Tetracycline for Helicobacter pylori eradication: a narrative review from quadruple to dual therapy

This review traces the evolving role of tetracycline in Helicobacter pylori eradication, from an adjunct in bismuth‑based quadruple therapy to a core component of modern vonoprazan‑tetracycline (VT) dual therapy, and identifies key knowledge gaps.

We conducted a narrative review of tetracycline‑based regimens, focusing on resistance rates, efficacy, safety, and dosing optimisation. Data were extracted from clinical trials, real‑world studies, meta‑analyses, and systematic reviews, especially those comparing VT with bismuth‑based quadruple therapy.

Tetracycline maintains extremely low resistance rates (1.2%-3.3% in China, 2.1% globally). As first-line treatment for penicillin-allergic patients, VT dual therapy achieved an eradication rate of 100% (per-protocol: 95.1% in a real-world study), with treatment-emergent adverse events significantly lower than bismuth-based quadruple therapy (14.0% vs. 48.0%). In patients with prior failure of amoxicillin-containing regimens, VT dual therapy achieved an eradication rate of 90.9%. Key unresolved issues include: lack of direct validation of TID tetracycline dosing in the VT dual therapy context (although TID is non-inferior to QID in bismuth-based quadruple therapy); absence of head-to-head comparisons between VT and VA dual therapy; and insufficient evidence for tetracycline use in special populations such as elderly or renally impaired patients.

Current data suggest that, VT dual therapy may represent a safe, simplified, effective option, especially for penicillin‑allergic or treatment‑failure patients. However, optimal tetracycline dosing in VT requires dedicated randomised controlled trials. Future guidelines will need robust evidence from dose‑optimisation studies, comparative trials with VA, and long‑term follow‑up.