Secondary prophylaxis of SBP in cirrhosis: trimethoprim-sulfamethoxazole vs. ciprofloxacin in a propensity-matched cohort

INTRODUCTION AND OBJECTIVES: ), but these agents have not been robustly compared head-to-head. We compared clinical outcomes among patients receiving TMP-SMX versus ciprofloxacin for secondary SBP prophylaxis. MATERIALS AND METHODS: We conducted a multicenter retrospective cohort study using the TriNetX de-identified electronic health record network. Adults with cirrhosis (ICD-10 K74.6) and SBP (ICD-10 K65.2) from January 2013 to July 2021 were included. Index date was the first prescription for TMP-SMX (RxNorm 10829/10180) or ciprofloxacin (RxNorm 2551), with follow-up through July 11, 2024. Exclusions included prior exposure to the alternative agent, liver transplant, or end-stage renal disease. We performed 1:1 greedy nearest-neighbor propensity score matching (caliper 0.1) on demographics, comorbidities, and hepatic/renal laboratory variables. Primary outcomes were SBP recurrence and all-cause mortality; secondary outcomes included all-cause hospitalization, variceal bleeding, hepatic encephalopathy, and ascites. Cox proportional hazards models estimated hazard ratios (HRs). RESULTS: Among 31,011 patients (TMP-SMX 11,166; ciprofloxacin 19,845), 11,140 well-balanced matched pairs were analyzed. TMP-SMX was associated with lower SBP recurrence (HR 0.75, 95% CI 0.72-0.79) and all-cause mortality (HR 0.84, 95% CI 0.80-0.87; both p<0.0001). TMP-SMX also reduced risks of variceal bleeding (HR 0.81), hepatic encephalopathy (HR 0.79), and ascites (HR 0.86), while hospitalization was not significantly different. CONCLUSIONS: TMP-SMX was associated with significantly lower SBP recurrence and mortality than ciprofloxacin, supporting TMP-SMX as a potentially more effective secondary prophylaxis option pending randomized confirmation.