•H. pyloriculture and PCR were performed from the same gastroduodenal biopsy•Primary clarithromycin resistance remained below 15% during the 22-year of study•Primary levofloxacin resistance showed an alarming increase between 2000 and 2021•Knowledge of local antimicrobial resistance allowed optimizing empirical treatments•A tailored treatment for H. pyloriavoided the emergence of antibiotic resistances