Susceptibility-guided versus empirical therapy for Helicobacter pylori infection: a meta-analysis of randomized controlled trials.

BACKGROUND

The rising global resistance to clarithromycin has substantially reduced the efficacy of empirical Helicobacter pylori eradication regimens. Whether susceptibility-guided tailored therapy offers superior clinical outcomes over empirical therapy remains debated.

METHODS

We systematically searched PubMed, Web of Science, Cochrane Library, Embase, and Scopus from inception to 1 March 2026 for randomized controlled trials comparing susceptibility-guided therapy with empirical therapy for H. pylori infection. The primary outcome was eradication rate; secondary outcomes included any adverse event and specific adverse events. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

RESULTS

29 studies were included. Susceptibility-guided therapy significantly improved eradication rates compared with empirical therapy (OR = 1.83, 95% CI: 1.38-2.43; I2 = 74.4%). The benefit was most pronounced in first-line treatment (OR = 2.02, 95% CI: 1.43-2.85), with culture-based phenotypic testing (OR = 2.02, 95% CI: 1.45-2.83), and when compared with triple therapy (OR = 3.41, 95% CI: 2.00-5.80). Ten-day regimens showed the most consistent effect (OR = 1.87, 95% CI: 1.17-3.01; I2 = 29.9%). Susceptibility-guided therapy also reduced the risk of any adverse event (OR = 0.75, 95% CI: 0.57-0.99), particularly abdominal pain, diarrhea, nausea/vomiting, dizziness, abdominal distension, and constipation.

CONCLUSIONS

Pretreatment antimicrobial susceptibility-guided tailored therapy is more effective than empirical therapy for first-line H. pylori eradication and is associated with fewer adverse events. These findings support integrating susceptibility testing into routine clinical practice.