Empirical therapy versus tailored therapy for Helicobacter pylori infection? A systematic review

The global decline in the efficacy of empirical treatment for Helicobacter pylori eradication driven largely by rising antibiotic resistance has prompted increasing interest in tailored therapeutic approaches. Tailored therapy, guided by antimicrobial susceptibility testing (AST), offers a theoretically superior strategy by enabling selection of effective, resistance-informed regimens. However, the comparative effectiveness of tailored versus empirical therapy remains uncertain across different clinical contexts and geographic regions. This systematic review was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search of PubMed, Embase, Web of Science, and CENTRAL was performed to identify studies published inception to August 2025 that directly compared empirical and AST-guided tailored therapy for H. pylori eradication. Eligible studies included randomized controlled trials and observational comparative studies reporting intention-to-treat or per-protocol eradication rates. Study selection, data extraction, and risk-of-bias assessments (Newcastle-Ottawa Scale) were performed independently by two reviewers. Fifty-five studies comprising approximately 14,940 patients were included. Tailored therapy demonstrated higher eradication rates in 85% of first-line studies, with PCR-guided regimens achieving the most consistent success. In rescue settings, tailored therapy showed variable outcomes, with several studies reporting comparable efficacy to empirical quadruple therapy. Overall, tailored regimens were more effective in high-resistance settings and when guided by timely and accurate AST. The summarized evidence suggests that tailored therapy, guided by antimicrobial susceptibility testing, often achieves higher H. pylori eradication rates than empirical therapy, especially as a first-line approach. However, the heterogeneity in study design and outcomes necessitates careful consideration when applying these findings. Tailored therapy appears to be a valuable strategy to optimize H. pylori eradication, potentially combating rising antibiotic resistance.