Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: A systematic review and meta-analysis

Background and Aim: Empirical therapy for Helicobacter pylori infection is limited by increasing antibiotic resistance and suboptimal eradication rates. Studies of the relative effectiveness of susceptibility-guided therapy have produced conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether susceptibility-guided therapy is superior to empirical therapy for H. pylori infection. Methods: We searched articles listed in PubMed, MEDLINE, EMBASE, and Web of Science through May 25, 2020, RCTs comparing susceptibility-guided versus empirical therapy for H. pylori infection. Outcomes, including effectiveness and safety, were analyzed in a meta-analysis. Results: Our final analysis included 16 studies, comprising 2374 patients who received susceptibility-guided therapy and 2451 patients who received empirical treatment. In previously untreated subjects, susceptibility-guided therapy was slightly more effective than empirical therapy (intent to treat risk ratio [RR], 1.14; 95% confidence interval [CI], 1.07–1.21; P < 0.0001, I² = 75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07–1.30; P = 0.001, I² = 81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92–1.13; P = 0.759, I² = 80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous. Conclusions: Our findings suggest that susceptibility-guided treatment may be slightly superior to empirical first line triple therapy. Susceptibility- guided treatment does not appear to be superior to empirical first-line quadruple therapy or empirical rescue therapy.