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

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

Francis Mégraud  1 , David Y Graham  2 , Colin W Howden  3 , Ernest Trevino  4 , Alice Weissfeld  4 , Barbara Hunt  5 , Neila Smith  5 , Eckhard Leifke  5 , William D Chey  6
Affiliations

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

Francis Mégraud et al. Am J Gastroenterol. .

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.

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Conflict of interest statement

Guarantor of the article: Francis Mégraud, MD.

Specific author contributions: F.M., D.Y.G., C.W.H., and W.D.C.: had a role in interpreting data and drafting the manuscript. E.T. and A.W.: had a role in conducting the study, collecting data and drafting the manuscript. B.H., N.S., and E.L.: had a role in planning and conducting the study, collecting and interpreting data, and drafting the manuscript. Each author approved the final draft to be submitted.

Financial support: The clinical study (NCT04167670) and this analysis were funded by Phathom Pharmaceuticals.

Potential competing interests: F.M. reported grants from Allergan, bioMerieux and Mobidiag. He is also a consultant for Phathom Pharmaceuticals. D.Y.G. is a consultant for RedHill Biopharma and Phathom Pharmaceuticals regarding novel H. pylori therapies and has received research support for culture of H. pylori. He is also a consultant for DiaSorin regarding H. pylori diagnostics and with Otsuka Japan regarding novel breath tests. He has ongoing collaborative research projects with American Molecular regarding molecular diagnostics for H. pylori. C.W.H. discloses compensation as a consultant and advisory board/committee member for Phathom Pharmaceuticals and RedHill Biopharma; consultancy fees from Allakos, Clexio, ISOThrive, and Alfasigma; and Speaker's Bureau fees from Alnylam, RedHill Biopharma, Sanofi and Alfasigma. E.T. and A.W. are employees of Microbiology Specialists Incorporated, paid by Phathom Pharmaceuticals to undertake this work. B.H., N.S. and E.L. are employees of Phathom Pharmaceuticals; E.L. also discloses stockholder interest in Phathom Pharmaceuticals. W.D.C. reported being a Board member of the American College of Gastroenterology, GI on Demand, International Foundation of Functional GI Disorders, and the Rome Foundation; compensation as a consultant from AbbVie, Alfasigma, Allakos, Alnylam, Bayer, BioAmerica, Cosmo, Intrinsic Medicine, Ironwood Pharmaceuticals, QOL Medical, Nestle, Phathom Pharmaceuticals, RedHill Biopharma, Salix/Valeant, Takeda, Urovant, and Vibrant; grant/research support from BioAmerica, Commonwealth Diagnostics International, QOL Medical, Salix, and Vibrant; stock/stock options in GI on Demand, and Modify Health; and patents relating to methods and kits for identifying food sensitivities and intolerances, digital manometry, and a rectal expulsion device.

Trial registration: Clinicaltrials.gov NCT04167670.

Figures

Figure 1.
Figure 1.
Clarithromycin, amoxicillin and metronidazole resistance rates in the US. Gray color-coding indicates states that did not contain centers that participated in the pHalcon-HP study. Participating states are color-coded according to their assigned US-subregion.
See this image and copyright information in PMC

References

    1. Hooi JKY, Lai WY, Ng WK, et al. . Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology 2017;153:420–9. - PubMed
    1. Malfertheiner P, Megraud F, O'Morain CA, et al. , European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus report. Gut 2017;66:6–30. - PubMed
    1. Nyssen OP, Bordin D, Tepes B, et al. , Hp-EuReg Investigators. European registry on Helicobacter pylori management (Hp-EuReg): Patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients. Gut 2021;70:40–54. - PubMed
    1. Chey WD, Leontiadis GI, Howden CW, et al. . ACG clinical guideline: Treatment of Helicobacter pylori infection. Am J Gastroenterol 2017;112:212–39. - PubMed
    1. Thung I, Aramin H, Vavinskaya V, et al. . Review article: The global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016;43:514–33. - PMC - PubMed

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