Asymptomatic Bacteriuria in Early Kidney Transplantation Follow up
Asymptomatic Bacteriuria in Early Kidney Transplantation Follow up
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).
I. 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.

 III. 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.

 IV. 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).

 V. 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.

 VIII. 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.
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.