Efficacy of Rifaximin in Prevention of Travelers' Diarrhea: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

Background. Rifaximin has been used successfully for the prevention of travelers' diarrhea (TD), the most general cause of disability among international travelers to developing tropical and semitropical regions. Methods. We sought to better evaluate the efficacy of rifaximin in the prevention of TD. Randomized controlled trials (RCTs) of rifaximin for the prevention of TD published in Pubmed, the Cochrane Central Register of Controlled Trials, Embase, and the Science Citation Index were searched. [Correction added on 3 October 2012, after first online publication: the phrase protection of TD was replaced with prevention of TD.] The primary efficacy outcome was occurrence of TD over a 2-week treatment period. Secondary outcomes were requirement for antibiotic treatment, occurrence of mild diarrhea (MD), occurrence of TD in the third week after drug withdrawal, incidence of TD associated with isolation of diarrheagenic Escherichia coli (ie, ETEC, EAEC), and adverse events. Results. Four RCTs with 502 participants were included in the systematic review. Rifaximin treatment showed a significant protection against TD (risk ratios, RR: 0.41, 95% CI: 0.30-0.56, p < 0.00001) and needed antibiotic-treated TD (relative risk [RR]: 0.30, 95% confidence interval [CI]: 0.18-0.49, p < 0.00001). There was no significant difference between rifaximin and placebo in the occurrence of MD (RR: 1.11, 95% CI: 0.78-1.59, p = 0.55) and the occurrence of TD in the third week after drug withdrawal (RR: 0.73, 95% CI: 0.30-1.73, p = 0.47). Enterotoxigenic E. coli was the major cause of TD, and all trials reported no differences in adverse events between rifaximin and placebo. Conclusions. Rifaximin can prevent TD caused by non-invasive enteric pathogens. Further research is needed for the treatment of invasive enteric pathogens. [Correction added on 3 October 2012, after first online publication: the phrase Rifaximin can protect TD was replaced with Rifaximin can prevent TD.]