Probiotics and rifaximin for the prevention of travelers' diarrhea: A systematic review and network meta-analysis

Background: Probiotics and rifaximin are treatments for gut microbiota dysbiosis in patients with traveler's diarrhea (TD), and they both proved beneficial for the prevention of TD. However, comparative effectiveness research between them has not been performed. A systematic review and network meta-analysis are to be performed to clarify which of them is more effective in the prevention of TD. Methods: Literature concerning the effectiveness of probiotics or rifaximin in the prevention of TD was searched in Medline, Embase, the Cochrane Central Register of Controlled Trials, and clinical registries for randomized controlled trials (RCTs) from inception of these databases to November 30, 2021 without any language restrictions. The primary efficacy outcome was the incidence of TD, and the safety outcome was the incidence of adverse events. The effect size of probiotics was measured by using relative ratio (RR), and the network meta-analysis was performed by using a frequentist approach and a random-effect model. Results: Totally 17 RCTs after screening 1119 retrieved records were included in analysis and 9 RCTs were with low risk of bias. Compared with placebo, both probiotics and rifaximin were associated with lower incidence of TD (probiotics, RR 0.85, 95% CI 0.76-0.95; rifaximin, RR 0.47, 95% CI 0.35-0.63), and rifaximin was more effective than probiotics (RR 0.56, 95% CI 0.4-0.78). Further analysis showed that sodium butyrate, rifaximin and L. acidophilus + L. bulgaricus + Bifido.bifidum + Strept. Thermophilus were the three most effective treatments for TD. Conclusions: Both rifaximin and probiotics are superior over placebo, and rifaximin has better treatment effect than probiotics in reducing the incidence of TD. Different types of probiotics have heterogeneous treatment effects.