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Multicenter Study
. 2026 Jan-Feb;31(1):e70107.
doi: 10.1111/hel.70107.

Long-Term Effect of Macrolides on Helicobacter pylori Eradication: Data From the European Registry on Helicobacter pylori Management (Hp-EuReg)

Olga P Nyssen  1 , Guillermo J Ortega  2 , Laimas Jonaitis  3 , Ángeles Pérez-Aísa  4 , Bojan Tepes  5 , Alfredo J Lucendo  6 , Javier Tejedor-Tejada  7 , Renate Bumane  8 , Ana Garre  1 , Jose M Huguet  9 , Monica Perona  10 , Óscar Núñez  11 , Manuel Pabón-Carrasco  12 , Manuel Castro-Fernández  12 , Miguel Areia  13 , Jesús Barrio  14 , Antonio Moreno Loro  15 , Thomas J Butler  16 , María Soledad Marcos  17 , Alma Keco-Huerga  18 , Manuel Domínguez Cajal  19 , Maja Denkovski  20 , Matteo Pavoni  21 , György Miklós Buzás  22 , Frode Lerang  23 , Giuseppe Losurdo  24 , Pablo M Wolfe García  25 , Perminder S Phull  26 , Samuel J Martínez-Domínguez  27 , Juozas Kupcinskas  3 , Mārcis Leja  8 , Ricardo Marcos-Pinto  28 , Sinead M Smith  29 , Antonio Gasbarrini  30 , Veronika Papp  31 , Blas José Gómez Rodríguez  18 , Mónica Sánchez Alonso  32 , Ramón Pajares Villarroya  33 , Pilar Pazo Mejide  34 , Manuel Jiménez-Moreno  35 , Marta Pascual-Mato  36 , Concepción Bravo-Pache  37 , Milagrosa Montes  38 , Anna Cano-Català  39 , Pablo Parra  1 , Leticia Moreira  40 , Francis Mégraud  41 , Colm O'Morain  29 , Luis Bujanda  42 , Javier P Gisbert  1 ; Hp‐EuReg investigators
Collaborators, Affiliations
Multicenter Study

Long-Term Effect of Macrolides on Helicobacter pylori Eradication: Data From the European Registry on Helicobacter pylori Management (Hp-EuReg)

Olga P Nyssen et al. Helicobacter. 2026 Jan-Feb.

Abstract

Background and aims: Previous antibiotic use influences Helicobacter pylori antibiotic resistance. This study evaluated how prior population-level macrolide (especially clarithromycin) use affects H. pylori eradication success in naïve patients.

Methods: Retrospective, multicenter, ecological study. Multivariate logistic regression was performed with modified intention-to-treat effectiveness as the main outcome. Key variables included first-line clarithromycin-based treatments, therapy duration (7, 10, 14 days), proton pump inhibitor dose (low, standard, high), compliance (> 90%), and clarithromycin consumption (defined daily doses/1000 inhabitants/day, from the European Surveillance of Antimicrobial Consumption Network). Nested hierarchical models incorporated macrolide consumption, matched by year and country, and assessed the interaction between consumption and first-line empirical treatments from the European Registry on H. pylori Management (Hp-EuReg).

Results: The study included 27,549 naïve patients from 23 countries with macrolide consumption data from 2013 to 2022. Higher macrolide consumption, within 0 to 8 years before treatment, was associated with reduced treatment effectiveness. The eradication rate consistently decreased as macrolide consumption increased, particularly within the previous 4 years. The efficacy of triple-clarithromycin-metronidazole, triple-clarithromycin-amoxicillin, and some bismuth-quadruple therapies containing clarithromycin decreased with higher macrolide consumption. At the country level, higher population consumption of clarithromycin 2 years before treatment was associated with a decrease in eradication rates from 93% to 82%.

Conclusion: Higher macrolide consumption in the general population negatively impacts the effectiveness of first-line H. pylori regimens. These findings support that clarithromycin should only be administered as a susceptibility-based therapy, with the strongest negative impact of prior population-level exposure observed within 5 years and diminishing thereafter. ClincialTrials.gov number, NCT02328131.

Keywords: H. pylori; antibiotic consumption; clarithromycin; eradication treatment; macrolide; resistance.

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Conflict of interest statement

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé, and Biocodex. Olga P. Nyssen has served as a speaker or has received research funding from Mayoly and Allergan. The remaining authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Hierarchical models. The flow chart depicts the construction of three models used in this study: the core model, the model with macrolide consumption, and the model with macrolide consumption–treatment interaction. mITT, modified intention‐to‐treat effectiveness; PPI, proton pump inhibitor.
FIGURE 2
FIGURE 2
Flow chart of patient selection. A, amoxicillin; B, bismuth; BQT: Bismuth quadruple therapy prescribed with metronidazole, tetracycline and bismuth administered separately; C, clarithromycin; M, metronidazole; n, number of treatment‐naïve patients prescribed with an empirical therapy; Sc‐BQT, bismuth quadruple therapy prescribed with metronidazole, tetracycline and bismuth all administered in a single capsule (Pylera); T, tinidazole; PPI, proton pump inhibitor.
FIGURE 3
FIGURE 3
Effect on the modified intention‐to‐treat effectiveness of macrolide community consumption a year before clarithromycin‐based treatment. DDD, defined daily dose (expressed as number/1000 inhabitants/day); mITT, modified intention to treat effectiveness.
FIGURE 4
FIGURE 4
Effect of macrolide community consumption on clarithromycin‐based treatment effectiveness for different delay periods between consumption and treatment. Different consumption levels (0.6, 2, 4, 6, 8 DDD/1000 inhabitants/day) are color‐coded. The x‐axis represents delay times between consumption and treatment year. Treatment effectiveness by modified intention to treat (mITT) was analyzed. *Significant model improvement with a likelihood ratio test (LRT), p < 0.05. DDD, defined daily dose.
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