Bismuth improves efficacy of proton-pump inhibitor clarithromycin, metronidazole triple Helicobacter pylori therapy despite a high prevalence of antimicrobial resistance.

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Helicobacter pylori (H. pylori) eradication has become increasingly difficult especially for penicillin allergy patients. To evaluate the efficacy of adding bismuth or high-dose metronidazole to an H.pylori eradication regimen containing a proton-pump inhibitor, clarithromycin, and metronidazole in patients allergic to penicillin. Pilot study in which penicillin-allergic, treatment-naive subjects were randomized (1:1) to 14-day esomeprazole (20mg q12h), clarithromycin (500mg q12h), and high dose of metronidazole (400mg q6h) with (BECM group) or without (ECM group) bismuth (600mg q12h). Eradication was confirmed by 13 C-urea breath test 6weeks after therapy. Antimicrobial susceptibility was assessed by the agar dilution method. Adverse events were recorded. Sixty-six subjects were randomized, four were lost to follow-up and eight violated the protocol. The eradication rates were 63.6% (95% CI: 47.2%-80.0%) for ECM vs 84.8% (95% CI 72.6%-97.1%) (p=.049) for BECM by intention-to-treat, 67.7% (95% CI 51.3%-84.2%) vs 90.3% (95% CI 79.9%-100%) (p=.029) by modified ITT, and 70% (95% CI 53.6%-86.4%) vs 96% (95% CI 88.3%-100%) (P=.033) by per-protocol. Metronidazole, clarithromycin, and dual-resistant rates were 74.2%, 24.2%, and 18.2%, respectively. The cure rates were significantly improved by the addition of bismuth for both clarithromycin-resistant isolates (100% vs 25%, P=.024) and metronidazole-resistant isolates (94.7% vs 63.6%, P=.043). Adverse events were reported by 45.5% of subjects in ECM group and 48.5% in the BECM group (P=.805). This prospective trial demonstrated that while high-dose metronidazole could not completely overcome metronidazole resistance, bismuth was additive and improved the overall cure rates by 21%-26%.