Sex Differences in Helicobacter pylori Antimicrobial Resistance among 890 Subjects over 20 Years in a Korean Tertiary Hospital

Background/Aims: to better inform eradication strategies. Methods: colonies were isolated from gastric mucosal biopsy specimens were consecutively enrolled between 2003 and 2025. Minimum inhibitory concentration tests were performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using the agar dilution method. Results: A total of 890 subjects (510 males and 380 females) were included. Females demonstrated higher resistance rates to clarithromycin (50.0% vs 35.9%; p<0.001), metronidazole (45.3% vs 38.4%; p=0.041), levofloxacin (45.8% vs 33.7%; p<0.001), and moxifloxacin (45.5% vs 34.1%; p=0.001) than males did; however, no significant differences were found for amoxicillin or tetracycline. Stratified analyses revealed significant sex differences in resistance to clarithromycin and levofloxacin among secondary strains (clarithromycin, 80.9% vs. 67.2%, p=0.007; levofloxacin, 61.1% vs. 48.9%, p=0.034), whereas metronidazole resistance among primary strains showed only a marginal sex difference (40.8% vs. 33.2%, p=0.064). Females also demonstrated significantly higher rates of multidrug resistance, and resistance rates progressively increased over time in both sexes. Conclusions: infection showed higher resistance rates to clarithromycin, metronidazole, fluoroquinolones, and multidrug regimens than males. These findings highlight the importance of considering sex differences when interpreting antimicrobial resistance patterns and selecting eradication strategies. (ClinicalTrials.gov identifier NCT05247112).