Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review

Due to increasing resistance rates of Helicobacter pylori (H. pylori) to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H. pylori infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory H. pylori infection.

To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H. pylori infection.

A systematic search of available rescue treatments for refractory H. pylori infection was conducted on the National Library of Medicine's PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H. pylori infection rescue therapies were included.

Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera^® (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.

We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.