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

## TL;DR

High use of macrolide antibiotics in the population reduces the success of Helicobacter pylori treatment, especially when used within the last few years.

## Contribution

This study shows that population-level macrolide consumption significantly impacts H. pylori eradication success in treatment-naïve patients.

## Key findings

- Higher macrolide consumption in the general population is linked to lower eradication rates of H. pylori.
- Clarithromycin-based therapies become less effective as population-level macrolide use increases.
- The strongest negative impact of prior macrolide use is observed within 5 years before treatment.

## Abstract

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.

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).

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%.

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.