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Asymptomatic Bacteriuria in Early Kidney Transplantation Follow up

Sponsor
Centenario Hospital Miguel Hidalgo (Other)
Overall Status
Completed
CT.gov ID
NCT04333602
Collaborator
(none)
80
Enrollment
1
Location
2
Arms
25.5
Actual Duration (Months)
3.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Urinary tract infection (UTI) continues to be the leading cause of infection and hospitalization in post-kidney transplant (RT) surveillance. Facts such as immunosuppression, anatomical alterations and catheters are part of the factors that contribute to a high prevalence of this condition. The incidence during the first trimester is highly variable and ranges between 15 and 50 %. This variability often depends on the definition of UTI, which sometimes overlaps with asymptomatic bacteriuria (AB). Currently the indication for treatment of AB is clear in pregnant patients and urological procedures. In post-RT surveillance, the treatment of AB is controversial. The use of Trimetropim Sulfamethoxazole during the first 6 months post RT is currently a recommendation, however new evidence has found the absence of benefit in the treatment of AB. Given the high prevalence of post RT AB and the increase in bacterial resistance, determining the usefulness of searching for and treating post RT AB is a priority in this population. Methodology: Randomized Controlled trial of kidney transplant candidates which will be randomized in the following groups: Group 1 (intervention) where the urine cultures will be analyzed openly, and in the case of asymptomatic bacteriuria, treatment based on the germ and antibiogram will be prescribed. Group 2 will undergo urine cultures at the same post-transplant times, the results will not be known by the clinical team and the participants will not receive treatment in the presence of present AB. Both groups, in the presence of UTI symptoms, will undergo urine culture and receive empirical treatment, which will be adjusted based on an antibiogram. The primary objective is to assess the prevalence of UTI, pyelonephritis, UTI-related hospitalizations, and antimicrobial resistance. As a secondary objective, the germs and associated virulence genes will be analyzed. Surveillance will be carried out for two months after transplantation and the predefined times for the evaluation of the BA will be: after the removal of the urinary catheter, week 3 and after the removal of the ureteral stent (month 2).

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: Urinary culture and treatment if asymptomatic bacteriuria is detected
 N/A

Detailed Description

  1. Background Urinary tract infection (UTI) is the most frequent infectious complication in renal transplant recipients (RTR) during the first year, reaching an incidence from 23% to 75%. (1,2) Asymptomatic bacteriuria (AB) and UTI are associated with graft pyelonephritis, sepsis, acute rejection, and long-term graft dysfunction. (3-5) Recently, recurrent UTI episodes have been reported to be associated with poorer patient and graft survival compared to those without recurrent infection. (6) Risk factors are classified as: patient-related (diabetes mellitus, anatomical abnormalities of the urinary tract) and transplant-related (type of immunosuppression, time of the bladder catheter (UC) and double J stent. (7,8) The recommendations of the clinical guidelines suggest prophylaxis with trimethoprim / sulfamethoxazole (TMP / SMX) 160/800 mg every 24 hr during the first 6 months after kidney transplant (KT) ( 9).

The incidence of UTI in RTR has remained between 30 and 36% despite TMP / SMX antimicrobial prophylaxis (7) in a third-level care center in Mexico City; This high incidence is explained in part by the high resistance rate to TMP / SMX (> 80%) in clinical isolates of Escherichia coli recovered from urine both in Mexico and other regions of the world, a condition that discourages its continued use as a prophylactic agent from UTI. (10-12) Given this problem, a clinical trial of kidney transplant recipients was started, comparing the usual prophylaxis with TMP / SMX vs Phosphomycin 3 grams every 10 days for 6 months. The study was suspended prematurely due to therapeutic futility (19). A new clinical trial was performed using intravenous phosphomycin disodium the day of the transplant, prior to the removal of the bladder catheter and the double J ureteral stent. In this study, the intervention group presented a lower incidence of UTI (7.3 vs. 36.6%, p = 0.001).

In both previously described trials, patients underwent UTI screening by urine culture on specific days. Asymptomatic bacteriuria episodes are treated according to the susceptibility of the germ. This alone represents a strategy to decrease the incidence of UTI. Treatment of AB episodes has clearly not been shown to be beneficial in this group of patients. Recently in a controlled clinical trial no benefit was found in KTR with screening and treatment of AB after the second month of post KT. (14) This study partially supports the recommendations of clinical practice of the American Society of Infectious Diseases, where the systematic scrutiny and treatment of the UTI in kidney transplantation is mentioned as not recommended, however the authors propose possible benefit during the first month after KT. (2) II. Definition of the problem Urinary tract infection is the most frequent infectious complication after KT. The systematic screening and treatment of AB during the first months after transplantation is controversial. Given the increase in bacterial resistance, it is important to limit the exposure of antibiotics in high-risk groups. Various studies have demonstrated the utility of the administration of antimicrobial prophylaxis during the first months after transplantation for the reduction of UTI and AB events. However, these studies and several centers carry out systematic scrutiny of UTI with treatment of episodes of AB. Recently a controlled clinical trial showed that the scrutiny and treatment of AB after the second month after transplantation is not useful.

  1. Justification UTI represents the most frequent cause of post kidney transplant infection. AB is highly prevalent during the first months after KT. Its prevalence during the first trimester is high and currently the treatment of AB is not fully justified. Due to the need to avoid the abuse of antibiotics in our setting, it is necessary to evaluate the usefulness of screening and treatment of AB in the first 8 weeks post KT. The Medical Center where the trial will be done, performs an average of 100 to 120 kidney transplants annually, which makes the clinical trial feasible.

  2. Hypothesis The screening and treatment of AB during the first 2 months will reduce the incidence of UTI, pyelonephritis and hospitalizations by 50% (composite outcome).

  3. Objectives. To assess the efficacy of AB screening and treatment in KT recipients during the first two months post KT.

To assess the incidence of UTI, pyelonephritis and hospitalizations associated with UTI Assess the prevalence of multi-resistant germs The urine culture samples will be labeled and in case of being positive, the isolated strain will be conserved for the subsequent identification of virulence genes. Said strain will be identified with the record of the study of the patient, in order to know the clinical variables of the time of obtaining said sample.

  1. Definition of monitoring variables Asymptomatic Bacteriuria: In the case of men, medium stream urine culture with isolation of > 1 x 105 colonies. In the case of women, medium-stream urine culture with isolation of > 1 x 105 colonies (2 cultures), must be the same germ.

Urinary tract infection: Isolation of medium stream urine culture >1 x 104 colonies coupled with symptoms such as fever, dysuria, leukocyturia or positive nitrites. If it is only fever, another infectious focus should be ruled out.

Pyelonephritis: Urinary tract infection coupled with fever, graft pain, systemic inflammatory response, or shock. It should not have another concomitant infection.

X. Sample Size:

Taking into account that UTI events occur on average 30% during the first 3 months after KT if the investigators want to reduce events to 10%. Taking the proportions formula. The sample required to be included is 62 patients per maneuver group.

Study Design

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Group 1: Asymptomatic Bacteriuria screening and treatment and Group 2: Asymptomatic Bacteriuria screening and No treatment for AB.Group 1: Asymptomatic Bacteriuria screening and treatment and Group 2: Asymptomatic Bacteriuria screening and No treatment for AB.
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:
Both the patient, the primary doctor and the laboratory worker do not know the result of the culture. Only the doctors in charge of this process know the result and contact the patient directly if they are in the treatment group.
Primary Purpose:
Treatment
Official Title:
Screening and Treatment of Asymptomatic Bacteriuria in the First Two Months After Kidney Transplant. Randomized Control Trial
Actual Study Start Date :
Jan 1, 2020
Actual Primary Completion Date :
Feb 16, 2022
Actual Study Completion Date :
Feb 16, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Screening and Treatment of Asymptomatic Bacteriruria

All patients assigned to this arm will be screen with urine culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal. If we detect asymptomatic bacteriuria specific treatment will be instituted.

Diagnostic Test: Urinary culture and treatment if asymptomatic bacteriuria is detected
Urinary culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal. Based in the assigned group If we detect asymptomatic bacteriuria specific treatment will be instituted or No treatment.
Other Names:
  • Clinical decision based in the presence of asymptomatic bacteriuria

    		•
    No Intervention: Screening and NO treatment of Asymptomatic Bacteriuria

    All patients assigned to this arm will be screen with urine culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal. No treatment will be instituted.

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of symptomatic urinary tract infection [Two months]

      urinary symptoms associated with positive urine culture

    2. Time to the first symptomatic urinary tract infection [Two moths]

      urinary symptoms associated with positive urine culture

    3. Incidence of pyelonephritis or hospitalization related to urinary tract infection [Two months]

    Secondary Outcome Measures

    1. Bacterial virulence genes related to urinary tract infection [Two moths]

      E. Coli and Klebsiella. sp virulence genes will be analysed

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Kidney transplant candidates scheduled for the procedure
    Exclusion Criteria:
    • Patients with urological complications that did not have a bladder catheter and/or double J ureteral stent removed during the study period.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Jose Manuel Arreola Aguascalientes Mexico 20230

    Sponsors and Collaborators

    • Centenario Hospital Miguel Hidalgo

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Jose Manuel Arreola Guerra, Head of the Research department and Nephrologist, Centenario Hospital Miguel Hidalgo
    ClinicalTrials.gov Identifier:
    NCT04333602
    Other Study ID Numbers:
    • 2019-R-03
    First Posted:
    Apr 3, 2020
    Last Update Posted:
    Feb 17, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Bacteriuria

    Study Results

    No Results Posted as of Feb 17, 2022