Abstract

Helicobacter pylori (H. pylori) infects over half of the world’s population and causes peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication rates for standard clarithromycin-based triple therapy, once above 90%, have fallen below 80% in most high-prevalence regions as clarithromycin resistance has climbed to between 15% and 50% worldwide. In this narrative review, sources published between 1998 and 2026 were synthesized, identified through a structured search of data bases using validated MeSH terms and free-text synonyms, and screened against eight pre-specified inclusion criteria. In the most recent first-line network meta-analyses, vonoprazan-based therapy ranks highest for both efficacy and safety, an advantage attributable to its CYP2C19-independent mechanism of acid suppression. Susceptibility-guided therapy was found to be most useful in the rescue setting, where secondary resistance was considerably higher, rather than as a first-line strategy in regions that have already moved to optimized empirical quadruple regimens. Adherence was found to be the strongest modifiable determinant of outcome (odds ratio 6.3 for adequate versus inadequate compliance), and adjunctive probiotics raise eradication by roughly 10% while markedly reducing adverse events. International guidelines broadly favor bismuth quadruple therapy as the preferred first-line option, though they differ appreciably on eradication indications and second-line preferences. The continuing gap between trial efficacy and real-world results stems from incomplete guideline uptake, suboptimal compliance, and insufficient attention to local resistance patterns rather than from any limitation of the available drugs.

Key words: Helicobacter pylori, eradication therapy, antibiotic resistance, bismuth quadruple therapy, vonoprazan, narrative review