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

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.