Resistance Patterns and Optimization of Empirical Therapy for Urinary Tract Infections in Patients on Trimethoprim-Sulfamethoxazole Prophylaxis Against Pneumocystis jirovecii

Abstract

Background: Trimethoprim-sulfamethoxazole (SXT) is widely used for Pneumocystis pneumonia prophylaxis. However, prolonged use may induce antimicrobial resistance, potentially compromising empirical therapy for urinary tract infections (UTIs). Methods: We retrospectively analyzed 3, 525 patients with positive urine cultures at Shizuoka General Hospital (2018–2023). Among them, 149 received SXT prophylaxis. Antimicrobial susceptibility and the relationship between prophylaxis duration and resistance were evaluated. Results: Escherichia coli and Klebsiella pneumoniae were the most common pathogens. In the SXT prophylaxis group, E. coli susceptibility to SXT was significantly reduced (21.2% vs. 87.4%). Susceptibility to other antibiotics also declined, including ampicillin (31.2% vs. 71.6%), piperacillin (32.5% vs. 74.8%), levofloxacin (57.5% vs. 74.7%), and ciprofloxacin (56.2% vs. 74.1%). Susceptibility to expanded-spectrum cephalosporins, including second-, third-, and fourth-generation agents remained preserved. Receiver operating characteristic analysis identified a prophylaxis duration >406 days as predictive of SXT resistance (area under the curve 0.82, sensitivity 94%, and specificity 60%). Short-term prophylaxis (≤30 days) mitigated resistance, although E. coli susceptibility to SXT was still limited (47.8%). Conclusions: Prophylactic SXT use markedly reduces susceptibility to multiple antibiotics, especially penicillins and fluoroquinolones. Resistance correlates with prophylaxis duration. For empirical UTI therapy, intravenous expanded-spectrum cephalosporins may be preferable.