S2119 Tailored Culture/PCR-Guided Therapy Beats Concomitant Quadruple for H. pylori With 9% Cure Rate and 33% Fewer Adverse Events: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Rising dual clarithromycin- and metronidazole-resistance has pushed empiric concomitant quadruple therapy for Helicobacter pylori to the brink of unacceptable failure rates, forcing gastroenterologists to balance cure against collateral antibiotic exposure. Culture-guided or 23S-rRNA PCR-guided regimens promise precision—prescribing only what each strain requires—yet their true advantage over standard therapy has remained uncertain across heterogeneous populations. To resolve this, we pooled 5 randomized controlled (RCTs) comparing susceptibility-tailored therapy with 10–14-day concomitant therapy, interrogating both efficacy and safety. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane Library identified RCTs comparing tailored vs concomitant therapy for H. pylori eradication through May 2025. Data were analyzed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using RoB 2.0. Results: Five RCTs encompassing 1,552 treatment-naïve adults (tailored = 763, concomitant = 789) met inclusion. Tailored (culture/PCR-guided) therapy produced a significantly higher primary eradication rate than concomitant therapy (RR 1.09, 95% CI 1.02–1.16; I² = 42%, P = 0.006). Any adverse event occurred in 21.7% (163/751) of tailored-treated versus 31.6% (246/778) of concomitant-treated patients, yielding a 33% relative risk reduction with tailoring (RR 0.67, 95% CI 0.47–0.95; I² = 70%, P = 0.03). Moderate–severe events were infrequent and statistically comparable (RR 0.50, 95% CI 0.12–2.05; I² = 57%, P = 0.34). Conclusion: The combined gains in eradication efficacy and tolerability translate into fewer retreatments, endoscopy visits, and antibiotic courses, directly benefiting patients and stewardship efforts. Where resistance profiling is feasible, culture or rapid PCR testing should shift from “optional” to preferred first-line practice, replacing the shotgun quadruple approach. Although upfront logistics require attention, the clinical payoff—higher cure, lower toxicity, and slower resistance accrual—strongly supports upgrading susceptibility-guided therapy in future guidelines for H. pylori management.