Susceptibility-Guided Versus Empirical First-Line Therapy of Helicobacter pylori Infection in Adults: A Systematic...

Antimicrobial resistance undermines empirical first-line regimens for Helicobacter pylori. We compared susceptibility-guided therapy (SGT) versus empirical therapy in adults receiving first-line treatment, focusing on intention-to-treat (ITT) eradication.

We searched MEDLINE (PubMed), Web of Science, and Scopus from inception to 30 September 2025 for randomized controlled trials (RCTs) and non-randomized comparative studies (NRS) in adults with confirmed H. pylori. Interventions included phenotypic (culture/E-test) or genotypic (PCR) SGT applied to biopsy, stool, or gastric juice specimens; comparators were empirical regimens including bismuth quadruple therapy (BQT) and non-BQT options. The primary outcome was ITT eradication. We pooled risk ratios (RR) with DerSimonian-Laird random-effects, reported I²/τ², and derived 95% prediction intervals (PI). Subgroups were prespecified by comparator family (BQT vs. other) and specimen/method. Multi-arm studies combined empirical arms within family or split across distinct families.

Forty-two studies met inclusion criteria; all contributed ITT data. RCTs (k = 33) favored SGT over empirical therapy (pooled RR 1.09, 95% CI 1.05-1.13; I² 73%; 95% PI 0.92-1.30). NRS (k = 12) were directionally consistent (pooled RR 1.15, 95% CI 1.10-1.22; I² 75%; 95% PI 0.99-1.35). In RCTs, effects were neutral-to-modest vs. BQT (RR 1.03, 95% CI 0.97-1.10) and clearer vs. other empirical regimens (RR 1.12, 95% CI 1.06-1.18).

In adult first-line therapy, SGT achieves at least non-inferior-and often superior-eradication versus empirical regimens; the incremental benefit is attenuated where BQT is standard. These findings support selective, and increasingly justified, integration of susceptibility testing in settings with clinically relevant resistance.