Higher Doses of Bismuth and Antibiotics Do Not Improve Helicobacter pylori Treatment Effectiveness: Results From the European Registry on Helicobacter pylori Management

Abstract

Background & aims: Evidence on optimal bismuth and antibiotic dosing is limited. We aimed to analyze the effectiveness of bismuth-containing quadruple regimens according to drug dosage.

Methods: This was an analysis of an international, prospective, noninterventional registry on the management of Helicobacter pylori infection by European gastroenterologists (European Registry on Helicobacter pylori Management [Hp-EuReg]). Patients receiving empirical bismuth-containing quadruple therapies in any treatment line and registered from 2013 to 2024 were included. Effectiveness was assessed using a modified intention-to-treat (mITT) analysis.

Results: A total of 10,767 first-line records were analyzed. The clarithromycin-amoxicillin-bismuth (CAB) scheme was >90% effective with standard doses of amoxicillin and clarithromycin (2000 mg/d and 1000 mg/d), regardless of bismuth dose. The bismuth-metronidazole-tetracycline (BMTc) regimen achieved >90% effectiveness with tetracycline ≥1500 mg/d, metronidazole 1500 mg/d, and bismuth ≥480 mg/d. The amoxicillin-metronidazole-bismuth (AMB) regimen reported ≈90% mITT with amoxicillin 2000 mg/d, metronidazole ≥1000 mg/d, and bismuth 480 mg/d. The clarithromycin-metronidazole-bismuth (CMB) showed ≥90% mITT with metronidazole ≥800 mg/d, without improvement from increasing bismuth dose. In the amoxicillin-levofloxacin-bismuth (ALB) regimen, mITT was >90%, with no benefit from increasing levofloxacin >500 mg/d. A total of 2952 second- to sixth-line treatments were analyzed, all showing mITT <90% (ALB, 83%; BMTc, 79%; CAB, 88%; MDB, 63%; AMB, 88%), with no significant differences with different bismuth doses.

Conclusions: Increasing antibiotic or bismuth doses above the standard did not improve effectiveness of H pylori treatment. Adherence, treatment length, and proton pump inhibitor cotherapy may be more impactful than escalation of antibiotics/bismuth doses.

Clinicaltrials: gov, Number: NCT02328131.

Keywords: Bismuth; Dosage; Effectiveness; H pylori.