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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Precision therapy guided by genotypic antibiotic resistance for Helicobacter pylori eradication: A prospective, randomized controlled trial
Yan Xu, Jing-Wen Hao, Cong-Cong Min, Lin Yang, Cui-Ping Ma, Chao Shi, Tao Mao, Zi-Bin Tian, Tong Wang, Ya-Nan Yu
Yan Xu, Jing-Wen Hao, Cong-Cong Min, Lin Yang, Tao Mao, Zi-Bin Tian, Ya-Nan Yu, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Cui-Ping Ma, College of Chemistry and Molecular Engineering, College of Biological Engineering, Qingdao Key Laboratory of Rapid Nucleic Acid Detection, Qingdao University of Science and Technology, Qingdao 266042, Shandong Province, China
Chao Shi, Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Qingdao University, Qingdao 266071, Shandong Province, China
Tong Wang, Department of Epidemiology and Health Statistics, Qingdao University, Qingdao 266071, Shandong Province, China
Co-first authors: Yan Xu and Jing-Wen Hao.
Author contributions: Xu Y and Hao JW were responsible for writing the original article and organizing the data and should be regarded as first co-authors. Yu YN designed this study and was responsible for its implementation; Min CC, Yang L, Ma CP, Shi C, Mao T, and Tian ZB contributed to patient recruitment, follow-up and acquisition of data; Wang T was responsible for data analysis; All authors reviewed the manuscript and approved the final version of this report.
Supported by Qilu Health Outstanding Young Talent Cultivation Project, No. QDFY-3839.
Institutional review board statement: The study was reviewed and approved by the Affiliated Hospital of Qingdao University Institutional Review Board (Approval No. QYFYKYLL 923711921).
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is ChiCTR2500095247.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no competing interests.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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: Ya-Nan Yu, MD, Professor, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China.
yananyu@qdu.edu.cn
Received: June 16, 2025
Revised: July 22, 2025
Accepted: October 9, 2025
Published online: November 14, 2025
Processing time: 153 Days and 18.8 Hours
BACKGROUND
Helicobacter pylori (H. pylori) is a Gram-negative bacillus classified as a Group I carcinogen by the World Health Organization. However, the efficacy of eradication therapies has declined in recent years, primarily due to the increasing prevalence of antibiotic resistance. The Maastricht VI/Florence Consensus Report highlights the importance of tailoring treatment strategies to local epidemiological data and individual antimicrobial susceptibility patterns.
AIM
To investigate the efficacy of precision-guided first-line therapy for H. pylori infection using genotypic antibiotic susceptibility testing (G-AST).
METHODS
This single-center randomized controlled trial enrolled 194 H. pylori-positive patients at a tertiary hospital in Qingdao, China (October 2022-August 2024). Participants were randomized to receive either a 14-day bismuth quadruple therapy (BQT: Amoxicillin, clarithromycin, esomeprazole, and bismuth) or a 14-day G-AST-guided regimen with tailored antibiotics (clarithromycin, levofloxacin, or tetracycline). Treatment efficacy and adverse events were compared between groups using intention-to-treat (ITT) and per-protocol (PP) analyses. Primary and secondary outcomes were analyzed with χ² tests.
RESULTS
Of 194 patients enrolled, 180 (92.8%) completed the study as planned. In the ITT analysis, the eradication rate was higher in the G-AST group than in the BQT group [92.8% (95%CI: 85.8-96.5) vs 79.4% (95%CI: 70.3-86.2), P = 0.007], with a risk difference of 13.4% (95%CI: 3.7-23.2). In the PP analysis, eradication rates were 97.8% (95%CI: 92.4-99.4) in the G-AST group and 84.1% (95%CI: 75.1-90.3) in the BQT group (P = 0.001), with a risk difference of 13.7% (95%CI: 5.5-23.0). Adverse event incidence did not differ significantly between groups (30.9% vs 28.9%, P = 0.754).
CONCLUSION
G-AST-guided therapy yielded higher eradication rates than empirical BQT in first-line H. pylori treatment without increasing adverse events, supporting the clinical utility of individualized, resistance-based therapy.
Core Tip: Antibiotic resistance in Helicobacter pylori (H. pylori) has reduced the efficacy of traditional eradication regimens. This randomized controlled trial in northern China used rapid genotypic antibiotic susceptibility testing (G-AST) to guide first-line therapy by tailoring regimens according to detected resistance mutations, including tetracycline for dual-resistant strains. G-AST-guided therapy significantly improved eradication rates compared with standard bismuth quadruple therapy without increasing adverse events. These findings demonstrate the feasibility and clinical benefit of molecular-guided personalized treatment, offering a promising strategy to overcome antibiotic resistance in H. pylori infection.
