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Hamze H, Payne M, Stefanovic A, Lowe CF, Romney MG, Matic N. Helicobacter pylori culture positivity and antimicrobial susceptibility profiles (Vancouver, Canada). J Antimicrob Chemother 2025:dkaf114. [PMID: 40202867 DOI: 10.1093/jac/dkaf114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 03/20/2025] [Indexed: 04/11/2025] Open
Abstract
INTRODUCTION Helicobacter pylori is associated with gastrointestinal diseases including gastritis and peptic ulcers. Despite its significance, there is a scarcity of antimicrobial susceptibility testing (AST) data available for this organism in North America. OBJECTIVES The aim of this study was to assess the AST profile and identify factors associated with H. pylori culture positivity in a cohort of patients with refractory H. pylori undergoing gastric biopsies. METHODS We retrospectively reviewed gastric biopsy specimens received for culture between July 2009 and February 2023. We analyzed specimen transport time, Gram smear results, direct urease test findings, culture positivity and AST profiles. Using gradient strip methodology and European Committee on Antimicrobial Susceptibility Testing breakpoints, AST was conducted for amoxicillin, clarithromycin, metronidazole, levofloxacin and tetracycline. RESULTS Of 579 biopsy samples received for H. pylori culture, 228 (39.4%) tested positive. Samples transported within <1 h had significantly higher odds (1.81 times, P < 0.015) of being culture positive compared to those with longer transport times. Smear-positive samples had substantially higher odds (18.8 times, P < 0.001) of culture positivity compared to smear-negative. Urease-positive samples demonstrated notably higher odds (7.7 times, P < 0.001) of culture positivity compared to urease-negative samples. The collection of isolates from gastric biopsies showed susceptibility rates of 97.3% to amoxicillin, 99.1% to tetracycline, 50.4% to levofloxacin, 25.9% to metronidazole and 12.9% to clarithromycin. CONCLUSIONS Short sample transport time was associated with improved H. pylori recovery rates. In this cohort of refractory H. pylori cases, susceptibility rates were high for amoxicillin and tetracycline and low for clarithromycin, metronidazole and levofloxacin. Susceptibility rates remained stable over time.
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Affiliation(s)
- Hasan Hamze
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
| | - Michael Payne
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
- Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, 1081 Burrard St., Vancouver, Bc V6Z 1Y6, Canada
| | - Aleksandra Stefanovic
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
- Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, 1081 Burrard St., Vancouver, Bc V6Z 1Y6, Canada
| | - Christopher F Lowe
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
- Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, 1081 Burrard St., Vancouver, Bc V6Z 1Y6, Canada
| | - Marc G Romney
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
- Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, 1081 Burrard St., Vancouver, Bc V6Z 1Y6, Canada
| | - Nancy Matic
- Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, Bc V6T 1Z7, Canada
- Department of Pathology and Laboratory Medicine, St. Paul's Hospital, Providence Health Care, 1081 Burrard St., Vancouver, Bc V6Z 1Y6, Canada
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Tang B, Sun Y, Song Y, Zhao G, Yue M. Global prevalence of acquired antimicrobial resistance genes in Helicobacter pylori revealed by whole-genome sequence. J Infect 2025; 90:106483. [PMID: 40187692 DOI: 10.1016/j.jinf.2025.106483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Affiliation(s)
- Biao Tang
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
| | - Yuhan Sun
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
| | - Yu Song
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
| | - Guoping Zhao
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China; National Genomics Data Center & Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China; Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, China.
| | - Min Yue
- Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
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Zhou W, Cheng H, Li M, Zhang R, Li Z, Sun G, Zhang D, Liu X, Pei Y. Effectiveness of Susceptibility-Guided Therapy for Helicobacter pylori Infection: A Retrospective Analysis by Propensity Score Matching. Infect Drug Resist 2025; 18:1149-1159. [PMID: 40027915 PMCID: PMC11871851 DOI: 10.2147/idr.s498052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 02/19/2025] [Indexed: 03/05/2025] Open
Abstract
Purpose This study evaluates and compares the eradication rates of Helicobacter pylori (H. pylori) achieved through susceptibility-guided therapy (SGT) based on resistance genotyping and empirical therapy (ET). Patients and Methods A retrospective study was conducted at Beijing Chaoyang Hospital (2021-2023) on patients with H. pylori infection receiving initial eradication therapy. Resistance genotypes for clarithromycin and levofloxacin were identified using fluorescent PCR of gastric biopsy samples. Patients underwent a 14-day bismuth-containing quadruple therapy (BQT) and were evaluated via the C13 urea breath test (UBT). Based on genotyping or clinical judgment, 550 patients were assigned to SGT (n = 125) or ET (n = 425). The SGT group received personalized treatment based on genotype testing results, avoiding the use of antibiotics to which the bacteria were resistant. The ET group received the standard bismuth-containing quadruple therapy (BQT). Additionally, 29 ET patients underwent follow-up genotypic testing and eradication rates were analyzed retrospectively. Results SGT achieved higher eradication rates than ET (ITT: 94.4% vs 86.1%, P = 0.012; PP: 95.2% vs 87.6%, P = 0.016). In levofloxacin-resistant strains, SGT showed significantly higher eradication rates in the PP analysis (95.7% vs 50.0%, P = 0.049). Conclusion SGT exhibited remarkably superior eradication rates, notably in levofloxacin-resistant strains, proposing a compelling alternative for the treatment of H. pylori, particularly in instances of antimicrobial resistance.
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Affiliation(s)
- Wenyue Zhou
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Haoxuan Cheng
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Miaomiao Li
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Ruian Zhang
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Zhiren Li
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Guangyong Sun
- Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, 100024, People’s Republic of China
| | - Dong Zhang
- Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Chaoyang District, Beijing, 100024, People’s Republic of China
| | - Xinjuan Liu
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yanxiang Pei
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
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Pan KF, Li WQ, Zhang L, Liu WD, Ma JL, Zhang Y, Ulm K, Wang JX, Zhang L, Bajbouj M, Zhang LF, Li M, Vieth M, Quante M, Wang LH, Suchanek S, Mejías-Luque R, Xu HM, Fan XH, Han X, Liu ZC, Zhou T, Guan WX, Schmid RM, Gerhard M, Classen M, You WC. Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial. Nat Med 2024; 30:3250-3260. [PMID: 39079993 DOI: 10.1038/s41591-024-03153-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Accepted: 06/25/2024] [Indexed: 09/07/2024]
Abstract
Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .
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Affiliation(s)
- Kai-Feng Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Wen-Qing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Lian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Jun-Ling Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kurt Ulm
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | | | - Lei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Monther Bajbouj
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | | | - Ming Li
- Health Bureau of Linqu County, Weifang, China
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Michael Quante
- School of Medicine and Health, Technical University of Munich, Munich, Germany
- Freiburg: Klinik für Innere Medizin II, Universitätsklinikum Freiburg, Freiburg, Germany
| | - Le-Hua Wang
- Health Bureau of Linqu County, Weifang, China
| | - Stepan Suchanek
- Department of Medicine & Department of Gastrointestinal Oncology, 1st Faculty of Medicine, Charles University and Military University Hospital, Prague, Czech Republic
| | - Raquel Mejías-Luque
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Heng-Min Xu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiao-Han Fan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xuan Han
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zong-Chao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei-Xiang Guan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Roland M Schmid
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Markus Gerhard
- School of Medicine and Health, Technical University of Munich, Munich, Germany.
| | - Meinhard Classen
- School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Wei-Cheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
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Morad Kasani S, Mofid M, Navidifar T, Golab N, Parvizi E, Badmasti F, Sholeh M, Beig M. Insights into Helicobacter pylori macrolide resistance: a comprehensive systematic review and meta-analysis. Front Microbiol 2024; 15:1481763. [PMID: 39539713 PMCID: PMC11557415 DOI: 10.3389/fmicb.2024.1481763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/10/2024] [Indexed: 11/16/2024] Open
Abstract
Background Helicobacter pylori infection is a primary global health concern. However, the widespread use of antibiotics, particularly macrolides such as clarithromycin, has increased resistance among H. pylori strains. This study aimed to investigate the prevalence of macrolide resistance in H. pylori in different world regions. Methods This systematic literature search was performed using the appropriate search syntax after searching PubMed, Embase, Web of Science, and Scopus databases between May 2015 and December 2023. Statistical analysis was performed using Pooled and random effects model in R and the metafor package. Results A total of 7,768 articles were retrieved. After a thorough evaluation, 155 studies (by 178 reports) were finally eligible for inclusion in this systematic review and meta-analysis. According to the results, the majority of studies (178 reports from 43 countries) assessed clarithromycin susceptibility, with a pooled prevalence of 33.3% and high heterogeneity between studies (I 2 = 98.57%, p < 0.001). The rate of erythromycin resistance was moderate (22.8%, 10 reports), while azithromycin resistance was 34.4% (4 reports). Subgroup analysis revealed significant differences in the prevalence of resistance based on geographic location, continent, and year of publication. Clarithromycin resistance increased from 29.1% (2015-2019) to 36.5% (2020-2023). Conclusion This study highlights the critical challenges of macrolide resistance in treating H. pylori infection. The high prevalence and geographic variation underscore the need for tailored treatment strategies based on regional resistance patterns. Furthermore, continuously monitoring resistance trends and investigating contributing factors are essential to optimize treatment. Systematic review registration https://www.crd.york.ac.uk/prospero; CRD42024557749.
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Affiliation(s)
| | - Maryam Mofid
- School of Medicine, Hamadan University of Medical Science, Hamadan, Iran
| | - Tahereh Navidifar
- Department of Basic Sciences, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran
| | - Narges Golab
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Elnaz Parvizi
- Department of Microbiology, Science and Research Branch, Islamic Azad University, Fars, Iran
| | - Farzad Badmasti
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Mohammad Sholeh
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
- Student Research Committee, Pasteur Institute of Iran, Tehran, Iran
| | - Masoumeh Beig
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
- Student Research Committee, Pasteur Institute of Iran, Tehran, Iran
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Xie J, Peng J, Liu D, Zeng R, Qiu J, Shen L, Gong X, Liu D, Xie Y. Treatment failure is a key factor in the development of Helicobacter pylori resistance. Helicobacter 2024; 29:e13091. [PMID: 38780150 DOI: 10.1111/hel.13091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/11/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Helicobacter pylori eradication failure influences its antibiotic resistance. AIMS This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. MATERIALS AND METHODS This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. RESULTS The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. CONCLUSION The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.
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Affiliation(s)
- Jinliang Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Jianxiang Peng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Dingwei Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Rong Zeng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Jiayu Qiu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Liting Shen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Xiaomin Gong
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Dongsheng Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
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Ng HK, Chua KH, Kee BP, Chuah KH, Por LY, Puah SM. Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia. J Med Microbiol 2024; 73. [PMID: 38712922 DOI: 10.1099/jmm.0.001832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2024] Open
Abstract
Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy.Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population.Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23).Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context.Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.
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Affiliation(s)
- Heng Kang Ng
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Kek Heng Chua
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Boon Pin Kee
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Kee Huat Chuah
- Department of Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Lip Yee Por
- Department of Computer System and Technology, Faculty of Computer Science and Information Technology, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Suat Moi Puah
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
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Ayaş M, Oktem-Okullu S, Özcan O, Kocagöz T, Gürol Y. Exploring the Molecular Mechanisms of Macrolide Resistance in Laboratory Mutant Helicobacter pylori. Antibiotics (Basel) 2024; 13:396. [PMID: 38786125 PMCID: PMC11117244 DOI: 10.3390/antibiotics13050396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/18/2024] [Indexed: 05/25/2024] Open
Abstract
Resistance to clarithromycin, a macrolide antibiotic used in the first-line treatment of Helicobacter pylori infection, is the most important cause of treatment failure. Although most cases of clarithromycin resistance in H. pylori are associated with point mutations in 23S ribosomal RNA (rRNA), the relationships of other mutations with resistance remain unclear. We examined possible new macrolide resistance mechanisms in resistant strains using next-generation sequencing. Two resistant strains were obtained from clarithromycin-susceptible H. pylori following exposure to low clarithromycin concentrations using the agar dilution method. Sanger sequencing and whole-genome sequencing were performed to detect resistance-related mutations. Both strains carried the A2142G mutation in 23S rRNA. Candidate mutations (T1495A, T1494A, T1490A, T1476A, and G1472T) for clarithromycin resistance were detected in the Mutant-1 strain. Furthermore, a novel mutation in the gene encoding for the sulfite exporter TauE/SafE family protein was considered to be linked to clarithromycin resistance or cross-resistance, being identified as a target for further investigations. In the Mutant-2 strain, a novel mutation in the gene that encodes DUF874 family protein that can be considered as relevant with antibiotic resistance was detected. These mutations were revealed in the H. pylori genome for the first time, emphasizing their potential as targets for advanced studies.
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Affiliation(s)
- Meltem Ayaş
- Department of Medical Laboratory Techniques, Vocational School of Health Services, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey
- Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey;
| | - Sinem Oktem-Okullu
- Department of Medical Microbiology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey; (S.O.-O.); (Y.G.)
| | - Orhan Özcan
- TrioScience Biotechnology, 34000 Istanbul, Turkey;
| | - Tanıl Kocagöz
- Department of Medical Biotechnology, Institute of Health Sciences, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey;
- Department of Medical Microbiology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey; (S.O.-O.); (Y.G.)
| | - Yeşim Gürol
- Department of Medical Microbiology, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey; (S.O.-O.); (Y.G.)
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Peypar MH, Yeganeh AV, Ramazani A, Alizadeh A, Abdorrashidi M, Tohidinia A, Shamlou MM, Heiat M. Oral immunotherapy for Helicobacter pylori: Can it be trusted? A systematic review. Helicobacter 2024; 29:e13067. [PMID: 38514932 DOI: 10.1111/hel.13067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 02/19/2024] [Accepted: 03/08/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a rod-shaped, gram-negative, microaerophilic bacterium that can be identified by gram staining. Its relationship with cancer is significant since it is involved in approximately 80% of gastric cancers and 5.5% of all malignant cancers. Two lines of treatment have been defined for H. pylori, but almost 40% of patients do not respond to the first line. Recent trials have investigated oral Immunotherapy as a new treatment method. The aim of this systematic review was to investigate the potential effects of oral Immunotherapy on eradication rate of H. pylori in human studies. METHODS The systematic review was performed according to PRISMA guidelines. We searched online databases, including Scopus, PubMed, and Web of Science (ISI). Our search strategy was limited to English articles and studies on human populations that use oral immunotherapy for H. pylori. RESULTS The total number of primary research records in different databases was 2775. After removing duplicate articles (n = 870), we excluded 1829 for reasons including non-human studies, irrelevance to our study objective, non-English language, or lack of information. Of the remaining 76 articles, only seven had sufficient information, and the rest were excluded. The studies were divided into two groups: those that used bovine antibody and those that used immunoglobulin Y to eradicate H. pylori. CONCLUSION In the group of Immunoglobulin Y, three out of four studies suggest that using Immunoglobulin Y for the treatment of H. pylori infection is significant. However, the group using bovine antibody for the treatment of H. pylori infection has various results, as two out of three studies concluded that bovine antibody therapy is not significant.
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Affiliation(s)
| | - Amin Vesal Yeganeh
- Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Ramazani
- Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Arman Alizadeh
- Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mahdi Abdorrashidi
- Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | | | - Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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10
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Hasanuzzaman M, Bang CS, Gong EJ. Antibiotic Resistance of Helicobacter pylori: Mechanisms and Clinical Implications. J Korean Med Sci 2024; 39:e44. [PMID: 38288543 PMCID: PMC10825452 DOI: 10.3346/jkms.2024.39.e44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
Helicobacter pylori is a pathogenic bacterium associated with various gastrointestinal diseases, including chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The increasing rates of H. pylori antibiotic resistance and the emergence of multidrug-resistant strains pose significant challenges to its treatment. This comprehensive review explores the mechanisms underlying the resistance of H. pylori to commonly used antibiotics and the clinical implications of antibiotic resistance. Additionally, potential strategies for overcoming antibiotic resistance are discussed. These approaches aim to improve the treatment outcomes of H. pylori infections while minimizing the development of antibiotic resistance. The continuous evolution of treatment perspectives and ongoing research in this field are crucial for effectively combating this challenging infection.
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Affiliation(s)
- Md Hasanuzzaman
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
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11
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Yu J, Jia Y, Yu Q, Lin L, Li C, Chen B, Zhong P, Lin X, Li H, Sun Y, Zhong X, He Y, Huang X, Lin S, Pan Y. Deciphering complex antibiotic resistance patterns in Helicobacter pylori through whole genome sequencing and machine learning. Front Cell Infect Microbiol 2024; 13:1306368. [PMID: 38379956 PMCID: PMC10878306 DOI: 10.3389/fcimb.2023.1306368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 12/06/2023] [Indexed: 02/22/2024] Open
Abstract
Introduction Helicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance. Methods In this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models. Results Our models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively. Discussion Our study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.
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Affiliation(s)
- Jianwei Yu
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yan Jia
- Department of Gastroenterology, the 7Medical Center of PLA General Hospital, Beijing, China
| | - Qichao Yu
- Center for Systems Biology, Intelliphecy, Main Building, Beishan Industrial Zone, Shenzhen, Guangdong, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Lan Lin
- Department of Gastroenterology, Xiamen Humanity Hospital, Xiamen, Fujian, China
| | - Chao Li
- Department of Gastroenterology, Peking University Aerospace School of Clinical Medicine, Beijing, China
| | - Bowang Chen
- Center for Systems Biology, Intelliphecy, Main Building, Beishan Industrial Zone, Shenzhen, Guangdong, China
- Department of Data Science, Intelliphecy, Nanjing, Jiangsu, China
| | - Pingyu Zhong
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Xueqing Lin
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Huilan Li
- Department of Nephrology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yinping Sun
- Department of Gastroenterology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Xuejing Zhong
- Department of Science and Education, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yuqi He
- Department of Gastroenterology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Xiaoyun Huang
- Center for Systems Biology, Intelliphecy, Main Building, Beishan Industrial Zone, Shenzhen, Guangdong, China
| | - Shuangming Lin
- Department of Gastrointestinal Surgery, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, China
| | - Yuanming Pan
- Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
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12
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Tan J, Fang Y, Yang C, Tay J, Tan N, Krishnan NDB, Chua BL, Zhao Y, Chen Y, Hedrick JL, Yang YY. pH-Responsive Polymeric Micelle Dynamic Complexes for Selective Killing of Helicobacter pylori. Biomacromolecules 2023; 24:5551-5562. [PMID: 37828909 DOI: 10.1021/acs.biomac.2c01374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Helicobacter pylori, the world's most common chronic infection-causing pathogen, is responsible for causing gastric ulcers, the fourth-leading cause of cancer-related death globally in 2020. In recent years, the effectiveness of the current treatment regimen (two antibiotics and one proton pump inhibitor) has often been plagued with problems such as resistance and the undesired elimination of commensal bacteria. Herein, we report the synthesis of block and random copolycarbonates, functionalized with cationic guanidinium and anionic acetate functional groups, aimed at selectively killing H. pylori in the acidic environment of the stomach, while remaining nontoxic to the commensal bacteria in the gut. The compositions of the polymers were fine-tuned so that the polymers were readily dispersed in water without any difficulty at both pH 3.0 and 7.4. The self-assembly behavior of the polymers at different pH values by dynamic light scattering showed that the random and block copolymers formed stable micelles in a simulated gastric environment (pH 3.0) while aggregated at pH 7.4. Both polymers demonstrated stronger antibacterial activity against H. pylori than the guanidinium-functionalized homopolymer without any acetate functional group at pH 3.0. The block copolymer was significantly more bactericidal at pH 3.0 across the concentrations tested, as compared to the random copolymer, while it did not show significant toxicity toward rat red blood cells (rRBCs) and HK-2 cells or bactericidal effect toward E. coli (a common gut bacterium) and nor caused aggregation of rRBCs at its effective concentration and at physiological pH of 7.4. Additionally, both the block and random copolymers were much more stable against hydrolysis at pH 3.0 than at pH 7.4. This study provides insight into the influence of both polymer architecture and dynamic assembly on the bioactivities of antimicrobial polymers, where the disassembly of coacervates into narrowly dispersed micelles at pH 3 make them potent antimicrobials aided by the protonated carboxylic acid block.
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Affiliation(s)
- Jason Tan
- Singapore Institute of Food and Biotechnology Innovation, Agency for Science Technology and Research (A*STAR), 31 Biopolis Way, Nanos #02-01, Singapore 138669, Singapore
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
| | - Yunhui Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 31003, China
| | - Chuan Yang
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore
| | - Joyce Tay
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore
| | - Nathanael Tan
- Institute of Bioengineering and Bioimaging, Agency for Science Technology and Research (A*STAR), 31 Biopolis Way, Nanos #07-01, Singapore 138669, Singapore
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore
| | - Nithiyaa D/O Bala Krishnan
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore
| | - Boon Lin Chua
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore
| | - Yanli Zhao
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
| | - Yunbo Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 31003, China
| | - James L Hedrick
- IBM Almaden Research Center, San Jose, California 95120, United States
| | - Yi Yan Yang
- Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), 20 Biopolis Way, Centros #06-01, Singapore 138668, Singapore
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119288, Singapore
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13
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Alsohaibani F, Peedikayil M, Alshahrani A, Somily A, Alsulaiman R, Azzam N, Almadi M. Practice guidelines for the management of Helicobacter pylori infection: The Saudi H. pylori Working Group recommendations. Saudi J Gastroenterol 2023; 29:326-346. [PMID: 36204804 PMCID: PMC10754383 DOI: 10.4103/sjg.sjg_288_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/07/2022] [Accepted: 08/19/2022] [Indexed: 11/06/2022] Open
Abstract
The eradication rates for Helicobacter pylori globally are decreasing with a dramatic increase in the prevalence of antibiotic resistant bacteria all over the world, including Saudi Arabia. There is no current consensus on the management of H. pylori in Saudi Arabia. The Saudi Gastroenterology Association developed these practice guidelines after reviewing the local and regional studies on the management of H. pylori. The aim was to establish recommendations to guide healthcare providers in managing H. pylori in Saudi Arabia. Experts in the areas of H. pylori management and microbiology were invited to write these guidelines. A literature search was performed, and all authors participated in writing and reviewing the guidelines. In addition, international guidelines and consensus reports were reviewed to bridge the gap in knowledge when local and regional data were unavailable. There is limited local data on treatment of H. pylori. The rate of clarithromycin and metronidazole resistance is high; therefore, standard triple therapy for 10-14 days is no longer recommended in the treatment of H. pylori unless antimicrobial susceptibility testing was performed. Based on the available data, bismuth quadruple therapy for 10-14 days is considered the best first-line and second-line therapy. Culture and antimicrobial susceptibility testing should be considered following two treatment failures. These recommendations are intended to provide the most relevant evidence-based guidelines for the management of H. pylori infection in Saudi Arabia. The working group recommends further studies to explore more therapeutic options to eradicate H. pylori.
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Affiliation(s)
- Fahad Alsohaibani
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Musthafa Peedikayil
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
| | | | - Ali Somily
- Department of Pathology and Laboratory Medicine, King Saud University Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Raed Alsulaiman
- Department of Medicine, King Fahad Hospital, Imam Abdulrahman bin Faisal University, Dammam, Kingdom of Saudi Arabia
| | - Nahla Azzam
- Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Majid Almadi
- Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia
- Division of Gastroenterology, McGill University Health Center, Montreal General Hospital, Montreal, QC, Canada
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14
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Ishibashi F, Suzuki S, Nagai M, Mochida K, Morishita T. Optimizing Helicobacter pylori Treatment: An Updated Review of Empirical and Susceptibility Test-Based Treatments. Gut Liver 2023; 17:684-697. [PMID: 36843419 PMCID: PMC10502504 DOI: 10.5009/gnl220429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/07/2022] [Accepted: 11/20/2022] [Indexed: 02/28/2023] Open
Abstract
As the rate of discovery of drug-resistant Helicobacter pylori cases increases worldwide, the relevant societies have updated their guidelines for primary eradication regimens. A promising strategy against drug-resistant H. pylori is tailored therapy based on the results of an antibiotic susceptibility test; however, it is difficult to apply this strategy to all cases. Although culture-based antibiotic susceptibility tests can assess resistance to any antimicrobial agent, their greatest disadvantage is the time required to draw a conclusion. In contrast, molecular-based methods, such as polymerase chain reaction, can rapidly determine the presence of resistance, although a single test can only test for one type of antimicrobial agent. Additionally, the limited availability of facilities for molecular-based methods has hindered their widespread use. Therefore, low-cost, minimally invasive, simple, and effective primary regimens are needed. Several studies have compared the efficacy of the latest primary eradication regimens against that of tailored therapies, and their results have shaped guidelines. This article reviews the latest research on empirical and tailored treatments for H. pylori infections. Evidence for the superiority of tailored therapy over empirical therapy is still limited and varies by region and treatment regimen. A network meta-analysis comparing different empirical treatment regimens showed that vonoprazan triple therapy provides a superior eradication effect. Recently, favorable results towards vonoprazan dual therapy have been reported, as it reached eradication levels similar to those of vonoprazan triple therapy. Both vonoprazan dual therapy and tailored therapy based on antibiotic susceptibility tests could contribute to future treatment strategies.
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Affiliation(s)
- Fumiaki Ishibashi
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Sho Suzuki
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Mizuki Nagai
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Kentaro Mochida
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Tetsuo Morishita
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
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15
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Li M, Wang X, Meng W, Dai Y, Wang W. Empirical versus tailored therapy based on genotypic resistance detection for Helicobacter pylori eradication: a systematic review and meta-analysis. Therap Adv Gastroenterol 2023; 16:17562848231196357. [PMID: 37667805 PMCID: PMC10475236 DOI: 10.1177/17562848231196357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/04/2023] [Indexed: 09/06/2023] Open
Abstract
Background The eradication rate of Helicobacter pylori infection with empirical therapy has decreased due to increased drug resistance. The latest guidelines recommend genotypic resistance-guided therapy, but its clinical efficacy remains unclear. Objectives The purpose of our study was to evaluate whether tailored therapy based on genotypic resistance is superior to empirical therapy for H. pylori infection. Design A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing tailored therapy based on genotypic resistance with empirical therapy was performed. Sources and methods We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate and the adverse events (AEs) was the secondary outcome. A random-effect model was applied to compare pooled risk ratios (RRs) with related 95% confidence intervals (CIs). Results A total of 12 qualified RCTs containing 3940 patients were identified in our systematic review and meta-analysis. The pooled eradication rates of tailored therapy based on the detection of genotypic resistance were consistently higher than those in the empirical treatment group, with no statistical significance. In triple therapy, the eradication rate was significantly higher in the tailored group than in the empirical group by intention-to-treat analysis (ITT) and per-protocol analysis (PP) analysis (p < 0.0001, RR: 1.20; 95% CI: 1.12-1.29; p < 0.0001, RR: 1.20; 95% CI: 1.15-1.25). In quadruple therapy, the eradication rate was higher in the empirical group (p = 0.001, RR: 0.93; 95% CI: 0.89-0.97; p = 0.009, RR: 0.95; 95% CI: 0.92-0.99). And this result was true for both bismuth quadruple therapy (BQT) and non-BQT. Regarding total AEs, the pooled rate was 34% in the tailored group and 37% in the empirical group, and no difference between the two groups was found (p = 0.17, RR: 0.88; 95% CI: 0.74-1.06). Conclusion In conclusion, tailored therapy based on molecular methods may offer better efficacy than empirical triple therapy, but it may not be superior to empirical quadruple therapy in eradicating H. pylori infection. Larger and more individualized RCTs are needed to aid clinical decision-making. Registration PROSPERO CRD42023408688.
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Affiliation(s)
- Meng Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiaolei Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wenting Meng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Weihong Wang
- Department of Gastroenterology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China
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16
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Ng HY, Leung WK, Cheung KS. Antibiotic Resistance, Susceptibility Testing and Stewardship in Helicobacter pylori Infection. Int J Mol Sci 2023; 24:11708. [PMID: 37511471 PMCID: PMC10380565 DOI: 10.3390/ijms241411708] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Despite the declining trend of Helicobacter pylori (H. pylori) prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of H. pylori to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to H. pylori. In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective H. pylori treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of H. pylori, so that it can be managed in a sustainable and efficient manner.
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Affiliation(s)
- Ho-Yu Ng
- School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Ka-Shing Cheung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China
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17
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Yin X, Lai Y, Du Y, Zhang T, Gao J, Li Z. Metal-Based Nanoparticles: A Prospective Strategy for Helicobacter pylori Treatment. Int J Nanomedicine 2023; 18:2413-2429. [PMID: 37192898 PMCID: PMC10182771 DOI: 10.2147/ijn.s405052] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/24/2023] [Indexed: 05/18/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with >90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori. Additionally, we discuss current challenges in this field and future perspectives that may be used in anti-H. pylori strategies.
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Affiliation(s)
- Xiaojing Yin
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Yongkang Lai
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
- Department of Gastroenterology, Ganzhou People’s Hospital Affiliated to Nanchang University, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Yiqi Du
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Tinglin Zhang
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Jie Gao
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Zhaoshen Li
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
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Kwon YH. Tailored Therapy Based on Antibiotic Resistance. HELICOBACTER PYLORI 2023:575-586. [DOI: 10.1007/978-981-97-0013-4_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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19
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Ingestible light source for intragastric antibacterial phototherapy: a device safety study on a minipig model. Photochem Photobiol Sci 2022; 22:535-547. [PMID: 36378410 DOI: 10.1007/s43630-022-00333-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 10/25/2022] [Indexed: 11/16/2022]
Abstract
AbstractHelicobacter pylori gastric infections are among the most diffused worldwide, suffering from a rising rate of antibiotic resistance. In this context, some of the authors have previously designed an ingestible device in the form of a luminous capsule to perform antibacterial photodynamic inactivation in the stomach. In this study, the light-emitting capsules were tested to verify the safety of use prior to perform clinical efficacy studies. First, laboratory tests measured the capsule temperature while in function and verified its chemical resistance in conditions mimicking the gastric and gut environments. Second, safety tests in a healthy minipig model were designed and completed, to verify both the capsule integrity and the absence of side effects, associated with its illumination and transit throughout the gastrointestinal tract. To this aim, a capsule administration protocol was defined considering a total of 6 animals with n = 2 treated with 8 capsules, n = 2 treated with 16 capsules and n = 2 controls with no capsule administration. Endoscopies were performed in sedated conditions before–after every capsule administration. Biopsies were taken from the corpus and antrum regions, while the gastric cavity temperature was monitored during illumination. The bench tests confirmed a very good chemical resistance and a moderate (about 3 °C) heating of the capsules. The animal trials showed no significant effects on the gastric wall tissues, both visually and histologically, accompanied with overall good animal tolerance to the treatment. The integrity of the administered capsules was verified as well. These encouraging results pose the basis for the definition of successive trials at the clinical level.
Graphical abstract
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20
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Nista EC, Pellegrino A, Giuli L, Candelli M, Schepis T, De Lucia SS, Ojetti V, Franceschi F, Gasbarrini A. Clinical Implications of Helicobacter pylori Antibiotic Resistance in Italy: A Review of the Literature. Antibiotics (Basel) 2022; 11:1452. [PMID: 36290110 PMCID: PMC9598780 DOI: 10.3390/antibiotics11101452] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/17/2022] [Accepted: 10/19/2022] [Indexed: 11/16/2022] Open
Abstract
Helicobacter pylori (H. pylori) resistance to antibiotics has increased worldwide in recent decades, especially to clarithromycin. As a result, the World Health Organization (WHO) identified clarithromycin-resistant H. pylori as a "high priority" pathogen in 2017. As international guidelines recommend empirical therapy as first-line treatment, it is crucial to know local resistance rates and history of antibiotic use to determine the most appropriate first-line antibiotic treatment. Italy is one of the European countries with the highest prevalence of H. pylori infection and the highest percentage of antibiotic-resistant H. pylori. The aim of this review is to summarize all data on H. pylori antibiotic resistance in Italy in order to quantify the current rate and determine the most effective therapeutic approach. The study confirms an elevated level of resistance to clarithromycin, metronidazole, and levofloxacin in Italy. In addition, our results show a satisfactory eradication rate for a bismuth-based regimen when used as first- or second-line treatment. Naive patients are also successfully treated with clarithromycin-based quadruple therapies. Considering the good results of bismuth-based therapy as recovery therapy, this argues for the potential use of clarithromycin quadruple therapy as a first-line treatment.
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Affiliation(s)
- Enrico Celestino Nista
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Pellegrino
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Lucia Giuli
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Marcello Candelli
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Tommaso Schepis
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Sara Sofia De Lucia
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Veronica Ojetti
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Franceschi
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A, Gemelli IRCCS, 00168 Rome, Italy
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21
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Karbalaei M, Keikha M, Talebi Bezmin Abadi A. Prevalence of Primary Multidrug-resistant Helicobacter pylori in Children: A Systematic Review and Meta-analysis. Arch Med Res 2022; 53:634-640. [PMID: 36089418 DOI: 10.1016/j.arcmed.2022.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/16/2022] [Accepted: 08/25/2022] [Indexed: 11/02/2022]
Abstract
BACKGROUND The emergence and global spread of multidrug-resistant Helicobacter pylori (MDR H. pylori) is a major health problem in children, which can increase the risk of serious complications such as gastric cancer. The aim of this study was to determine the prevalence of primary MDR H. pylori in children via a comprehensive systematic literature review and meta-analysis. METHODS All potential studies were collected from international databases like: ISI Web of Science, Embase, PubMed, Google Scholar, and Scopus from 2011-July 24, 2022. Ultimately, primary MDR H. pylori in children was measured as an event rate with corresponding 95% confidence intervals. RESULTS A total of 19 studies met the inclusion criteria. The overall prevalence of primary MDR H. pylori in children was measured at 6.0% (95% CI: 3.1-11.6); There was a significant difference in primary MDR H. pylori resistance rates between Asian populations and Western countries. CONCLUSIONS The global spread of MDR H. pylori strains could significantly limit the options of anti-H. pylori treatment regimens. The frequency of primary MDR H. pylori infection differs between various geographical regions. Thus, drug susceptibility testing and the eradication of H. pylori infection can effectively reduce and control the spread of H. pylori antibiotic resistance throughout the world.
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Affiliation(s)
- Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Masoud Keikha
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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22
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Jia X, Huang Q, Lin M, Chu Y, Shi Z, Zhang X, Ye H. Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori. Front Microbiol 2022; 13:962354. [PMID: 36147839 PMCID: PMC9485998 DOI: 10.3389/fmicb.2022.962354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/15/2022] [Indexed: 11/21/2022] Open
Abstract
Background Helicobacter pylori (H. pylori) infects half of the human population globally. Eradication rates with triple or quadruple therapy have decreased owing to the increasing rate of antibiotic resistance. Jinghua Weikang capsule (JWC) is the first and most popular Chinese patent medicine approved by the state for the treatment of gastritis and peptic ulcers caused by H. pylori infection in China. Previous studies have found that JWC has a certain bactericidal effect on drug-resistant H. pylori and its major component, Chenopodium ambrosioides L. inhibits biofilm formation, but the mechanism remains unclear. This study focused on drug-resistant H. pylori and explored whether JWC could reverse drug resistance and its related mechanisms. Method The agar plate dilution method, E-test method, and killing kinetics assay were used to evaluate the bactericidal effect of JWC on antibiotic-resistant H. pylori and its effect on antibiotic resistance. Sanger sequencing was used to detect mutations in drug resistance genes. The crystal violet method, scanning electron microscopy, and confocal laser scanning microscopy were used to evaluate the effects of JWC on biofilms. qPCR was performed to evaluate the effect of JWC on the expression of efflux pump-related genes. qPCR and immunofluorescence were used to evaluate the effects of JWC on H. pylori adhesion. Results JWC showed considerable antibacterial activity against drug-resistant H. pylori strains, with minimum inhibitory concentration (MIC) values ranging from 64 to 1,024 μg/ml. The MIC of metronidazole (MTZ) against H. pylori 26,695–16R decreased from 64 to 6 μg/ml after treatment with 1/2 MIC of JWC. The resistance of H. pylori 26,695–16R to MTZ was reversed by JWC, and its effect was better than that of PaβN and CCCP. H. pylori 26,695–16R is a moderate biofilm-forming strain, and JWC (16–64 μg/ml) can inhibit the formation of biofilms in H. pylori 26,695–16R. JWC reduced the expression of HP0605-HP0607 (hefABC), HP0971-HP0969 (hefDEF), HP1327-HP1329 (hefGHI), and HP1489-HP1487. JWC reduced the adhesion of H. pylori to GES-1 cells and the expression of adhesives NapA, SabA, and BabA. Conclusion The reversal of MTZ resistance by JWC may be achieved through the adhesin/efflux pump-biofilm pathway.
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23
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Kim SJ, Jee SR, Park MI, Jung K, Kim GH, Lee MW, Lee J, Jang JS, Koh M. A randomized controlled trial to compare Helicobacter pylori eradication rates between the empirical concomitant therapy and tailored therapy based on 23S rRNA point mutations. Medicine (Baltimore) 2022; 101:e30069. [PMID: 35984159 PMCID: PMC9387952 DOI: 10.1097/md.0000000000030069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Increasing clarithromycin resistance has led to changes in several guidelines for treatment of Helicobacter pylori infections. We compared the H. pylori eradication rates of the empirical concomitant therapy (CoT) and a tailored therapy (TaT) using dual-priming oligonucleotide-based polymerase chain reaction to detect mutations in the 23S rRNA gene that are related to clarithromycin resistance. METHODS Between June 2020 and May 2021, 290 patients were enrolled and randomly assigned to 2 groups. In the CoT group, the patients received rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 14 days. In the TaT group, point mutation-negative patients received rabeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 14 days and point mutation-positive patients received rabeprazole 20 mg twice daily, metronidazole 500 mg thrice daily, and bismuth 120 mg and tetracycline 500 mg 4 times daily for 14 days. RESULTS A total of 290 and 261 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. A2142G and/or A2143G point mutations were identified in 28.6% of the patients. No significant difference in eradication rates were observed between the 2 groups as per ITT (CoT, 82.8% and TaT, 85.5%, P = .520) and PP (CoT, 88.6% and TaT, 94.6%, P = .084) analyses. In point mutation-positive patients, the eradication rates in the CoT group were lower than those in the TaT group as per ITT (69.8% and 87.5%, respectively, P = .050) and PP (76.9% and 97.1%, respectively, P = .011) analyses. CONCLUSION CoT and TaT showed similar overall eradication rates for H. pylori. However, CoT eradication rate was suboptimal, especially in point mutation-positive patients.
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Affiliation(s)
- Su Jin Kim
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
- *Correspondence: Sam Ryong Jee, MD, Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan 47392, Korea (e-mail: )
| | - Sam Ryong Jee
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Moon Won Lee
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Jin Lee
- Department of Internal Medicine, Haeundae Paik Hospital, Busan, Koreaand
| | - Jin Seok Jang
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
| | - Myeongseok Koh
- Department of Internal Medicine, Dong-A University Hospital, Busan, Korea
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24
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Zou X, Hu J, Zhao M, Qin C, Zhu Y, Tian G, Cai J, Seeberger PH, Yin J. Chemical Synthesis of the Highly Sterically Hindered Core Undecasaccharide of Helicobacter pylori Lipopolysaccharide for Antigenicity Evaluation with Human Serum. J Am Chem Soc 2022; 144:14535-14547. [PMID: 35939326 DOI: 10.1021/jacs.2c03068] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Helicobacter pylori, listed as a human carcinogen by the Department of Health and Human Services, colonizes the gastric mucosa of more than half of the world's population. The individuals infected with H. pylori have a high risk to develop chronic gastritis, peptic ulcers, and even gastric cancer. The conserved core structure of H. pylori lipopolysaccharide (LPS) has been regarded as a promising candidate structure for development of a glycoconjugate vaccine targeting multiple serotypes. Here, we report a total synthesis of the core undecasaccharide of H. pylori LPS and its subunit antigens. The match and mismatch between the glycosyl donor and acceptor caused by the inert hydroxyl groups were addressed by a judicious choice of orthogonal protection strategies and glycosylation conditions. A combination of acyl remote participation and solvent effects has been applied for selective formation of the five 1,2-cis-glucosidic bonds. The high steric hindrance induced by the high carbon sugars and trinacriform architecture required that the core undecasaccharide was synthesized through a finely tuned linear assembly [2 + (1 + (3 + (1 + (1 + 3))))] rather than convergent strategies. An antigenicity evaluation using glycan microarrays showed that an α-(1 → 6)-glucan trisaccharide is recognized by IgG antibodies in sera of H. pylori-infected patients. The phosphate group of the inner core trisaccharide key epitope is very important for IgG recognition. These findings are an important step toward designing carbohydrate-based vaccines against H. pylori.
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Affiliation(s)
- Xiaopeng Zou
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China.,Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muhlenberg 1, 14476 Potsdam, Germany
| | - Jing Hu
- Wuxi School of Medicine, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
| | - Ming Zhao
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
| | - Chunjun Qin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
| | - Yuntao Zhu
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muhlenberg 1, 14476 Potsdam, Germany
| | - Guangzong Tian
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
| | - Juntao Cai
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
| | - Peter H Seeberger
- Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Muhlenberg 1, 14476 Potsdam, Germany
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu214122, P. R. China
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Garrido-Treviño LF, López-Martínez M, Flores-Hinojosa JA, Tijerina-Rodríguez L, Bosques-Padilla F. Empiric treatment vs susceptibility-guided treatment for eradicating H. pylori: Is it possible to change that paradigm using modern molecular methods? REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2022; 87:330-341. [PMID: 35778343 DOI: 10.1016/j.rgmx.2022.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 01/06/2022] [Indexed: 01/03/2025]
Abstract
Helicobacter pylori (H. pylori) infection is the most widespread infectious-contagious disease worldwide, reaching a prevalence of 50-80% in developing countries. Chronic infection is considered the main cause of chronic gastritis and has been related to other diseases, such as peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The most common treatment is with eradication regimens that utilize three or four drugs, including a proton pump inhibitor (PPI) and the antibiotics, clarithromycin and amoxycillin or metronidazole. Empiric antibiotic use for eradicating the bacterium has led to a growing resistance to those drugs, reducing regimen efficacy and increasing costs for both the patient and the healthcare sector. In such a context, the development of noninvasive next-generation molecular methods holds the promise of revolutionizing the treatment of H. pylori. The genotypic and phenotypic detection of the resistance of the bacterium to antibiotics enables personalized treatment regimens to be provided, reducing costs and implementing an antibiotic stewardship program. The aims of the present narrative review were to analyze and compare the traditional and next-generation methods for diagnosing H. pylori, explain the different factors associated with eradication failure, and emphasize the impact of the increasing antibiotic resistance on the reversal and prevention of H. pylori-associated diseases.
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Affiliation(s)
- L F Garrido-Treviño
- Instituto de Salud Digestiva, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico
| | - M López-Martínez
- Instituto de Salud Digestiva, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico
| | - J A Flores-Hinojosa
- Instituto de Salud Digestiva, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico
| | | | - F Bosques-Padilla
- Instituto de Salud Digestiva, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, Mexico; Hospital Universitario, Departamento de Gastroenterología, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
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Antibiotic resistance of Helicobacter pylori isolated from children in Chongqing, China. Eur J Pediatr 2022; 181:2715-2722. [PMID: 35469031 DOI: 10.1007/s00431-022-04456-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 12/14/2022]
Abstract
The resistance of Helicobacter pylori (H. pylori) to antibiotics has been increasing worldwide and varies across different geographic areas and times. Limited studies reported the prevalence of antibiotic resistance and its related gene mutations in children in Chongqing, a city located in southwest China. We collected 112 H. pylori strains isolated from gastric biopsies of 156 children at Children's Hospital of Chongqing Medical University and calculated resistance rates of these strains to six antibiotics. The A2143G and A2142G mutations in 23S rRNA gene, which are related to clarithromycin resistance, and Asn87 and Asp91 mutations in gyrA gene, which are related to levofloxacin resistance, were investigated in 102 strains. The resistance rates to clarithromycin, metronidazole, and levofloxacin were 47.3% (53/112), 88.4% (99/112), and 18.8% (21/112), respectively. No resistance to amoxicillin, tetracycline, and furazolidone was observed. Dual and triple resistance percentages were 37.5% (42/112) and 10.7% (12/112), respectively. The detection rate of A2143G mutation in 23S rRNA gene was 83.3% (40/48). The detection rates of mutations of Asn87 and Asp91 in gyrA gene were 52.6% (10/19) and 36.8% (7/19), respectively. Conclusion: The prevalence of H. pylori resistance to clarithromycin, metronidazole, and levofloxacin was high in children in Chongqing, China. The A2143G mutation was detected in most clarithromycin-resistant strains, and Asn87 and Asp91 of gyrA mutation points were common in levofloxacin-resistant strains. In clinical practice, anti-H. pylori therapy should be individualized based on a susceptibility test. What is Known: • The resistance of H. pylori to antibiotics changes with the geographic areas and that in Asia the resistance rate is high. • Mutation plays a vital role in antibiotics resistance of H. pylori. What is New: • High resistance rates to single and multiple antibiotics in children of Chongqing, a city located in southwest China, were observed. • Molecular assays showed good conformance with susceptibility test results to direct antibiotic resistance of H. pylori.
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27
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Empiric treatment vs susceptibility-guided treatment for eradicating H. pylori: Is it possible to change that paradigm using modern molecular methods? REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2022; 87:330-341. [DOI: 10.1016/j.rgmxen.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 01/06/2022] [Indexed: 11/24/2022] Open
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Guo Z, Tian S, Wang W, Zhang Y, Li J, Lin R. Correlation Analysis Among Genotype Resistance, Phenotype Resistance, and Eradication Effect After Resistance-Guided Quadruple Therapies in Refractory Helicobacter pylori Infections. Front Microbiol 2022; 13:861626. [PMID: 35330762 PMCID: PMC8940283 DOI: 10.3389/fmicb.2022.861626] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 02/15/2022] [Indexed: 11/29/2022] Open
Abstract
Objectives The antimicrobial resistance of Helicobacter pylori (H. pylori) in most countries and regions has increased significantly. It has not been fully confirmed whether the detection of H. pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical personalized treatment. The objective of this study was to assess and compare the efficacy of different antimicrobial resistance-guided quadruple therapies in refractory H. pylori-infected individuals who had undergone unsuccessful prior eradication treatments. Methods From January 2019 to February 2020, genotypic and phenotypic resistances were determined by polymerase chain reaction (PCR), whole genome sequencing (WGS) and broth microdilution test, respectively, in 39 H. pylori-infected patients who have failed eradication for at least twice. The patients were retreated with bismuth quadruple therapy for 14 days according to individual antibiotic resistance results. Eradication status was determined by the 13C-urea breath test. Results The overall eradication rate was 79.5% (31/39, 95% CI 64.2–89.5%) in the intention-to-treat (ITT) analysis and 88.6% (31/35, 95% CI 73.5–96.1%) in the per- protocol analysis (PP) analysis. The presence of amoxicillin resistance (OR, 15.60; 95% CI, 1.34–182.09; p = 0.028), female sex (OR, 12.50; 95% CI, 1.10–142.31; p = 0.042) and no less than 3 prior eradication treatments (OR, 20.25; 95% CI, 1.67–245.44; p = 0.018), but not the methods for guiding therapy (p > 0.05) were associated with treatment failure. Resistance-guided therapy achieved eradication rates of more than 80% in these patients. The eradication rate of H. pylori in the phenotypic resistance-guided group was correlated well with genotype resistance-guided groups, including PCR and WGS. Conclusion Culture or molecular method guiding therapy can enable personalized, promise salvage treatments, and achieve comparably high eradication rates in patients with refractory H. pylori infection. The detection of H. pylori resistance mutations has a good clinical application prospect. Protocol Study Register [clinicaltrials.gov], identifier [ChiCTR1800020009].
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Affiliation(s)
- Zijun Guo
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shuxin Tian
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Gastroenterology, The First Affiliated Hospital, Shihezi University, Shihezi, China
| | - Weijun Wang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanbin Zhang
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rong Lin
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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29
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Cho JH, Jin SY, Park S. Comparison of tailored Helicobacter pylori eradication versus modified bismuth quadruple therapy in Korea: a randomized controlled trial. Expert Rev Anti Infect Ther 2021; 20:923-929. [PMID: 34883037 DOI: 10.1080/14787210.2022.2017280] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to compare the success rate, adverse drug events, and cost-effectiveness of tailored Helicobacter pylori eradication and modified bismuth-containing quadruple therapy. METHODS The diagnosis of H. pylori infection was randomly based on either rapid urease test (RUT) or dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) in 1:1 ratio. According to the presence of point mutations that cause clarithromycin resistance, patients in the tailored therapy (TT) group received standard triple therapy or classic bismuth quadruple therapy. Patients with positive RUT results received 40 mg pantoprazole, 1000 mg amoxicillin, 750 mg metronidazole, and 600 mg bismuth subcitrate twice daily for 14 days (PAM-B therapy). RESULTS Between the TT (n = 141) and PAM-B groups (n = 141), H. pylori eradication rate did not differ significantly according to intention-to-treat (TT: 80.9% vs. PAM-B: 85.8%, P = 0.262), modified intention-to-treat (TT: 89.1% vs. PAM-B: 91.0%, P = 0.606), and per-protocol (TT: 89.0% vs. PAM-B: 93.5%, P = 0.198) analyses. The average cost for successful eradication was higher in the TT group than in the PAM-B group ($340.7 vs. $263.9 per patient). CONCLUSION PAM-B therapy exhibits similar efficacy and improved cost-effectiveness compared to TT based on the results of DPO-PCR tests. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov identifier is NCT05002595.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, Korea
| | - So Young Jin
- Department of Pathology, Soonchunhyang University Hospital, Seoul, Korea
| | - Suyeon Park
- Department of Medical Biostatistics, Soonchunhyang University Hospital, Seoul, Korea
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30
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Griffith DM, Li H, Werrett MV, Andrews PC, Sun H. Medicinal chemistry and biomedical applications of bismuth-based compounds and nanoparticles. Chem Soc Rev 2021; 50:12037-12069. [PMID: 34533144 DOI: 10.1039/d0cs00031k] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Bismuth as a relatively non-toxic and inexpensive metal with exceptional properties has numerous biomedical applications. Bismuth-based compounds are used extensively as medicines for the treatment of gastrointestinal disorders including dyspepsia, gastric ulcers and H. pylori infections. Recently, its medicinal application was further extended to potential treatments of viral infection, multidrug resistant microbial infections, cancer and also imaging, drug delivery and biosensing. In this review we have highlighted the unique chemistry and biological chemistry of bismuth-209 as a prelude to sections covering the unique antibacterial activity of bismuth including a description of research undertaken to date to elucidate key molecular mechanisms of action against H. pylori, the development of novel compounds to treat infection from microbes beyond H. pylori and the significant role bismuth compounds can play as resistance breakers. Furthermore we have provided an account of the potential therapeutic application of bismuth-213 in targeted alpha therapy as well as a summary of the biomedical applications of bismuth-based nanoparticles and composites. Ultimately this review aims to provide the state of the art, highlight the untapped biomedical potential of bismuth and encourage original contributions to this exciting and important field.
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Affiliation(s)
- Darren M Griffith
- Department of Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.,SSPC, Synthesis and Solid State Pharmaceutical Centre, Ireland
| | - Hongyan Li
- Department of Chemistry and CAS-HKU Joint Laboratory of Metallomics for Health and Environment, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
| | | | - Philip C Andrews
- School of Chemistry, Monash University, Melbourne, VIC, Australia
| | - Hongzhe Sun
- Department of Chemistry and CAS-HKU Joint Laboratory of Metallomics for Health and Environment, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
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Cardos IA, Zaha DC, Sindhu RK, Cavalu S. Revisiting Therapeutic Strategies for H. pylori Treatment in the Context of Antibiotic Resistance: Focus on Alternative and Complementary Therapies. Molecules 2021; 26:molecules26196078. [PMID: 34641620 PMCID: PMC8512130 DOI: 10.3390/molecules26196078] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 10/01/2021] [Accepted: 10/02/2021] [Indexed: 12/15/2022] Open
Abstract
The prevalence of Helicobacter pylori infection remains significant worldwide and it depends on many factors: gender, age, socio-economic status, geographic area, diet, and lifestyle. All successful infectious diseases treatments use antibiotic-susceptibility testing, but this strategy is not currently practical for H. pylori and the usual cure rates of H. pylori are lower than other bacterial infections. Actually, there is no treatment that ensures complete eradication of this pathogen. In the context of an alarming increase in resistance to antibiotics (especially to clarithromycin and metronidazole), alternative and complementary options and strategies are taken into consideration. As the success of antibacterial therapy depends not only on the susceptibility to given drugs, but also on the specific doses, formulations, use of adjuvants, treatment duration, and reinfection rates, this review discusses the current therapies for H. pylori treatment along with their advantages and limitations. As an alternative option, this work offers an extensively referenced approach on natural medicines against H. pylori, including the significance of nanotechnology in developing new strategies for treatment of H. pylori infection.
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Affiliation(s)
- Ioana Alexandra Cardos
- Faculty of Medicine and Pharmacy, Doctoral School of Biomedical Sciences, University of Oradea, 1 University Street, 410087 Oradea, Romania;
| | - Dana Carmen Zaha
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 1 University Street, 410087 Oradea, Romania
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
| | - Rakesh K. Sindhu
- Chitkara College of Pharmacy, Chitkara University, Chandigarh 140401, India
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
| | - Simona Cavalu
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 1 University Street, 410087 Oradea, Romania
- Correspondence: (D.C.Z.); (R.K.S.); (S.C.)
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Jo HG, Kim YS. Helicobacter pylori Eradication Therapy-associated Diarrhea. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Eradication of Helicobacter pylori has contributed to the treatment of peptic ulcers and mucosa-associated lymphoid tissue lymphoma. Moreover, it has possibly decreased the prevalence of gastric cancer. However, eradication therapy is associated with various adverse effects, of which diarrhea is the most common. The incidence of diarrhea after eradication treatment varies from 8% to 48%. In particular, the incidence is higher in patients who receive first-line standard triple therapy compared with those who receive second-line therapy. Both antibiotics and proton pump inhibitors, components of eradication therapy, have short-term and long-term impacts on gut microbiota. The alterations of gut microbiota may not recover until 1 year after eradication therapy. Most cases of diarrhea that occur after eradication therapy are antibiotic-associated diarrhea caused by the destruction of the normal gut microbiota. In some cases, Clostridioides difficile-associated diarrhea occurs after eradication therapy. If bloody diarrhea occurs after eradication therapy and the Clostridioides difficile toxin is not detected, antibiotic-associated hemorrhagic colitis associated with Klebsiella oxytoca infection should be suspected. It is crucial to explain the possibility of diarrhea before initiating eradication therapy to increase compliance. Furthermore, probiotics may be administered to reduce diarrhea. If severe diarrhea or symptoms other than the usual antibiotic-associated diarrhea occur during or after eradication therapy, antibiotics should be discontinued. In addition, appropriate tests to determine the cause of diarrhea should be performed. This review summarizes the alteration of the gut microbiota, the causes of diarrhea after Helicobacter pylori eradication therapy, and its management.
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Song X, Liu P, Liu X, Wang Y, Wei H, Zhang J, Yu L, Yan X, He Z. Dealing with MDR bacteria and biofilm in the post-antibiotic era: Application of antimicrobial peptides-based nano-formulation. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 128:112318. [PMID: 34474869 DOI: 10.1016/j.msec.2021.112318] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 07/05/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023]
Abstract
The rapid development of multidrug-resistant (MDR) bacteria due to the improper and overuse of antibiotics and the ineffective performance of antibiotics against the difficult-to-treat biofilm-related infections (BRIs) have urgently called for alternative antimicrobial agents and strategies in combating bacterial infections. Antimicrobial peptides (AMPs), owing to their compelling antimicrobial activity against MDR bacteria and BRIs without causing bacteria resistance, have attracted extensive attention in the research field. With the development of nanomaterial-based drug delivery strategies, AMPs-based nano-formulations have significantly improved the therapeutic effects of AMPs by ameliorating their hydrolytic stability, half-life in vivo, and solubility as well as reducing the cytotoxicity and hemolysis, etc. This review has comprehensively summarized the application AMPs-based nano-formulation in various bacterial infections models, including bloodstream infections (specifically sepsis), pulmonary infections, chronic wound infections, gastrointestinal infections, among others. The design of the nanomaterial-based drug delivery systems and the therapeutic effects of the AMPs-based nano-formulations in literature have been categorized and in details discussed. Overall, this review provides insights into the advantages and disadvantages of the current developed AMPs-based nano-formulations in literature for the treatment of bacterial infections, bringing inspirations and suggestions for their future design in the way towards clinical translation.
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Affiliation(s)
- Xinyu Song
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Pengyan Liu
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Xiaohu Liu
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Yanan Wang
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Huichao Wei
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Jingwen Zhang
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Liangmin Yu
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China.
| | - Xuefeng Yan
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China
| | - Zhiyu He
- Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao 266100, China.
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Kim SY, Park JM, Lim CH, Lee HA, Shin GY, Choe Y, Cho YK, Choi MG. Types of 23S Ribosomal RNA Point Mutations and Therapeutic Outcomes for Helicobacter pylori. Gut Liver 2021; 15:528-536. [PMID: 33376228 PMCID: PMC8283296 DOI: 10.5009/gnl20225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori clarithromycin resistance. This study aimed to detect the prevalence of these point mutations and to investigate the role of different point mutations in the success of eradication therapy. Methods We retrospectively investigated a total of 464 consecutive patients who underwent an endoscopic examination and dual-priming oligonucleotide-based multiplex polymerase chain reaction for H. pylori between June 2014 and October 2019. For 289 patients with negative point mutations, standard triple therapy was used in 287 patients, and the bismuth-quadruple regimen was used in two patients. For 175 patients with positive point mutations (A2142G, A2143G, and both mutations), standard triple and bismuth-quadruple therapies were used in 37 patients and 138 patients, respectively. Results The eradication rates of standard triple and bismuth-quadruple therapies showed no significant difference in mutation-negative patients or those with the A2142G point mutation. However, the eradication rate with bismuth-quadruple therapy was significantly higher than that with standard triple therapy in the group with the A2143G mutation or with the double mutation. The eradication rates for standard triple and bismuth-quadruple therapies, respectively, were 25.8% and 92.1% in the per-protocol group (p<0.001) and 24.2% and 85.2% in the intention-totreat analysis (p<0.001). Conclusions The A2143G point mutation is the most prevalent cause of clarithromycin resistance. Bismuth-quadruple therapy is superior to standard triple therapy in patients with the A2143G or double point mutation.
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Affiliation(s)
- Sang Yoon Kim
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Jae Myung Park
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.,Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Ga-Yeong Shin
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Younghee Choe
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Yu Kyung Cho
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Myung-Gyu Choi
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.,Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea
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Ochoa S, Collado L. Enterohepatic Helicobacter species - clinical importance, host range, and zoonotic potential. Crit Rev Microbiol 2021; 47:728-761. [PMID: 34153195 DOI: 10.1080/1040841x.2021.1924117] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The genus Helicobacter defined just over 30 years ago, is a highly diverse and fast-growing group of bacteria that are able to persistently colonize a wide range of animals. The members of this genus are subdivided into two groups with different ecological niches, associated pathologies, and phylogenetic relationships: the gastric Helicobacter (GH) and the enterohepatic Helicobacter (EHH) species. Although GH have been mostly studied, EHH species have become increasingly important as emerging human pathogens and potential zoonotic agents in the last years. This group of bacteria has been associated with the development of several diseases in humans from acute pathologies like gastroenteritis to chronic pathologies that include inflammatory bowel disease, and liver and gallbladder diseases. However, their reservoirs, as well as their routes of transmission, have not been well established yet. Therefore, this review summarizes the current knowledge of taxonomy, epidemiology, and clinical role of the EHH group.
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Affiliation(s)
- Sofia Ochoa
- Faculty of Sciences, Institute of Biochemistry and Microbiology, Universidad Austral de Chile, Valdivia, Chile.,ANID - Millennium Science Initiative Program - Millennium Nucleus in the Biology of the Intestinal Microbiota, Santiago, Chile
| | - Luis Collado
- Faculty of Sciences, Institute of Biochemistry and Microbiology, Universidad Austral de Chile, Valdivia, Chile.,ANID - Millennium Science Initiative Program - Millennium Nucleus in the Biology of the Intestinal Microbiota, Santiago, Chile
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36
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Zhou Q, Xue B, Gu R, Li P, Gu Q. Lactobacillus plantarum ZJ316 Attenuates Helicobacter pylori-Induced Gastritis in C57BL/6 Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:6510-6523. [PMID: 34096709 DOI: 10.1021/acs.jafc.1c01070] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Helicobacter pylori is a highly prevalent human-specific pathogen that causes various gastric diseases. In the present study, Lactobacillus plantarum ZJ316, which could survive well in simulated gastrointestinal conditions, was found to have significant anti-H. pylori ability. Animal assays revealed that L. plantarum ZJ316 had preventive and therapeutic effects on H. pylori-induced gastritis. L. plantarum ZJ316 significantly decreased interferon γ (IFN-γ) and interleukin 6 (IL-6) levels, increased the IL-10 level, and repaired mucosal damage. Moreover, 16S rRNA gene sequencing revealed that the relative abundance of H. pylori could be significantly reduced by L. plantarum ZJ316 administration. Members of the families Dehalobacteriaceae and Geodermatophilaceae were more prevalent in the prevention group, while Lactobacillaceae and Actinomycetaceae were more prevalent in the treatment group. These results indicate that L. plantarum ZJ316 serves as a potential candidate for the prevention and treatment of H. pylori-induced gastritis by regulating the gastric microbiota and reducing mucosal inflammation.
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Affiliation(s)
- Qingqing Zhou
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China
| | - Bingyao Xue
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China
| | - Rongcheng Gu
- Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China
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37
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Zhong Y, Tang L, Deng Q, Jing L, Zhang J, Zhang Y, Yu F, Ou Y, Guo S, Huang B, Cao H, Huang P, Xu Y. Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of Helicobacter pylori. Front Microbiol 2021; 12:674560. [PMID: 34149664 PMCID: PMC8206506 DOI: 10.3389/fmicb.2021.674560] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/20/2021] [Indexed: 12/17/2022] Open
Abstract
The long-term colonization of Helicobacter pylori can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of H. pylori. Patchouli alcohol (PA) shows a highly efficient activity against H. pylori in vitro and in vivo. And this study aims to explore whether PA can reduce the resistance of H. pylori and determine the underlying mechanism. Checkerboard and time–kill bactericidal curve assay reveal that the combination of PA and clarithromycin (CLR) promoted the inhibition and bactericidal effect against H. pylori. Stimulation of CLR leads to the internalization of H. pylori, but PA can effectively inhibit the invasion induced by CLR. Compared with antibiotics, PA remarkably eradicated the intracellular H. pylori, and this intracellular sterilized ability was further improved in combination with antibiotics (CLR and metronidazole). The expression of H. pylori efflux pump genes (hp0605, hp1327, and hp1489) was dose-dependently downregulated by PA. Digital droplet PCR indicated that the H. pylori mutant of A2143G can be inhibited by PA. Cellular uptake and transport assays showed that PA is rapidly absorbed, which promotes its activity against intracellular bacteria. Therefore, PA can act synergistically with CLR as a candidate treatment against drug-resistant H. pylori.
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Affiliation(s)
- Yuanzun Zhong
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Liyao Tang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiuhua Deng
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li Jing
- School of Basic Medical Science, Tianjin Medical University, Tianjin, China
| | - Jiao Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yao Zhang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Feng Yu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yijun Ou
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shaoju Guo
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Bin Huang
- Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Hongying Cao
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ping Huang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yifei Xu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.,Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
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Lee JW, Kim SJ, Choi CW, Kim HJ, Kang DH, Kim HW, Park SB, Nam HS, Ryu DG. Seven-day triple therapy is sufficient to eradicate infection caused by Helicobacter pylori without 23S rRNA point mutation. Medicine (Baltimore) 2021; 100:e26133. [PMID: 34032763 PMCID: PMC8154452 DOI: 10.1097/md.0000000000026133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 01/25/2021] [Accepted: 05/05/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Tailored therapy based on dual priming oligonucleotide-based polymerase chain reaction (DPO-PCR) can be considered an alternative to overcome the low eradication rate in high clarithromycin-resistance areas. The triple therapy (TT) duration of the tailored approach in most studies was 7 days for patients without point mutation. However, recent western guidelines have recommended a treatment duration of 14 days. The aim of this study was to compare the success rate of 7 and 14 days of TT for eradicating Helicobacter pylori without point mutation, as determined by DPO-PCR.Between Feb 2016 and Feb 2019, medical records of patients who underwent DPO-PCR were reviewed. Patients without point mutation as determined by DPO-PCR were enrolled in this study. The eradication success rate and adverse events were evaluated.A total of 366 patients without A2142G and A2143G point mutation were enrolled. The success rates of 7-day and 14-day TT were 88.4% (168/190) and 85.9% (151/176) by intention to treat analysis (P = .453) and 90.8% (168/185) and 90.4% (151/167) by per-protocol analysis (P = .900), respectively. The adverse event rates showed no significant difference between the 2 groups.In patients without point mutation based on DPO-PCR results, 7-day TT is as effective as 14-day TT. Therefore, 7 days may be considered as a cost-effective treatment duration in Korea.
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Cui R, Song Z, Suo B, Tian X, Xue Y, Meng L, Niu Z, Jin Z, Zhang H, Zhou L. Correlation Analysis Among Genotype Resistance, Phenotype Resistance and Eradication Effect of Helicobacter pylori. Infect Drug Resist 2021; 14:1747-1756. [PMID: 34012273 PMCID: PMC8127322 DOI: 10.2147/idr.s305996] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/15/2021] [Indexed: 12/13/2022] Open
Abstract
Background It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test. Materials and Methods The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined. Results The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001). Conclusion A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.
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Affiliation(s)
- Rongli Cui
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Baojun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Xueli Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Yan Xue
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Lingmei Meng
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhanyue Niu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Zhu Jin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Hejun Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People's Republic of China
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Saracino IM, Pavoni M, Zullo A, Fiorini G, Lazzarotto T, Borghi C, Vaira D. Next Generation Sequencing for the Prediction of the Antibiotic Resistance in Helicobacter pylori: A Literature Review. Antibiotics (Basel) 2021; 10:437. [PMID: 33919811 PMCID: PMC8070836 DOI: 10.3390/antibiotics10040437] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/08/2021] [Accepted: 04/13/2021] [Indexed: 12/12/2022] Open
Abstract
Background and aims: Only a few antimicrobials are effective against H. pylori, and antibiotic resistance is an increasing problem for eradication therapies. In 2017, the World Health Organization categorized clarithromycin resistant H. pylori as a "high-priority" bacterium. Standard antimicrobial susceptibility testing can be used to prescribe appropriate therapies but is currently recommended only after the second therapeutic failure. H. pylori is, in fact, a "fastidious" microorganism; culture methods are time-consuming and technically challenging. The advent of molecular biology techniques has enabled the identification of molecular mechanisms underlying the observed phenotypic resistance to antibiotics in H. pylori. The aim of this literature review is to summarize the results of original articles published in the last ten years, regarding the use of Next Generation Sequencing, in particular of the whole genome, to predict the antibiotic resistance in H. pylori.Methods: a literature research was made on PubMed. The research was focused on II and III generation sequencing of the whole H. pylori genome. Results: Next Generation Sequencing enabled the detection of novel, rare and complex resistance mechanisms. The prediction of resistance to clarithromycin, levofloxacin and amoxicillin is accurate; for other antimicrobials, such as metronidazole, rifabutin and tetracycline, potential genetic determinants of the resistant status need further investigation.
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Affiliation(s)
- Ilaria Maria Saracino
- Microbiology Unit, Department of Specialized, Experimental, and Diagnostic Medicine, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (I.M.S.); (T.L.)
| | - Matteo Pavoni
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, ‘Nuovo Regina Margherita’ Hospital, 00153 Rome, Italy;
| | - Giulia Fiorini
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Tiziana Lazzarotto
- Microbiology Unit, Department of Specialized, Experimental, and Diagnostic Medicine, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (I.M.S.); (T.L.)
| | - Claudio Borghi
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
| | - Dino Vaira
- Department of Medical and Surgical Sciences, IRCCS St. Orsola Polyclinic, University of Bologna, 40138 Bologna, Italy; (M.P.); (G.F.); (C.B.)
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Domanovich-Asor T, Craddock HA, Motro Y, Khalfin B, Peretz A, Moran-Gilad J. Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny. Helicobacter 2021; 26:e12782. [PMID: 33491828 DOI: 10.1111/hel.12782] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/25/2020] [Accepted: 12/31/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny. MATERIALS/METHODS A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in-house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST). RESULTS Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences). CONCLUSIONS This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.
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Affiliation(s)
- Tal Domanovich-Asor
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hillary A Craddock
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Yair Motro
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Boris Khalfin
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Avi Peretz
- Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriyah and Azrieli Faculty of Medicine, Bar-Ilan University, Galilee, Israel
| | - Jacob Moran-Gilad
- MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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Albasha AM, Elnosh MM, Osman EH, Zeinalabdin DM, Fadl AAM, Ali MA, Altayb HN. Helicobacter pylori 23S rRNA gene A2142G, A2143G, T2182C, and C2195T mutations associated with clarithromycin resistance detected in Sudanese patients. BMC Microbiol 2021; 21:38. [PMID: 33535966 PMCID: PMC7856789 DOI: 10.1186/s12866-021-02096-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 01/13/2021] [Indexed: 12/31/2022] Open
Abstract
Background Clarithromycin resistant Helicobacter pylori (H. pylori) strains represent a worldwide health problem. These stains are usually carrying mutations within the 23S rRNA gene associated with clarithromycin resistance. This study aimed to detect H. pylori and clarithromycin resistant associated mutations from Sudanese patients with gastritis symptoms. Materials and methods Two hundred and eighty-eight gastric biopsies were collected using gastrointestinal endoscopy from patients with gastritis symptoms in different hospitals in Khartoum state. H. pylori was detected by PCR using primer targeting 16S rRNA. Then allele-specific PCR and DNA sequencing were used to screen for the presence of A2142G and A2143G point mutations. Results Out of 288 samples, H. pylori was detected in 88 (~ 30.6%) samples by 16 s RNA. Allele-specific PCR detected the variant A2142G in 9/53 (~ 17%) sample, while A2143G mutation was not found in any sample. The DNA sequencing revealed the presence of mutations associated with clarithromycin-resistance in 36% (9/25) of samples; the A2142G was present in one sample, A2143G in 5 samples and T2182C in 4 samples. Additionally, another point mutation (C2195T) was detected in 3 samples. There was no association of 23S rRNA gene point mutations with gender, age group, and patients’ geographical distribution. Conclusion This study revealed a high frequency (36%) of mutations associated with clarithromycin resistance using DNA sequencing of the 23S rRNA gene’s V domain. This information should be taken into consideration to avoid eradication therapy failing.
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Affiliation(s)
- Aalaa Mahgoub Albasha
- Department of Microbiology, College of Medical Laboratory Sciences, Sudan University for Science and Technology, Khartoum, Sudan.
| | - Maram M Elnosh
- Department of Microbiology, College of Medical Laboratory Sciences, Sudan University for Science and Technology, Khartoum, Sudan
| | - Esraa Hassan Osman
- Department of Microbiology, College of Medical Laboratory Sciences, Sudan University for Science and Technology, Khartoum, Sudan
| | - Duha M Zeinalabdin
- Department of Microbiology, College of Medical Laboratory Sciences, Sudan University for Science and Technology, Khartoum, Sudan
| | - Amira A M Fadl
- Department of Medicine, The National Ribat University, Ribat University Hospital, Khartoum, Sudan
| | - Musa Abdalla Ali
- Department of Microbiology, faculty of Medical Laboratory Science, University of Khartoum, Khartoum, Sudan
| | - Hisham N Altayb
- Department of Microbiology, College of Medical Laboratory Sciences, Sudan University for Science and Technology, Khartoum, Sudan.,Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, 21452, Saudi Arabia
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Kumar S, Metz DC, Kaplan DE, Goldberg DS. Low Rates of Retesting for Eradication of Helicobacter pylori Infection After Treatment in the Veterans Health Administration. Clin Gastroenterol Hepatol 2021; 19:305-313.e1. [PMID: 32272245 PMCID: PMC7541590 DOI: 10.1016/j.cgh.2020.03.059] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/23/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Expert consensus mandates retesting for eradication of Helicobacter pylori infection after treatment, but it is not clear how many patients are actually retested. We evaluated factors associated with retesting for H pylori in a large, nationwide cohort. METHODS We performed a retrospective cohort study of patients with H pylori infection (detected by urea breath test, stool antigen, or pathology) who were prescribed an eradication regimen from January 1, 1994 through December 31, 2018 within the Veterans Health Administration (VHA). We collected data on demographic features, smoking history, socioeconomic status, facility poverty level and academic status, and provider specialties and professions. The primary outcome was retesting for eradication. Statistical analyses included mixed-effects logistic regression. RESULTS Of 27,185 patients prescribed an H pylori eradication regimen, 6486 patients (23.9%) were retested. Among 7623 patients for whom we could identify the provider who ordered the test, 2663 patients (34.9%) received the order from a gastroenterological provider. Female sex (odds ratio, 1.22; 95% CI, 1.08-1.38; P = .002) and history of smoking (odds ratio, 1.24; 95% CI, 1.15-1.33; P < .001) were patient factors associated with retesting. There was an interaction between method of initial diagnosis of H pylori infection and provider who ordered the initial test (P < .001). There was significant variation in rates of retesting among VHA facilities (P < .001). CONCLUSIONS In an analysis of data from a VHA cohort of patients with H pylori infection, we found low rates of retesting after eradication treatment. There is significant variation in rates of retesting among VHA facilities. H pylori testing is ordered by nongastroenterology specialists two-thirds of the time. Confirming eradication of H pylori is mandatory and widespread quality assurance protocols are needed.
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Affiliation(s)
- Shria Kumar
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - David C. Metz
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - David E. Kaplan
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania,Division of Gastroenterology, Veterans Health Administration
| | - David S. Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine
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Exquisite binding interaction of 18β-Glycyrrhetinic acid with histone like DNA binding protein of Helicobacter pylori: A computational and experimental study. Int J Biol Macromol 2020; 161:231-246. [DOI: 10.1016/j.ijbiomac.2020.06.039] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 06/04/2020] [Accepted: 06/04/2020] [Indexed: 02/07/2023]
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Windham IH, Merrell DS. Analysis of fitness costs associated with metronidazole and amoxicillin resistance in Helicobacter pylori. Helicobacter 2020; 25:e12724. [PMID: 32677105 DOI: 10.1111/hel.12724] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 06/17/2020] [Accepted: 06/21/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Increasing rates of antibiotic resistance are a major concern for all pathogens, including H. pylori. However, increased resistance often coincides with a decrease in relative fitness of the pathogen in the absence of the antibiotic, raising the possibility that increased resistance can be mitigated for some antibiotics by improved antibiotic husbandry. Therefore, a greater understanding of which types of antibiotic resistance create fitness defects in H. pylori may aid rational treatment strategies. MATERIALS AND METHODS While a wealth of H. pylori literature reports mutations that correlate with increased resistance, few studies demonstrate causation for these same mutations. Herein, we examined fitness costs associated with metronidazole and amoxicillin resistance. Isogenic strains bearing literature reported point mutations in the rdxA and pbp1 genes were engineered and tested in in vitro competition assays to assess relative fitness. RESULTS None of the metronidazole resistance mutations resulted in a fitness cost under the tested conditions. In contrast, amoxicillin-resistant mutant strains demonstrated a defect in competition by 24 hours. This change in fitness was further enhanced by moderate osmotic stress. However, under extreme osmotic stress, the amoxicillin-resistant N562Y PBP1 mutant strain showed enhanced fitness, suggesting that there are some pbp1 mutations that can give a conditional fitness advantage. CONCLUSIONS Our results demonstrate the role of specific point mutations in rdxA and pbp1 in antibiotic resistance and suggest that amoxicillin-resistant strains of H. pylori show environmentally dictated changes in fitness. These later finding may be responsible for the relatively low rates of amoxicillin resistance seen in the United States.
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Affiliation(s)
- Ian H Windham
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - D Scott Merrell
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
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Kim SY, Chung JW. Best Helicobacter pylori Eradication Strategy in the Era of Antibiotic Resistance. Antibiotics (Basel) 2020; 9:antibiotics9080436. [PMID: 32717826 PMCID: PMC7459868 DOI: 10.3390/antibiotics9080436] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/11/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
Antibiotic resistance is the major reason for Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy (proton pump inhibitor, amoxicillin, and clarithromycin) is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.
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Affiliation(s)
- Su Young Kim
- Divison of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 26426, Korea;
| | - Jun-Won Chung
- Divison of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, 21, Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea
- Correspondence: ; Tel.: +82-32-460-3778; Fax: +82-32-460-3408
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Cho JH, Jin SY. Optimized diagnosis of Helicobacter pylori and tailored eradication therapy for preventing gastric cancer: a proposal for SHAKE strategy. Expert Rev Gastroenterol Hepatol 2020; 14:553-564. [PMID: 32410515 DOI: 10.1080/17474124.2020.1770594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION To decrease gastric cancer-related mortality, the Korean National Cancer Screening Program provides biennial screening gastroscopy to all individuals aged >40 years. However, a test-and-treat strategy of Helicobacter pylori for preventing gastric cancer has not been established. AREAS COVERED In this review, we present up-to-date results of endoscopic findings of H. pylori gastritis, optimal sites for H. pylori detection, gastric cancer risk assessment using serum pepsinogen, tailored eradication based on the antimicrobial resistance against H. pylori, and post-eradication surveillance. EXPERT OPINION Here we propose approaches to H. pylori diagnosis and treatment for preventing gastric cancer, termed 'Screening for H. pylori in Korea and Eradication (SHAKE)' strategy. This strategy consists of the following: (1) optimized H. pylori diagnosis, (2) individualized management based on the H. pylori infection status, and (3) tailored eradication therapy. H. pylori gastritis can be diagnosed by endoscopic observation of the gastric mucosal pattern at the greater curvature of the corpus. Measurement of the serum pepsinogen I/II ratio is useful for assessing the risk of gastric cancer. As a first-line treatment, tailored eradication based on the results of molecular testing is effective in a country with a high rate of clarithromycin-resistant H. pylori.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital , Seoul, Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University Hospital , Seoul, Korea
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Antimicrobial Susceptibility Pattern of Helicobacter heilmannii and Helicobacter ailurogastricus Isolates. Microorganisms 2020; 8:microorganisms8060957. [PMID: 32630563 PMCID: PMC7355750 DOI: 10.3390/microorganisms8060957] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 06/04/2020] [Accepted: 06/23/2020] [Indexed: 12/13/2022] Open
Abstract
A combined agar and broth dilution method followed by qPCR was used to determine the antimicrobial susceptibility of feline H. heilmannii and H. ailurogastricus isolates. All H. ailurogastricus isolates showed a monomodal distribution of MICs for all the antimicrobial agents tested. For H. heilmannii, a bimodal distribution was observed for azithromycin, enrofloxacin, spectinomycin, and lincomycin. Single nucleotide polymorphisms (SNPs) were found in 50S ribosomal proteins L2 and L3 of the H. heilmannii isolate not belonging to the WT population for azithromycin, and in 30S ribosomal proteins S1, S7, and S12 of the isolate not belonging to the WT population for spectinomycin. The antimicrobial resistance mechanism to enrofloxacin and lincomycin remains unknown (2 and 1 H. heilmannii isolate(s), resp.). Furthermore, H. heilmannii isolates showed higher MICs for neomycin compared to H. ailurogastricus isolates which may be related to the presence of SNPs in several 30S and 50S ribosomal protein encoding genes and ribosomal RNA methyltransferase genes. This study shows that acquired resistance to azithromycin, spectinomycin, enrofloxacin, and lincomycin occasionally occurs in feline H. heilmannii isolates. As pets may constitute a source of infection for humans, this should be kept in mind when dealing with a human patient infected with H. heilmannii.
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Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains. J Clin Med 2020; 9:jcm9061930. [PMID: 32575584 PMCID: PMC7356929 DOI: 10.3390/jcm9061930] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/10/2020] [Accepted: 06/17/2020] [Indexed: 12/12/2022] Open
Abstract
Background: The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. Methods: A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. Results: Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. Conclusions: All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.
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Kumar S, Metz DC, Kaplan DE, Goldberg DS. The association of Helicobacter pylori with pancreatic cancer. ACTA ACUST UNITED AC 2020; 2:157-164. [PMID: 33692655 DOI: 10.1002/ygh2.398] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background & Aims Infection with Helicobacter pylori (HP) affects 50% of the world. Previous studies have suggested an association between HP and pancreatic adenocarcinoma (PC). These association studies have been limited in their ability to identify the incidence and risk factors of PC among HP infected individuals and the impact of HP eradication on PC. Methods Retrospective cohort study within the Veterans Administration of 103,595 patients (median age 62.3; 92.0% male) with HP diagnosis based on pathology, stool antigen, urea breath test, or serum antibody between 1/1/1994-12/31/2018. Primary outcome was future PC diagnosis. A time to event with competing risk analysis was performed, evaluating patient demographics and history, method of HP diagnosis, and whether the patient received HP treatment. Secondary analysis of those treated evaluated whether confirmed eradication was associated with PC. Results The cumulative incidence of PC at 5 and 10 years was 0.37% and 0.54%, respectively. Patients who developed PC were older, male, reside in areas with higher poverty. Preceding diabetes and chronic pancreatitis were strongly associated with PC. Factors not associated with PC included receiving an eradication regimen, diagnosis of an active infection (versus prior exposure alone), and eradication of HP. Conclusions PC after HP is rare. Chronic pancreatitis is the main risk factor for PC. Active HP infection, treatment of HP infection, or eradication of HP are not associated with future PC. This study calls into question the association between PC and HP.
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Affiliation(s)
- Shria Kumar
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - David C Metz
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania
| | - David E Kaplan
- Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania.,Division of Gastroenterology, Veterans Health Administration
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine
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