Should Metronidazole Be Included in Second-Line Treatment After Standard Triple Therapy for Helicobacter pylori? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Aim: Although standard triple therapy remains the first-line eradication treatment for H. pylori worldwide, it is unclear whether metronidazole should be included empirically in second-line eradication treatments. The aim of this study was to compare the efficacy of metronidazole-containing regimens with that of metronidazole-free regimens after failure of first-line eradication using standard triple therapy. Methods: PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify RCTs eligible for inclusion in this systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Thirteen eligible RCTs were included, with a total of 2039 patients assigned to metronidazole-containing (975 patients) or metronidazole-free (1064 patients) regimens. Metronidazole-containing regimens had significantly lower eradication failure rates than regimens without metronidazole (OR 0.55; 95% CI, 0.39–0.78). Subgroup analysis based on the regional risk of metronidazole resistance demonstrated that metronidazole-containing regimens had lower eradication failure rates not only in low-risk regions but also in high-risk regions (OR, 0.29; 95% CI, 0.11–0.74 and OR, 0.66; 95% CI, 0.49–0.91, respectively). Conclusion: After failure of standard triple therapy, secondary eradication treatment regimens containing metronidazole demonstrate higher eradication rates than those without metronidazole.