Advances in the Management of Refractory Helicobacter pylori Infection: From Antimicrobial Resistance to Precision Eradication.

Helicobacter pylori infection represents a global public health issue strongly associated with gastric cancer and peptic ulcer disease. Increasing antibiotic resistance has markedly reduced the efficacy of standard eradication regimens, resulting in a growing prevalence of refractory infection and a critical clinical challenge. Refractory H pylori causes substantial patient discomfort and economic costs while worsening antimicrobial resistance. This review summarizes the mechanisms underlying eradication failure and advances in diagnostic approaches from conventional culture to molecular testing. We critically evaluate evidence for personalized salvage therapies based on drug susceptibility and novel acid-suppressive agents including potassium-competitive acid blockers. We propose an integrated clinical framework for diagnosis, treatment, and management and highlight future directions such as new antimicrobials, vaccines, digital health, and global antibiotic stewardship. We stress that a shift from empirical therapy to test-guided precision medicine is essential. Optimized diagnostics, individualized regimens, and comprehensive management will help achieve successful first-line eradication and control the further spread of antibiotic resistance.