Contemporary first-line pharmacological management of Helicobacter pylori infection

Eradication of Helicobacter pylori has become challenging as antimicrobial resistance has risen worldwide. The efficacy of clarithromycin-based triple therapy has declined to unacceptable levels in most regions, urging a fundamental evaluation of first-line treatment and emergence of several competing regimens whose relative benefits depend on local resistance and drug availability.

This review assesses the pharmacological basis and clinical evidence for contemporary first-line H. pylori eradication regimens in treatment-naive adults - bismuth quadruple, non-bismuth quadruple concomitant, potassium-competitive acid blocker-based, and rifabutin-based therapy. The impact of antimicrobial resistance, relative effectiveness of these regimens, current guideline recommendations, susceptibility-guided treatment, and safety and tolerability are examined. PubMed, the Cochrane Library, and Google Scholar were searched from January 2012 through August 2026, emphasizing the past five years.

Bismuth quadruple therapy is the preferred first-line option where available, given its resilience across resistance profiles; where bismuth is unavailable, concomitant quadruple therapy is appropriate provided dual clarithromycin-metronidazole resistance is low. Potassium-competitive acid blocker-based dual therapy is well-tolerated, but the evidence remains predominantly Asian. Susceptibility-guided therapy is ideal but constrained by limited testing and infrastructure. Improving outcomes depends less on new regimens than on resistance surveillance and susceptibility testing directing existing regimens where effective.