Eradication of Helicobacter pylori Infection with Non-Bismuth Quadruple Concomitant Therapy

Background: The main recommended regimens to eradicate Helicobacter pylori infection fail in ≥20% of the cases. Several substitutes for triple therapies have been proposed, and non-bismuth quadruple therapy is one of the most widely used.

Aim: To systematically review the efficacy of non-bismuth quadruple regimen (proton pump inhibitor, clarithromycin, amoxicillin and a nitroimidazole) in the eradication of H. pylori infection.

Methods: Bibliographical searches were performed in MEDLINE/EMBASE and relevant congresses. We pooled studies evaluating the concomitant regimen, and of the randomized controlled trials comparing concomitant vs. standard triple therapy, and concomitant vs. sequential therapy.

Results: Fifty-five studies were included (6,906 patients). The meta-analysis showed that concomitant regimen offers an overall eradication rate of 87%. A sub-analysis of studies comparing one-to-one concomitant and triple therapies showed an odds ratio of 2.14 (95% CI=1.51-3.04) towards higher efficacy with concomitant regimen. This figure increased up to 2.41 (95% CI=1.80-3.24; 85% vs. 72%) when comparing arms lasting the same number of days. We also sub-analyzed the comparative efficacy between non-bismuth quadruple concomitant and sequential treatments, and concomitant achieved an odds ratio of 1.49 (95% CI=1.21-1.85) towards higher eradication results than sequential regimen.

Conclusions: Non-bismuth quadruple (concomitant) therapy achieves high efficacy in H. pylori eradication, superior to standard triple and sequential therapy. Concomitant may be more appropriate than sequential therapy for patients with clarithromycin and/or metronidazole resistance. Higher acid suppression and/or longer duration are optimizations that can increase even more its efficacy.

Keywords: Amoxicillin, Clarithromycin, Concomitant therapy, Helicobacter pylori, Metronidazole, Non-bismuth quadruple, Proton pump inhibitor, Resistance, Sequential therapy, Treatment.