Abstract
BACKGROUND: Helicobacter pylori (H. pylori) infection is a global health concern, affecting approximately two-thirds of the world's population. Standard first-line treatment regimens often fail, necessitating alternative rescue therapies. OBJECTIVES: This review aims to evaluate the efficacy and safety of newer treatment regimens in patients who have failed initial H. pylori eradication therapy. METHODS: A comprehensive literature search was conducted in PubMed, the Cochrane Library, and Embase. Inclusion criteria were randomized controlled trials (RCTs) published after 2010, involving patients with previous H. pylori treatment failure and interventions with vonoprazan-based therapy, high-dose PPI-amoxicillin dual therapy (HDDT), or rifabutin-containing triple therapy. RESULTS: 10 RCTs were included. HDDT demonstrated high eradication rates (81.3% to 89.2%), particularly when combined with metronidazole (92.6%), although at an increased frequency of adverse events. Vonoprazan-based regimens achieved comparable or higher eradication rates (83.3% to 89.5%) compared to PPI-based therapies, with similar adverse events. Rifabutin-containing triple therapy showed high efficacy (80.7% to 100%), particularly in patients with a history of multiple treatment failures, and it was associated with lower adverse events compared to bismuth-containing regimens. CONCLUSIONS: HDDT, vonoprazan-based therapy, and rifabutin-based therapy have proven to be effective and safe rescue regimens for treating H. pylori infection. Additional large-scale randomized studies are needed to determine the optimal doses and durations of these regimens to achieve the highest eradication rate with the lowest incidence of adverse events among patients with refractory H. pylori infections globally.