2273. Outcomes of Trimethoprim/Sulfamethoxazole as Definitive Therapy for Urinary Tract Infections with Multi-Drug-Resistant Enterobacteriaceae

Abstract

BackgroundTrimethoprim/Sulfamethoxazole (TMP/SMX) is not routinely employed for urinary tract infections (UTI) with multi-drug-resistant organisms (MDRO) due to paucity of effectiveness data, concerns regarding inadequate urinary penetration, and risk of adverse effects. We describe our experience with TMP/SMX as definitive therapy for MDRO Enterobacteriaceae (MDRO-E).MethodsWe carried out a retrospective review of patients hospitalized at a tertiary care center and treated with TMP/SMX as definitive therapy for UTI with MDRO-E (as defined by resistance to third-generation cephalosporins in culture). We evaluated rates of overall cure rate (CR), adverse events (AE), recurrence (RC) and reinfection (RI). Repeat growth of same or different pathogen in urine culture (UC) within 30 days of completion of treatment was defined as RC or RI, respectively.Results92 patients had 101 episodes of MDRO-E UTIs treated with TMP/SMX as initial (n = 26, 25.7%) or as step-down therapy (n = 23, 77%) after broad-spectrum empiric antimicrobials (ceftriaxone n = 22, cefepime n = 21, piperacillin/tazobactam n = 12, carbapenems n = 6, ciprofloxacin n = 3). 63 (68.5%) patients were 65 years or older. MDRO-E in 10 (9.9%) episodes were also resistant to carbapenems. Empiric therapy was appropriate in 56 (55.5%) episodes. Median duration of treatment was 8.5 (range 3–24) days for all antimicrobials and 7 (range 2–15) days for TMP-/SMX. Overall CR was 100%. RC/RI was seen in 23/101 (22.8%) episodes (RC n = 9; RI n = 14); UC data were available for 20 of which 8/20 (40%) had a TMP/SMX-resistant organism. 4 (3.9%) patients required readmission for a RC/RI UTI. In terms of AEs: 10 (9.9%) episodes of hyperkalemia (median maximum potassium level 4.5 mmol/L, range 2.7–6.4), 3 (2.9%) episodes of acute kidney injury, 5 episodes of Clostridium difficile infection, and 4 (3.9%) readmissions for a RC/RI UTI within 90 days.ConclusionOur findings suggest that TMP/SMX can be safe and effective as definitive therapy for ESBL-E UTI. The major AE are hyperkalemia and AKI, the incidence of which is high when TMP/SMX is used in combination with ACEI/ARBs. No clinical factors were found to be predictive of recurrence of reinfection. Disclosures All authors: No reported disclosures.