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

Abstract

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.

Keywords: GRADE; cirrhosis; liver; norfloxacin.