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.
Nyssen et al. (Thu,) studied this question.