Efficacy of Rifaximin to Eradicate Small Intestine Bacterial Overgrowth and to Get Symptom Relief: A Systematic Review and Meta-Analysis

Abstract

Introduction: Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterized by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. The aim of this study was to perform a systematic review and meta-analysis to summarize evidence about the efficacy of rifaximin to eradicate SIBO and to get symptoms relief. Methods: MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for randomized controlled trials (RCTs) and observational studies. Furthermore, abstract books of major European, American, and Asian gastroenterological meetings were also examined. To explore heterogeneity regarding the efficacy and the safety, a meta-regression analysis including several variables were performed. Studies reporting lower GI symptom assessment before and after treatment with rifaximin were evaluated in order to identify those showing symptoms relief after therapy from those which did not. A sub-group analysis was also performed to evaluate the eradication rate in patients with irritable bowel syndrome (IBS). Results: 32 studies involving 1331 patients were included. The overall eradication rate according to intention to treat analysis was 70.8% (95% CI: 61.4 to 78.2; I2 = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5 to 79.8; I2 = 87.5%). Meta-regression identified three covariates (namely the drug dose, the study design and co-therapy) independently associated with an increased eradication rate. In IBS patients, the pooled eradication rate according to the ITT analysis was 71.6% (95% CI: 56.7 to 84.4) and according to PP analysis was 75.4% (95% CI: 65.0 to 84.5). The evaluation of studies assessing symptoms before and after treatment with rifaximin showed a high heterogeneity, not allowing a proper meta-analysis. However, a thorough analysis of the studies showed that symptom improvement was reported in a large proportion (≥75%) of studies, an effect seen more frequently in studies including IBS patients. The overall rate of adverse events was 4.6% (95% CI = 2.3 to 7.5; I2 = 63.6%). Conclusion: Rifaximin treatment seems to be effective and safe to eradicate SIBO and to get symptoms relief, even in patients with IBS. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.