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Minimizing the Impact of Antibiotic Resistance on Helicobacter pylori Eradication: From Mechanisms to Clinical Application

Xiaoying Zhou, Zizhuang Wang, Hui Yang, Yan Wang, Colm O’Moráin, Harry Hua‐Xiang Xia

Journal of Translational Gastroenterology, 2026

Abstract

Rising resistance in Helicobacter pylori to metronidazole, clarithromycin, and fluoroquinolones has significantly reduced eradication efficacy. This narrative review explores evidence-based strategies that minimize the impact of antibiotic resistance. Current practical approaches include empirical therapy (EMT), in which regimens are selected without individual susceptibility testing based on local or regional resistance patterns, previous antibiotic exposure, guideline recommendations, and expected effectiveness, and susceptibility-guided therapy (SGT), which avoids antibiotics to which the infecting strain is resistant. EMT does not simply exclude every antibiotic with a high resistance prevalence because regimen-level efficacy may remain high despite resistance to one component. When susceptibility testing is unavailable, optimized 14-day bismuth quadruple therapy is a guideline-preferred empirical regimen and can remain effective despite metronidazole resistance with adequate dosing and treatment duration. Rifabutin-based triple therapy provides an additional empirical or rescue option for selected patients without penicillin allergy. SGT is not universally superior to well-selected EMT, but may improve eradication rates in selected populations, particularly in settings with high clarithromycin resistance or where rapid molecular testing is available. However, susceptibility testing may be time-consuming, costly, and limited to only a few antibiotics. Emerging approaches…

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