An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection.

Introduction: Eradication of Helicobacter pylori (H. pylori) becomes more challenging due to increasing antimicrobial resistance. Consequently, the performance of clarithromycin-containing triple therapies is now declining to unacceptable levels and should be abandoned unless a prior susceptibility test precludes clarithromycin resistance.Areas covered: This review summarizes updated evidence concerning new and advancing pharmacotherapy options for H. pylori eradication.Expert opinion: Due to the declining efficacy of legacy triple therapies, most guidelines recommend bismuth quadruple therapy as the best initial empiric treatment. Concomitant, sequential and hybrid therapies are remarkable bismuth-free quadruple options, provided that dual clarithromycin-metronidazole resistance is low. Levofloxacin-, rifabutin-, furazolidone- and sitafloxacin-containing regimens remain useful, particularly as salvage options. To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation. Molecular testing methods promise convenient characterization of H. pylori antibiotic susceptibility. High-dose dual therapy (proton-pump-inhibitor plus amoxicillin) and vonoprazan, a more potent acid inhibitor that likely enhances the activity of amoxicillin, are promising alternatives that could decrease misuse of antibiotics. Addition of certain probiotics could somewhat increase the performance of H. pylori eradication regimens, while improving tolerability.