Lack of Usefulness of Literature‐Based Helicobacter pylori Resistance Data for Predicting First‐Line Empirical Treatment Effectiveness in the European Registry on H. pylori Management (Hp‐ EuReg )

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Abstract
Background: Helicobacter pylori ( H. pylori ) infection causes gastritis, peptic ulcer disease, and gastric cancer. Without an effective vaccine, eradication therapy remains crucial. However, increasing antibiotic resistance compromises treatment effectiveness. Objective: To evaluate whether literature‐based resistance data could predict first‐line empirical treatment effectiveness. Methods: Resistance rates for clarithromycin, metronidazole, and levofloxacin were extracted from bibliographic reviews and estimated for three timeframes: the treatment year, the preceding year, and the last five years average. These rates (2008–2024) were matched with outcomes from the European Registry on H. pylori Management (Hp‐EuReg, WorldHpReg partner), a prospective real‐world study involving 40 countries. Analyses included Spearman's correlations, multivariate logistic regressions adjusted for demographic, clinical, and therapeutic‐related variables, bootstrap resampling stratified by eradication success, and Random Forest models. Results: Analysis included 37,659 patients receiving first‐line empirical treatment from 13 countries. Moderate negative correlations were observed between metronidazole and clarithromycin resistances for some regimens. In the regression model, including either contemporaneous or previous‐year resistance rates, clarithromycin resistance showed a negligible positive association, while metronidazole resistance was negatively associated. In regimen‐specific models, previous‐year clarithromycin resistance was positively associated with success in concomitant therapy, whereas higher five‐year mean clarithromycin resistance reduced eradication odds in quadruple clarithromycin–amoxicillin–bismuth therapy. Random Forest models identified compliance, proton‐pump inhibitor dose, regimen duration, and treatment as the strongest predictors of eradication, while resistance variables contributed minimally. Conclusion: Literature‐based resistance data are not useful for guiding real‐world first‐line H. pylori therapy, highlighting the need for individualized antibiotic susceptibility testing to obtain reliable resistance information. Trial Registration: ClinicalTrials.gov identifier: NCT02328131
Funding Information
  • Asociación Española de Gastroenterología
  • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
  • UK Research and Innovation (10058099)

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