S2346 Comparative Effectiveness of Trimethoprim-Sulfamethoxazole, Ciprofloxacin, and Norfloxacin for Spontaneous Bacterial Peritonitis Prophylaxis in Cirrhosis: A TriNetX Network Analysis

Introduction: Spontaneous bacterial peritonitis (SBP) prophylaxis is critical in cirrhosis, but optimal antibiotic selection remains debated. We compared real-world outcomes of 3 first-line agents for SBP prophylaxis, norfloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). Methods: This retrospective TriNetX study analyzed de-identified EHRs of adults with cirrhosis (International Classification of Diseases, Tenth Revision (ICD-10)) initiating SBP prophylaxis. We compared TMP-SMX (n = 57,625) vs ciprofloxacin (n = 81,037) and norfloxacin (n = 1,246) vs ciprofloxacin in patients with ascites. Outcomes included risk differences, odds ratios, and Kaplan-Meier survival. Results: After propensity matching, TMP-SMX was associated with significantly lower incidence of SBP (3.9% vs 6.3%; OR 0.61, 95% CI: 0.58-0.65, P-value < 0.001) and mortality (17.6% vs 25.5%; OR 0.63, 95% CI 0.61-0.64, P-value < 0.001) in comparison to ciprofloxacin. However, there was an increased risk of clostridium difficile infection (3.3% vs 2.5%; OR 1.33, 95% CI 1.24-1.42, P-value < 0.001) and pneumonia (9.8% vs 9.2%; OR 1.08, 95% CI 1.03-1.12, P-value < 0.001) with TMP-SMX. The results were statistically non-significant for AKI (TMP-SMX, 22.7% vs ciprofloxacin, 23.3%; OR 0.97, 95% CI: 0.93-1.0, P-value 0.07) and sepsis (TMP-SMX, 13% vs ciprofloxacin, 13.2%; OR 0.99, 95% CI 0.95-1.03, P-value 0.57). Propensity matched comparative analysis of norfloxacin and ciprofloxacin showed that norfloxacin was associated with significantly higher incidence of SBP (10.1% vs 6.3%; OR 1.68, 95% CI: 1.36-2.08, P-value < 0.001) and pneumonia (11.1% vs 9.2%; OR 1.23, 95% CI 1.02-1.50, P-value 0.035). Norfloxacin had significantly decreased mortality rates (18.8% vs 25.5%; OR 0.68, 95% CI 0.59-0.78, P-value < 0.001) compared to ciprofloxacin. The results of for AKI (norfloxacin, 23.4% vs ciprofloxacin, 23.3%; OR 1.01, 95% CI: 0.84-1.20, P-value 0.95), clostridium difficile infection (norfloxacin, 3.3% vs ciprofloxacin, 2.5%; OR 1.21, 95% CI 0.86-1.69, P-value 0.27) and sepsis (norfloxacin, 12% vs ciprofloxacin, 13.2%; OR 0.90, 95% CI 0.74-1.09, P-value 0.27) were not significant. Conclusion: In this real-world study, TMP-SMX reduced SBP and mortality compared to ciprofloxacin but carried higher risks of C. difficile infection and pneumonia. Ciprofloxacin outperformed norfloxacin in preventing SBP and pneumonia, though with higher mortality. Other adverse event rates were similar, highlighting the need to individualize SBP prophylaxis based on patient risk profiles.