Efficacy and Safety of Quadruple Therapy With Semisynthetic Tetracycline for Helicobacter pylori Eradication: A Meta‐Analysis

BACKGROUND: High antibiotic resistance and limited tetracycline accessibility severely restrict the clinical application of classic bismuth quadruple therapy (BQT), creating an urgent demand for alternative regimens. METHODS: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to June 3, 2025, for trials comparing Helicobacter pylori eradication rates and adverse events between semisynthetic tetracycline-containing quadruple therapies and non-semisynthetic tetracycline controls. Statistical analysis was performed using RevMan 5.4. RESULTS: This meta-analysis included 11 randomized controlled trials (RCTs) and two retrospective studies (3667 participants). Semisynthetic tetracycline-containing regimens yielded significantly higher Hp eradication rates (per-protocol [PP] analysis: 91.8% vs. 85.6%; OR = 1.47, 95% CI: 1.08-2.00; p = 0.01) and fewer adverse events (32% vs. 39.2%; OR = 0.73, 95% CI: 0.56-0.94; p = 0.02). Minocycline-containing regimens were associated with a higher incidence of dizziness/headache (18.9% vs. 10.5%; OR = 2.22, 95% CI: 1.74-2.84; p < 0.00001). Subgroup PP analysis showed doxycycline-containing regimens outperformed controls (82.6% vs. 71.8%; OR = 1.56, 95% CI: 1.03-2.35; p = 0.04), and a 14-day course improved eradication rates (92.3% vs. 88.5%). CONCLUSIONS: Semisynthetic tetracycline-containing regimens exhibit favorable efficacy and safety for H. pylori eradication, representing promising alternatives to traditional tetracyclines in clinical practice.