Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe

Am J Gastroenterol. 2023 Feb 1;118(2):269-275. doi: 10.14309/ajg.0000000000002045. Epub 2022 Sep 30.

Abstract

Introduction: Guidelines recommend that proton pump inhibitor-based triple regimens with clarithromycin not be used for Helicobacter pylori infection in areas where clarithromycin resistance is ≥15%, or in patients with prior macrolide use. Up-to-date information on local resistance patterns is limited, especially in the US. Here, we report resistance rates to antibiotics commonly used to treat H. pylori from a large study conducted in the US and Europe (pHalcon-HP).

Methods: Gastric mucosal biopsies were collected from adult participants with H. pylori infection during screening. Minimum inhibitory concentrations were determined via agar dilution for clarithromycin, amoxicillin, and metronidazole, with breakpoints ≥1 μg/mL, >0.125 μg/mL, and >8 μg/mL, respectively. Resistance rates were obtained for the US and Europe, and also for US subregions and participating European countries.

Results: Resistance rates were established in isolates from 907 participants. Overall, 22.2% were resistant to clarithromycin, 1.2% to amoxicillin, and 69.2% to metronidazole. Resistance in the US and Europe was similar; metronidazole resistance was the most prevalent (50%-79%) and amoxicillin the least (≤5%). In all subregions, ≥15% of isolates were resistant to clarithromycin, except the UK (0/8 isolates). Among clarithromycin-resistant isolates, 75% were also metronidazole-resistant. Two US isolates were resistant to clarithromycin and amoxicillin; one of these was also metronidazole-resistant.

Discussion: The resistance rates observed in this study argue against the continued empiric use of proton pump inhibitor-based triple therapy containing clarithromycin, per treatment guidelines, and highlight the need for antibiotic resistance surveillance and novel treatment strategies for H. pylori infection in the US and Europe.

Trial registration: ClinicalTrials.gov NCT04167670.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Clarithromycin / pharmacology
  • Clarithromycin / therapeutic use
  • Drug Resistance, Bacterial
  • Europe / epidemiology
  • Helicobacter Infections* / diagnosis
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Humans
  • Metronidazole / therapeutic use
  • Microbial Sensitivity Tests
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Metronidazole
  • Clarithromycin
  • Proton Pump Inhibitors
  • Amoxicillin

Associated data

  • ClinicalTrials.gov/NCT04167670