Urinary tract infections (UTIs) are frequent infectious complications post-kidney transplant (KT). In regions with high glucose-6-phosphate dehydrogenase (G6PD) deficiency, using alternatives to trimethoprim-sulfamethoxazole (TMP-SMX) creates a prophylactic gap, increasing UTI risk. We assessed the prevalence and risk factors for early post-KT UTIs and evaluated impact of an antimicrobial prophylaxis protocol. This single-center quasi-experimental study included adult KT recipients enrolled in two sequential phases. Phase I (n = 182; 2017-2023) identified predictors of UTI within 60 days post-KT, informing a prophylaxis protocol, implemented in March 2024. Phase II (n = 155; April 2024-November 2025) evaluated outcomes following protocol implementation, including extended nitrofurantoin or ciprofloxacin prophylaxis for patients unable to receive TMP-SMX. The primary endpoint was 60-day post-KT UTI; secondary endpoints included urinary-source bacteremia, UTI-related readmission, time to first UTI, and UTI-attributable hospital length of stay (LOS). Cohorts were comparable in age (median: 49 vs. 50 years, p = 0.45) and female representation (41.7% vs. 41.9%, p = 0.94). In Phase I, female sex (OR: 3.88, 95%CI: 1.99-7.59) and omission of TMP-SMX (OR: 2.14, 95%CI: 1.04-4.43; p < 0.001) independently predicted 60-day UTI. Post-protocol implementation, 60-day UTI odds declined (OR: 0.42, 95%CI: 0.22-0.82), secondary bacteremia decreased (12.6% vs 3.9%, p = 0.005), median time to first UTI doubled (14 vs. 27 days, p < 0.001), and UTI-related readmissions dropped (27.3% vs. 12.5%, p = 0.027). Median UTI-attributable LOS remained 5 days in both groups, the interquartile range narrowed from 3-8 to 0-7 days (p = 0.031). Risk-stratified antimicrobial prophylaxis significantly reduced early post-KT UTIs and complications. Early TMP-SMX omission emerged as a modifiable determinant, highlighting a critical prophylactic gap in G6PD-deficient populations.
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