Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2023; 29(2): 390-409
Published online Jan 14, 2023. doi: 10.3748/wjg.v29.i2.390
Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review
Pedro Vieira de Moraes Andrade, Yan Mosca Monteiro, Ethel Zimberg Chehter
Pedro Vieira de Moraes Andrade, Yan Mosca Monteiro, Ethel Zimberg Chehter, Department of Gastroenterology, Faculdade de Medicina do ABC, Santo André 09060-650, SP, Brazil
Author contributions: de Moraes Andrade PV, Monteiro YM, and Chehter EZ conceived, designed, wrote, and revised the manuscript; All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pedro Vieira de Moraes Andrade, Academic Research, Department of Gastroenterology, Faculdade de Medicina do ABC, Av. Lauro Gomes 2000, Santo André 09060-650, SP, Brazil. pvieira.m.andrade@gmail.com
Received: August 12, 2022
Peer-review started: August 12, 2022
First decision: September 2, 2022
Revised: September 12, 2022
Accepted: December 1, 2022
Article in press: December 1, 2022
Published online: January 14, 2023
Processing time: 146 Days and 12.5 Hours
Abstract
BACKGROUND

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.

AIM

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

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Helicobacter pylori; Refractory infection; Third-line therapy; Rescue therapy; Eradication; Treatment

Core Tip: The eradication of Helicobacter pylori is widely discussed given the high prevalence and incidence of its infection. Even with established criteria in the V Maastricht Consensus for the eradication of infection and treatment algorithms for choosing first-line and second-line therapeutic regimens, therapeutic failure is frequent. Therefore, establishing safe, effective, and accessible third-line and rescue therapies for patients in need of eradication is necessary in the management of such infection. Due to this need, the present systematic review performed a systematic review evaluating the efficacy and safety of rescue therapies against refractory Helicobacter pylori infection.