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
ARTICLE HIGHLIGHTS
Research background

The eradication of Helicobacter pylori (H. pylori) is widely discussed given the high prevalence and incidence of its infection and since therapeutic failure is frequent establishing safe, effective, and accessible third-line and rescue therapies for patients in need of eradication is necessary in the management of such infection.

Research motivation

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.

Research objectives

To evaluate the efficacy and safety of rescue therapies against refractory H. pylori infection and to establish safe, effective, and accessible third-line and rescue therapies for patients in need of eradication.

Research 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. Different descriptors were used throughout the study for maximization of the database, namely: Helicobacter pylori multidrug resistance and rescue therapy; H. pylori multiresistant and rescue treatment; Helicobacter pylori multidrug resistance and rescue treatment; Helicobacter pylori rescue therapy; Helicobacter pylori and third line treatment; and fourth line therapy and Helicobacter pylori. Upon reliable data detection and collection, a statistical analysis was performed to compare eradication rates both by intention to treat and per protocol, and adverse effects found in the different therapeutic approaches to assess their feasibility in clinical practice.

Research results

Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for mean eradication rate analysis as third-line treatment. Rifabutin-, sitafloxacin-, levofloxacin-, and metronidazole-based triple therapies, bismuth quadruple therapy (BQT), BQT, three-in-one, Pylera® (BQT-Pylera), non-BQT, and susceptibility-guided therapy were assessed. Furthermore, sitafloxacin-based and rifabutin-based triple therapies achieved higher efficacy than other therapeutic approaches.

Research conclusions

We managed to create a recommendation flowchart regarding rescue therapies in different situations, such as regions with previously known resistance to macrolides and in areas where bismuth is unavailable. These results can aid the clinical management of the H. pylori infection and furthermore prevent an increase in resistance rates to different antibiotics.

Research perspectives

New clinical trials should be developed in order to assess the efficacy of regimens with different associations between antimicrobials and vonoprazan, based on the promising results reported from the comparison between conventional proton pump inhibitors and vonoprazan.