients and the related consequence of antibiotic resistance and required stewardship regarding the use of the aforementioned antibiotics.
Introduction
Urinary tract infections are common the early post transplant period. They can lead to sepsis and death if left untreated. It can also cause significant damage to life. Even a single episode of urinary tract infection can impact function of the allograft. Taking all these factors into consideration, it is imperative that urinary tract infections are prevented, and if not, at the very least treated in a timely manner.
Discussion
Measures to prevent infection in renal transplant recipients include the following:
Treatment
Conclusion
Prevention and effective treatment are crucial with regards to urinary tract infections. Rational use of antibiotics is key to prevention of resistance. Solid organ transplant recipients are at high risk for development of septicemia and fatal infections. Thus adequate monitoring and quick diagnosis and treatment is to be done. Antibiotic stewardship teams are essential in the fight against antibiotic resistance and poor treatment choices.
Level of evidence
Level of evidence is 2.
This study revealed single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation. It also emphasizes the necessity for antibiotic stewardship in kidney transplant recipients. The most significant information in this text is that early posttransplant screening and treatment for asymptomatic bacteriuria (ASB) is common, and that UTI is assumed to be lower in living donor kidney transplantation due to shorter waiting times, higher volume urine output, and early onset graft function. Due to their broad availability, oral and intravenous formulations, and good urinary tract penetration, fluoroquinolones are among the most often used antibiotics in the treatment of urinary tract infections in KT users.
From January 2015 to August 2020, 207 kidney transplant patients (KT) were the subject of this study, which focused on their clinical characteristics.
68 of the 130 UTI patients exhibited the usual symptoms and/or clinical or laboratory evidence of inflammation.
Ten of these 68 individuals had typical symptoms along with laboratory and urine chemistry results compatible with UTI, and 58 of these patients had growth of a urinary pathogen on urine culture.
166 (80%) of the 207 patients of kidney transplants had at least one round of antibiotic therapy (excluding preoperative and periinterventional prophylaxis).
Within the first 30 days following the transplant, 262 antibiotic treatment sessions were provided to the patient cohort. The most common pathogen, E. coli, was discovered in 49 cultures, followed by E. faecium (n = 23).
For the first month following transplantation, patients are subjected to weekly screening for urine pathogens in attempt to identify ASB and UTI early.
TMP-SMX is recommended for use for 6–12 months following KT in order to avoid Pneumocystis jiroveci pneumonia. After KT, TMP-SMX decreased UTIs after six months.
In cases when the patient was receiving TMP-SMX prophylaxis, Lee et al. discovered that skipping the periinterventional antibiotics (often Ciprofloxacin) was not hazardous.
· Carbapenem is the best option for critically unwell patients, and empiric antibiotics should always cover gram-negative enterobacteria. An oral narrow-spectrum antibiotic may be necessary following the results of the culture.
can postpone using empiric broad spectrum antibiotics in favor of tailored treatment while awaiting the results of the final ASB antibiotic resistance testing.
Data on antibiotic stewardship and hospital cleanliness can be helpful, but they must be carefully watched.
Summary
· This article discusses the need for antibiotic stewardship in kidney transplant recipients.
· This study presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
· The most important details in this text are that asymptomatic bacteriuria (ASB) is commonly screened for and treated in the early posttransplant phase, and that UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
· Fluoroquinolones are among the most common antibiotics in the treatment of urinary tract infections in KT recipients due to their widespread availability, intravenous and oral formulations, and excellent penetration into the urinary tract.
· This study examined the clinical characteristics of 207 kidney transplant recipients (KT) from January 2015 to August 2020.
· Of 130 patients with a UTI, 68 had typical symptoms and/or clinical/laboratory signs of inflammation.
· In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded, and ten patients found typical symptoms accompanied by laboratory and urine chemistry findings consistent with UTI.
· Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis).
· 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant.
· E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
· The most commonly isolated gram-positive bacteria was E. faecalis
· In this cohort, urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
· Prevention and adequate treatment of urinary tract infections in KT recipients is crucial, and several measures have been proposed to prevent infections.
· In order to detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant.
· TMP-SMX is prescribed for 6–12 months after KT to prevent Pneumocystis jirovecii pneumonia. TMP-SMX reduced UTIs for 6 months after KT.
· For ureteral stent removal, Lee et al. found that omitting periinterventional antibiotics (usually Ciprofloxacin) was not harmful if the patient was on TMP-SMX prophylaxis.
· Empiric antibiotics should always cover gram-negative enterobacteria. , carbapenem is the best choice for critically ill patients. After culture result , an oral narrow-spectrum antibiotic may be appropriate.
· can wait for the final antibiotic resistance testing in ASB and use targeted therapy instead of empiric broad spectrum .
· Antibiotic stewardship and hospital hygiene data can be useful but must be monitored and updated.
Level of evidence
· Level 2, retrospective cohort study
Our practice:
– Supportive measures.
– IV AB, carbapenem , tazocin , or depending on last previous positive culture if recurrent.
– Chronic suppressive therapy with ciprofloxacin low dose , TMP/SMX , Fosfomycin or nitrofurantoin.
Urinary tract infections (UTIs) are a common occurrence in the early postoperative phase after kidney transplantation (KT). The incidence of UTI after KT ranges from 4-80%, and is defined as the growth of 105 colony forming units of bacteria in the presence of symptoms such as dysuria, urinary frequency or localized pain. Asymptomatic bacteriuria (ASB) is also frequently encountered in KT recipients and is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms. Fluoroquinolones were commonly used to treat UTIs in KT recipients due to their good coverage of uropathogenic bacteria, including Pseudomonas species, and their excellent penetration into the urinary tract. However, the FDA’s warning in 2019 regarding the use of fluoroquinolones in KT recipients has forced clinicians to re-evaluate their empiric antibiotic choice.
This study evaluated the antibiotic prescription practice, incidence of ASB and UTIs, and antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients compared to the local population. The study was performed on a consecutive database of adult patients (age ≥ 16 years) who underwent KT at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany between January 2015 and August 2020. The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation.
Per protocol, all episodes of UTIs and ASB were treated with antibiotics. The recommended empiric treatment for UTIs was Ciprofloxacin with a dose equivalent of 250 mg twice daily for 5 days with dose adjustments according to the glomerular filtration rate (GFR). After the recommendation to avoid fluoroquinolones, Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR was the recommended empiric antibiotic. For critically ill patients, Meropenem 1000 mg 3×/day was the recommended substance and dose.
Urinary cultures were routinely taken every Monday until discharge. Perioperative antibiotics consisted of a Single-Dose Beta-Lactam or 3 × 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant surgeons’ discretion. Urinary catheters were placed preoperatively and removed on postoperative day 5 in patients with retained diuresis prior to transplant. Ureterocystoneostomy was performed according to Lich-Gregoir. Intraoperatively a Double-J-ureteral stent was placed which was removed on postoperative day 21 per protocol (or earlier if urinary tract infection was detected).
Multi-resistant gram-negative bacteria were defined as those resistant to three out of four of the following substance classes: acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, and carbapenems. Bacterial strains resistant to all four substance classes were classified as 4-MRGN.
Comparison between groups was carried out using the Chi-Square test or Fisher’s exact test for nominal variables and the Mann–Whitney U-test for continuous variables. The statistical analysis was carried out using IBM SPSS Statistics for Windows, Version 26.0.
The study analyzed the medical records of 207 consecutive adult kidney transplant recipients who underwent transplantation at the University Hospital Tuebingen, Germany, from January 2015 to August 2020. Urine samples were collected every Monday and based on postoperative labs and clinical course. During the first 30 days after their transplant, 63% of patients were suspected to have a urinary tract infection, with 68 patients fulfilling the criteria of a UTI.
The most common isolates were gram-negative enterobacteriaceae and enterococcus species, with E. coli being the leading pathogen. Of the 207 patients, 80% underwent at least one course of antibiotic treatment, with fluoroquinolones being the most commonly prescribed antibiotic. Nine patients presented with multiresistant gram-negative bacteria, and Ciprofloxacin was the most prescribed antibiotic, with E. coli being resistant to fluoroquinolones in 45%.
The resistance rates to different empiric treatment options were high, with resistance to Ampicillin/Sulbactam being present in 76 of the 135 strains. Overall, the results suggest that antibiotic resistance is a significant concern in kidney transplant recipients, and more efforts are needed to optimize antibiotic use in this population.
UTIs are the most common infection in the early postoperative, incidence of 4-80%.
UTI -10^5 CFU on proper urine sample, early morning sample, or from a sterile catheter associated with upper or lower urinary tract symptoms, (dysuria, frequency, or localized pain).
Asymptomatic bacteriuria – presence of > or more 10^5CFU of bacteria without symptoms, occurs in around 25% of KTR
KTR- threshold of ASB treatment is lower due to increased risk of septicemia or atypical presentation
Multi-resistant gram-negative bacteria (MRGN) = bacteria resistant to three or more of the following antibiotics (acyl ureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems)
The most common pathogen kidney transplant – Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae.
UTI incidence is lower in living donor KTRs because: shorter waiting time, higher volume UOP prior, during transplantation & early onset graft function.
Peri-operative antibiotic prophylaxis is a standard in kidney transplant.
EAU guidelines recommend a single shot antibiotic prophylaxis.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KTRs, but after FDA warning in 2019 re-evaluation of empiric antibiotic is considered.
The observational longitudinal cohort study evaluated antibiotic prescription practice in first 30 days post-transplant and incidence of ASB and UTI
The study also compared antibiotic susceptibility of isolated urinary tract bacteria from KTR to local population.
The study analyzed the charts of all consecutive adult kidney transplant recipients from January 2015 to August 2020 at the University Hospital Tuebingen, Tuebingen, Germany.
During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection. In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded.
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.Ureaplasma (1%) was excluded from this analysis.
The most common indication for antibiotic treatment in kidney transplant recipients was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-
Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria were E. coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
UTI is associated with lower graft function and so prevention and early and proper treatment is highly recommended.
Screening for ASB using urine culture or urine analysis with subsequent culture in suspicious patients is recommended during the first month after transplantation, and treatment should be given upon confirmation of the ASB.
UTI usually occurs due to infection with gram negative organism, so the use of empiric antibiotics with gram negative coverage is recommended.
It is recommended to treat UTI using empiric IV antibiotic according to the local drug resistance, then switching to an oral antibiotic after culture and sensitivity result
ASB should be treated only in the first month after transplantation using narrow spectrum antibiotics or waiting till culture result.
Carbapenems is the drug of choice in the treatment of UTI in critically ill patients.
Antibiotic stewardship programs are essential to reduce the number of antibiotics prescribed to solid organ transplant recipients.
Peri-transplant surgery, one dose of perioperative antibiotic is recommended, (Cefazolin or Vancomycin).
Screening of UTI by either urine culture or urine analysis (and culture taken if urine analysis is suspicious for UTI) every week in the first month after transplantation, some recommends screening for 3 months after transplantation, but this is debatable since after the first month the incidence of ASB decrease to 4%.
Removal of urinary catheter as soon as possible after transplantation
Removal of stents as soon as possible at 3 weeks after transplantation and may be before if there is bacteriuria.
Prolonged antibiotic prophylaxis, the most important regimen is the use of SMX-TMP used already for PCP prophylaxis for 6-12 m which was associated with reduction of UTI episodes and severity.
Antibiotic prophylaxis using ciprofloxacin during the period of stent removal, but it is not needed if the patient is already on SMX-TMP prophylaxis.
Cohort study -The level 2 of evidence
How do you treat recurrent UTI at your workplace?
In our centre, we tend to treat ASB with augmentin and unasyn, some might prefer cefuroxime. We usually send C n S whle treating. Recurrent ASB will be investigated for ? stone by doing CTU
Lifestyle changes such drinking plenty of water, frequent voiding, post coital voiding, wiping from front to back in females will be advised
◇ Introduction
● Urinary tract infections (UTI) are the most common infection in the early postoper-ative phase after KTx
● The incidence of a UTI 4–80%
● A symptomatic bacteriuria (ASB) is defined as the presence of ≥10^5 colony-forming units of bacteria in the absence of symptoms 25% of KT recipients
● Threshold for treatment in KTx is lower due to the increased risk of septicemia or atypical presentation due to IS
● The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function
● The most common pathogens after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae
● Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci.
◇ Materials and Methods
● Data Acquisition
☆ A retrospectively study included All adult patients (age ≥ 16 years) who underwent KT at one center between January 2015 and August 2020
☆ Patients with simultaneous pancreas or
liver transplantation were excluded.
☆ Intra- and perioperative microbiological cultures within 30 days after KTx were screened for all patients
☆ The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients.
● Immunosuppressive Protocol
☆ Induction therapy was MP and Basiliximab for low immunologic risk
or ATG with 3 doses for intermediate risk or an Anti-CD56-Antibody (Alemtuzumab 20 mg) for high risk patients (without MMF until lymphocytes have regenerated).
☆ Maintenance immunosuppression consisted of steroid tapering, CNi, MMF
● Perioperative Antibiotic Prophylaxis
☆ TMP-SMX 960 mg 3× per week.
☆ Bladder irrigation with Gentamicin Prior to ureteral anastomosis
● Treatment Protocols for Urinary Tract Infections
☆ When clinical suspicion for a UTI arose empiric antibiotics were initiated.
☆ After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days
with dose adjustments according to GFR.
☆ For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
● Urinary Catheter and Double-J-Stent Management
☆ Urinary catheters were placed pre-operatively and removed on (POD) 5 in patients with retained diuresis prior to transplant.
☆ In patients with reduced urine output prior to transplantation the urinary catheter was scheduled to be removed on POD.
☆ Ureterocystoneostomy was performed according to Lich-Gregoir.
☆ Double-J-ureteral stent was placed which was removed on POD 21 (or earlier
if urinary tract infection was detected).
● Postoperative Follow-Up
☆ Blood workup three times per week and urinary sampling (chemistry and culture) every Monday or whenever clinical or laboratory signs of inflammation/infection were present.
☆ All patients had at least two ultrasounds per week to evaluate graft perfusion, rule out ureteral stenosis and perirenal fluid collections.
☆ Renal biopsies were taken according
to the Banff classification.
● Clinical Definitions
☆ A symptomatic bacteriuria: Asymptomatic patients without systemic signs of infection and >10^5 colony
☆ Uncomplicated UTI :
When symptoms were present
☆ Complicated UTI :
When signs of septicemia were present.
☆ Multi-resistant gram-negative bacteria:
when bacteria were resistant to three out of four of the following substance classes (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems)
◇ Discussion
● Aside from progression to septicemia, recent data has suggested a negative impact of even single episodes of (complicated) urinary tract infections on allograft function
● Urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT.
● The increasing use of extended donor allocation and overall comorbidities of the
recipients adds to this complexity.
● Measures to prevent infections in KTRs:
☆ A single shot antibiotic is administered prior to incision
☆ Prolonged antibiotics have not proven
beneficiary for the prevention of urinary tract or surgical site infection
☆ Intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis
☆ The best studied drug is TMP-SMX for prophylaxis isTMP-SMX for 6–12 months after KT
☆ UTI rate was significantly lower in patients that were on TMP-SMX.
☆ Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly gram-negative bacteria.
☆ Gram-negative bacteria were more frequently associated with infections, while gram-positive were more common in bacteriuria.
☆ Due to low resistance to carbapenems it is the best choice for critically ill patients.
☆ Resistance to Ciprofloxacin was as high as (29%).
☆ Tesistance to aminopenicillins in over 50% and a resistance to cephalosporins of nearly 20%
☆ It is recommended to treat urinary tract infections after Kidney Transplantation
with empiric intravenous antibiotics according to local resistance patterns.
☆ Most transplant centers treat ASB within the first month after KT so further screening is likely unnecessary.
☆ There are no difference in progression to UTI when treated ASBs during first month after TRx or left untreated
☆ TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
☆ 40% were resistant to TMP-SMX.
☆ Resistance to antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
● Strength points :
☆ Study demonstrated distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
● Limitations :
☆ A retrospective study
☆ It was difficult to distinguish between colonization/bacteriuria and urinary tract infection as it retrospective study
☆ As it a single center study we need a multicentric comparative data prior to generalization this data.
☆ Statistical comparisons were limited to exploratory data due to uneven sample sizes between the study and control group
● Conclusions
☆ Prevention of infections after surgery as well as rational use of antibiotics is a main
goal of antibiotic stewardship programs.
☆ Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
● Level : 2
● In our practice we use TMP-SMX for PCP protection for 6 months which also offers UTi protection
● Urine analysis weekly first month after transplantation then every two week for 3 month then monthly for one year
● If there is abnormalities in Urine analysis we do Urine culture
● We treat empirically with cephalosporins until culture results were available
● USS for transplant kidney and other investigations as VCUG and renogram if the patient has recurrent UTI or transplant kidney hydronephrosis with urolog consult
1- Introduction
Urinary tract infections (UTI) are the most common infection in the early postoperative phase after kidney transplantation (KT) [1,2]. The incidence of a UTI ranges from 4–80%. UTIs are defined as the growth of 105 colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria is encountered in around 25% of KT recipients
The incidence of UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
A perioperative antibiotic prophylaxis is standard in KT.
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae.
Fluoroquinolones were among the most common antibiotics in the treatment of urinary tract infections in KT recipients.
2. Materials and Methods
Retrospectively all patients who underwent kidney transplantation at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany. between January 2015 and August 2020 were included in the final analysis.
3- results:
E. coli was the most commonly isolated gram-negative bacteria.
UTI is suspected so treatment with antibiotic is indicated such as fluoroquinolones.
4- discussion:
Urinary tract infections are the most common infecti9*on in the early postoperative phase after kidney transplantation They can lead to sepsis and are a potential threat to life.
Preoperative: antibiotic is indicated to prevent infections in KT recipients.
prophylactic antibiotic regimens have been studied, including Ciprofloxacin, Fosfomycin, and TMP-SMX.99
Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly gram-negative bacteria.
To detect ASB and UTI early, our patients unde9rgo weekly screening for urinary pathogens for the first month post-trans*9plant
The treatment of asymptomatic bacteriuria is the n9iche for narrow-spectrum antibiotics such as TMP-9SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not r*9ecommended as first line therapy for urinary tract infections in tra9nsplant recipients.
5- conclusion:
Preve9ntion of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
Level of evidence is II
How do you treat recurrent UTI at your workplace?
First treat the predisposing factors
Do culture and sensitivity
Renal US and CT KUB
Involve the urologist
IV. Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
Summarise this article
Introduction
– UTIs are the most common infections in the early postoperative period following kidney transplantation, incidence ranges from 4-80%
– UTI is defined as growth of 10⁵ CFU on a proper urine sample i.e., morning urine, puncture urine, urine from sterile single catheterization in the presence of symptoms like dysuria, frequency, localized pain
– asymptomatic bacteriuria (ASB) is defined as presence of ≥10⁵ CFU of bacteria in the absence of symptoms
– 25% of KTRs experience ASB
– in as much as the impact of UTI and ASB on patient and graft outcomes is still controversial, ASB is commonly screened for and treated in the early posttransplant period
– clinicians should have a low threshold to treat UTI and ASB in KTRs due to the risk of septicemia, urosepsis, potential threat to the graft and atypical presentation due to immunosuppression
– incidence of UTIs is thought to be lower in LDKT due to the shorter waiting time, higher volume urine output before and during kidney transplantation, early onset graft function
– perioperative antibiotic prophylaxis is standard practice in kidney transplantation- common uropathogens in kidney transplantation include E. coli, enterococcus faecalis, klebsiella pneumoniae
– gram negative bacteria are more pathogenic than gram positive enterococci
– fluoroquinolones were commonly used in management of UTI in KTRs given that they are readily available, have oral and IV formulations, have excellent penetration into the urinary tract, cover most uropathogenic bacteria including pseudomonas
– in 2019 there was an FDA warning regarding use of fluoroquinolones both in general and KTRs in particular, forcing clinicians to reevaluate their empiric antibiotic choice
– this study evaluated the antibiotic prescription practice in the 1st 30 days post kidney transplant, the incidence of ASB and UTIs, compared the antibiotic susceptibility patterns of the isolated urinary tract bacteria from KTRs to those isolated from the local population
Materials and methods
– retrospective chart review of 207 consecutive adult kidney transplantations
– all charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and UTIs
– patients clinical characteristics and outcomes were then evaluated
– induction therapy: methylprednisolone 500mg, Basiliximab 20mg IV day 0 and day 4 for low immunologic risk patients or ATG 1.5mg/kg/d on day 0-1 for intermediate risk patients and Alemtuzumab 20mg for high-risk patients
– maintenance therapy: steroid tapered dose, CNI (tacrolimus 0.1mg/kg/day as well as mycophenolic acid 1g BD
– perioperative antibiotics: single dose beta lactam (ampicillin/ sulbactam or cefotaxime) or 3 doses of ampicillin/ sulbactam 3g at Q0h, 12h,24h); TMP-SMX 960mg 3*/week for PCP prophylaxis, bladder irrigation with gentamicin prior to ureteral anastomosis
– treatment protocols for UTI: all episodes of UTI and ASB were to be treated with antibiotics (per protocol), empiric treatment entailed use of ciprofloxacin 250mg BD for 5 days (dose adjusted according to renal function), following the recommendation to avoid fluoroquinolones, there was a switch to piperacillin/ tazobactam 4.5g TID for 5 days (dose adjusted according to renal function), meropenem 1g TID was recommended in the critically ill patients
– antibiotics were deescalated according to the urine culture results and antibiotic resistance testing was recommended
– urine catheter and double-J-stent management: urine catheter was placed preoperatively and removed on the 5th POD in patients with retained diuresis prior to transplant and removed on the POD in patients with reduced urine output prior to transplant, DJ stent was placed intraoperatively and removed on POD21 per protocol or earlier if a UTI was detected
– postoperative follow-up: blood works thrice weekly (per protocol); routine urine sampling (m/c/s) every Monday or whenever clinical or laboratory signs of infection were present; twice weekly ultrasounds to assess for graft perfusion, ureteral stenosis, perirenal fluid collections; indication kidney biopsies which were assessed using the Banff classification; patients were reviewed 1 week after discharge for blood and urine investigations, clinical and sonographic examination
– clinical definitions: UTI (presence of ≥10⁵ CFU of bacteria plus symptoms); ASB (presence of ≥10⁵ CFU of bacteria in the absence of symptoms); multi-resistant gram-negative bacteria (MRGN) refers to bacteria resistant to 3 out of 4 of the following drug class i.e., carbapenems, fluoroquinolones, 3rd generation cephalosporins, acylureidopenicillin; 3-MRGN refers to bacterial strains resistant to 3 out of 4 drug classes, 4-MRGN refers to bacterial strains resistant to all 4 drug classes
– microbiological culture, identification of strains and resistance testing: urine cultures were done every Monday and when there was suspicion for UTI, antimicrobial susceptibility testing was also done
Results
Clinical characteristics
– 207 patients met the inclusion criteria; 35% (73 patients) underwent LDKT, 57% (119 patients) were male, median age was 55±14 years
– during the first 30 days posttransplant, 63% (130 patients) were suspected to have UTI
– 68 out of these 130 patients fulfilled the criteria for UTI; 58/68 patients had growth of a urine pathogen on m/c/s while 10 patients were unable to culture the pathogen
Microbiological results
– most common isolates were gram-negative Enterobacteriaceae and enterococcus species i.e., E. coli (n=49), E. faecium (n=23), E. faecalis (n=23), Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=6)
– 62 uropathogenic bacteria were cultured during ASBs
– in total 135 bacterial isolates were cultured, 88 (65%) were gram negative, 46 (34%) were gram positive, ureaplasma (1%) was excluded
– 56 of the 88 gram-negative bacteria isolates were recorded during a UTI while 32 (36%) were found in ASB
– 30 out of the 46 gram-positive isolates were recorded during ASB while 16 (35%) were found during an episode of UTI
Antibiotic prescription
– 80% (166 patients) received at least a single course of antibiotic treatment
– median duration of antibiotic treatment was 5±4 days
– 262 courses of antibiotic treatments were prescribed within the first 30 days posttransplant
– (suspected) UTI was the most common indication for antibiotic treatment, 2.4% (5 patients) had urosepsis, 127 patients had suspected UTI
– of these 127 patients, 85 patients received a single course of antibiotics, 33 patients received 2 courses, 7 received 3 courses and 2 patients received 4 courses of antibiotics
– patients who received a single course of antibiotics had a significantly worse GFR at discharge
– most commonly prescribed antibiotics were ciprofloxacin (n=101), piperacillin/ tazobactam (n=17), linezolid (n=17), meropenem (n=8), amoxiclav (n=6), TMP-SMX (n=5), cefuroxime (n=4), fosfomycin (n=4), nitrofurantoin (n=1)
Antibiotic resistance
– 9 patients had 3-MRGN, with a relevant percentage being resistant to piperacillin/ tazobactam, 3rd generation cephalosporin, ciprofloxacin
– none of the patients had carbapenem-resistant gram-negative bacteria
– E. coli was the most commonly isolated gram-negative bacteria whereas E. faecalis was the most commonly isolated gram positive
– E. coli was resistant to ampicillin/ sulbactam in 73% of KTRs, TMP-SMX in 67% of KTRs, fluoroquinolones in 45% of KTRs
– E. faecalis was resistant to fluoroquinolones in 87% of the KTRs
Bacterial resistance to empiric antibiotic treatment options
– resistance was highest in ampicillin/ sulbactam (56%), 3rd generation cephalosporins (46%), fluoroquinolones (39%), piperacillin/ tazobactam (26%), carbapenems (17%)
Discussion
– UTIs are the most common infection in the early posttransplant period and can lead to sepsis
– complicated UTIs have a negative impact on graft function therefore prevention and proper treatment of UTIs in KTRs is crucial
– ASB does not directly affect graft function but inadequate antibiotic use does
– patients who developed UTI had worse graft function at discharge and at 12 months follow-up
– most commonly prescribed antibiotics were ciprofloxacin and piperacillin/tazobactam
– bacterial resistance was more common in the study group compared to the control group hence the need for antibiotic stewardship teams
– measures taken to prevent infection in KTRs include:
·antibiotic stat dose prior to incision
·intraoperative bladder irrigation with gentamicin prior to ureteral anastomosis so as to decontaminate the bladder
·remove the ureteral stent 21 days posttransplant or earlier if there is suspicion for bacteriuria or infection so as to remove the biofilms (presence of indwelling catheters i.e., ureteral stents, foley’s catheters, is an independent risk factor for UTIs)
– ciprofloxacin was previously used for prophylaxis but is now reserved for treatment
– fosfomycin has been shown to have preventative efficacy
– TMP-SMX is now considered the best drug for prophylaxis
– previously patients would get peri-interventional antibiotics (usually ciprofloxacin) for ureteral stent removal, this is no longer the case as long as the patient is on TMP-SMX prophylaxis
– gram-negative bacteria were associated with infections whereas gram-positive bacteria were common in bacteriuria
– UTIs in KTRs require empiric antibiotics against gram-negative bacteria
– carbapenems are preferred in the critically ill patients since there was no resistance to the gram-negative bacteria
– piperacillin-tazobactam had the least gram-negative bacteria
– in this cohort there was a high bacterial resistance to ciprofloxacin
– there was over 50% resistance to aminopenicillins and almost 20% resistance to cephalosporins hence the recommendation to treat UTIs post kidney transplantation with empiric IV antibiotics then de-escalate to oral narrow-spectrum antibiotics once the bacterial strain has been identified
– however, for ASB, it is safe to wait for the final antibiotic resistance testing and use targeted therapy rather than empiric broad-spectrum antibiotic treatment followed by a step-down approach
– to detect ASB and UTI early, weekly screening for urinary pathogens can be done for the first month posttransplant
– treat ASB within the first month
– treatment of ASB after the 1st month has not been found to be beneficial, the prevalence of ASB decreases beyond the 1st month
– narrow-spectrum antibiotics e.g., TMP-SMX, nitrofurantoin, fosfomycin, pivmecilinam are used in the treatment of ASB
– these agents are safe and effective against MRGN bacteria
– the choice of antibiotics for empiric treatment for UTIs should be guided by the local antibiogram which should be updated regularly
– resistance to commonly used antibiotics seems to be greater in patients on dialysis and KTRs then in their healthy counterparts
– antibiotic stewardship data for SOT recipients and transplant programs is scarce
Study strengths
– ability to demonstrate different resistance patterns to antibiotics commonly used in UTIs between the KTRs and the control group
Study limitations
– retrospective study hence it was slightly difficult to distinguish between colonization/ bacteriuria and UTI
– single center study
– statistical comparisons were limited to exploratory data due to the uneven sample sizes between the study and control group – hence the need for multicentric comparative data prior to generalization of this data
Conclusion
– antibiotic stewardship programs should aim at preventing of postoperative infections as well as rational antibiotic use
– SOT recipients are at increased risk of fatal infections hence the low threshold for initiating antibiotics when an infection is suspected
– there is need to reduce antibiotic use by applying the different preventive measures to avoid infections
Level of evidence provided by this article
– Level II
How do you treat recurrent UTI at your workplace?
– all kidney transplant recipients are initiated on TMP-SMX prophylaxis posttransplant for 9-12 months
– we do not routinely do weekly urine cultures in the 1st month however we do weekly urine dipstick tests
– if there are features suggestive of UTI on the urine dipstick or if the patient is symptomatic, we request for urine cultures (m/c/s)
– empiric antibiotic therapy is initiated:
~ for outpatient treatment we commonly prescribe nitrofurantoin, amoxicillin-clavulanic acid or 2nd generation cephalosporins
~ for inpatient management we usually prescribe 3rd generation cephalosporins unless the patient has sepsis in which case we prescribe piperacillin-tazobactam or meropenem
– the antibiotic prescription is then adjusted according to the sensitivity pattern
– foley’s catheter is usually removed on the 5th POD unless the patient is still very polyuric
– ureteral stents are routinely removed at week 6 unless there are complications warranting early removal
– for recurrent UTIs we exclude other causes e.g., TB, structural and functional abnormalities by doing cystoscopy, uroflow dynamics, graft ultrasound, further imaging as is deemed appropriate
Aim of the study
Authors looked at antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of asymptomatic bacteriuria (ASB) and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those from local community.
Study design: Observational longitudinal cohort study.
Inclusion criteria: adutls16 years who had kidney transplantation between January 2015 and August 2020.
Exclusion criteria: combined Tx
All patient had the standard immunosuppressive therapy, induction with basiliximab, ATG and alemtuzumab, and MMF, CNIN+ prednisolone maintenance. Perioperative antibiotic prophylaxis used is Beta-Lactam or Ampicillin/Sulbactam, with TMP-SMX 960 mg 3×/week for Pneumocystis prophylaxis, and gentamycin bladder irrigation before ureter anastomosis.
Results
total inclusion 207
63% were suspected to have UTI and halve of them fulfilled the criteria for UTI with 6/7 had positive culture. Most common organisms were E.coli, klebsiella and E.faecalium.
166 of all participants received antibiotic course with median duration was 5 days and clinical indication was suspected UTI.
Fluoroquinolones were the most commonly prescribed.
9 patients had multi-resistant gram negative bacteria.
Discussion
UTI are the most common infections in the early post-transplant period.
Studies have shown that even one episode of UTI negatively impacts the allograft function. ASB doesn’t affect the allograft function however the inappropriate use of antibiotics does.Indwelling catheters are an independent risk factor.
prevention of UTIs.
Gram negative bacilli: most common UTI, emperic Abx should cover
Gram positve bacilli: mainly ASB
Strenght
-Demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group.
2-Clearly demonstrate the role of prophylactic antibiotics and prevalence of resistance.
Weakness.
1-Difficult to distinguish between colonization/bacteriuria and urinary tract infection.
2-Single center study.
3-Small sample size.
4- Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data
Level of evidence: 2
Urinary tract infections (UTI) are the most common infection in the early postoper- ative phase after kidney transplantation (KT). In this article Jens Strohaeker and colleagues have tried to look into impact of UTI on graft outcome and importance of appropriate antibiotic management.
UTIs are defined as the growth of 10-5colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
In contrast to UTIs asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
Materials and Methods
They retrospectively screened their hospital information system for all patients who underwent kidney transplantation at the department of General, Visceral and Transplan- tation Surgery of the University Hospital of Tuebingen, Germany.
All adult patients (age ≥ 16 years) who underwent KT at their center between January 2015 and August 2020 were included in the final analysis.
Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) or 3 × 3 g of Ampicillin/Sulbactam (Q0h/12h/24h) at the transplant surgeons’ discretion.
Treatment Protocols for Urinary Tract Infections
Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics.
Recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR. For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
Urinary catheters we’re removed on day 5 and meticulous follow up was ensured.
RESULTS
During the study period, 207 patients met the inclusion criteria.
Of these 207 patients 73 patients underwent living donation kidney transplantation (35%)
134 received a kidney from a deceased donor (65%).
Overall 119 (57%) of patients were male compared to 88 (43%) females.
The median age during KT was 55 years with a standard deviation (SD) of ±14 years.
During the first 30 days after their transplant 130 patients (63%) were suspected to have a urinary tract infection.
The most common isolates from urinary cultures were gram-negative enterobacteri- aceae as well as enterococcus species.
E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23).
Antibiotic Prescription
Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis). The median duration of antibiotic treatment was 5 days with a SD of ±4 days.
Antibiotic Resistance
Overall nine patients presented with multiresistant gram-negative bacteria (MRGN). All nine were 3-mrgn (E. coli n = 7, Enterobacter cloacae n = 1, Citrobacter koseri, n = 1). Of the gram-negative bacteria a relevant percentage was resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
Strengths and Limitations
The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data. Therefore, multicentric comparative data will be necessary prior to generalization of our data.
Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
In this cohort between 207 patients 262 courses of antibiotics were prescribed. Of these, 180 were prescribed antibiotics for suspected urinary tract infection. Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
LEVEL OF EVIDENCE
2
We at our center treat recurrent UTI
according to culture results and usually use Meropenem and try to find out an obvious reason for recurrent UTI. We usually keep such patients on Nitrofurantoin prophylaxis.
We keep all patients on TMP/SMX for six months
Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
Summarise.
Introduction;
Materials and methods.
Data acquisition.
Immunosuppressive protocol;
Peri op antibiotic prophylaxis;
Tx protocols for UTI;
Urinary catheter and double J stent mgt;
Post op follow up;
Clinical definitions;
Microbiological culture, identification of strains and resistance testing.
Statistics;
Results;
Discussion;
Limitations;
Conclusion;
LEVEL OF EVIDENCE;2
OUR CENTRE PRACTICE;
Introduction
Post renal transplant UTI is by the most common recognized infection worldwide with incidence ranging from 4–80%.The growth of (10)5 colony forming units on a proper urine sample is significant when accompanied by symptoms in the form of dysuria, urinary frequency or even localized pain. While asymptomatic bacteriuria (ASB) is characterized by the presence of (10)5 colony-forming units of bacteria in the absence of any symptom. Astonishingly, it was estimated by 25% of renal transplant recipients. This mandated the necessary screening and proper treatment consequently.
This raised the question for the need for antimicrobial administration to avoid the occurrence of urosepsis or other atypical presentation owing to immunosuppression and renal denervation or the posing the patients to worse long-term graft survival. This came out clear in 2018 after the European Association of Urology Guidelines recommended the administration of a single shot antibiotic prophylaxis.
Most cultures revealed that the common pathogens were detected are Escherichia coli, Enterococcus and Klebsiella species. Thus, Fluoroquinolones were considered the best line due to their widespread availability, intravenous and oral formulations and excellent penetration into the urinary tract up to the detection of pseudomonas species which required different approach then.
So, our study was directed to evaluate the antibiotic prescription practice during the first month post operatively after renal transplantation, the incidence of ASB and UTIs besides comparing the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those of the local population.
Materials and Methods
The study was retrospective for renal transplant recipients at University Hospital of Tuebingen, Germany. It included adult patients who were exceeding 16 years from January 2015 till August 2020. Patients with Simultaneous pancreas or liver transplantation were excluded.
Perioperative antibiotics consisted of a Beta-Lactam and Trimethoprim-Sulfametoxazole (TMP-SMX). Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
Before the recommendation to avoid fluoroquinolones the proposed empiric treatment was Ciprofloxacin. Piperacillin/Tazobactam and Meropenem have been suggested then.
Urinary catheters were removed on the fifth postoperative day while the Double-J-ureteral stent was removed after 21 days postoperatively according to the centre protocol.
Statistics were performed by the Chi-Square test (X2), Fisher’s exact test (FET) and the Mann–Whitney U-test (MWU). P-values less than 0.05 was considered to be statistically significant.
Results
The study included 207 patients; 73 patients underwent living donation kidney transplantation (35%) 134 received a kidney from a deceased donor (65%).study population involved 119 (57%) male patients and 88 female patients (43%). The median age was 55 years with a standard deviation (SD) of 14 years.
A total of 130 patients (63%) were suspected to have a urinary tract infection during the first 30 days postoperatively. Only 68 patients fulfilled the criteria of a UTI among them 58 patients showed growth of a urinary pathogen on urine culture while only ten patients were unable to culture the pathogen.
E. coli was the leading pathogen as it was detected in 49 cultures followed by enterococcus species. It was found that 73 uropathogenic bacteria were cultured from the whole 68 cultures. Mixed cultures of two uropathogenic organisms were detected in 5 cultures as well. One patient only experienced four individual episodes of UTI with four different bacteria being recorded. The presence of ASB was detected in 59 individuals.
Data of culture results of UTI compared to asymptomatic bacteriuria is totally different. A total of 135 bacterial isolates were cultured; 88 (65%) were gram-negative and 46 (34%) were gram positive. Regarding the 88 gram negative; UTI patients were 56, while 32 patients were ASB.
Concerning the 46 cultures of gram-positive isolates; 30 patients (65%) had ASB and only 16 patients (35%) had UTI with (p = 0.001).
The need of further antibiotic prescription was 262 courses to the whole patient cohort within the first 30 days posttransplant. Five patients had urosepsis (2.4%). A total of 127 patients were treated for suspected UTI who required 180 courses of antibiotics. Among the 127 patients; 85 patients received a single course of antibiotics, 33 patients received two courses, 7 received three courses and two patients received four courses of antibiotics. About 25% of these patients had showed a rise in creatinine.
Antibiotic Resistance was encountered in nine patients presented with multiresistant gram-negative bacteria (MRGN). Fortunately, none of them showed carbapenem resistant gram-negative bacteria. E. coli being the most common isolate have been resistant to fluoroquinolones in 45%.
Data from the control group revealed that E. coli was resistant to Ampicillin / Sulbactam in 37%, to Piperacillin/Tazobactam in 5%, to 3rd generation cephalosporins in 9%, to fluoroquinolones in 17%, to TMP-SMX in 20%. In our renal transplant recipients E- coli was found to be resistant to Ampicillin/Sulbactam in 73%, to Piperacillin/Tazobactam in 14%, to 3rd generation cephalosporins in 16%, to fluoroquinolones in 45%, to TMP-SMX in 67%.
The most commonly isolated gram-positive bacteria was E. faecalis which was resistant in our renal transplant recipients to Fluoroquinolones in 87% and carbapenems in 4% while in the control group E. faecalis was resistant to only fluoroquinolones in 10% .
Among both gram-negative and gram-positive bacteria in both UTI and ASB the overall bacterial resistance was actually high. Resistance to Ampicillin/Sulbactam was detected in 76 of the 135 strains (56%), to Piperacillin/Tazobactam in 35 strains (26%), to 3rd generation cephalosporins in 62 strains (46%), to fluoroquinolones in 52 strains (39%) and even to carbapenems in 23 strains (17%).
The resistance to Piperacillin/Tazobactam and carbapenems can be explained by the prevalence of Enterococcus species.
Discussion
The conflict of UTI and ASB was aroused only after recent data has suggested the negative impact of even a single episodes of complicated urinary tract infections on allograft function.
According to this study, UTI can be accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT. This highlights the crucial role of prevention and proper treatment in KT recipients.
The facts of the increasing use of extended donor allocation and overall comorbidities of the recipients make the whole process more complicated particularly after revealing that 10% were treated with antibiotic doses that were above the recommended limit caused more than 25% of the patients to have more deterioration of graft function.
Some strategies were adopted according to the variable centres protocols to avoid the occurrence of UTI postoperatively as the administration of single shot antibiotic prior to incision, intraoperative Gentamicin irrigation of the bladder also prior to ureteral anastomosis and removal of urinary catheters as well ureteric stents without delay per protocol.
The Mayo clinic study declared that there is a reduction in UTIs after TMP-SMX was used for 6 months after KT. Horwedel et al. also confirmed that as our study did. Oppositely, Singh et al. had different data against the decline of incidence of UTIs and ASB in patients adopted the pneumocystis prophylaxis in their cohort.
Lee et al. raised another concern regarding the omission of extra peri-interventional antibiotics didn’t seem to be disadvantageous provided that our patient was on TMP-SMX prophylaxis at the time of stent removal.
The most attractive choice for critically ill patients is carbapenems owing to its zero resistance in the common gram-negative bacteria. Followed by the Piperacillin/ Tazobactam that had the least gram-negative resistance estimated by a rate of 15%.
The study also adopted a weekly screening strategy to ensure early detection of ASB and UTI variable urinary pathogens in the first month post-transplant.
A meta-analysis from Spain recommended not to treat ASB after the first month post KT, whereas Origuën et al. and Coussement et al. both confirmed no extra benefits concerning treating ASB two months after kidney transplant. This can be explained by the after that time the prevalence of ASB was generally reported to be decreasing to below 4% of patients. Bohn et al. reported on a small cohort of ASBs during the first month post-transplant that no difference in progression to UTI both when treated or left untreated conflicting this principle.
This study believes that it is safe to wait for the final antibiotic resistance testing in ASB and use targeted therapy rather than empiric broad spectrum coverage. This is attributed to the fact that the resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy population. So, the next challenge is to adopt the idea of prevention of the development of resistant strains in dialysis patients for antibiotic stewardship teams worldwide. The barrier that is faced now is the scarce data for Antibiotic stewardship of solid organ transplant recipients and transplant programs.
This study stated that the MRGN rate of 10% that was found to be similar to other German KT centers. Fortunately, it was lower than what Tekkarismaz et al. reported to be 41% MRGN urinary tract infections in their cohort in Turkey. However, 10% was considerably higher than the average of 5% described in a 2017 meta-analysis reflecting that the global numbers are increasing.
Strengths and Limitations
Limitations are mainly being only single center data, 200 kidney transplant recipients only, for limited time early after kidney transplantation and the fact that uneven sample sizes between the study and control group might affect statistical comparisons data.
Strengths are essentially the ability to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between recipients and the control group based on urinary cultures ordered at a massive tertiary university hospital.
Conclusions
Solid organ transplant recipients are at higher risk of fatal infection. Low threshold for initiating antibiotic treatment when infection is suspected can therefore be justified.
Multicentric comparative data are required besides the collaboration of efforts of transplant surgeons, physicians and antibiotic stewardship teams should be coordinated to face this serious infection impacts.
Level of evidence is II.
Our centre protocol include perioperative antibiotic prophylaxis, urinary catheter insertion occurs in the operation, monitoring the patient by ultrasound postoperatively. After discharge weekly screening for UTI and ASB for the first month.
TMP-SMX prophylaxis for the first 6 months post renal transplantation is a must. Management of both UTI and ASB is only culture based.
Cases of recurrent UTI after being assessed by ultrasound, the urology team is consulted for the co-management in addition to urine flow metric studies are considered.
Summary
· This article discusses the need for antibiotic stewardship in kidney transplant recipients.
· This study presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
· The most important details in this text are that asymptomatic bacteriuria (ASB) is commonly screened for and treated in the early posttransplant phase, and that UTI is assumed to be lower in living donation kidney transplantation due to shorter waiting time, higher volume urine output, and early onset graft function.
· Fluoroquinolones are among the most common antibiotics in the treatment of urinary tract infections in KT recipients due to their widespread availability, intravenous and oral formulations, and excellent penetration into the urinary tract.
· This study examined the clinical characteristics of 207 kidney transplant recipients (KT) from January 2015 to August 2020.
· Of 130 patients with a UTI, 68 had typical symptoms and/or clinical/laboratory signs of inflammation.
· In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded, and ten patients found typical symptoms accompanied by laboratory and urine chemistry findings consistent with UTI.
· Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment (excluding perioperative and periinterventional prophylaxis).
· 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant.
· E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
· The most commonly isolated gram-positive bacteria was E. faecalis
· In this cohort, urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
· Prevention and adequate treatment of urinary tract infections in KT recipients is crucial, and several measures have been proposed to prevent infections.
· In order to detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant.
· TMP-SMX is prescribed for 6–12 months after KT to prevent Pneumocystis jirovecii pneumonia. TMP-SMX reduced UTIs for 6 months after KT.
· For ureteral stent removal, Lee et al. found that omitting periinterventional antibiotics (usually Ciprofloxacin) was not harmful if the patient was on TMP-SMX prophylaxis.
· Empiric antibiotics should always cover gram-negative enterobacteria. , carbapenem is the best choice for critically ill patients. After culture result , an oral narrow-spectrum antibiotic may be appropriate.
· can wait for the final antibiotic resistance testing in ASB and use targeted therapy instead of empiric broad spectrum .
· Antibiotic stewardship and hospital hygiene data can be useful but must be monitored and updated.
Level of evidence
· Level 2, retrospective cohort study
Our practice:
– Supportive measures.
– IV AB, carbapenem , tazocin , or depending on last previous positive culture if recurrent.
– Chronic suppressive therapy with ciprofloxacin low dose , TMP/SMX , Fosfomycin or nitrofurantoin.
Q1- Please summarise this article.
1. Introduction:
Urinary tract infections (UTI) are the most common infection in the early postoperative
phase after kidney transplantation (KT) .
The incidence of a UTI ranges from 4–80% .
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 .
asymptomatic bacteriuria (ASB) is defined as the presence of105 colony-forming units of bacteria in the absence of symptoms .
Asymptomatic bacteriuria is encountered in around 25% of KT recipients .
Thus, ASB is commonly screened for and treated in the early posttransplant phase , even though there is ongoing controversy about the impact of ASB and UTI on the overall patient and graft outcome .
In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression.
The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function .
A perioperative antibiotic prophylaxis is standard in KT.
But the regimens is heterogenous .
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus
faecalis and Klebsiella pneumoniae .
Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci .
Fluoroquinolones are among the most commonly used antibiotics.
After the FDA warning in 2019 regarding the use of fluoroquinolones both in general and KT recipients in particular.
AIM OF STUDY:
To evaluated our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based on data provided by our hygiene department
Methods:
retrospectively analysis of the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020. All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated.
Results:
Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed
UTI had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam. To both,
bacterial resistance was more common in the study cohort than in the control group.
Discussion
Urinary tract infections are the most common infection in the early postoperative phase
after kidney transplantation .
They can lead to sepsis and are a potential threat to life.
It has a negative impact on allograft function .
UTI associated with worse creatinine clearance both at the end of our study and one year after KT.
prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
that asymptomatic bacteriuria (ASB) does not affect graft function but
inadequate use of antibiotics certainly has the potential to do so .
Several measures have been proposed to prevent infections in KT recipients.
1- A single shot antibiotic is administered prior to incision.
2- Prolonged antibiotics have not proven beneficiary for the prevention of UTI or surgical site infection .
3- intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, is proven promising .
The presence of indwelling catheters, mainly ureteral stents and Foley catheters
is an independent risk factor of urinary tract infections .
the ideal timing of stent removal is three weeks post-transplant .
Ciprofloxacin was shown to prevent UTIs 25 years ago, but was later reserved for treatment rather than prophylaxis.
a recent randomized trial that showed the preventative efficacy of Fosfomycin .
TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic
dose for 6–12 months after KT.
The Mayo clinic group reported a reduction in UTIs when TMP-SMX was prescribed for 6 months after KT .
There is a report of , a lower rate of septicemia while patients were on TMP-SMX prophylaxis .
In contrast, Singh et al. reported no difference in the incidence of urinary tract infections
and asymptomatic bacteriuria in patients that underwent Pneumocystis prophylaxis in their
cohort .
At our center the UTI rate was significantly lower in patients that were on TMP-SMX.
Urinary tract infections in KT recipients require empiric antibiotic coverage of mainly
gram-negative bacteria.
In this dtudy 89 gram-negative strains of bacteria were isolated compared to 46 gram-positive ones.
Gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria.
Empiric antibiotics should therefore always cover gram-negative enterobacteria.
There was no resistance to carbapenems in our gram-negative bacteria, which makes them the
most attractive choice for critically ill patients.
Of the remaining antibiotics Piperacillin / Tazobactam was the substance to which the least gram-negative resistance existed to, at a rate of 15%.
In this study there is high bacterial resistance to Ciprofloxacin was in our cohort (29%).
With a resistance to aminopenicillins in over 50% and a resistance to cephalosporins of nearly
20% we strongly recommend treating urinary tract infections after Kidney Transplantation
with empiric intravenous antibiotics according to local resistance patterns. This study report 59 episodes of ASB (29%) is comparable to other reports .
A meta-analysis from Spain recommended not to treat ASB after the
first month post KT .
This practice has been backed by two randomized controlled multicenter trials report that no benefits in treating ASB two months after kidney transplant .
Unfortunately, there are no randomized controlled trials on the treatment of ASB within the first month after KT.
The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics
such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not
recommended as first line therapy for urinary tract infections in transplant recipients.
In this study , not a single strain of E. coli was resistant to Fosfomycin or Nitrofurantoin, while over 40% were resistant to TMP-SMX.
The author strongly advocate against the use of fluoroquinolones in ASB.
While symptomatic patients need to be treated empirically to avoid development of
septicemia, we believe it is safe to wait for the final antibiotic resistance testing in ASB and
use targeted therapy rather than empiric broad spectrum coverage followed by a step- down
approach.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind which may vary a lot regionally.
More specifically, the resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
Strengths and Limitations
1- We presented single center data on bacterial isolates from urine samples of over200 kidney transplant recipients early after kidney transplantation.
2- The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
3- Still, we were able to demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group that consisted of all urinary cultures ordered at this tertiary university hospital.
4- Given the uneven sample sizes between the study and control group statistical omparisons were limited to exploratory data.
5- Therefore, multicentric comparative data will be necessary prior to generalization of our data.
5. Conclusions
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs. Solid organ transplant recipients are at increased risk of fatal infection.
This leads to a low threshold for initiating antibiotic treatment when infection is suspected. In our cohort between 207 patients 262 courses of antibiotics were prescribed. Of these, 180 were prescribed antibiotics for suspected urinary tract infection. Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
Q2- What is the level of evidence provided by this article?
Level of evidence 2
Q3- How do you treat recurrent UTI at your workplace?
Exclude any structural abnormalties.
Patient usually treated depending on the result of C/S .
Treat and control other medical disease DM ,
Education of female patient regarding preventive measures.
Please summarise this article.1) A retrospective study looking at 207 kidney transplantation at a single centre between January 2015 and August 2020
2) The cohort was divided into No UTI (139 patients) vs UTI (68 patients) (asymptomatic bacteriuria, UTI)
3) The outcome was graft functions upon discharge and 12 months. Patients with UTI were associated with poorer graft outcomes. The most commonly prescribed antibiotics were ciprofloxacin and piperacillin/tazobactam
What is the level of evidence provided by this article?Level 2: Cohort study
How do you treat recurrent UTIs at your workplace?1) Asymptomatic vs symptomatic
2) Serum creatinine to look at concomitant raises in serum creatinine
3) Urine culture
4) If symptomatic treat empirically, and if asymptomatic to wait and evaluate the culture
5) Reduction of immunosuppression in recurrent UTI
6) Further investigations in recurrent UTI ie: ultrasound, cystoscopy and cystourethrogram
Please summarise this article.
UTIs are defined as the growth of 105 colony forming units on a proper urine sample (i.e., morning urine, puncture urine or from sterile single catheterization) in the presence of symptoms such as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
Controversy about the impact of ASB and UTI on the overall patient and graft outcome
The incidence of UTI is assumed to be lower in living donation kidney transplantation.
The most common pathogens found in urine samples after KT are Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae
This study evaluated our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population based
Methodology
They retrospectively analyzed the charts of adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
As protocol all KT recipients had urine samples sent for culture every Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. Simultaneous pancreas or liver transplantation were excluded.
Results
Of the 207 patients included, 73 underwent living donation , and 134 received deceased donor kidney transplantation
The median length of stay was 20 days (range 10–53)
During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection.
In 58 of these 68 patients, growth of a urinary pathogen on urine culture
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.
The most common indication for antibiotic treatment was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria was E.coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
Discussion
In this study urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
Prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
Prolonged antibiotics for the prevention of urinary tract or surgical site infection may not be benificial
To decontaminate the bladder, intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, shown promising in patients with recurrent UTIs.
The presence of indwelling catheters is an independent risk factor of urinary tract infections.
For reduction rate of UTI after KTx, early removal of the ureteral stent is suggested.
A meta-analysis from Spain recommended not to treat ASB after the first month post KT.
The treatment of asymptomatic bacteriuria with narrow-spectrum antibiotics such as TMP-SMX/ Fosfomycin/ Nitrofurantoin/ Pivmecillinam are not recommended as first line therapy for urinary tract infections in transplant recipients.
Limitation
Single center data.
Retrospective analysis of data
Uneven sample size between study & control group statistical comparison limited to exploratory data.
Strength
Demonstration of distinct different resistant pattern to commonly used antibiotics in UTI between KTR & control group.
.
Conclusion
Solid organ transplant recipients are at increased risk of fatal infection. This leads to a low threshold for initiating antibiotic treatment when infection is suspected
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Level of evidence: 2 Cohort study
How do you treat recurrent UTI at your workplace?
Empiric oral antibiotic according to susceptible patten of bacteria.
Then treatment as urine c/s report- oral or iv
Prophylactic antibiotic TMB-SMX or nitrofurantoin (at prophylactic dose) for 3-6 months.
Exclusion of any structural or functional causes do as needed U/S KUB, MCUG, CT KUB ,Urodynamics
Introduction
Materials and Methods
· Retrospectively, the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral, and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020 have been analyzed.
Results
· The most common indication for antibiotic treatment was suspected urinary tract infection, with fluoroquinolones being the most commonly prescribed antibiotic.
· E. coli was the most commonly isolated gram-negative bacteria.
Discussion
Conclusions
Antibiotic stewardship programs aim to prevent infections after surgery and rationally use antibiotics. Solid organ transplant recipients are at increased risk of fatal infection, leading to a low threshold for initiating antibiotic treatment. To reduce this number, a team effort of transplant surgeons and physicians and antibiotic stewardship teams is needed.
==========================
Level of Evidence II
==========================
How do you treat recurrent UTI at your workplace?
Recurrent UTI after limited workup including (Ultrasound, MCUG, Urine culture, and sensitivity) to manage any structural abnormalities, and foreign bodies, then start them with proper empirical and culture-based antibiotics promptly.
Urinary Tract Infections in Kidney Transplant Recipients—Is There a Need for Antibiotic Stewardship?
Introduction.
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 and if no symptoms considered asymptomatic bacteriuria which is encountered in around 25% of KT recipients, risk of UTI is less in LKTX than cadaveric TX, and still short – long term graft effect is controversial.
Prophylactic pre-operative antibiotics is decreasing incidence of UTI, because gram negative bacteria is the most common cause of UTI in KTX recipient as well as in general population thus fluoroquinolones is considered the most common used medications for treating UTI.
Aim of the work:
1-To evaluate antibiotic prescription practice during the first 30 days after kidney transplant.
2-To detect the incidence of ASB and UTIs.
3-To compare the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population.
Materials and Methods.
A retrospective study that screened our hospital information system for all patients who
underwent kidney transplantation at the department of General, Visceral and Transplantation
Surgery of the University Hospital of Tuebingen, Germany. All adult patients who underwent KT at our center between January 2015 and August 2020 which are 207 patients.
Results:
1-During the first 30 days after their transplant ,130 patients (63%) were suspected
to have a urinary tract infection, 68 patients of 130 patients fulfilled the criteria of a UTI (typical symptoms and/or clinical/laboratory signs of inflammation) In 58 of these 68 patients growth of a urinary pathogen on urine culture was recorded.
2-The most common isolates from urinary cultures were gram-negative enterobacteriaceae
as well as enterococcus species and E-coli was the most common one.
3-Of the 180 suspected UTIs, fluoroquinolones were the most commonly prescribed
antibiotic followed by Piperacillin/Tazobactam), aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporin, Fosfomycin, Pivmecillinam, Nitrofurantoin , Linezolid, and others.
4-Resistance to Ampicillin / Sulbactam, fluoroquinolones and Trimethoprim-Sulfamethoxazole (TMP–SMX) is substantially higher in the Kidney Transplant cohort.
5-Urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after KT.
Discussion.
Prevention is so much important to prevent UTI, starting from single dose pre-operative antibiotics, intra-operative antibiotic irrigation, early removal of Foleys catheter as well as ureteric stent, now trimethoprim-Sulfamethoxazole (TMP–SMX) prophylaxis against PJP has a prophylactic role in UTI prevention and empiric antibiotics therapy has preventive effect of UTI progression till C/S result released and chosen antibiotics mainly depends on hospital local policy with microbiologist guidance (antibiotic stewardship teams) according to most common isolation organism and the common resistant antibiotics.
Strength.
1-Demonstrate distinctly different resistance patterns to commonly used antibiotics in urinary tract infections between our KT recipients and the control group.
2-Clearly demonstrate the role of prophylactic antibiotics and prevalence of resistance.
Weakness.
1-Difficult to distinguish between colonization/bacteriuria and urinary tract infection.
2-Single center study.
3-Small sample size.
Conclusion.
UTI is a common complication post kidney transplant and prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Using prophylactic antibiotics and empirical use of high sensitive antibiotics according to local institution survey of organism resistance and prevalence of infection can decrease rate of complicated UIT in PKTX which can affect graft and patient survival.
A retrospective cohort study (level of evidence III).
How do you treat recurrent UTI at your workplace?
We are treating UTI on culture base.
Fine tuning of immunosuppression.
Treat predisposing factors (uncontrolled DM for example ), behavior management.
KUB.USG, up to CT KUB.
Urodynamic and involve the urologist.
Introduction:
-Urinary tract infections (UTI) are the most common infections after kidney transplantation.
-The incidence of a UTI ranges from 4–80% in the early postoperative phase after kidney transplantation (KT) , a symptomatic bacteriuria is encountered in around 25% of KT recipients
-Given the risk of urosepsis and the potential threat to the graft, the threshold for treating UTI and asymptomatic bacteriuria with broad spectrum antibiotics is low.
-The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
-The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumonia.
Aim:
-This study evaluated the effect of antibiotic during the first 30 days after kidney transplant , and the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population.
Methodology:
-They retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
-As protocol all KT recipients had urine samples sent for culture every Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
-The median length of stay was 20 days (range 10–53).
-Patients that underwent simultaneous pancreas or liver transplantation were excluded.
-All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated.
Results:
-Of the 207 patients, 68 patients suffered from urinary tract infections. Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up.
-The most common isolates from urinary cultures were gram-negative enterobacteriaceae as well as enterococcus species , E. coli was the leading pathogen and was found in 49 cultures followed by E. faecium (n = 23) and E. faecalis (n = 23)
-The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam.
-To both, bacterial resistance was more common in the study cohort than in the control group.
Discussion;
-In this cohort urinary tract infections were accompanied by significantly worse creatinine clearance both at the end of the study period and one year after KT.
-Thus, prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
-Prolonged antibiotics have not proven beneficiary for the prevention of urinary tract or surgical site infection.
-In order to decontaminate the bladder they perform intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis, which has been proven promising in patients with recurrent UTIs.
-The presence of indwelling catheters, mainly ureteral stents and Foley catheters is an independent risk factor of urinary tract infections.
-So, for reduction rate of UTI after KTx, it require removal the ureteral stent at 21 days after KT or earlier if there is suspicion for bacteriuria or infection in order to remove biofilms & TMP-SMX was prescribed for 6 months after KT .
-Following the 2019 FDA warning against the use of fluoroquinolones in KT recipients, this has slowly led to a decrease in Ciprofloxacin use.
-Recently, more data is becoming available on the treatment of ASB early after transplantation.
-A meta-analysis from Spain recommended not to treat ASB after the first month post KT.
-The treatment of asymptomatic bacteriuria is the niche for narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam which are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Limitations;
-They presented single center data on bacterial isolates from urine samples of over 200 kidney transplant recipients early after kidney transplantation.
-The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
-Given the uneven sample sizes between the study and control group statistical comparisons were limited to exploratory data.
-Therefore, multicentric comparative data will be necessary prior to generalization of this data.
Conclusion:
-Urinary tract infections appear to be linked to worse graft functions.
-Thus, prevention and treatment should be accompanied by antibiotic stewardship teams.
-This Article is Cohort study with ( LOE 2b ).
-How do you treat recurrent UTI at your workplace?
-According the severity of UTI; Admission and start him IVF.
-Strat empiric antibiotic if patient has symptomatic dysuria and urine analysis suggestive for UTI.
-Usually we start broad spectrum antibiotic Piperacillin/Tazobactam or meropenem then switch according to the culture result for 2 weeks.
-Prophylactic TMB-SMX for 3-6 months.
-In recurrent UTI we usually exclude any structural or functional causes, do U/S KUB & MCUG, and urology review.
-Patients especially females should be educated about self hygiene.
Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
1. Please summarise this article.
2. What is the level of evidence provided by this article?
3. How do you treat recurrent UTI at your workplace?
Please summarise this article.
Introduction
The Urinary tract infections (UTIs) are the most common infection in the early postoperative with an incidence of 4-80%.
UTI defined as growth of 10^5 CFU on proper urine sample, early morning sample, or from a sterile catheter associated with upper or lower urinary tract symptoms, (dysuria, frequency, or localized pain).
Asymptomatic bacteriuria (ASB) defined as presence of > or more 10^5CFU of bacteria without symptoms, it occurs in around 25% of KTR.
ASB frequently screened and treated in post-transplant period.
In transplant recipient’s threshold of ASB treatment is lower due to increased risk of septicemia or atypical presentation.
Multi-resistant gram-negative bacteria (MRGN) = bacteria resistant to three or more of the following antibiotics (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems).
The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis and Klebsiella pneumoniae.
UTI incidence is lower in living donor kidney transplant recipients because: shorter waiting time, higher volume UOP prior, during transplantation & early onset graft function.
Peri-operative antibiotic prophylaxis is a standard in kidney transplant.
EAU guidelines recommend a single shot antibiotic prophylaxis.
Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in kidney transplant recipients, but after FDA warning in 2019 re-evaluation of empiric antibiotic is considered.
Aims of the study:
Evaluation of antibiotic prescription practice in first 30 days post-transplant.
Evaluation of ASB and UTI incidence
Compare antibiotic susceptibility of isolated urinary tract bacteria from KTR to isolated bacteria from local population.
Materials and Methods:
Observational longitudinal cohort study.
Inclusion criteria: Patients above 16 years who underwent kidney
transplantation between January 2015 and August 2020.
Exclusion criteria: Patients who underwent simultaneous liver and pancreas transplant.
Data acquisition was conducted for all patients who underwent kidney transplantation at the University Hospital of Tuebingen, Germany between January 2015 and August 2020.
Medical reports were screened for intra- and perioperative microbiological cultures, and the control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene.
Immunosuppressive protocols included 500 mg of iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
Perioperative antibiotics included Single-Dose Beta-Lactam, Ampicillin/Sulbactam, or 3 3 g of Ampicillin/Sulbactam.
Treatment protocols for Urinary Tract Infections included iv Methylprednisolone, Basiliximab, Anti-Thymocyte Globulin, or an Anti-CD56-Antibody.
The protocol recommended empiric antibiotics for urinary tract infections and asymptomatic bacteriuria.
Urinary catheters were placed preoperatively and removed on postoperative day (POD) 5 in patients with retained diuresis.
Ureterocystoneostomy was performed according to Lich-Gregoir.
Intraoperatively, a Double-J-ureteral stent was placed and removed on POD 21.
Postoperative follow-up included blood workup, urine sampling, ultrasounds, and renal biopsies.
Patients were seen at the outpatient clinic for blood and urine workup, clinical and sonographic follow-up.
Results:
Clinical Characteristics:
The study analyzed the charts of all consecutive adult kidney transplant recipients from January 2015 to August 2020 at the University Hospital Tuebingen, Tuebingen, Germany.
207 patients met the inclusion criteria, 73 underwent living donation kidney transplantation, and 134 received a kidney from a deceased donor.
During the first 30 days after their transplant, 130 patients (63%) were suspected to have a urinary tract infection. In 58 of these 68 patients, growth of a urinary pathogen on urine culture was recorded.
The most common isolates from urinary cultures were gram-negative Enterobacteriaceae and enterococcus species. E. coli was the leading pathogen, followed by E. faecium and E. faecalis.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
135 bacterial isolates were cultured, with 88 (65%) gram-negative and 46 (34%) gram-positive.
Ureaplasma (1%) was excluded from this analysis.
The most common indication for antibiotic treatment in kidney transplant recipients was suspected urinary tract infection.
Of the 180 suspected UTIs, fluoroquinolones were the most prescribed antibiotic, followed by piperacillin/Tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and others.
Nine patients presented with multiresistant gram-negative bacteria (MRGN), all of which were resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin.
The most commonly isolated gram-negative bacteria was E.coli, which was resistant to fluoroquinolones in 45%.
The most isolated gram-positive bacteria were E. faecalis, which was resistant to Ampicillin/Sulbactam in 73%, Piperacillin/Tazobactam in 14%, 3rd generation cephalosporins in 9%, fluoroquinolones in 17%, carbapenems in 0%, TMP-SMX in 67%, Fosfomycin in 0% and Nitrofurantoin in 0%.
Overall bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam present in 76 of the 135 strains (56%) Piperacillin/Tazobactam in 35 strains (26%), 3rd generation cephalosporins in 62 strains (46%), fluoroquinolones in 52 strains (39%) and carbapenems in 23 strains (17%).
Discussion:
Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation and can lead to sepsis and a potential threat to life.
Recent data suggests a negative impact of even single episodes of (complicated) urinary tract infections on allograft function.
To prevent infections in KT recipients, several measures have been proposed, such as a single shot antibiotic administered prior to incision, Gentamicin irrigation of the bladder prior to ureteral anastomosis, and removal of indwelling catheters.
Prophylactic antibiotic regimens have been studied, with Ciprofloxacin being the best studied drug.
TMP-SMX is recommended for the prevention of Pneumocystis jirovecii pneumonia and is usually administered in a prophylactic dose for 6-12 months after kidney transplant.
TMP-SMX prophylaxis was initiated in 2018 in all KTX recipients, and the UTI rate was significantly lower in patients on TMP-SMX.
Gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria.
There was no resistance to carbapenems in the gram-negative bacteria, and Piperacillin / Tazobactam was the least gram-negative resistant substance.
Oral treatment alternatives for empiric treatment of UTIs are highly sought after but did not exist in this study.
Patients undergo weekly screening for urinary pathogens for the first month post-transplant.
Recently, more data is becoming available on the treatment of ASB early after transplantation.
A potential alternative to screening cultures could be reflex urinary cultures triggered by positive urinary nitrite or a threshold urinary white blood count.
Narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Fluoroquinolones should not be used in ASB.
The choice of antibiotic for empiric treatment of UTIs must be made with the centers’ urinary tract infection’s spectrum and antibiotic resistance in mind.
Resistance to commonly used antibiotics appears higher in dialysis patients and transplant recipients than in healthy peers.
Prevention of the development of resistant strains in dialysis patients will be an upcoming challenge for antibiotic stewardship teams worldwide.
The MRGN rate of 10% was like other German KTX centers but was higher than the average of 5% in a 2017 meta-analysis.
Strengths and Limitations:
Single center data showed distinct differences in resistance to commonly used antibiotics in urinary tract infections between kidney transplant recipients and a control group.
All urinary cultures done at tertiary university hospital.
Multi-centric comparative data is needed for generalization.
Limitation:
Single center data.
Retrospective analysis of data (poor > Prospective)
Uneven sample size between study & control group statistical comparison limited to exploratory data.
Conclusions:
UTI is associated with lower graft function and so prevention and early and proper treatment is highly recommended.
Screening for ASB using urine culture or urine analysis with subsequent culture in suspicious patients is recommended during the first month after transplantation, and treatment should be given upon confirmation of the ASB.
UTI usually occurs due to infection with gram negative organism, so the use of empiric antibiotics with gram negative coverage is recommended.
It is recommended to treat UTI using empiric IV antibiotic according to the local drug resistance, then switching to an oral antibiotic after culture and sensitivity result
ASB should be treated only in the first month after transplantation using narrow spectrum antibiotics or waiting till culture result.
Carbapenems is the drug of choice in the treatment of UTI in critically ill patients.
Antibiotic stewardship programs are essential to reduce the number of antibiotics prescribed to solid organ transplant recipients.
Prevention of UTI:
Peri-transplant surgery, one dose of perioperative antibiotic is recommended, (Cefazolin or Vancomycin).
Screening of UTI by either urine culture or urine analysis (and culture taken if urine analysis is suspicious for UTI) every week in the first month after transplantation, some recommends screening for 3 months after transplantation, but this is debatable since after the first month the incidence of ASB decrease to 4%.
Removal of urinary catheter as soon as possible after transplantation
Removal of stents as soon as possible at 3 weeks after transplantation and may be before if there is bacteriuria.
Prolonged antibiotic prophylaxis, the most important regimen is the use of SMX-TMP used already for PCP prophylaxis for 6-12 m which was associated with reduction of UTI episodes and severity.
Antibiotic prophylaxis using ciprofloxacin during the period of stent removal, but it is not needed if the patient is already on SMX-TMP prophylaxis.
What is the level of evidence provided by this article?
Cohort study ==> The level of evidence is II.
How do you treat recurrent UTI at your workplace?
Prolonged Ab prophylaxis, the most common regimens TMP-SMX is used to treat recurrent UTI in renal transplant patients for 3 months, Dose of SMX-TMP DS tablet Q MWF 3 times weekly or SS tablet daily or nitrofurantoin 100 mg once daily for 6-12 months.
Lifestyle changes, including drinking plenty of water, frequent voiding, post coital voiding, wiping from front to back in females.
For premenopausal women, modification of contraception may be advised such as removal of IUD and Vaginal Estrogen twice weekly cream or tablets.
We can use cranberry juice and d- mannose.
Do not forget, KUB Imaging to rule out any urological abnormality and cystoscopy.
Introduction
In the early postoperative phase after kidney transplantation, urinary tract infections (UTIs) are a common infection. UTIs are defined as the growth of 10^5 colony forming units on a proper urine sample in the presence of symptoms such as dysuria, urinary frequency or localized pain. Asymptomatic bacteriuria (ASB) is defined as the presence of ≥ 10^5 colony-forming units of bacteria in the absence of symptoms. ASB is common in kidney transplant recipients.
In transplant recipients the threshold for treatment is commonly set lower due to the increased risk of septicemia or atypical presentation due to immunosuppression. The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
The most commonly found pathogens in the urine of kidney transplant recipients are: E. coli, E. faecalis and K. pneumoniae. Common antibiotics used for the treatment of UTIs in kidney transplant recipients initially were fluoroquinolones. However, their use had to be reevaluated due to the recent FDA warnings.
The aim of this study was to evaluate antibiotic prescription practice the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population.
Materials and methods
Adult patients who underwent kidney transplantation at the hospital between January 2015 and August 2020 were included in the study. The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation.
The immune suppression protocol included 500 mg of IV Methylprednisolone as well as either Basiliximab or Anti-Thymocyte Globulin for intermediate risk or an Anti-CD56-Antibody for high risk patients.
Maintenance immunosuppression consisted of steroids in a tapering dose, calcineurin inhibitor and mycofenolic acid. Perioperative antibiotics consisted either of a Single-Dose Beta-Lactam or Ampicillin/Sulbactam.
From 2018 all patients received Pneumocystis prophylaxis with TMP-SMX. Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
As per the protocol, all episodes of urinary tract infections and asymptomatic bacteriuria were treated with antibiotics. The initial emperic treatment was Ciprofloxacin, but after the recommendation to avoid fluoroquinolones, it was changed to Piperacillin/Tazobactam. For patients who were critically ill, Meropenem was used. Urinary catheters were placed preoperatively and removed on postoperative day 5. Until discharge all patients received blood workup three times per week as per the protocol. They also underwent routine urinary sampling (chemistry and culture) every Monday and when clinical or laboratory signs of inflammation/infection were present. l patients had at least two ultrasounds per week to evaluate graft perfusion, rule out ureteral stenosis and perirenal fluid collections. After discharge, the patients were reviewed after one week in outpatient clinic.
Results
207 patients met the inclusion criteria. Out of these patients 73 patients underwent living donation kidney transplantation, 134 underwent deceased donor transplantation. 119 patients were male, 88 were female. The median age of transplantation was 55 years. During the first 30 days after their transplant 130 patients (63%) were suspected to have a urinary tract infection, out of which 68 patients fulfilled the criteria of a UTI.
The most common isolates from urinary cultures were gram-negative enterobacteriaceae as well as enterococcus species. E. coli was the most common pathogen and was found in 49 cultures, followed by E. faecalis. The culture results during urinary tract infections compared to asymptomatic bacteriuria is distinctly different. In total, 135 bacterial isolates were cultured. Of these, 88 (65%) were gram-negative and 46 (34%) were gram-positive. Of the 207 kidney transplant recipients 166 (80%) underwent at least a single course of antibiotic treatment. This was excluding perioperative and periinterventional prophylaxis. Overall, 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post transplant. Suspected UTI was the most common indication for antibiotic treatment. 5 patients were treated for urosepsis. The patients that used at least one course of antibiotics during the initial hospital admission has significantly worse GFR at discharge.
9 patients presented with multiresistant gram-negative bacteria. A significant percentage of gram negative bacteria was resistant to Piperacillin/Tazobactam, 3rd generation cephalosporins and Ciprofloxacin. None of the patients had carbapenem resistant gram-negative bacteria. It was noted that Ciprofloxacin was the most prescribed antibiotic, and E. coli, the common isolate, was resistant to fluoroquinolones in 45%. They study attempted to specifically compare resistance patterns in the bacteria grown from urinary samples of KT recipients and the general population, and the resistance patterns were distinctly different. Resistance to Ampicillin/Sulbactam was present in 76 of the 135 strains (56%), to Piperacillin/Tazobactam in 35 strains (26%), to 3rd generation cephalosporins in 62 strains (46%), to fluoroquinolones in 52 strains (39%) and to carbapenems in 23 strains (17%). It was thought that a large proportion of the resistance to Piperacillin/Tazobactam and carbapenems may be due to the prevalence of Enterococcus species.
Discussion
UTIs are a common infection in the early postoperative phase after kidney transplantation and can lead to sepsis. Recent data has also suggested that UTIs may have a negative impact on allograft function. In this study, UTIs were accompanied by significantly worse creatinine clearance both at the end of our study period and one year after transplantation. Therefore, the prevention and treatment of UTIs in kidney transplant recipients is important. Inadequate use of antibiotics in asymptomatic bacteriuria may also affect the allograft function. The overall status and comorbidities of the patient may also add to the complications. Intraoperstive Gentamicin irrigation of the bladder prior to ureteral anastomosis has proved promising in patients with recurrent UTIs. The presence of indwelling catheters, mainly ureteral stents and Foley catheters is an independent risk factor of urinary tract infections.
UTIs in patients who have received kidney transplants require empiric antibiotic coverage of mainly gram-negative bacteria. This study showed that gram-negative bacteria were more frequently associated with infections, while gram-positive bacteria were more common in bacteriuria. There was no resistance to carbapenem by the gram-negative bacteria, which makes them an apt choice for critically ill patients. The strength of the study is its ability to demonstrate distinctly different resistance patterns to commonly used antibiotics. The limitations include the retrospective nature of the study and that it was conducted a single center.
Conclusion
Kidney transplant recipients are at an increased risk of infection, and some may be fatal. This leads to a low threshold for initiating antibiotic treatment when infection is suspected. It is important to lower the numbers of patients receiving antibiotics, and it requires a multidisciplinary approach between the transplant surgeons, physicians and antibiotic stewardship teams.
Study Limitations
Level of Evidence:
This is a retrospective study, therefore the LOE is II
Local Practice
In my center, we treat ASB and UTIs. The preferred drugs are second generation or third generation cephalosporins for outpatient treatment. For in-patient treatment, we use tazobactum/piperacillin then tailor the antibiotic based on the culture and sensitivity results
We routinely give TMP/SMX to all our patients for six months
Introduction :
UTI is the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%. Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients. Fluoroquinolones are the most common antibiotics for treatment.
Materials and Methods:
The study retrospectively screened the hospital information system for all adult patients who underwent kidney transplantation at the University Hospital of Tuebingen between January 2015 and August 2020.
The medical reports of these patients were screened for intra- and perioperative microbiological cultures within 30 days after transplantation.
The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients.
Immunosuppressive protocol consisted of 500 mg of iv Methylprednisolone and either Basiliximab or Anti-Thymocyte Globulin. Maintenance immunosuppression consisted of steroid tapering, calcineurin inhibitor, tacrolimus 0.1 mg/kg/day starting day 1, and mycofenolic acid.
Urinary catheters and double-J-ureteral stents were placed preoperatively and removed on postoperative day 5 in patients with retained diuresis and reduced urine output prior to transplantation, followed by postoperative follow-up. Multi-resistant gram-negative bacteria were defined as 3-MRGN, 4-MRGN and 5-MRGN according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) thresholds and minimal inhibitory concentrations.
Results:
Microbiological Results:
The most common isolates from urinary cultures were gram-negative enterobacteriaceae and enterococcus species, with E. coli being the leading pathogen.
The culture results during urinary tract infections compared to asymptomatic bacteriuria are different, with 56 gram-negative isolates recorded during a UTI compared to 32 gram-positive isolates. The most commonly prescribed antibiotics were fluoroquinolones, followed by aminopenicillins, cephalosporins, and others.
The most commonly isolated gram-negative bacteria was E. coli, which was resistant to Ampicillin/Sulbactam, Piperacillin/Tazobactam, fluoroquinolones, carbapenems, Fosfomycin, and Nitrofurantoin.
Bacterial resistance to empiric treatment options was high, with resistance to Ampicillin/Sulbactam, Piperacillin/Tazobactam, fluoroquinolones, and carbapenems due to Enterococcus species.
Strength : Different patterns of resistance among study groups are identified to commonly used antibiotics in urinary tract infections.
Limitation : This is a single center prospective study, the different sample sizes between the study and control groups .
Conclusions:
Antibiotic stewardship programs are essential to reduce the risk of fatal infection in solid organ transplant recipients.
level 2
In recurrent UTI we usually exclude any structural or functional causes,take C/S and check for other predisposing medical problems like DM ,prophylaxis TMB-SMX for 3-6 months and patient education about self hygiene especially females
Introduction
· Urinary tract infections (UTIs) are the most common infection in the early postoperative phase after kidney transplantation, with an incidence of 4-80%.
· Asymptomatic bacteriuria (ASB) is encountered in 25% of KT recipients, and ASB is commonly screened for and treated in the early posttransplant phase.
· In living donation kidney transplantation, the incidence of UTI is lower due to shorter waiting time, higher volume urine output, and early onset graft function.
· The most common pathogens found in urine samples after kidney transplant are Escherichia coli, Enterococcus faecalis, and Klebsiella pneumonia.
· Fluoroquinolones are the most common antibiotics in the treatment of urinary tract infections in KT recipients.
Materials and Methods
· Retrospectively, the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral, and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020 have been analyzed.
· All charts were screened for the diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patient’s clinical characteristics and outcomes were evaluated.
Results
· The most common indication for antibiotic treatment was suspected urinary tract infection, with fluoroquinolones being the most commonly prescribed antibiotic.
· E. coli was the most commonly isolated gram-negative bacteria.
Discussion
· Urinary tract infections are the most common infection in the early postoperative phase after kidney transplantation, leading to sepsis and a potential threat to life.
· To prevent infections, several measures have been proposed, such as a single-shot antibiotic administered prior to incision, Gentamicin irrigation of the bladder prior to the ureteral anastomosis, and removal of indwelling catheters.
· Prophylactic antibiotic regimens have been studied, including Ciprofloxacin, Fosfomycin, and TMP-SMX.
· Empiric antibiotic coverage of gram-negative enterobacteria was found to be the most attractive choice for critically ill patients.
·Narrow-spectrum antibiotics such as TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are safe and effective in treating asymptomatic bacteriuria, but should not be used as first-line therapy.
Conclusions
· Antibiotic stewardship programs aim to prevent infections after surgery and rationally use antibiotics.
· Solid organ transplant recipients are at increased risk of fatal infection, leading to a low threshold for initiating antibiotic treatment.
· To reduce this number, a team effort of transplant surgeons and physicians and antibiotic stewardship teams is needed.
==========================
Level of Evidence II
==========================
How do you treat recurrent UTI at your workplace?recurrent UTI passes through some workups including (Ultrasound, MCUG, Urine culture, and sensitivity) to manage any structural abnormalities, and foreign bodies, and to start the proper empirical or culture-based antibiotics promptly.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Many thanks, dear professor.
So nice of you Dr Saiwan
I appreciate your short summary.
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.
1.Please summarise this article.
Introduction
The most frequent (the incidence is 4–80%.) infections after KTX are urinary tract infections (UTI). UTIs are characterized as the presence of symptoms (dysuria, frequency, or localized pain) along with the growth of 105 CFUs on an appropriate urine sample.
Asymptomatic bacteriuria (ASB) is defined as the presence of =/>105 CFUs of bacteria in the absence of symptoms. Asymptomatic bacteriuria is seen in around 25% of KTX recipients. Even though there is ongoing debate regarding how ASB & UTI affect the overall patient & graft outcome, ASB is frequently detected & treated in the early post-TX phase.
The threshold for using broad spectrum antibiotics to treat UTI & asymptomatic bacteriuria is low due to the possibility of urosepsis & probable danger to the graft. Previously, in individuals who received KTX fluoroquinolones were the preferred prescription medication. However, other therapeutic approaches need to be researched after the new advice to avoid them in these individuals.
The study
Asymptomatic bacteriuria (ASB) & UTI, as well as the patients’ clinical features & outcomes, were retrospectively analyzed in 207 consecutive adult KTX done between January 2015 & August 2020 at the University Hospital of Tuebingen.
Induction therapy was Methylprednisolone as well as either Basiliximab for low immunologic risk or ATG for intermediate risk or Alemtuzumab for high-risk patients (without MMF until lymphocytes have regenerated).
At the option of the transplant surgeons, perioperative antibiotics were either a Single-Dose Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) or 3X3 g of Ampicillin/Sulbactam (Q0h/12h/24h).
According to protocol, antibiotics were to be used to treat any bouts of urinary tract infections & asymptomatic bacteriuria.
In patients who had retained diuresis before TX, urinary catheters were removed on POD 5. Patients with decreased urine output had their catheters removed on POD. A DJ-ureteral stent was implanted intra-operatively & removed on POD 21.
Urinary samples were sent for urinary culture once weekly & once there was suspicion for UTIs.
Results
130 patients (63%) were suspected to have a UTI.
68/130 patients fulfilled the criteria of a UTI (typical symptoms &/or clinical/laboratory signs of inflammation) In 58/68 patients, growth of a urinary pathogen on urine culture was recorded.
Enterococcus species & gram-negative enterobacteriaceae were the most typical isolates from urine cultures. E. coli was the most prevalent pathogen, followed by E. faecium & E. faecalis.
Overall, 9 patients presented with multi-resistant gram-negative bacteria.
Patients who developed UTI had worse graft function at discharge & at the 12 months follow-up.
Ciprofloxacin and Piperacillin/Tazobactam were the most often recommended antibiotics.
Resistance to Ampicillin/Sulbactam was present in 56% of the strains, to Piperacillin/Tazobactam in 26%, to 3rd generation cephalosporins in 46%, to fluoroquinolones in 39% & to carbapenems in 17% of the strains.
To both, bacterial resistance was more common in the study cohort than in the control group.
Discussion
In this cohort, UTIs were associated with significantly poorer creatinine clearance. Therefore, it’s essential for KTX recipients to avoid & manage UTIs appropriately.
Although there is growing evidence that ASB does not influence graft function, improper antibiotic administration undoubtedly can do so.
A number of strategies have been suggested to prevent UTIs. Prior to the incision, a single shot of an antibiotic is given. Long-term antibiotic use has not been found to be helpful. In individuals with recurrent UTIs, gentamicin irrigation of the bladder prior to ureteral anastomosis has shown promise. Ureteral stents & Foley catheters are standalone risk factor for UTIs. It is optimal to remove the ureteral stent 21 days following KTX (Visser et al.).
Limitations
The study’s retrospective design.
Sample sizes between the study & control groups are not equal. Comparative statistics were limited to exploratory data.
Prior to generalizing the study data, a multicentric comparison analysis will be required.
Conclusions:
It seems that worse graft functioning is related to UTIs. Thus, teams of antibiotic stewards should be present along with prevention and treatment.
======================
2.What is the level of evidence provided by this article?
Level II
======================
3.How do you treat recurrent UTI at your workplace?
After sending a suitable urine sample for bacteriological culture, we provide a broad range antibiotic while we wait for the results. The two antibiotics that are most frequently used in our facility are carbapenems, such meropenem, or third generation cephalosporins like ceftazidime.
We use TMP-SMX for 6 months in all our KTX patients.
After the first six months following transplantation, we also utilize low doses of nitrofurantoin for three to six months after treating the confirmed infection for recurrent UTIs.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Summary
Introduction
UTI are common infections in the early post-transplant period.
UTIs are defined as the growth of colony plus the presence of symptoms, while asymptomatic bacteriuria lack symptoms.
Most common organisms attributed are E.coli, klebsiella, and enterobacter faecalis.
Aim of the study
They examined the antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those from local community.
Methodology
Study design: Observational longitudinal cohort study.
Inclusion criteria: Patients above 16 years who underwent kidney transplantation between January 2015 and August 2020.
Exclusion criteria: Patients who underwent simultaneous liver and pancreas transplant.
Results
Of the 207 patients included, 130 (63%) were suspected to have UTI.
68 of the 130 fulfilled the criteria for UTI.
58 of the 68 had a positive culture growth.
Most common organisms were E.coli, klebsiella and E.faecalium.
The organisms isolated in ASB were distinctly different from those of UTI.
166 of all participants received antibiotic course with median duration was 5 days and clinical indication was suspected UTI.
Fluoroquinolones were the most commonly prescribed.
9 patients had multi-resistant gram negative bacteria.
Discussion
UTI are the most common infections in the early post-transplant period.
Studies have shown that even one episode of UTI negatively impacts the allograft function.
ASB doesn’t affect the allograft function however the inappropriate use of antibiotics does.
Several measures have been proposed to prevent UTI in recipients:
Prolonged antibiotic use have not been shown to prevent infection.
Indwelling catheters are an independent risk factor.
TMP-SMX is the best studied prophylaxis that is given for 6-12 months.
Empiric antibiotic cover should always cover GNB since there are the most common of UTI while GPB are mainly seen in ASB.
TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for UTI in transplant recipients.
Strengths
They were able to demonstrate distinctly different resistance patterns to commonly used antibiotics.
Limitations.
The retrospective nature of the analysis complicates distinguishing between colonization /bacteriuria and urinary tract infection.
There was uneven sample sizes between the study and control group, hence statistical comparisons were limited to exploratory data.
Level of evidence: 2, this was an observational longitudinal cohort study
How do you treat recurrent UTI at your workplace?
All recipients receive TMP/SMX prophylaxis for 6 months.
Antibiotics guided by culture and sensitivity panel.
Imaging to rule out any urological abnormality.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Definition of UTI and asymptomatic bacteruria (ASB)
Incidence
Causative organism
Prevention of UTI
Treatment of UTI and ASB
The current study is a retrospective study (level of evidence III) evaluating 207 adult kidney transplantation performed in the University Hospital of Tuebingen from 2015 till 2020 regarding the incidence of UTI and ASB , center specific antibiotic prescription in the first month of transplantation and the antibiotic susceptibility of the organisms isolated in renal transplant recipients and compare it to the general population
Results
Conclusions:
How do you treat recurrent UTI at your workplace?
In my work place, I first treat the current UTI, and after successful treatment, I implement strategies to prevent the recurrence of UTI including :
I like your well-structured detailed summary, analysis and take home messages.
Please summarise this article.
Introduction:
Urinary tract infections (UTI) are the most prevalent infection, post kidney transplants, with incidence range between 4-80%.
Asymptomatic bacteriuria (ASB), which is frequently detected and treated, affects 25% of KT recipients.
Fluoroquinolones are the most frequently prescribed prophylactic antibiotic due to their widespread availability, oral and intravenous formulations, and excellent urinary tract penetration.
Study design:
A retrospective study screened all adult patients who underwent kidney transplantation at the University Hospital of Tuebingen between January 2015 and August 2020.
Urinary cultures were sent at the surgeon’s discretion and the control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology.
All patient had the standard immunosuppressive therapy, induction with basiliximab, ATG and alemtuzumab, and MMF, CNIN+ prednisolone maintenance.
Perioperative antibiotic prophylaxis used is Beta-Lactam or Ampicillin/Sulbactam, with TMP-SMX 960 mg 3×/week for Pneumocystis prophylaxis, and gentamycin bladder irrigation before ureter anastomosis.
Empiric treatment with Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR was the protocol, and deescalation of treatment according to urinary culture/antbiotic resistance results.
Urinary catheter removed in 5th day post op., and on the post op. day to those recipients with minimal urine output.
Ureterocystoneostomy was performed according to Lich-Gregoir, and DJ removed in the 21st day post-op.
Post-operative follow-up:
Patients received blood and urinalysis and culture, twice weekly ultrasound, renal biopsies when needed.
Definitions:
Results:
During the first 30 days post transplant 63% patients suspected to have UTI, almost half of them have full clinical and laboratory evidence of UTI.
The most common culture isolates were E.coli (gram negative bacteria), followed by enterococcus (gram positive bacteria), and rarely mixed cultures.
262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days posttransplant, for suspected UTI, ciprofloxacin the most commonly prescribed antibiotic, followed by Piperacillin/Tazobactam, aminopenicillins, Amoxicillin/Clavulanic acid, and Meropenem.
Nine patients presented with multi resistant gram-negative bacteria (MRGN). Of these, a relevant percentage was resistant to Piperacillin/Tazobactam,3rd generation cephalosporins and Ciprofloxacin, but no resistance to meropenem were seen.
Strength: urinary cultures ordered, identify different patterns of resistance among study groups to commonly used antibiotics in urinary tract infections.
Limitations: single center prospective study, the different sample sizes between the study and control groups.
Conclusions:
Antibiotic stewardship programs are essential to reduce the risk of fatal infection in solid organ transplant recipients.
What is the level of evidence provided by this article?
Level of evidence III – retrospective study.
How do you treat recurrent UTI at your workplace?
At our center in case of recurrent UTI:
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
Why level 3 evidence for this article?
Do you mean prophylactic rotating antibiotics once a day to be changed every month and then repeating the cycle after 3 months and so on?
Thank you Prof. Ajay
you are right, it is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2.
Do you mean prophylactic rotating antibiotics once a day to be changed every month and then repeating the cycle after 3 months and so on?
Yes, absolutely
It is so nice to read your response, dear Dr Hasan.
1- Summary
This article discusses the issue of urinary tract infections (UTIs) in kidney transplant recipients and the potential role of antibiotic stewardship in their management.
The author highlights the prevalence and impact of UTIs in this
population, which can lead to serious complications such as pyelonephritis,
graft dysfunction, and even graft loss. The author argues that while
antibiotics are often necessary to treat UTIs in kidney transplant recipients,
indiscriminate use can contribute to the development of antibiotic resistance,
which poses a threat to patient outcomes and public health.
In this article the authors analysed retrospectively 207 adult patients
with kidney transplantations that were performed at the University Hospital of
Tuebingen, Germany, between January 2015 and August 2020.
The analysis included screening for all patients with a diagnosis and treatment of asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) and the patients’ clinical characteristics and outcomes were evaluated. Results: Of the 207 patients, 68 patients suffered from urinary tract infections and had worse graft function at discharge (p = 0.024) and at the 12 months follow-up (p < 0.001).
As Per protocol all episodes of urinary tract infections and asymptomatic bacteriuria were supposed to be treated with antibiotics empirically. After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic was Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR. For critically ill patients Meropenem 1000 mg 3×/day was the recommended Rx. Whenever possible de-escalation of treatment according to urinary culture results and antibiotic resistance testing was recommended.
The most common isolates from urinary cultures were gram-negative enterobacteria and enterococcus species. E. coli was the leading pathogen. Fifty-nine individual episodes of ASB were recorded.
Overall, 262 courses of antibiotic treatments were prescribed to the patient cohort within the first 30 days post-transplant. Overall, nine patients presented with multi-resistant gram-negative bacteria (MRGN).
In general, the Conclusions are:
· There is increasing data that asymptomatic bacteriuria (ASB) does not affect graft function.
· Empiric antibiotics should therefore always cover gram-negative enterobacteria.
· A meta-analysis from Spain recommended not to treat ASB after the first month post KT. This practice has been backed by two randomized controlled multicenter trials by Origuën et al. and Coussement et al. which both reported no benefits in treating ASB two months after kidney transplant.
· Symptomatic patients need to be treated empirically to avoid development of septicemia,
· For asymptomatic bacteriuria (ASB) it is safe to wait for the final antibiotic resistance testing and use targeted therapy rather than empiric broad spectrum coverage followed by a step- down approach.
· Overall, the article highlights the importance of addressing the issue of UTIs in kidney transplant recipients and the potential role of antibiotic stewardship in improving patient outcomes while minimizing the risk of antibiotic resistance.
2- Level 3 evidence, retrospective analysis
3- In our centre we treat all episodes of UTI (symptomatic and asymptomatic), particularly in the first month post-transplant.
Only those asymptomatic with indwelling catheters we don’t treat unless became symptomatic.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
Why level 3 evidence for this article?
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.
Summary
Introduction
UTIs are the most prevalent early postoperative infection following kidney transplantation (KT). UTIs are 4–80%. In the presence of dysuria, urinary frequency, or localized discomfort, 105 colony-forming units on a suitable urine sample (morning pee, puncture urine, or sterile single catheterization) indicate a UTI.
Asymptomatic bacteriuria (ASB) is the presence of 105 colony-forming units of bacteria without symptoms, unlike UTIs. 25% of KT recipients had asymptomatic bacteriuria.
Consequently, ASB is widely tested for and treated in the early posttransplant period, despite continued disagreement concerning the effects of ASB and UTI on patient and graft outcomes.
Infections and inadequate long-term transplant function have been studied.
Aim:
This research examined our antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs, and the antibiotic susceptibility of isolated urinary tract bacteria from KT recipients and the surrounding community.
Material and Techniques:
We retrospectively reviewed our hospital information system for all kidney transplantation patients at the University Hospital of Tuebingen, Germany’s General, Visceral, and Transplantation Surgery department.
Results:
Urinary cultures often yield gram-negative Enterobacteriaceae and various forms of enterococcus were the most prevalent types of bacterial isolates. The most prevalent disease-causing organism was E. coli, followed by E. faecium and E. faecalis.
Five different cultures showed evidence of mixed cultures consisting of two uropathogenic cultures.
135 different bacterial isolates were cultivated, with gram-negative bacteria making up 65% of the total and gram-positive bacteria making up 34%.
This study did not include ureaplasma, which made up 1% of the sample.
Antibiotic Prescription
The most prevalent reason for administering antibiotic medication to kidney transplant patients was the clinical suspicion of having an infection in the urinary system.
Fluoroquinolones were the most commonly prescribed antibiotics for the 180 suspected cases of urinary tract infections (UTIs).
This was followed by piperacillin/tazobactam, aminopenicillins, Meropenem, Trimethoprim-Sulfamethoxazole, cephalosporins, Fosfomycin, Pivmecillinam, Nitrofurantoin, Linezolid, and a variety of other antibiotics.
Multiresistant gram-negative bacteria (MRGN) were found in nine individuals, all of which were resistant to piperacillin/tazobactam, third-generation cephalosporins, and ciprofloxacin.
In this particular research, E. coli did not exhibit any resistance to fosfomycin or nitrofurantoin; nevertheless, there was a 40% rate of resistance to TMP-SMX.
limitations
single-center and retrospective data.
Making the distinction between colonization, bacteriuria, and a UTI becomes somewhat more difficult.
strength:
were able to identify unique resistance patterns to antibiotics that are often used in the treatment of UTIs.
conclusion:
Antibiotic stewardship initiatives aim to prevent post-surgery infections and rationally manage antibiotics. Infections kill solid organ transplant patients. This lowers the infection threshold for antibiotic therapy. 207 individuals received 262 antibiotic treatments. 180 received medication for suspected UTIs.
Level of evidence:
2b, cohort study
How do you treat recurrent UTIs at your workplace?
We start by doing an Ultrasound of the graft, if normal, we are proceeding with MCUG
We check the previous sensitivity and maintain the patient on the long-term prophylactic antibiotic.
I like your well-structured detailed summary, level of evidence as 2b, limitations and strengths based on analysis and take home messages.
Introduction:
Aims of the study:
Materials & method:
Result & discussion:
Limitation:
Strength :
Level of evidence is 2
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Summary of the article
Discussion
a) A single shot antibiotic prior to incision.
b) Intraoperative gentamicin irrigation to the bladder prior to anastomosis in recurrent UTI.
c) Early removal of ureteral stent 21 days after KT or earlier if there is a suspicion of bacteriuria of infection in order to remove biofilms.
Prophylaxis
a) The best studied and recommended for prevention of PJP and given for 6-12 months after KT.
b) Myoclinic reported a reduction of UTI in KT by TMP-SMX was prescribed for 6 months.
c) Horwedel et al; describe a lower rate of septicemia with TMP-SMX prophylaxis.
d) In the center that published this article, showed a significant reduction of UTI in patients on TMP-SMX.
e) Lee at al; reported that the omission of peri interventional antibiotics on patients already on TMP-SMX does not disadvantageous.
ASB and UTI detection post-transplantation
Strengths and limitations
Conclusion
Level of incidence
Level ((III)) retrospective study.
In our local place;
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
Why level 3 evidence for this article?
Thank you, Prof Ajay
A retrospective study compared the use of TMP-SMX in recurrent UTI in kidney transplants during 3 and 6 months.
They concluded that; there is a higher rate of UTI among those who receive a 3 months course.
But the treatment I think should always be individualized according to the;
Level III because it is a retrospective study
Retrospective study level II
Does not matter, retrospective or prospective, all the cohort studies are level 2. Case control would be level 3. Of course, retrospective are poorer than prospective one.
Summary of the article
Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
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%).
3. Asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms(encountered in around 25% of KT recipients).
4. UTI can lead to sepsis and are a potential threat to life. Recent data has suggested a negative impact of even single episodes of (complicated) urinary tract infections on allograft function.
5. Fluoroquinolones offer decent coverage of most uropathogenic bacteria, including Pseudomonas species.
· After the recommendation to avoid fluoroquinolones the recommended empiric antibiotic are Piperacillin/Tazobactam 4500 mg 3×/day for 5 days with dose adjustments according to GFR.
· For critically ill patients Meropenem 1000 mg 3×/day was the recommended substance and dose.
6. Measures to prevent UTI in KTR:
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.
7. TMP-SMX/Fosfomycin/Nitrofurantoin/Pivmecillinam are currently not recommended as first line therapy for urinary tract infections in transplant recipients.
Strengths and Limitations
1. The retrospective nature of this analysis slightly complicates distinguishing between colonization/bacteriuria and urinary tract infection.
2. Statistical comparisons were limited to exploratory data(multicentric comparative data will be necessary prior to generalization of data.).
What is the level of evidence provided by this article?
This is a retrospective study with level of evidence grade 3.
How do you treat recurrent UTI at your workplace?
1. Treatment according to culture and sensitivity panel.
2. Cystoscopy may be required for recurrent cases to rule out bladder pathology.
3. Use of prophylactic antibiotic, based on the C&S beside the estimated GFR. TMP-SMX is commonly prescribed for prophylaxis.
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
Why level 3 evidence for this article?
IV. Urinary Tract Infections in Kidney Transplant Recipients—Is Is there a Need for Antibiotic Stewardship?
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Please summarise this article.
Introduction
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Materials and Methods
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Clinical Definitions
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Results
Clinical Characteristics
Microbiological Results
Antibiotic Prescription
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Discussion
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Strengths and Limitations
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Conclusions
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What is the level of evidence provided by this article?
The level of evidence is 2
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How do you treat recurrent UTI at your workplace?
With the goal of preventing resistance, TMP-SMX is used to treat recurrent UTI in renal transplant patients 3 months.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Typing whole sentence in bold or typing in capitals amounts to shouting.
Many thanks for you Prof.Sharma
So nice of you Dr Wadi.
Please summarise this article.
Introduction
o UTIs are the most common infections after kidney transplantation (The incidence ranges from 4–80%)
o Asymptomatic bacteriuria (ASB) accounts for 25% of KT recipients
o Threshold for treatment is commonly low due to the increased risk of septicemia or atypical presentation due to immunosuppression
o The most common pathogens found in urine samples after KT are Escherichia coli, Enterococcus faecalis and Klebsiella pneumonia
o Fluoroquinolones were among the most common antibiotics in the treatment of UTI in KT recipients
Aim of the study: evaluation of antibiotic prescription practice during the first 30 days after kidney transplant, the incidence of ASB and UTIs and compared the antibiotic susceptibility of the isolated urinary tract bacteria from KT recipients to those isolated from the local population
Materials and Methods
o Retrospectively analyzed the charts of 207 consecutive adult kidney transplantations that were performed at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen (January 2015-August 2020)
o All charts were screened for the diagnosis and treatment of ASB and UTI and the patients’ clinical characteristics and outcomes were evaluated
o Until discharge all patients received blood workup three times per week as well as routine urinary sampling (chemistry and culture) every Monday or whenever clinical or laboratory signs of inflammation/infection were present
o All patients had at least two ultrasounds per week
Results
o 207 patients met the inclusion criteria [73 patients underwent living donation kidney transplantation (35%) and 134 received a kidney from a deceased donor (65%)]
o 119 (57%) of patients were and 88 (43%) were females
o The most common isolates from urinary cultures were gram-negative enterobacteriaceae and enterococcus species (E. coli cultures followed by E. faecium)
o Of the 207 patients, 68 patients suffered from urinary tract infections
o Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up
o The most commonly prescribed antibiotics were Ciprofloxacin and Piperacillin/Tazobactam
o Bacterial resistance was more common in the study cohort than in the control group
Discussion
o Even single episodes of (complicated) UTIs have a negative impact of on allograft function
o UTI were accompanied by significantly worse creatinine clearance both at the end of this study period and one year after KT (prevention and adequate treatment of UTI in KT recipients is crucial)
o To detect ASB and UTI early, patients undergo weekly screening for urinary pathogens for the first month post-transplant [59 episodes of ASB (29%) in this study]
o Treat ASB within the first month after KT
Measures to prevent infections in KT recipients:
1. single shot of antibiotic prior to incision
2. intraoperative Gentamicin irrigation of the bladder prior to ureteral anastomosis
3. remove the ureteral stent 21 days after KT or earlier if there is suspicion for bacteriuria or infection
Strengths and Limitations:
Strength: samples > 200 kidney transplant recipients
Limitations:
1. Reretrospective study
2. uneven sample sizes between the study and control group
Conclusions
o As SOT recipients are at increased risk of fatal infection, initiate antibiotic treatment when infection is suspected
o Urinary tract infections are linked to worse graft functions, thus, prevention and treatment should be accompanied by antibiotic stewardship teams
What is the level of evidence provided by this article?Level II (retrospective cohort study)
How do you treat recurrent UTI at your workplace?o TMP-SMX (prophylaxis)
o Nitrofurantoin for ASB
o Carbapenems (meropenem)/cephalosporins for UTI
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
Introduction:
-Urinary tract infections (UTI) are the most common infection in the early postoperative phase after KT
-UTI is defined as; growth of 105 CFU in the presence of symptoms, while asymptomatic bacteriuria (ASB) is defined as the presence of 105 CFU of bacteria in the absence of symptoms.
-The threshold for treatment is low due to the increased risk of septicemia or uro-sepsis and negative impact on graft function.
– Overall heterogeneous regimens exist to treat UTI.
Study Aim:
-Evaluate antibiotic prescription practice during the first 30 days after KT.
-The incidence of ASB and UTIs
-Compared the antibiotic susceptibility of the isolated bacteria from KT recipients to those isolated from the local population
Materials and Methods
-Retrospective chart review of all adult (>16 year) had KT at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen between January 2015 and August 2020.
– Patient with simultaneous pancreas or liver transplantation were excluded.
-The control group consisted of all urinary tract bacterial isolates cultured from both outpatients and inpatients.
– Induction therapy with IV methylprednisolone with either Basiliximab, ATG or Alemtuzumab based on the risk.
– Maintenance therapy steroid tapering, tacrolimus and MMF.
– Antibiotic prophylaxis was giver perioperatively and bladder irrigation with gentamicin.
– Urinary catheters removed on POD 5 ,and DJ-ureteral stent was removed on POD 21.
-All charts were screened for the diagnosis and treatment of ASB and UTI and the patients’ clinical characteristics and outcomes were evaluated.
Results:
– Of the 207 patients, 68 patients suffered from UTI and 59 had ASB
– E.coli was the most common isolated organism followed by E. faecium.
– Gram-negative bacteria were more frequently associated with UTI, while gram-positive bacteria were more common in ASB
-80% underwent at least a single course of antibiotic treatment with median duration of 5 days.
– Patients who developed UTI had worse graft function at discharge and at the 12 months follow-up
-The most commonly prescribed antibiotics were Ciprofloxacin, followed by Piperacillin/Tazobactam, aminopenicillins, Meropenem and TMB-SMX.
– 9 patients presented with multi-drug resistant gram-negative bacteria.
– Resistance patterns were distinctly different between the KTR and the control group( more common in KTR)
-To both, bacterial resistance was more common in the study cohort than in the control group. (
Conclusions:
UTI prevention and treatment should be accompanied by antibiotic stewardship teams.
Level of evidence: level 2 retrospective cohort.
How do you treat recurrent UTI at your workplace?
Strat empiric antibiotic when suspected clinically and UA was suggestive for UTI.
Usually we cover with broad spectrum antibiotic Piperacillin/Tazobactam or meropenum then switch according to the culture result for 2 weeks.
Prophylactic TMB-SMX for 3-6 months.
Education about the general measures to reduce UTI risk.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
Introduction
Urinary tract infection (UTI) are the most common infection in the early postoperative phase after kidney transplant (KT).
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.
In contrast to UTIs asymptomatic bacteriuria (ASB) is defined as the presence of ≥105 colony-forming units of bacteria in the absence of symptoms.
ASB is commonly screened for and treated in the early posttransplant phase , even though there is ongoing controversy about the impact of ASB and UTI on the overall patient and graft outcome.
The incidence of UTI is assumed to be lower in living donation kidney transplantation since these patients often have shorter waiting time, higher volume urine output prior to and during transplantation as well as early onset graft function.
Methods
We retrospectively screened our hospital information system for all patients who underwent kidney transplantation at the department of General, Visceral and Transplantation Surgery of the University Hospital of Tuebingen, Germany.
All adult patients who underwent KT at our center between January 2015 and August 2020 were included in the final analysis.
Patients that underwent simultaneous pancreas or liver transplantation were excluded.
The medical reports of these patients were screened for intraand perioperative microbiological cultures within 30 days after transplantation.
Urinary cultures were sent at the surgeon’s discretion as well as routinely every Monday until discharge.
The control group consisted of all urinary tract bacterial isolates cultured by the department of microbiology and hygiene from both outpatients and inpatients
Results
Per protocol all KT recipients had urine samples sent for culture every.
Monday of their initial stay as well as at the surgeons’ discretion based on postoperative labs and clinical course.
Mixed cultures of two uropathogenic cultures were recorded in 5 cultures.
One patient developed four individual episodes of urinary tract infection and grew four different bacteria (E-coli, Vancomycin sensitive E.faecium , Vancomycin-resistant E. Faecium followed by a different strain of E.coli).
Fifty-nine individual episodes of ASB were recorded.
A total of 62 uropathogenic bacteria were cultured during ASBs.
Discussion
Urinary tract infection are the most common infection in the early postoperative phase after kidnet transplantation
They can lead to sepsis and are a potential threat to life.
Aside from progression to seticemia recent data has suggested a negative impact of even single episodes of urinary tract infections on allograft function.
Prevention and adequate treatment of urinary tract infections in KT recipients is crucial.
While there is increasing data that ASB does not affect graft function, inadequate use of antibiotics certainly has the potential to do so.
While about 10% were treated with antibiotic doses that were above the recommended limit more than 25% of patients had a deterioration of graft function.
The increasing use of extended donor allocation and overall comorbidities of the recipients adds to this complexity
Conclusion
Prevention of infections after surgery as well as rational use of antibiotics is a main goal of antibiotic stewardship programs.
Solid organ transplant recipients are at increased risk of fatal infection.
This leads to a low threshold for initiating antibiotic treatment when infection is suspected.
In our cohort between 207 patients 262 courses of antibiotics were prescribed.
180 were prescribed antibiotics for suspected urinary tract infection.
Lowering these numbers is a team effort of transplant surgeons and physicians accompanied by antibiotic stewardship teams.
level of evidence: retrospective cohort (level 2)
I will screen and confirm any structural and functional defect that can be curable before start any treatment
I’d like to know if switching to culture-based antibiotics would be beneficial, especially if the patient’s fever, dysuria, pus cells in the urine, and CRP are improving.
The typical antibiotics we used were: Quinolone, typically for 3–4 weeks, plus a dose of Nitrofurantoin for one week.
Based on the results of the culture, other antibiotics could be taken for a minimum of three weeks.
I will further use prophylactic tools like;
Educate people to drink at least 2.5 liters of water per day and to avoid retaining their urine for too long.
After having sex, ladies should wipe from front to back and urinate. They should also refrain from using creams that contain spermicidal agents.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
-Summary
Introduction
Urinary tract infections (UTI) are the most common infection in the early postoperative period after renal transplant.
UTIs is defined as the growth of 10 5 colony forming units on a proper urine sample with symptoms as dysuria, urinary frequency or localized pain.
Asymptomatic bacteriuria (ASB) is the presence of ≥105 colony-forming units of bacteria in the absence of symptoms
ASB is screened and treated in the early post transplant period.
Treatment threshold is lower in transplant recipients due to the increased risk of septicemia or atypical presentation due to immunosuppression. UTI incidence is lower in living donation kidney transplantation.
In kidney transplant perioperative antibiotic prophylaxis is a standard.
Escherichia coli Enterococcus faecalis and Klebsiella pneumoniae are the most common infectious organisms in urine samples of KT recipients.
Gram negative bacteria is more virulent than gram positive enterococcus .
Fluoroquinolones are the commonly antibiotic used which forced FDA to recommend against it’s widespread use in KT and general population.
Methods
Retrospectively KT recipient data concerning ASB and UTI were analysed within nearly 5 years and 8 months at Tuebingen university hosiptal .
Results
68 patients out of 207 had UTI there by had worse graft function at discharge and at the 12 months follow-up .
Ciprofloxacin and Piperacillin/Tazobactam were the most prescribed antibiotics, to which the bacterial resistance was more prevalent in patients compared to control.
A big percentage of resistance to Piperacillin/Tazobactam and carbapenems is
Rendered to prevalence of Enterococcus species.
Discussion
A single episode of UTI can have negative effects on the allograft function therefore prevention and treatment is essential.
There were data which states that ASB doesnot affect graft function.
Patients used antibiotic doses above recommended limits were associated with decreased graft function, extended donor usage and comorbidities of the recipients worsen the outcome.
Prolonged antibiotic course is not preventive for UTI and surgical site infection.
Decontaminate the bladder by intraoperative Gentamicin irrigation of the bladder before ureteral anastomosis which showed efficacy in recurrent UTI.
Indwelling catheter and ureteral stents represent an important risk factor for UTI.
Ureteral stent removal 21 days after KT or earlier if bacteria is suspected is a safe practice.
Ciprofloxacin was used to prevent UTIs 25 years ago, but afterwards was used for treatment rather than prophylaxis.
TMP-SMX is usually administered in a prophylactic dose for 6–12 months after KT.
Lee et al demonstrated that at the time of stent removal, TMP-SMX prophylaxis can be enough without the need of periinterventional antibiotics
UTI in KT recipients need empirical antibiotic coverage of mainly gram-negative bacteria.
Carbapenem resistance was not detected for gram negative bacteria in the study therefore it can be used in critically ill cases .
Piperacillin/ Tazobactam had the least gram-negative resistance, Ciprofloxacin had the highest bacterial resistance.
2019 FDA warned against the fluoroquinolones use in KT recipients. Aminopenicillins resistance in >50% and to cephalosporins of nearly 20% .It is recommended to treat UTI after Kidney Transplantation with empiric intravenous antibiotics according to local resistance patterns. Oral narrow-spectrum antibiotic can be given as soon as the bacterial strain is known
Weekly screening for the first month post-transplant to detect early ASB and UTI.
Multiple studies recommended to treat ASB in the first month only.
Narrow-spectrum antibiotics as TMPSMX/Fosfomycin/Nitrofurantoin/Pivmecillinam can be used for treatment of ASB in KT being safe and effective even against MRGN bacteria.
Ecoli starin was resistant to TMP-SMX as it is used as prophylaxis against pseudomonus while there was no resistance against Fosfomycin/Nitrofurantoin
Fluoroquinolones better to be avoided in ASB .
In ASB treatment it can be safe to wait for culture results instead of starting empirical therapy.
Empirical antibiotic therapy for UTI have to be guided by the centers’ urinary tract infection’s spectrum and antibiotic resistance.
Antibiotic stewardship data for SOT recipients are limited.
Limitations are being retrospective single centered study
Strength include demonstrating variable resistance patterns
Conclusions
Prevention of infections post KT and antibiotic stewardship programs is an essential practice.
-level of evidence is II
– Treatment of recurrent UTI in renal transplant by early identification of structural or functional urological abnormalities to be corrected surgically if possible . Before antibiotics use a culture have to be collected to prevent emergence of resistance and also interaction with immunosuppressives as CNI have to be watched out for.
Antibiotic used is TMP-SMX.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “And all of our cases are kept on SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
UTI in KTRs—Is There a Need for Antibiotic Stewardship?
⭐⭐⭐⭐Summary:
· UTI post kidney transplantation is common, incidence 4–80%.
· UTIs are defined as the growth of 105 CFU/ML on a proper urine sample + (presence of symptoms as frequency, urgency and dysuria).
· It carries a poor prognosis in both graft and patient outcome, even single episodes of (complicated) UTI can have negative impact on allograft function.
· Asymptomatic bacteriuria is presence of 105 CFU/ML on a proper urine sample (without any symptoms), present in ¼ cases of KTRs. It is still debatable to treat or not as the consequence on graft survival is not well defined.
· Fear of urosepsis, atypical presentation and mortality (due to use of immunosuppression) raised the question to treat asymptomatic bacteriuria. Still questionable, but most centers treat it especially in 1st month Posttransplant 9others treat it up to 2 months Posttransplant).
· Treatment of asymptomatic bacteriuria we can wait till result of culture and sensitivity which is better than starting empirical therapy with TMP-SMX/ Fosfomycin/ Nitrofurantoin/Pivmecillinam.
· While in treatment of symptomatic UTI: Empirical treatment for 3-9 days (mean 5 days), must be started till result of culture and sensitivity, was mainly fluoroquinolones (Ciprofloxacin) (available, both IV and oral, high penetration of kidney tissue, anti psudomonal activity). Then, FDA warning in 2019 against empirical use of Cipro in general and KTR s in particular. so Piperacillin/Tazobactam was used as empirical therapy and for critically ill patients Meropenem was used.
· Shift to antibiotics according to culture and sensitivity is done thereafter. Sometimes, step down using oral narrow-spectrum antibiotic is possible once the bacterial strain is identified.
· Risk factors for UTI: deceased donor (DGF and low UOP).
· Organism: G-ve as (E coli, Enterococcus faecalis and Klebsiella pneumoniae ), G +ve enterococci and staph aureus.
· Measures to decrease incidence of UTI after KT:
o Perioperative Single-Dose Antibiotic Prophylaxis: Beta-Lactam (Ampicillin/ Sulbactam or Cefotaxime) and Prior to ureteral anastomosis the bladder was irrigated with Gentamicin.
o Urinary catheters were placed preoperatively and removed on postoperative day 5, Ureterocystoneostomy was performed according to Lich-Gregoir to guard against reflux in the allograft, Intraoperative a Double-J-ureteral stent (placed and then removed on POD 21) per protocol (or earlier if UTI occurs, to remove the biofilm).
o Follow up urine analysis, CBC and CRP were done weekly or when symptoms are present, to detect any evidence of UTI.
o Posttransplant antibiotic prophylaxis: was initially quinolones (but now used for treatment), so TMP-SMX which is used for PJP is now the most common prophylactic agent used for 1st 3-6 month posttransplant (decreased incidence of UTI and asymptomatic bacteriuria after KT).
o Periinterventional antibiotics (usually Ciprofloxacin) for ureteral stent removal may be used (debatable benefit).
· UTI is suspected with (symptoms, urinary dipstick showed leukocyturia or nitrite +ve).
· Multi-resistant G-ve bacteria were defined as: bacteria resistant to 3 out of 4 of the following substance classes (acylureidopenicillin, 3rd generation cephalosporins, fluoroquinolones, carbapenems) called as 3- MRGN. Bacterial strains that were resistant to all 4 of the aforementioned substance classes were classified as 4-MRGN.
· Resistant organisms are present in dialysis and transplant patients more than in the healthy population.
· Antibiotic stewardship means putting an effort to measure and improve how antibiotics are prescribed by clinicians and used by patients (correct antibiotic choice, correct dose and duration, avoid unnecessary use) to decrease emergence of resistance.
⭐⭐⭐Level of evidence: retrospective cohort (level 2)
Treatment of UTI in my work place:
· In pediatric transplantation, we usually start empirical fortum or meronam antibiotics to cover pseudomonal infection, till culture result.
· I would like to ask about shift to culture based antibiotics, mostly if the patient is improving regarding fever, symptoms as dysuria, pus cells in urine and CRP …we tend to continue on the same empirical antibiotics. Is it right or must shift to culture based one?
· And all of our cases are kept on SMX-TMP.
· Patients with lower urinary tract problems may be maintained on CIC and life-long SMX-TMP especially if positive hx of recurrent UTI.
I like your well-structured detailed summary, level of evidence, limitations and strengths based on analysis and take home messages.
You mention and I quote from your reply, “And all of our cases are kept on SMX-TMP.”
My question: For how long would you give prophylactic SMX-TMP?
Thanks dear professor , we use it for 6 months post transplant.
SUMMARY
Introduction
The most common infection after kidney transplantation is urinary tract infection with an incidence rate that ranges from 4-80% and is defined as the presence of >105 CFU of sterile urine with clinical signs and symptoms in the patient. Asymptomatic UTIs are the absence of symptoms of UTI but in the presence of significant bacteriuria, and the incidence is 25% in KT.
The most common pathogens found in urine samples after KT are Escherichia coli Enterococcus faecalis and Klebsiella pneumonia. The Gram-negative bacteria are usually more pathogenic than gram-positive Enterococci.
Aim of the study
Materials and Methods
Results and Discussions
Limitations of the study
Strength of the study
Conclusion
Antibiotics stewardship is very key in taming the proliferation of growing resistance to antibiotic. Prevntion and proper treatment of UTI in kidney transplant patient should be a team work to obtain maximum output from such programme.
The level of evidence is 3
Treatment of recurrent infection in my centre
The first thing is to investigatigate for any structural problems like:
If none of the above above is present then
The common antibiotic we used are:
Other antibiotics could be used based on culture results for minimum of 3 weeks
Educations
I like your well-structured detailed summary, limitations and strengths based on analysis and take home messages.
What is your reason to give level 3 evidence to this study that is a retrospective cohort study.
Q: We know that it is a longitudinal study. Is it a cohort study or case control study?
A : Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies ( that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary).
Conclusion: This is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2. Case control studies are level 3.
Article 4
Q1. Introduction
· Urinary tract infections (UTI) are the most prevalent problem immediately after kidney transplantation (KT) with incidence rate between 4 to 80%
· It is defined by the growth of 100,000 colony forming units (CFU) in the urine sample plus clinical features of infection such as burning micturition, frequency, or localized pain. The identification growth of 100,000 CFU without symptoms is called asymptomatic bacteriuria (ASB)
· ASB is seen in 25% of KT recipients
· Generally, the threshold for treatment is low for these group of patients due to elevated risk of septicemia or a typical presentation as a results of immune suppression
· Common organisms isolated are E. coli, Enterococcus faecalis, and Klebsiella pneumoniae
· The use of perioperative antibiotic prophylaxis is rout in transplant practice. There are different protocols and importantly FDA recommend against the use of fluroquinolones in these patients
· This study assessed the use of antibiotics in in the first months after KT, incidence of ASB, UTI and compared their antibiotic susceptibility to general population
Methodology
· Retrospective control study at the unit of transplant surgery university of Tuebingen, Germany
· The study was conducted in the period between January 2015 and August 2020
· They included 207 transplant recipients
· All the data were examined for the diagnosis, treatment of both UTI, and ASB
· Treatment outcome were assessed
Results
· Around 32% of recipients had UTI
· They had poor graft outcome at discharge and t 12 months follow up
· Ciproflaxocin or pipercillin /Tazobacam were the used to treat the UTI
· Higher antibiotic resistance in these group compared to the control from the general population
Limitation
· Retrospective data
· Single center
· Relatively small sample size
Strength
· They demonstrated different resistant profile to the common antibiotics utilized in treatment of UTI between KT recipients and the control group
· They acknowledged that, more multicenter studies are needed
Conclusion
· Based on these results, UTI may be associated with poor allograft outcomes and therefore, it is essential to prevent and treat UTI with the help of antibiotic stewardship teams
Q.2
· Retrospective cohort study, level 3
Q.3
· Prophylaxis: Trimethoprim-Sulfamethoxazole
· Treatment: Fosfomycin for ASB, and Meropenem for UTI
What is your reason to give level 3 evidence to this study that is a retrospective cohort study.
Q: We know that it is a longitudinal study. Is it a cohort study or case control study?
A : Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies ( that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary).
Conclusion: This is an observational longitudinal cohort study with population data as controls. Cohort studies (retrospective or propective) are level 2. Case control studies are level 3.
Thank you prof for analyzing this