Comparative efficacy of long-term antibiotic treatments in the primary prophylaxis of spontaneous bacterial peritonitis

Background & Aims Several antibiotic treatments aiming to prevent spontaneous bacterial peritonitis (SBP) in cirrhotic patients with low-protein content in ascitic fluid have been tested; however, there are limited data on the comparative efficacy of these regimens. We assessed their comparative efficacy through a network meta-analysis and using GRADE criteria to appraise quality of evidence. Methods Through literature review through October 2018, we identified 10 randomized controlled trials comparing antibiotic treatments (norfloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifaximin) with each other or placebo. Primary outcome was SBP occurrence, with mortality rate and rate of other infections as secondary outcomes. Results In comparison with placebo, moderate quality evidence supports the use of norfloxacin and ciprofloxacin in primary prophylaxis of SBP (risk ratio 0.23; 95% CI, 0.09-0.56; P = 0.001 and 0.23; 0.07-0.79; P = 0.02 respectively) while only low quality evidence suggests superiority of rifaximin (risk ratio 0.15; 0.05-0.42). When antimicrobial agents were compared to each other, no significant difference was found. With regard to mortality, moderate quality supports the superiority of norfloxacin over placebo (risk ratio, 0.68; 95% CI, 0.47-0.99; P = 0.04), while ciprofloxacin and rifaximin showed only a non-significant benefit and no significant difference was found in the other comparisons. None of the tested antibiotics proved to significantly decrease the rate of other infections. Conclusions Norfloxacin appears to have significant benefit both in terms of SBP prevention and mortality; ciprofloxacin represents a valuable option although without a clear survival benefit. Rifaximin shows interesting results but needs to be tested in further trials.