WHY HELICOBACTER PYLORI TREATMENT FAILS IN PAKISTAN? ANTIBIOTIC RESISTANCE AND TRIPLETHERAPY FAILURE: A RAPID SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Background. Standard triple therapy (a proton-pump inhibitor, clarithromycin and amoxicillin or metronidazole) remains widely used for H. pylori in Pakistan, yet clinicians regularly see patients who are not cured. We asked how common antibiotic resistance is among Pakistani isolates and how often clarithromycin based triple therapy fails. Methods. We identified Pakistani primary studies through the reference list of a prior South Asian meta analysis and through targeted web searches (17 October 2026). Event counts were extracted by one reviewer. Proportions were pooled on the logit scale with a DerSimonian–Laird random-effects model; we also report Hartung–Knapp–Sidik–Jonkman (HKSJ) intervals, 95% prediction intervals, leave-one-out analyses and an Egger-type test. Results. Nine unique studies were included (six resistance studies, 656 isolates for clarithromycin; four triple therapy studies, 387 patients). Pooled clarithromycin resistance was 36.3% (95% CI 22.9–52.3; HKSJ 14.3 66.0; I² = 92.5%), with five of six studies above the 15% threshold at which guidelines advise against empirical clarithromycin. Pooled metronidazole resistance was 88.6% (63.4–97.2; k = 4) and fluoroquinolone resistance 35.6% (13.5–66.0; k = 3). Amoxicillin resistance was low but very imprecise (7.5%; 0.7–48.0; k = 3). Clarithromycin-based triple therapy failed in 25.2% of patients (17.8–34.3; HKSJ 14.0–41.0; k = 4). In the one study that linked resistance to outcome, 28 of 30 treatment failures involved clarithromycin-resistant strains. Conclusions. In the Pakistani data we could retrieve, clarithromycin resistance is well above the guideline threshold, metronidazole resistance is near-universal, and fluoroquinolones are not a safe fallback. These findings support moving away from empirical clarithromycin triple therapy and toward susceptibility-guided or bismuth-based regimens. The evidence base is small, heterogeneous and mostly from Karachi, so the pooled figures should be read as a warning signal rather than a national estimate.