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Salahi-Niri A, Nabavi-Rad A, Monaghan TM, Rokkas T, Doulberis M, Sadeghi A, Zali MR, Yamaoka Y, Tacconelli E, Yadegar A. Global prevalence of Helicobacter pylori antibiotic resistance among children in the world health organization regions between 2000 and 2023: a systematic review and meta-analysis. BMC Med 2024; 22:598. [PMID: 39710669 DOI: 10.1186/s12916-024-03816-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 12/11/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance. This systematic review and meta-analysis aimed to comprehensively assess the global prevalence of antibiotic resistance in pediatric H. pylori infection. METHODS We performed a systematic search of publication databases that assessed H. pylori resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline in children. The WHO region classification was used to group pooled primary and secondary resistance estimates along with 95% confidence interval (CI). H. pylori antibiotic resistance rates were retrieved and combined with odds ratios (95% CI) to investigate the global prevalence and temporal trends. Subgroup analysis of the prevalence of antibiotic resistance was conducted by country, age groups, and susceptibility testing methods. RESULTS Among 1417 records obtained initially, 152 studies were selected for eligibility assessment after applying exclusion criteria in multiple steps. Ultimately, 63 studies involving 15,953 individuals were included comprising data from 28 countries in 5 WHO regions. The primary resistance rates were metronidazole 35.3% (5482/15,529, 95% CI: 28.7-42.6), clarithromycin 32.6% (5071/15,555, 95% CI: 27.7-37.9), tetracycline 2.1% (148/7033, 95% CI: 1.3-3.6), levofloxacin 13.2% (1091/8271, 95% CI: 9.3-18.4), and amoxicillin 4.8% (495/10305, 95% CI: 2.5-8.8). Raising antibiotic resistance was detected in most WHO regions. CONCLUSIONS The escalating trend of H. pylori antibiotic resistance in children warrants urgent attention globally. National and regional surveillance networks are required for antibiotic stewardship in children infected with H. pylori.
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Affiliation(s)
- Aryan Salahi-Niri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tanya Marie Monaghan
- National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK
- Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Theodore Rokkas
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece
- Medical School, European University of Cyprus, Nicosia, Cyprus
| | - Michael Doulberis
- Gastroklinik, Private Gastroenterological Practice, Horgen, 8810, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau, 5001, Switzerland
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Oita, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA
- Research Center for Global and Local Infectious Diseases, Oita University, Oita, Japan
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Uyduran Ünal N, Barutçu A, Nagiyev T, Ağın M, Kandemir T, Üsküdar O, Doran F, Köksal F, Tümgör G. Pathogenic and Genetic Characteristics of Helicobacter Pylori, and its Relationship with Drug-Resistance. GAZI MEDICAL JOURNAL 2024; 35:351-356. [DOI: 10.12996/gmj.2024.3624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025] Open
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Cheung KS, Lyu T, Deng Z, Han S, Ni L, Wu J, Tan JT, Qin J, Ng HY, Leung WK, Seto WK. Vonoprazan Dual or Triple Therapy Versus Bismuth-Quadruple Therapy as First-Line Therapy for Helicobacter pylori Infection: A Three-Arm, Randomized Clinical Trial. Helicobacter 2024; 29:e13133. [PMID: 39244723 DOI: 10.1111/hel.13133] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. METHODS This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4-6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance. RESULTS A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: -2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: -3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: -2.9% and -2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively. CONCLUSIONS VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection. TRIAL REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.
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Affiliation(s)
- Ka Shing Cheung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Tao Lyu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Zijie Deng
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Shaowei Han
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Li Ni
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Juan Wu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jing Tong Tan
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Jian Qin
- Department of Medicine, Yulin Traditional Chinese Medicine Hospital, Guangxi, China
| | - Ho Yu Ng
- School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong
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Zhou Y, Zhang Y, Du S. Antibiotic resistance in Helicobacter pylori among children and adolescents in East Asia: A systematic review and meta-analysis. Chin Med J (Engl) 2024; 137:1926-1938. [PMID: 38230488 PMCID: PMC11332731 DOI: 10.1097/cm9.0000000000002884] [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] [Received: 09/13/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND In East Asia, Helicobacter pylori ( H. pylori ) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations. METHODS We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori , and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies. RESULTS We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40-62%) for metronidazole; 37% (95% CI: 20-53%) for clarithromycin; 19% (95% CI: 11-28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21-36%) and 10% (95% CI: 7-14%), highlighting the potential for diverse resistance patterns. CONCLUSIONS H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem. REGISTRATION PROSPERO, No. CRD42023402510.
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Affiliation(s)
- Yuhang Zhou
- Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yanli Zhang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shiyu Du
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Cabrera C, Torres J, Serrano CA, Gallardo P, Orellana V, George S, O'Ryan M, Lucero Y. Antimicrobial Resistance of Helicobacter pylori Isolated From Latin American Children and Adolescents (2008-2023): A Systematic Review. Helicobacter 2024; 29:e13101. [PMID: 38987862 DOI: 10.1111/hel.13101] [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: 03/20/2024] [Revised: 05/18/2024] [Accepted: 05/28/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Latin America has a high prevalence of Helicobacter pylori in children that may lead to peptic ulcer disease and eventually gastric cancer in adulthood. Successful eradication is hindered by rising antimicrobial resistance. We summarize H. pylori resistance rates in Latin American children from 2008 to 2023. MATERIAL AND METHODS Systematic review following PRISMA guidelines and National Heart, Lung, and Blood Institute checklist to assess risk of bias (PROSPERO CRD42024517108) that included original cross-sectional observational studies reporting resistance to commonly used antibiotics in Latin American children and adolescents. We searched in PubMed, LILACS, and SciELO databases. RESULTS Of 51 studies, 45 were excluded. The quality of the six analyzed studies (297 H. pylori-positive samples) was satisfactory. Phenotypic methods (N = 3) reported higher resistance rates than genotypic studies (N = 3). Clarithromycin resistance ranged from 8.0% to 26.7% (6 studies; 297 samples), metronidazole from 1.9% to 40.2% (4 studies; 211 samples), amoxicillin from 0% to 10.4% (3 studies; 158 samples), tetracycline resistance was not detected (3 studies; 158 samples), and levofloxacin resistance was 2.8% (1 study; 36 samples). CONCLUSION Scarce Latin American studies on H. pylori resistance, along with methodological heterogeneity, hinder conclusive findings. Clarithromycin and metronidazole (first-line drugs) resistance is worrisome, likely impacting lower eradication rates. Urgent systematic surveillance or individual testing before treatment is necessary to enhance eradication.
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Affiliation(s)
- Camila Cabrera
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Joaquín Torres
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Carolina A Serrano
- Department of Pediatric Gastroenterology and Nutrition, School of Medicine, Pontitifica Universidad Católica de Chile, Santiago, Chile
| | - Paulina Gallardo
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Vicente Orellana
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Sergio George
- Department of Pediatrics and Pediatric Surgery (Eastern Campus), Hospital Luis Calvo Mackenna, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Miguel O'Ryan
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Yalda Lucero
- Microbiology and Mycology Program, Institute of Biomedical Sciences, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Department of Pediatrics and Pediatric Surgery (Northern Campus), Hospital de niños Roberto del Río, Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Pediatric Gastroenterology Unit, Clínica Alemana de Santiago, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile
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Zhao P, Zhao J, Shi H, Meng F, Yang N, Dong L, Gong J. Relationship between antibiotic resistance and the cagA and vacA genotypes among Helicobacter pylori strain isolates from patients in Xi'an. Braz J Microbiol 2023; 54:2773-2780. [PMID: 37779175 PMCID: PMC10689652 DOI: 10.1007/s42770-023-01133-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 09/19/2023] [Indexed: 10/03/2023] Open
Abstract
The issue of drug resistance of Helicobacter pylori is becoming increasingly serious. To analyze the correlation between the cagA and vacA genotypes of H. pylori strains and their resistance to metronidazole, levofloxacin, and clarithromycin in patients in Xi'an, we studied 117 H. pylori strains isolated from patients in Xi'an. Antibiotic susceptibility testing of H. pylori was performed. The cagA and vacA genotypes were investigated using PCR. Among 117 strains of H. pylori, the rate of detection of cagA was 91.45% (107/117), among which the detection rate of East Asian-type cagA was 85.05% (91/107) and that of Western-type cagA was 14.95% (16/107). There were only two genotypes of vacA: s1m1 and s1m2. The detection rate of vacAs1m1 was 47.01% (55/117) and that of vacAs1m2 was 52.99% (62/117). The dominant strains in Xi'an were cagA + vacAs1m2 strains. The metronidazole resistance rate of vacAs1m2 H. pylori strains was significantly higher than that of vacAs1m1 H. pylori strains (91.94% vs. 69.09%, P = 0.002). The levofloxacin resistance rate of Western-type cagA strains was significantly higher than that of East Asian-type cagA strains (56.25% vs. 20.88%, P = 0.004). The metronidazole resistance rate of cagA + vacAs1m2 H. pylori strains was significantly higher than that of cagA + vacAs1m1 H. pylori strains (91.23% vs. 66.00%, P = 0.001). Our results showed that Western-type cagA strains were more likely to develop levofloxacin resistance than East Asian-type cagA strains. VacAs1m2 strains were more prone to metronidazole resistance than vacAs1m1 strains.
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Affiliation(s)
- Ping Zhao
- Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West No. 5 Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
| | - Juhui Zhao
- Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West No. 5 Road, Xi'an, 710004, Shaanxi Province, People's Republic of China
| | - Haitao Shi
- Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West No. 5 Road, Xi'an, 710004, Shaanxi Province, People's Republic of China
| | - Fei Meng
- Zhiyuan Medical Inspection Institute Co., Ltd., Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Ningmin Yang
- Zhiyuan Medical Inspection Institute Co., Ltd., Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Lei Dong
- Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West No. 5 Road, Xi'an, 710004, Shaanxi Province, People's Republic of China
| | - Jun Gong
- Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, 157 West No. 5 Road, Xi'an, 710004, Shaanxi Province, People's Republic of China
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Han S, Deng Z, Cheung K, Lyu T, Chan P, Li Y, Ni L, Luo X, Li K. Vonoprazan-based triple and dual therapy versus bismuth-based quadruple therapy for Helicobacter pylori infection in China: a three-arm, randomised clinical trial protocol. BMC Gastroenterol 2023; 23:231. [PMID: 37420205 DOI: 10.1186/s12876-023-02872-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 07/04/2023] [Indexed: 07/09/2023] Open
Abstract
BACKGROUND Helicobacter pylori infection and associated diseases are a growing global public health issue. H. pylori infection is the major cause of gastric cancer, over 90% of duodenal ulcers, and over 70% of gastric ulcers. The infection rate of H. pylori is approximately 50%, and approximately 50% of new cases of gastric cancer worldwide occur in China. Bismuth (BI)-based quadruple therapy is recommended as the first-line treatment for H. pylori in China. Vonoprazan (VPZ), a new potassium-competitive acid blocker that can inhibit gastric acid secretion more effectively than proton pump inhibitors (PPIs), has been combined with antibiotics to effectively eradicate H. pylori. In this study, we compared the efficacy and safety of two VPZ-based therapies with that of BI-based therapy for H. pylori treatment. METHODS A three-armed randomised controlled trial (RCT) is being conducted in Shenzhen, with 327 participants recruited from the Gastroenterology Clinic of the University of Hong Kong-Shenzhen Hospital. Patients were diagnosed with H. pylori infection based on a positive 13C-urea breath test (UBT). Patients are kept naïve to their treatment and are randomly assigned in a 1:1:1 ratio to either VPZ-based triple, VPZ-based dual, or BI-based quadruple therapy for 14 days. All groups are subjected to follow-up evaluations of safety, adverse drug reactions, and clinical variables in the first, second, and fourth weeks after treatment. Successful eradication is confirmed by a negative 13C-UBT six weeks after treatment. If initial treatment fails, (1) those patients are turned to another regimen, or (2) a drug resistance test is conducted, after which an individualised treatment regimen shall be prescribed according to antimicrobial susceptibility testing. The resulting data will be evaluated using intention-treat and a per-protocol analysis. DISCUSSION This study is the a RCT aims to evaluate the efficacy and safety of 14-day VPZ-based triple and dual therapies in comparison with BI-based quadruple therapy. The outcomes of this study may allow treatment recommendations and update drug instructions in China. TRIAL REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=141314.
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Affiliation(s)
- ShaoWei Han
- Shantou University Medical College, Shantou, China
- Department of Pharmacy, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - ZiJie Deng
- Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - KaShing Cheung
- Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Tao Lyu
- Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - PuiLing Chan
- Department of Pharmacy, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ying Li
- Department of Pharmacy, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Li Ni
- Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - XiaPeng Luo
- Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Kuan Li
- Department of Pharmacy, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, China.
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Sholeh M, Khoshnood S, Azimi T, Mohamadi J, Kaviar VH, Hashemian M, Karamollahi S, Sadeghifard N, Heidarizadeh H, Heidary M, Saki M. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. PeerJ 2023; 11:e15121. [PMID: 37016679 PMCID: PMC10066884 DOI: 10.7717/peerj.15121] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/03/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori (H. pylori) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics. METHOD A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance. RESULTS The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41-29.69]). The heterogeneity between reports was significant (I2 = 97.80%, P < 0.01). The resistance rate increased from 24.28% in 2010-2017 to 32.14% in 2018-2021 (P < 0.01). Iran, with 38 articles, has the most report. Nevertheless, Switzerland, Portugal, and Israel had the highest resistance rates (67.16%, 48.11%, and 46.12%, respectively). The heterogeneity between the continents and the antimicrobial susceptibility methods also interpreted standard guidelines and breakpoints was insignificant (P > 0.05). CONCLUSION Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains.
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Affiliation(s)
- Mohammad Sholeh
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Taher Azimi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jasem Mohamadi
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Vahab Hassan Kaviar
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Marzieh Hashemian
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Somayeh Karamollahi
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Hedayat Heidarizadeh
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Gao W, Teng G, Wang C, Xu Y, Li Y, Cheng H. Eradication rate and safety of a "simplified rescue therapy": 14-day vonoprazan and amoxicillin dual regimen as rescue therapy on treatment of Helicobacter pylori infection previously failed in eradication: A real-world, retrospective clinical study in China. Helicobacter 2022; 27:e12918. [PMID: 35877765 PMCID: PMC9542484 DOI: 10.1111/hel.12918] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/31/2022] [Accepted: 06/17/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND The currently recommended quadruple regimens as rescue therapy on Helicobacter pylori infection were not as effective as being supposed, especially in those who had failed two or more times. Dual regimen composed of vonoprazan (a potassium-competitive acid blocker) and amoxicillin might be an option since it's effective in eradication therapy as first-line treatment. OBJECTIVE As a real-world retrospective study, data were collected to evaluate the efficacy and safety of vonoprazan and amoxicillin dual regimen as rescue therapy in Helicobacter pylori positive patients who had failed one or more times in their previous treatment. METHODS From May 2020 to June 2021, the clinical data of patients who had failed in Helicobacter pylori infection treatment were collected in GI department of Peking University First Hospital, Beijing, China. Patients were given vonoprazan 20 mg or 40 mg per day and amoxicillin 3000 mg per day (VA dual therapy) for 14 days as rescue treatment. Helicobacter pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects during treatment were recorded. RESULTS A total of 186 patients were enrolled, including 67 males and 119 females. All of them had failed for 1 ~ 7 times in their previous treatment. Successful eradication was achieved in 172 patients (92.5%, 172/186). The adverse effects (referring to skin rash, abdominal pain, diarrhea, and headache), mainly mild and did not cause quit of treatment, occurred in 14 patients (7.5%, 14/186) and all symptoms relieved spontaneously. CONCLUSIONS Dual regimen composed of vonoprazan and amoxicillin for 14 days was effective and safe as rescue therapy in Helicobacter pylori infection treatment. It could be chosen as a "simplified rescue therapy" with relatively high eradication rate no matter how many times the patients had failed and what regimens they had used previously.
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Affiliation(s)
- Wen Gao
- GI DepartmentPeking University First HospitalBeijingChina
| | - Guigen Teng
- GI DepartmentPeking University First HospitalBeijingChina
| | - Chi Wang
- GI DepartmentPeking University First HospitalBeijingChina
| | - Ying Xu
- GI DepartmentPeking University First HospitalBeijingChina
| | - Yixuan Li
- GI DepartmentPeking University First HospitalBeijingChina
| | - Hong Cheng
- GI DepartmentPeking University First HospitalBeijingChina
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10
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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] [MESH Headings] [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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11
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Pop R, Tăbăran AF, Ungur AP, Negoescu A, Cătoi C. Helicobacter Pylori-Induced Gastric Infections: From Pathogenesis to Novel Therapeutic Approaches Using Silver Nanoparticles. Pharmaceutics 2022; 14:pharmaceutics14071463. [PMID: 35890358 PMCID: PMC9318142 DOI: 10.3390/pharmaceutics14071463] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 06/29/2022] [Accepted: 07/11/2022] [Indexed: 02/01/2023] Open
Abstract
Helicobacter pylori is the first formally recognized bacterial carcinogen and the most important single digestive pathogen responsible for the induction of gastroduodenal diseases such as gastritis, peptic ulcer, and, finally, gastric neoplasia. The recently reported high rates of antimicrobial drug resistance hamper the current therapies of H. pylori, with therapeutic failure reaching up to 40% of patients. In this context, new treatment options and strategies are urgently needed, but the successful development of these new therapeutic tools is conditioned by the understanding of the high adaptability of H. pylori to the gastric acidic environment and the complex pathogenic mechanism. Due to several advantages, including good antibacterial efficiency, possible targeted delivery, and long tissular persistence, silver nanoparticles (AgNPs) offer the opportunity of exploring new strategies to improve the H. pylori therapy. A new paradigm in the therapy of H. pylori gastric infections using AgNPs has the potential to overcome the current medical limitations imposed by the H. pylori drug resistance, which is reported for most of the current organic antibiotics employed in the classical therapies. This manuscript provides an extensive overview of the pathology of H. pylori-induced gastritis, gastric cancer, and extradigestive diseases and highlights the possible benefits and limitations of employing AgNPs in the therapeutic strategies against H. pylori infections.
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12
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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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13
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Nemr N, Kishk RM, Salem A, Abdalla MO, Abd El-Fadeal NM, Soliman NM. Genotypic detection of metronidazole and clarithromycin resistance in dyspeptic patients with helicobacter pylori. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:41467-41474. [PMID: 35088259 DOI: 10.1007/s11356-021-18198-4] [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: 07/12/2021] [Accepted: 12/14/2021] [Indexed: 06/14/2023]
Abstract
In Egypt, antibiotic sensitivity analysis for Helicobacter pylori is not routinely performed. We aimed to identify the clarithromycin and metronidazole resistance directly from gastric biopsies for better guide treatment regimens. This cross-sectional descriptive study included 75 adult dyspeptic patients referred to the upper endoscopy unit in Suez Canal University Hospital, Ismailia, Egypt. Gastric biopsies were taken for rapid urease test (RUT) and cultured on brucella agar with antibiotic supplements. Genomic DNA was extracted directly from the specimen, and PCR was performed for direct detection of H. pylori. Also, to explore clarithromycin and metronidazole resistance, mutations in the 23S rRNA gene and the rdxA gene were investigated. We found that 60 samples were positive to RUT (80%), and only 4 samples were positive by culture. UreC gene was detected in 45 specimens. Meanwhile, 26 isolates were contained mutations at positions 2142 and 2143. Amplification of the metronidazole rdx gene was performed by conventional PCR. Out of 45 isolates, DNA sequence analysis of PCR product showed the wild type (ACA) in 9 isolates, while the mutant type (ATA) was detected in 28 isolates. We found a significant proportion of clarithromycin and metronidazole resistance among H. pylori infected patients in our region.
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Affiliation(s)
- Nader Nemr
- Endemic and Infectious Diseases Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt
| | - Rania M Kishk
- Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt.
| | - Ayman Salem
- Internal Medicine Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt
| | - Mohamed O Abdalla
- Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt
| | - Noha M Abd El-Fadeal
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt
| | - Nashaat M Soliman
- Endemic and Infectious Diseases Department, Faculty of Medicine, Suez Canal University, Ismailia, 4155, Egypt
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14
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Feng Y, Hu W, Wang Y, Lu J, Zhang Y, Tang Z, Miao S, Zhou Y, Huang Y. Efficacy of Phenotype-vs. Genotype-Guided Therapy Based on Clarithromycin Resistance for Helicobacter pylori Infection in Children. Front Pediatr 2022; 10:854519. [PMID: 35425727 PMCID: PMC9002118 DOI: 10.3389/fped.2022.854519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 02/28/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Clarithromycin resistance reduces the eradication rate of Helicobacter pylori (H. pylori). Cultures with susceptibility testing and molecular determination of genotypes are recommended to guide-tailored therapy. METHODS We retrospectively enrolled patients aged 6 and 18 years with H. pylori infection, who underwent an endoscopy and agreed to undergo both culture and genetic testing for clarithromycin resistance. Patients receiving tailored therapy based on traditional culture results (phenotype-guided therapy) or genetic testing results (genotype-guided therapy) were included in the study. 13C-urea breath test was used to evaluate the success of eradication at least 4 weeks after the completion of treatment. We aimed to determine whether the eradication rate of phenotype- or genotype-guided therapy based on clarithromycin resistance is greater than 90% in children. RESULTS Between September 2017 and October 2020, 226 eligible patients were enrolled. There were 71 with clarithromycin-sensitive strains in the phenotype-guided therapy group and 87 without 23S rRNA point mutations (A2142G, A2142C, and A2143G) in the genotype-guided therapy group. Eradication rates were 70.4% (50/71, [95% CI: 58.4-80.7%] for phenotype-guided therapy and 92.0% (80/87, [95% CI: 84.1-96.7%]) for genotype-guided therapy (P < 0.01). The incidence of side effects was 4.2% (3/71) and 10.3% (9/87), with no major differences between these two groups (P = 0.15), respectively. The compliance rate was also similar (97.2 vs. 95.4%, P = 0.87). CONCLUSION Tailored therapy according to genetic testing results achieved eradication rates of 92% and was superior to tailored therapy guided by traditional culture results.
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Affiliation(s)
- Yan Feng
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Wenhui Hu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Junping Lu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ye Zhang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Zifei Tang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Shijian Miao
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Zhou
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
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15
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Mišak Z, Hojsak I. Helicobacter Pylori Gastritis and Peptic Ulcer Disease. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:169-184. [DOI: 10.1007/978-3-030-80068-0_12] [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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16
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Zhao Y, Li Y, Luan Z, Ma C, Yang L, Zhang W, Shi C. Establishment of a TaqMan-MGB probe multiplex real-time PCR system for one-step levofloxacin and clarithromycin resistant Helicobacter pylori detection. J Microbiol Methods 2021; 192:106393. [PMID: 34919971 DOI: 10.1016/j.mimet.2021.106393] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/10/2021] [Accepted: 12/10/2021] [Indexed: 12/16/2022]
Abstract
Due to the abuse of antibiotics, the prevalence of antibiotic resistant Helicobacter pylori strains continues to increase. Therefore, antibiotic resistance assessment is now essential in addition to general H. pylori diagnosis in medical institutions to fulfill clinicians administering effective antibiotic regimens. However, the conventional antibiotic resistance assessment methods, such as in vitro antibiotic susceptibility test and E-test, are skilled-staff dependent and time-consuming. The aim of this study was to establish an easy-operating TaqMan-MGB probe multiplex real-time PCR system for one-step detection of levofloxacin and clarithromycin resistance mutations with concurrent H. pylori infection diagnosis. Through the optimization of primers, probes and reaction buffers, this proposed system could accurately distinguish the recombinant plasmids with different mutation markers. More importantly, the diagnosis results of this detection system exhibited excellent consistence with the gold standard of gastric biopsy and Sanger sequencing on the detection of H. pylori infection and relevant antibiotic resistant strains, the Kappa values of which all exceeded 0.90. In addition, the results of this detection system could also be applied for the prevalence statistics of antibiotic resistance patterns for patients by age, gender and geographical location. This simple and rapid system should be beneficial for clinicians issuing personalized treatments according to the patient's H. pylori strains and avoid the abuse of antibiotics.
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Affiliation(s)
- Yan Zhao
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Yang Li
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Zhixian Luan
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China
| | - Cuiping Ma
- Shandong Provincial Key Laboratory of Biochemical Engineering, Qingdao Nucleic Acid Rapid Detection Engineering Research Center, College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China
| | - Lin Yang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wang Zhang
- Department of Gastroenterology, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chao Shi
- Qingdao Nucleic Acid Rapid Testing International Science and Technology Cooperation Base, College of Life Sciences, Department of Pathogenic Biology, School of Basic Medicine, and Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, PR China.
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17
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Li SY, Li J, Dong XH, Teng GG, Zhang W, Cheng H, Gao W, Dai Y, Zhang XH, Wang WH. The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: A retrospective study over 8 years in Beijing. Helicobacter 2021; 26:e12804. [PMID: 33860967 DOI: 10.1111/hel.12804] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/23/2021] [Accepted: 03/17/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.
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Affiliation(s)
- Si-Yu Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Jiang Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xin-Hong Dong
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Gui-Gen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Hong Cheng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wen Gao
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiao-He Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei-Hong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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18
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Lyu T, Cheung KS, Ni L, Guo J, Mu P, Li Y, Yang Q, Yu X, Lyu Z, Wu J, Guo H, Leung WK, Seto WK. High prevalence and risk factors of multiple antibiotic resistance in patients who fail first-line Helicobacter pylori therapy in southern China: a municipality-wide, multicentre, prospective cohort study. J Antimicrob Chemother 2021; 75:3391-3394. [PMID: 32785699 DOI: 10.1093/jac/dkaa315] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 06/19/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND We aimed to study the prevalence of secondary antibiotic resistance of Helicobacter pylori in southern China and its risk factors, particularly geographical and socio-economic factors. METHODS This was a municipality-wide, multicentre, prospective cohort study involving five major hospitals. Patients aged ≥18 years who failed first-line bismuth-based quadruple anti-H. pylori therapy between September 2016 and February 2018 were recruited. Participants underwent upper gastrointestinal endoscopy with biopsy from the antrum and body for H. pylori culture and antimicrobial susceptibility testing for six antibiotics (clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline and furazolidone). Patients with failure of H. pylori culture were excluded. Participants completed a questionnaire profiling 22 potential risk factors of H. pylori infection and antibiotic resistance, including medical, social, household and birthplace factors. RESULTS A total of 1113 patients failed first-line therapy, with successful H. pylori culture in 791 (71.1%) [male = 433 (54.7%); median age = 43 years]. Secondary resistance rates of dual antibiotics (clarithromycin + metronidazole and levofloxacin + metronidazole) and triple antibiotics (clarithromycin + levofloxacin + metronidazole) were 34.0%, 38.7% and 17.8%, respectively. Risk factors for clarithromycin + metronidazole resistance were history of ≥2 courses of H. pylori therapies [adjusted OR (aOR) = 1.71; 95% CI = 1.17-2.54], ≥3 household members (aOR = 2.00; 95% CI = 1.07-3.90) and family history of gastric cancer (aOR = 1.85; 95% CI = 1.18-2.85). Risk factors for levofloxacin + metronidazole resistance were age ≥40 years (aOR = 1.94; 95% CI = 1.37-2.75), lower gross domestic product per capita (aOR = 0.29; 95% CI = 0.10-0.80) and higher number of doctors/10 000 population (aOR = 1.59; 95% CI = 1.07-2.39). A higher human development index was of borderline significance (aOR = 2.79; 95% CI = 0.97-8.70). CONCLUSIONS The rates of secondary resistance of H. pylori to multiple antibiotics were high in southern China. Certain population-level risk factors were associated with levofloxacin + metronidazole resistance.
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Affiliation(s)
- Tao Lyu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ka Shing Cheung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
| | - Li Ni
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jiaqi Guo
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Pei Mu
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Yinpeng Li
- Division of Gastroenterology, Shenzhen People's Hospital Longhua Branch, Shenzhen, China
| | - Qiu Yang
- Division of Gastroenterology, Shenzhen People's Hospital Longhua Branch, Shenzhen, China
| | - Xiqiu Yu
- Division of Gastroenterology, Shenzhen Luohu Hospital Group Luohu People's Hospital, Shenzhen, China
| | - Zhiwu Lyu
- Division of Gastroenterology, Baoan People's Hospital of Shenzhen (Group), Shenzhen, China
| | - Jianwei Wu
- Division of Gastroenterology, Baoan People's Hospital of Shenzhen (Group), Shenzhen, China
| | - Haijian Guo
- Division of Gastroenterology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.,Department of Medicine, The University of Hong Kong, Hong Kong
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19
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Li J, Deng J, Wang Z, Li H, Wan C. Antibiotic Resistance of Helicobacter pylori Strains Isolated From Pediatric Patients in Southwest China. Front Microbiol 2021; 11:621791. [PMID: 33574804 PMCID: PMC7870467 DOI: 10.3389/fmicb.2020.621791] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/31/2020] [Indexed: 02/05/2023] Open
Abstract
The number of antibiotics that are appropriate for Helicobacter pylori eradication in children is limited. Profiling regional or population-specific antibiotic resistance is essential in guiding the H. pylori eradication treatment in children. The aim of this study was to evaluate the antibiotic resistance in H. pylori strains isolated from children and adolescents in Southwest China. Gastric biopsies from 157 pediatric patients with or without previous H. pylori eradication treatment were collected for H. pylori culture. Susceptibility to amoxicillin (AML), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET), furazolidone (FZD), and rifampicin (RIF) was determined by E-test or a disk diffusion assay. A total of 87 patients from three ethnic groups (Han/Tibetan/Yi) were H. pylori culture positive (55.4%). The overall resistance rates were 55.2% for CLR, 71.3% for MTZ, 60.9% for RIF, and 18.4% for LEV. No isolate was found to be resistant to AML, TET, and FZD. Among the 53 treatment-naïve pediatric patients, primary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 45.3, 73.6, 15.1, and 60.4%, respectively. Among the 34 treatment-experienced patients, secondary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 70.6, 67.6, 23.5, and 61.8%, respectively. Isolates exhibiting simultaneous resistance to clarithromycin and metronidazole were 28.3 and 52.9% among the treatment-naïve and treatment-experienced patients, respectively. In conclusion, among pediatric patients in Southwest China, resistance rates were high for clarithromycin, metronidazole, levofloxacin, and rifampicin, whereas nil resistance was found to amoxicillin, tetracycline, and furazolidone. Our data suggest that the standard clarithromycin-based triple therapy should be abandoned as empiric therapy, whereas the bismuth quadruple therapy (bismuth/PPI/amoxicillin/tetracycline) would be suitable as first-line empiric treatment regimen for this pediatric population. Tetracycline and furazolidone may be considered for treating refractory H. pylori infections in adolescent patients.
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Affiliation(s)
- Juan Li
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Department of Infection Control, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Jianjun Deng
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Department of Infection Control, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Zhiling Wang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Chaomin Wan
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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Crowley E, Hussey S. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:275-292.e12. [DOI: 10.1016/b978-0-323-67293-1.00027-x] [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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21
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Ye L, Meng F, Mao X, Zhang Y, Wang J, Liu Y, Zhu W, Gu B, Huang Q. Using next-generation sequencing to analyze Helicobacter pylori clones with different levofloxacin resistances from a patient with eradication failure. Medicine (Baltimore) 2020; 99:e20761. [PMID: 32769862 PMCID: PMC7593070 DOI: 10.1097/md.0000000000020761] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 04/15/2020] [Accepted: 05/19/2020] [Indexed: 01/11/2023] Open
Abstract
The regimens containing levofloxacin (LVX) have been recommended as an alternate to standard triple therapy to treat Helicobacter pylori infections and H pylori mixed infection always lead to H pylori chronic infection. Although the molecular mechanism of LVX resistance with gyrA gene mutation has been clearly understood in H pylori, other genes involved in antibiotic resistance remain unclear. Efflux pump plays an important role in clinically relevant multidrug resistance. Furthermore, the relationship between the strains with different LVX level-resistances from individuals is also unknown.Helicobacter pylori monoclonal strains were isolated from patients with eradication failure. E test was used to detect the minimal inhibitory concentration of LVX. One lower-level LVX-resistant clone and 2 higher-level LVX-resistant clones from the same patient were selected to sequence the complete genomes. Single-nucleotide variants (SNVs) and mutations were extracted and analyzed from gryA and resistance-nodulation-division family efflux genes.Two clones with higher-level resistance had the mutation pattern of Asn87Lys and one lower-level LVX-resistant clone had an Asp91Asn mutation. Compared to clones with higher-level resistance, the higher genetic variations were found in genes belonging to the resistance-nodulation-division family in H pylori strains with lower-level resistance to LVX. There were significantly more SNVs of Hp0970 (hefE) and Hp1329 (hefI) in the lower-level LVX-resistant clone than those in the higher-level LVX-resistant clones (P = .044).The mutation pattern of the Asn87Lys of the gyrA gene confers a higher resistance to LVX than that of the Asp91Asn in H pylori. Increase in the number of SNVs of the Hp0970 (hefE) and Hp1329 (hefI) genes change the resistance to LVX. Twelve mutations verified by Sanger sequencing in Hp0970 (hefE) and Hp1329 (hefI) may decrease resistant levels to LVX.
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Affiliation(s)
- Liping Ye
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
- Department of Gastroenterology, Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou
| | - Fei Meng
- Department of Research Service, Zhiyuan Inspection Medical Institute, Hangzhou, Zhejiang, China
| | - Xinli Mao
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
| | - Yu Zhang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
| | - Jun Wang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
| | - Yunhui Liu
- Department of Research Service, Zhiyuan Inspection Medical Institute, Hangzhou, Zhejiang, China
| | - Wei Zhu
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
| | - Binbin Gu
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
| | - Qin Huang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province
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22
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Lu HH, Lai FP, Lo HY, Sheu BS, Yang YJ. Increasing antimicrobial resistance to clarithromycin and metronidazole in pediatric Helicobacter pylori infection in southern Taiwan: A comparison between two decades. Helicobacter 2019; 24:e12633. [PMID: 31295754 DOI: 10.1111/hel.12633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 05/01/2019] [Accepted: 06/15/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Antimicrobial resistance of Helicobacter pylori reduces the eradication rate. This study aimed to investigate changes in antimicrobial susceptibility of H pylori isolated from children in Taiwan in the past two decades. METHODS This study enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a national tertiary referring hospital from 1998 to 2018. H pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E test. The antibiotic resistance rates and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018. RESULTS A total of 70 Helicobacter pylori isolates (29 from 1998 to 2008 and 41 from 2009 to 2018) were identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n = 31), gastric ulcers (n = 9), and gastritis (n = 30). The overall antimicrobial resistance rates of clarithromycin and metronidazole were 22.9% and 21.4%, respectively. The dual resistance rate of clarithromycin and metronidazole was 10%. Resistance rates of levofloxacin and amoxicillin were 8.3% and 2.9%, respectively. None of the isolates were resistant to tetracycline. Compared with the isolates from 1998 to 2008, those from 2009 to 2018 had higher MICs and resistance rates of clarithromycin (26.8% vs 17.2%, P = 0.35) and metronidazole (26.8% vs 13.8%, P = 0.19), but not levofloxacin (9.8% vs 5.3%, P = 1.0) or coresistance to clarithromycin and metronidazole (12.2% vs 6.9%, P = 0.69). CONCLUSIONS The antimicrobial resistance rates of pediatric H pylori isolates to clarithromycin and metronidazole increased during the past decade. The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H pylori eradication rates.
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Affiliation(s)
- Hsiao-Han Lu
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Fu-Ping Lai
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Hsiao-Yu Lo
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Departments of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Yao-Jong Yang
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
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Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155:1372-1382.e17. [PMID: 29990487 PMCID: PMC6905086 DOI: 10.1053/j.gastro.2018.07.007] [Citation(s) in RCA: 799] [Impact Index Per Article: 114.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 06/27/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. METHODS We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. RESULTS We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). CONCLUSIONS Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
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Affiliation(s)
- Alessia Savoldi
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany
| | - Elena Carrara
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Michela Conti
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany; Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy.
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24
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Diab M, El-Shenawy A, El-Ghannam M, Salem D, Abdelnasser M, Shaheen M, Abdel-Hady M, El-Sherbini E, Saber M. Detection of antimicrobial resistance genes of Helicobacter pylori strains to clarithromycin, metronidazole, amoxicillin and tetracycline among Egyptian patients. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2018. [DOI: 10.1016/j.ejmhg.2018.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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25
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Yousefi-Avarvand A, Vaez H, Tafaghodi M, Sahebkar AH, Arzanlou M, Khademi F. Antibiotic Resistance of Helicobacter pylori in Iranian Children: A Systematic Review and Meta-Analysis. Microb Drug Resist 2018; 24:980-986. [PMID: 29227738 DOI: 10.1089/mdr.2017.0292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Antibiotic therapy for children infected with Helicobacter pylori is important. However, resistance to antibiotics is one of the main causes of treatment failure. This study was designed to evaluate the prevalence pattern of antibiotic resistance of H. pylori in Iranian children using a systematic review and meta-analysis of literature. A computerized search (until June 10, 2017) using related keywords in the national and international databases was performed. A total of 261 original articles on antibiotic resistance of H. pylori in Iranian children were collected. After screening for inclusion and exclusion criteria, six eligible articles were included in the meta-analysis. Resistance rates of H. pylori to different antibiotics were as follows: metronidazole: 71%, clarithromycin: 12.2%, amoxicillin: 20.4%, tetracycline: 8.4%, ampicillin: 21.4%, rifampin: 28.6%, furazolidone: 8.4%, ciprofloxacin: 16.2%, azithromycin: 19%, erythromycin: 15.3%, and nitrofurantoin: 0%. The prevalence of H. pylori resistance to metronidazole, amoxicillin, ampicillin, and rifampin among Iranian children was high. Therefore, a careful monitoring of antibiotic resistance to select the best treatment options and prevent treatment failure is required. Although resistance to some antibiotics such as clarithromycin, tetracycline, furazolidone, and ciprofloxacin was less prevalent, frequent consumption of these drugs in children should be controlled owing to their known adverse events.
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Affiliation(s)
- Arshid Yousefi-Avarvand
- 1 Department of Medical Bacteriology and Virology, School of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran
| | - Hamid Vaez
- 2 Department of Microbiology, School of Medicine, Zabol University of Medical Sciences , Zabol, Iran
| | - Mohsen Tafaghodi
- 3 Nanotechnology Research Center, Mashhad University of Medical Sciences , Mashhad, Iran
| | - Amir Hossein Sahebkar
- 4 Biotechnology Research Center, School of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran
| | - Mohsen Arzanlou
- 5 Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences , Ardabil, Iran
| | - Farzad Khademi
- 5 Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences , Ardabil, Iran
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Droplet Digital PCR-Based Detection of Clarithromycin Resistance in Helicobacter pylori Isolates Reveals Frequent Heteroresistance. J Clin Microbiol 2018; 56:JCM.00019-18. [PMID: 29925646 DOI: 10.1128/jcm.00019-18] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 06/15/2018] [Indexed: 12/14/2022] Open
Abstract
Chronic infection with Helicobacter pylori causes peptic ulcers and stomach cancer in a subset of infected individuals. While standard eradication therapy includes multiple antibiotics, treatment failure due to resistance is an increasing clinical problem. Accurate assessment of H. pylori antimicrobial resistance has been limited by slow growth and sampling of few isolates per subject. We established a method to simultaneously quantify H. pylori clarithromycin-resistant (mutant) and -susceptible (wild-type) 23S rRNA gene alleles in both stomach and stool samples using droplet digital PCR (ddPCR). In 49 subjects, we assessed the performance of these assays alongside clarithromycin MIC testing of up to 16 H. pylori isolates per subject and included both cancer (25 subjects) and noncancer (24 subjects) cases. Gastric ddPCR and H. pylori culture showed agreement with urea breath test (UBT) detection of infection in 94% and 88% of subjects, respectively, while stool ddPCR showed agreement with UBT in 92% of subjects. Based on MIC testing of 43 culture-positive cases, 20 subjects had only susceptible isolates, 14 had a mix of susceptible and resistant isolates, and 9 had only resistant isolates. ddPCR of gastric samples indicated that 21 subjects had only wild-type alleles, 13 had a mixed genotype, and 9 had only mutant alleles. Stool ddPCR detected mutant alleles in four subjects for which mutant alleles were not detected by stomach ddPCR, and no resistant isolates were cultured. Our results indicate that ddPCR detects H. pylori clarithromycin resistance-associated genotypes, especially in the context of heteroresistance.
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27
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Shu X, Yin G, Liu M, Peng K, Zhao H, Jiang M. Antibiotics resistance of Helicobacter pylori in children with upper gastrointestinal symptoms in Hangzhou, China. Helicobacter 2018. [PMID: 29528162 DOI: 10.1111/hel.12481] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The decreasing eradication rate of Helicobacter pylori is mainly because of the progressive increase in its resistance to antibiotics. Studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to investigate the resistance rates and patterns of H. pylori strains isolated from children. MATERIALS AND METHODS Gastric mucosa biopsy samples obtained from children who had undergone upper gastrointestinal endoscopy were cultured for H. pylori, and susceptibility to six antibiotics (clarithromycin, amoxicillin, gentamicin, furazolidone, metronidazole, and levofloxacin) was tested from 2012-2014. RESULTS A total of 545 H. pylori strains were isolated from 1390 children recruited. The total resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin were 20.6%, 68.8%, and 9.0%, respectively. No resistance to amoxicillin, gentamicin, and furazolidone was detected. 56.1% strains were single resistance, 19.6% were resistant to more than one antibiotic, 16.7% for double resistance, and 2.9% for triple resistance in 413 strains against any antibiotic. And the H. pylori resistance rate increased significantly from 2012-2014. There was no significant difference in the resistance rates to clarithromycin, metronidazole, and levofloxacin between different gender, age groups, and patients with peptic ulcer diseases or nonulcer diseases. CONCLUSIONS Antibiotic resistance was indicated in H. pylori strains isolated from children in Hangzhou, and it increased significantly during the 3 years. Our data strongly support current guidelines, which recommend antibiotic susceptibility tests prior to eradication therapy.
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Affiliation(s)
- Xiaoli Shu
- Gastrointestinal Laboratory, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Guofeng Yin
- Gastrointestinal Laboratory, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Pediatrics, Shaoxing Women & Children's Hospital, Shaoxing, China
| | - Mingnan Liu
- Gastrointestinal Laboratory, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kerong Peng
- Department of Gastroenterology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Hong Zhao
- Department of Gastroenterology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mizu Jiang
- Gastrointestinal Laboratory, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Department of Gastroenterology, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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28
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Zhu XL, Liu Z, Wu ZQ, Li D, Jiang AP, Yu GX. [Clinical effects of different therapeutic regimens for Helicobacter pylori infection in children]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2017. [PMID: 28606235 DOI: 10.7499/j.issn.1008-8830.2017.06.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To investigate the clinical effects of sequential therapy, triple therapy, sequential therapy combined with Lactobacillus, and triple therapy combined with Lactobacillus in the eradication of Helicobacter pylori (H.pylori) infection in children. METHODS A total of 416 children with H.pylori infection were randomly assigned to sequential group (102 children), triple group (100 children), sequential-Lactobacillus group (109 children), and triple-Lactobacillus group (105 children). The clinical outcome, H.pylori eradication rate, cost-effect ratio, and incidence of adverse events were compared between the four groups. RESULTS The sequential-Lactobacillus and triple-Lactobacillus groups had significantly better clinical outcomes than the sequential group and the triple group (P<0.05). The sequential-Lactobacillus group had the highest marked response rate, followed by the triple-Lactobacillus group. The triple group had the lowest marked response rate. The sequential-Lactobacillus group also had the highest H.pylori eradication rate, followed by the triple-Lactobacillus group. The triple group had the lowest H.pylori eradication rate (P<0.05). The sequential group had the lowest cost-effect ratio, followed by the sequential-Lactobacillus group. The triple group had the highest cost-effect ratio (P<0.01). The sequential-Lactobacillus group had the lowest incidence rate of adverse events, followed by the triple-Lactobacillus group. The triple group had the highest incidence rate. CONCLUSIONS Sequential therapy combined with Lactobacillus seems to be the best regimen for the eradication of H.pylori infection in children.
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Affiliation(s)
- Xiang-Li Zhu
- Department of Pediatrics, Tai'an Maternal and Child Health Care Hospital, Tai'an, Shandong 271000, China.
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Li L, Ke Y, Yu C, Li G, Yang N, Zhang J, Li Y. Antibiotic resistance of Helicobacter pylori in Chinese children: A multicenter retrospective study over 7 years. Helicobacter 2017; 22. [PMID: 28098401 DOI: 10.1111/hel.12373] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND To determine the prevalence of resistance to metronidazole, clarithromycin, levofloxacin, amoxicillin, and furazolidone in Helicobacter pylori isolated from Chinese children. MATERIALS AND METHODS This multicenter retrospective study was conducted from January 2009 to December 2015. A total of 1746 isolates of H. pylori were collected from nine areas of Zhejiang province in the southeast coastal region of China. H. pylori strains were examined for antibiotics susceptibility by agar dilution method. RESULTS The resistance rates were 75.20% for metronidazole, 16.38% for clarithromycin, 6.70% for levofloxacin, 0.06% for amoxicillin, and 0.06% for furazolidone. The pattern of H. pylori antibiotic resistance demonstrated no significant changes in the rates of resistance to clarithromycin, amoxicillin, furazolidone, and metronidazole over 7 years. A significant trend of increasing resistance to metronidazole was observed as children aged, but a downward trend in clarithromycin resistance was observed as children aged. No difference in the resistance to other antibiotics was observed among different age groups. Also, there was no significant difference between male and female subjects in rates of resistance to these five types of antibiotics. The predominant dual resistance to metronidazole and clarithromycin was presented in 10.65% of the isolates. CONCLUSIONS The resistance rates of H. pylori in children from southeast coastal region of China were very high to metronidazole, moderate to clarithromycin and levofloxacin, and low to amoxicillin and furazolidone. It is important to continue monitoring the resistance profiles of H. pylori isolated in this region.
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Affiliation(s)
- Lan Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yini Ke
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Guogang Li
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ningmin Yang
- Zhiyuan Medical Inspection Institute Co., Ltd., Hangzhou, China
| | - Jianzhong Zhang
- State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China
- National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Regnath T, Raecke O, Enninger A, Ignatius R. Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany. Helicobacter 2017; 22. [PMID: 27400262 DOI: 10.1111/hel.12327] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasing antibiotic resistance has been reported for Helicobacter pylori, but data on the prevalence of antibiotic resistance of H. pylori in pediatric patients and the development of resistance over time are sparse. METHODS Data for 610 H. pylori isolates obtained between 2002 and 2015 from gastric biopsies of 582 (mainly treatment-naïve) pediatric patients from southwest Germany were analyzed retrospectively regarding the antibiotic susceptibility determined by Etest and patients' characteristics. RESULTS Overall resistance to metronidazole, clarithromycin, and rifampicin was 28.7%, 23.2%, and 13.3%, respectively, while resistance to amoxicillin was rare (0.8%). Simultaneous resistance to metronidazole and clarithromycin was observed for 7.7% of the isolates, and 2.3% were resistant to metronidazole, clarithromycin, and rifampicin. Differences between primary vs secondary resistance existed for metronidazole (24.7% vs 38.8%, P=.01) and clarithromycin (17.2% vs 54.1%, P=.0001). From 2002-2008 to 2009-2015, resistance to metronidazole increased from 20.8% to 34.4% (P=.003) and to rifampicin from 3.9% to 18.8% (P=.0001); this was not associated with increased numbers of patients previously treated for H. pylori infection in the second study period. In contrast, resistance to clarithromycin did not change significantly over time. Resistance was not associated with age, sex, or family origin in Europe. CONCLUSIONS The considerable antibiotic resistance of H. pylori isolates argues for standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of antibiotic therapy.
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Affiliation(s)
| | - Olaf Raecke
- Children's Hospital, Pediatric Gastroenterology, Klinikum Esslingen, Esslingen, Germany
| | - Axel Enninger
- Center for Pediatric Medicine, Olgahospital, Stuttgart, Germany
| | - Ralf Ignatius
- Laboratory Enders & Partners, Stuttgart, Germany.,Department of Microbiology and Hygiene, Charité, Berlin, Germany
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Hanafi A, Lee WC, Loke MF, Teh X, Shaari A, Dinarvand M, Lehours P, Mégraud F, Leow AHR, Vadivelu J, Goh KL. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori. Front Microbiol 2016; 7:2015. [PMID: 28018334 PMCID: PMC5157799 DOI: 10.3389/fmicb.2016.02015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 12/01/2016] [Indexed: 12/19/2022] Open
Abstract
Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains.
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Affiliation(s)
- Aimi Hanafi
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Woon Ching Lee
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Mun Fai Loke
- Department of Medical Microbiology, Faculty of Medicine, University of MalayaKuala Lumpur, Malaysia; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of SingaporeSingapore, Singapore
| | - Xinsheng Teh
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Ain Shaari
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Mojdeh Dinarvand
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Philippe Lehours
- Laboratoire de Bactériologie, Université de BordeauxBordeaux, France; Institut National de la Santé et de la Recherche Médicale U853Bordeaux, France
| | - Francis Mégraud
- Laboratoire de Bactériologie, Université de BordeauxBordeaux, France; Institut National de la Santé et de la Recherche Médicale U853Bordeaux, France
| | - Alex Hwong Ruey Leow
- Department of Medicine, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Jamuna Vadivelu
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
| | - Khean Lee Goh
- Department of Medicine, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia
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Shi J, Jiang Y, Zhao Y. Promising in vitro and in vivo inhibition of multidrug-resistant Helicobacter pylori by linezolid and novel oxazolidinone analogues. J Glob Antimicrob Resist 2016; 7:106-109. [DOI: 10.1016/j.jgar.2016.07.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 07/23/2016] [Indexed: 02/07/2023] Open
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Kim BJ, Kim HS, Song HJ, Chung IK, Kim GH, Kim BW, Shim KN, Jeon SW, Jung YJ, Yang CH, Kim JH, Kim TH, Kim SG, Shin WG, Kim SM, Han SW, Lee JH, Kim KH, Park SK, Park BJ, Lee J, Kim JG, Korean College of Helicobacter and Upper Gastrointestinal Research. Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis. J Korean Med Sci 2016; 31:1246-1253. [PMID: 27478335 PMCID: PMC4951554 DOI: 10.3346/jkms.2016.31.8.1246] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 04/09/2016] [Indexed: 12/14/2022] Open
Abstract
Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Joo Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Il-Kwun Chung
- Department of Internal Medicine, Cheonan Hospital, Soon Chun Hyang University College of Medicine, Cheonan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University Medical Center, Daegu, Korea
| | - Yun Jin Jung
- Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea
| | - Chang-Hun Yang
- Department of Internal Medicine, Dongguk University College of Medicine Gyeongju Hospital, Gyeongju, Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Pusan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Ho Kim
- Department of Gastroenterolgy, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Sun Moon Kim
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Sok Won Han
- Department of Gastroenterolgy, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyung Ho Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Sue K. Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Byung-Joo Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Joongyub Lee
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
| | - Jae G. Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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Luo XF, Jiao JH, Zhang WY, Pu HM, Qu BJ, Yang BY, Hou M, Ji MJ. Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori. World J Gastroenterol 2016; 22:5822-5830. [PMID: 27433095 PMCID: PMC4932217 DOI: 10.3748/wjg.v22.i25.5822] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 04/08/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR).
METHODS: The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion.
RESULTS: The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin.
CONCLUSION: The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori.
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Zhou L, Zhang J, Song Z, He L, Li Y, Qian J, Bai P, Xue Y, Wang Y, Lin S. Tailored versus Triple plus Bismuth or Concomitant Therapy as Initial Helicobacter pylori Treatment: A Randomized Trial. Helicobacter 2016; 21:91-9. [PMID: 26104022 DOI: 10.1111/hel.12242] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND With markedly increased antibiotic resistance and unsatisfactory efficacies of common empiric eradication regimens in the mainland of China, tailored therapy may be the best choice to achieve good efficacy. This study compared the eradication rates, safety, and compliance of tailored therapy to those of triple therapy plus bismuth and concomitant therapy in the naïve patients with Helicobacter pylori infection. MATERIALS AND METHODS Between September 2013 and April 2014, 1050 patients with H. pylori infection at three tertiary hospitals were randomly assigned to 10-day treatment with tailored, triple plus bismuth, or concomitant regimens. In tailored therapy, medications were adjusted according to clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype. The antimicrobial susceptibility testing (E test) was performed. Eradication status was assessed 4-12 weeks after treatment. RESULTS The eradication rate was significantly higher in tailored group than in triple plus bismuth and concomitant groups in both intention-to-treat (88.7 vs 77.4 vs 78.3%, p < .001) and per-protocol (93.3 vs 87.0 vs 87.4%, p = .021) analyses in a setting with high antibiotic resistance (clarithromycin 48.8%, metronidazole 65.7%, and dual resistance 35.3%). Significantly, fewer adverse effects occurred in tailored group than in concomitant group (22.0 vs 31.7%, p = .018). The eradication rates of dual clarithromycin and metronidazole resistance, isolated clarithromycin resistance, isolated metronidazole resistance, and dual susceptible were 78.7, 82.4, 94.8, and 94.4% in triple therapy plus bismuth and 75.9, 87.2, 92.9, and 95.2% in concomitant therapy, respectively. CONCLUSIONS First-line tailored therapy achieves significantly higher eradication rates and fewer side effects, compared to triple therapy plus bismuth and concomitant therapy in a setting with high rates of clarithromycin and metronidazole resistance.
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Affiliation(s)
- Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Shandong, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China
| | - Peng Bai
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yan Xue
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ye Wang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Sanren Lin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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Ji Z, Han F, Meng F, Tu M, Yang N, Zhang J. The Association of Age and Antibiotic Resistance of Helicobacter Pylori: A Study in Jiaxing City, Zhejiang Province, China. Medicine (Baltimore) 2016; 95:e2831. [PMID: 26937912 PMCID: PMC4779009 DOI: 10.1097/md.0000000000002831] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The antibiotic resistance of Helicobacter pylori (H pylori) is steadily increasing worldwide, resulting in the low efficiency of the current therapeutic approaches for eradication. In this study, we investigated the relationship between antibiotic resistances, the year of sample collection, and the ages of the infected individuals.A total of 29,034 gastric mucosa biopsy samples were randomly collected from January 1, 2009 to December 9, 2014 in Jiaxing City, Zhejiang Province, China. An antibiotic susceptibility testing was determined using an agar-dilution method. The statistical significance was tested using the chi-squared (χ) test.A total of 9687 strains were isolated. The resistance rate to clarithromycin, levofloxacin, and metronidazole were 17.76%, 19.66%, and 95.5%, respectively. Resistance was rare against amoxicillin, gentamicin, and furazolidone. The metronidazole resistance rate stayed at a consistently high level. In contrast, the resistance rates of clarithromycin and levofloxacin increased rapidly from 2009 to 2011, gradually decreased from 2012 to 2013, and then increased again in 2014. Although patients ages 31 to 50 and 71 to 80 years had lower infection rates of H pylori, they also had higher resistance rates to clarithromycin and levofloxacin. The highest antibiotic resistance rate was observed in patients' ages 71 to 80 years old. Younger patients (below 30 years old) had a lower resistance to levofloxacin. Patients' ages 51 to 60 years old may thus represent an important category for the future study of H pylori infection.Age plays a key element in H pylori resistance to clarithromycin and levofloxacin. It is therefore necessary to consider individualized therapy for the optimized treatment of H pylori-infected patients.
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Affiliation(s)
- Zizhong Ji
- From the First Hospital of Jiaxing (ZJ, FH), Zhiyuan Inspection Medical Institute (FM, MT), Zhiyuan Medical Inspection Institute Co., LTD (NY), and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (JZ), Hangzhou, Zhejiang, China and State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (JZ)
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Tong YF, Lv J, Ying LY, Xu F, Qin B, Chen MT, Meng F, Tu MY, Yang NM, Li YM, Zhang JZ. Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance. World J Gastroenterol 2015; 21:13073-13079. [PMID: 26672777 PMCID: PMC4674725 DOI: 10.3748/wjg.v21.i46.13073] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Revised: 09/10/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.
METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.
RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin-resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city.
CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.
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Boyanova L, Markovska R, Yordanov D, Gergova G, Mitov I. Clarithromycin Resistance Mutations in Helicobacter pylori in Association with Virulence Factors and Antibiotic Susceptibility of the Strains. Microb Drug Resist 2015; 22:227-32. [PMID: 26618567 DOI: 10.1089/mdr.2015.0199] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Antibiotic resistance is the major cause for Helicobacter pylori eradication failure. H. pylori clarithromycin resistance mutations were evaluated in 84 (82 phenotypically clarithromycin resistant and 2 intermediately susceptible) strains by allele-specific PCR and 3'-mismatched PCR. Many (57.1%) of these strains were metronidazole resistant. Prevalence of cagA(+), cagE(+), vacA s1a, m1, i1, and i2 strains was 76.2%, 58.0%, 82.1%, 35.7%, 50.0%, and 50.0%, respectively. A2143G, A2142G, A2142C, and A2143G+A2142G mutation rates were 64.3%, 23.8%, 1.2%, and 10.7%, respectively. Strains harboring the A2142G mutation showed 5.3-fold higher clarithromycin MIC50 than those harboring the A2143G mutation. The A2143G mutation alone was 1.7-fold more common in vacA i2 strains compared with vacA i1 strains, while the A2142G mutation alone was 3-fold more frequent in vacA i1 strains than vacA i2 strains and 3.1-fold more common in metronidazole-susceptible compared with metronidazole-resistant strains. Briefly, clarithromycin resistance mutations were significantly linked to vacA i allele and metronidazole susceptibility. This is the first report about associations between the A2143G mutation and less virulent vacA i2 strains, and between the A2142G mutation and more virulent vacA i1 strains. As the 2143G mutation often predicts eradication failure by clarithromycin-based regimens, the results may be linked to the better eradication of more virulent strains compared with the less virulent strains.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria
| | - Rumyana Markovska
- Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria
| | - Daniel Yordanov
- Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria
| | - Galina Gergova
- Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria
| | - Ivan Mitov
- Department of Medical Microbiology, Medical University of Sofia , Sofia, Bulgaria
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Ghotaslou R, Leylabadlo HE, Asl YM. Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review. World J Methodol 2015; 5:164-174. [PMID: 26413490 PMCID: PMC4572030 DOI: 10.5662/wjm.v5.i3.164] [Citation(s) in RCA: 149] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 07/29/2015] [Accepted: 08/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To review previous studies (the last 6 years) about the Helicobacter pylori (H. pylori) antibiotic resistance in order to evaluate the trend in antibiotic resistance. METHODS In this study, the PubMed, MEDLINE, Science Direct, Google Scholar and Scielo manuscripts were reviewed from 2009 to 2014. RESULTS On the whole rates of H. pylori antibiotic resistance were 47.22% (30.5%-75.02%) for metronidazole, 19.74% (5.46%-30.8%) for clarithromycin, 18.94% (14.19%-25.28%) for levofloxacin, and 14.67% (2%-40.87%) for amoxicillin, 11.70% (0%-50%) for tetracycline, 11.5% (0%-23%) for furazolidon and 6.75% (1%-12.45%) for rifabutin. The frequency of tetracycline, metronidazole and amoxicillin resistance was higher in Africa, while clarithromycin and levofloxacin resistance was higher in North America and Asian, respectively. CONCLUSION The most sensitive drug is rifabutin and the lowest sensitive drug is metronidazole in the world. The worldwide H. pylori antibiotic resistance to clarithromycin and levofloxacin has increased during the last 6 years. The present systematic review show alarming results and a novel plan is needed for eradication therapy of H. pylori infections.
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Zhang YX, Zhou LY, Song ZQ, Zhang JZ, He LH, Ding Y. Primary antibiotic resistance of Helicobacter pylori strains isolated from patients with dyspeptic symptoms in Beijing: A prospective serial study. World J Gastroenterol 2015; 21:2786-2792. [PMID: 25759550 PMCID: PMC4351232 DOI: 10.3748/wjg.v21.i9.2786] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 10/24/2014] [Accepted: 12/01/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the resistance patterns of Helicobacter pylori (H. pylori) strains isolated from patients in Beijing and monitor the change of antibiotic resistance over time.
METHODS: In this prospective, serial and cross-sectional study, H. pylori cultures were successfully obtained from 371 and 950 patients (never receiving eradication) during 2009-2010 and 2013-2014, respectively. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin was determined by Epsilometer test.
RESULTS: The resistance rates of isolates obtained during 2009-2010 were 66.8%, 39.9%, 34.5%, 15.4%, 6.7%, and 4.9% to metronidazole, clarithromycin, levofloxacin, rifampicin, amoxicillin and tetracycline, respectively; and the corresponding rates for isolates during 2013-2014 were 63.4%, 52.6%, 54.8%, 18.2%, 4.4% and 7.3%, respectively. The resistance rates to clarithromycin and levofloxacin were significantly increased after four years. In 2009-2010, 14.6% of H. pylori isolates were susceptible to all tested antibiotics, with mono (33.7%), double (28.3%), triple (16.7%), quadruple (6.2%), quintuple (0.3%) and sextuple resistance (0.3%) also being detected. In 2013-2014, 9.4% were susceptible to all tested antibiotics, and mono (27.6%), double (28.4%), triple (24.9%), quadruple (7.3%), quintuple (2.3%) and sextuple resistance (0.1%) was also observed. More multiple resistant H. pylori isolates were found during 2013-2014. Gender (to levofloxacin and metronidazole), age (to levofloxacin) and endoscopic findings (to clarithromycin) were independent factors influencing antibiotic resistance.
CONCLUSION: H. pylori resistance to commonly used antibiotics in Beijing is high with increased multiple antibiotic resistance.
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Efficacy of real-time PCR-based detection of Helicobacter pylori infection and genotypic resistance-guided quadruple therapy as the first-line treatment for functional dyspepsia with Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2015; 27:221-5. [PMID: 25629566 DOI: 10.1097/meg.0000000000000186] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The eradication rate of Helicobacter pylori is steadily decreasing because of increasing resistance to clarithromycin. According to the new version of Maastricht IV guidelines, molecular tests can be performed as a substitute for bacterial culture and the standard clarithromycin susceptibility test for the detection of H. pylori and clarithromycin resistance directly on gastric biopsy samples. OBJECTIVE To evaluate the clinical efficacy of H. pylori detection using a molecular test and treatment outcomes of the clarithromycin-based genotypic resistance test. MATERIALS AND METHODS A total of 385 patients diagnosed with functional dyspepsia were recruited in this clinical trial. Total DNA was extracted from formalin-fixed paraffin-embedded samples and prepared for a molecular test and H. pylori detection was performed simultaneously by modified Giemsa staining. Genotypically sensitive patients with positive H. pylori were treated by quadruple therapy: bismuth potassium citrate, rabeprazole, amoxicillin, and clarithromycin (BRAC) and genotypically resistant individuals were treated by bismuth potassium citrate, rabeprazole, amoxicillin, and furazolidone (BRAF) twice daily for 7 consecutive days. The eradication rate of H. pylori was assessed using the C-urea breath test at 6 weeks after treatment. RESULTS The prevalence of H. pylori infection in functional dyspepsia patients was 35.3% (136/385), 29.1% for women (53/182) and 40.9% for men (83/203). The sensitivities of real-time PCR and histological examinations were 95.6% (130/136) and 69.9% (95/136). Forty-one samples were found to be positive by real-time PCR alone and six by histological examination alone, the majority of which (32/41, 5/6) were identified as grade 1 multiplicity of infection. The overall resistance rate to clarithromycin was 37.7% (49/130): 37.3% (19/51) for women and 38.0% for men (30/79). Eighty-nine patients with positive H. pylori detected by both real-time PCR and histological examinations received quadruple therapies. For the intention-to-treat analysis, the eradication rates of BRAC and BRAF were 98% (52/53) and 92% (33/36), or 100% (52/52) and 94% (33/35) for per-protocol analysis. CONCLUSION Real-time PCR is efficacious for H. pylori detection and genotypic resistance-guided quadruple therapy has a high efficacy in treating functional dyspepsia with H. pylori infection.
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Abstract
Helicobacter pylori (H. pylori) infection has been associated with gastric disorders. The situation of H. pylori infection in China-where a high prevalence of H. pylori infection, a high incidence of gastric cancer, and widespread resistance to clarithromycin, metronidazole, and levofloxacin exist-is quite different from that in Western countries. In order for Chinese clinicians to better manage H. pylori infection, a Chinese Study Group on H. pylori published four consensus reports regarding the management of H. pylori infection in China between 1999 and 2012. The eradication rate with standard triple therapy was <80% in most areas of China. Bismuth is available in China, and bismuth-containing quadruple therapy has been shown to produce a high eradication rate; thus, bismuth quadruple therapy could be recommended both as an initial and as a rescue therapy in China. There is no advantage of sequential therapy over triple therapy in Chinese patients, but the efficacy of concomitant therapy must be studied further. This review introduces the epidemiology, diagnosis, indicators, and therapies for the eradication of H. pylori in China in recent years.
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Affiliation(s)
- Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
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Song Z, Zhang J, He L, Chen M, Hou X, Li Z, Zhou L. Prospective multi-region study on primary antibiotic resistance of Helicobacter pylori strains isolated from Chinese patients. Dig Liver Dis 2014; 46:1077-1081. [PMID: 25220697 DOI: 10.1016/j.dld.2014.08.038] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 07/30/2014] [Accepted: 08/19/2014] [Indexed: 01/06/2023]
Abstract
BACKGROUND Large-scale multi-region studies are urgently needed to provide comprehensive and up-to-date information on the antibiotic resistance of Helicobacter pylori that is critical for selecting the most optimal eradication regimens. AIMS To determine the resistance patterns of Helicobacter pylori strains isolated from dyspeptic patients. METHODS This is a prospective, multicentre, cross-sectional, observational study. Helicobacter pylori cultures were successful in 600 patients (never receiving eradication therapy) from Northern, Eastern, Middle, and Southern regions between 2008 and 2012. Resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin was determined by Epsilometer test. RESULTS The overall resistance rate was highest for metronidazole (403, 67.2%), followed by clarithromycin (225, 37.5%), levofloxacin (201, 33.5%), rifampicin (85, 14.2%), amoxicillin (41, 6.8%), and tetracycline (21, 3.5%). There were 16.3% isolates susceptible to all tested antibiotics, followed by mono-resistance (34.2%), double resistance (27.0%), triple resistance (16.8%), quadruple resistance (4.7%), quintuple resistance (0.7%) and sextuple resistance (0.3%). Independent factors influencing antibiotic resistance were gender (to levofloxacin), age (to levofloxacin), and endoscopic finding (to clarithromycin, metronidazole, and levofloxacin). Among the clarithromycin-resistant isolates, 75.6% and 48.0% were also resistant to metronidazole and levofloxacin, respectively. CONCLUSIONS Helicobacter pylori resistance to commonly used antibiotics in China is a very serious issue, due to the high resistance rate and general multiple resistance.
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Affiliation(s)
- Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jianzhong Zhang
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lihua He
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Minhu Chen
- Department of Gastroenterology, First Affiliated Hospital of SunYat-sen University, Guangzhou, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Technology and Science, Wuhan, China
| | - Zhaoshen Li
- Department of Digestive Diseases, Changhai Hospital of Second Military Medical University, Shanghai, China
| | - Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
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Chung KH, Lee DH, Jin E, Cho Y, Seo JY, Kim N, Jeong SH, Kim JW, Hwang JH, Shin CM. The efficacy of moxifloxacin-containing triple therapy after standard triple, sequential, or concomitant therapy failure for Helicobacter pylori eradication in Korea. Gut Liver 2014; 8:605-11. [PMID: 25368747 PMCID: PMC4215445 DOI: 10.5009/gnl13303] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/05/2013] [Accepted: 10/06/2013] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Retreatment after initial treatment failure for Helicobacter pylori is very challenging. The purpose of this study was to evaluate the efficacies of moxifloxacin-containing triple and bismuth-containing quadruple therapy. Methods A total of 151 patients, who failed initial H. pylori treatment, were included in this retrospective cohort study. The initial regimens were standard triple, sequential, or concomitant therapy, and the efficacies of the two following second-line treatments were evaluated: 7-day moxifloxacin-containing triple therapy (rabeprazole 20 mg twice a day, amoxicillin 1,000 mg twice a day, and moxifloxacin 400 mg once daily) and 7-day bismuth-containing quadruple therapy (rabeprazole 20 mg twice a day, tetracycline 500 mg 4 times a day, metronidazole 500 mg 3 times a day, and tripotassium dicitrate bismuthate 300 mg 4 times a day). Results The overall eradication rates after moxifloxacin-containing triple therapy and bismuth-containing quadruple therapy were 69/110 (62.7%) and 32/41 (78%), respectively. Comparison of the two regimens was performed in the patients who failed standard triple therapy, and the results revealed eradication rates of 14/28 (50%) and 32/41 (78%), respectively (p=0.015). The frequency of noncompliance was not different between the two groups, and there were fewer adverse effects in the moxifloxacin-containing triple therapy group (2.8% vs 7.3%, p=0.204 and 25.7% vs 43.9%, p=0.031, respectively). Conclusions Moxifloxacin-containing triple therapy, a recommended second-line treatment for initial concomitant or sequential therapy failure, had insufficient efficacy.
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Affiliation(s)
- Kwang Hyun Chung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eunhyo Jin
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yuri Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Yeon Seo
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sook Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Sequential therapy versus standard triple therapy for Helicobacter pylori eradication in children: any advantage in clarithromycin-resistant strains? Eur J Gastroenterol Hepatol 2014; 26:1202-8. [PMID: 25171023 DOI: 10.1097/meg.0000000000000190] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE There has been a marked decrease in the eradication rates of Helicobacter pylori infection with standard triple therapy worldwide. Hence, sequential therapy has gained attention as a promising treatment during the last few years. This study was carried out to compare the efficacy of sequential versus standard triple therapy in the context of clarithromycin (CLA) resistance. MATERIALS AND METHODS In this study, children between 3 and 18 years of age, who had documented H. pylori infection, were randomized to receive either standard triple or sequential therapy. H. pylori eradication was ascertained using the C-urea breath test 4-6 weeks after the completion of the treatment. Real-time PCR was performed on gastric biopsy samples for assessment of CLA resistance. RESULTS In all, 148 children (median age: 12.18±3.51 years) were recruited randomly into the study. The intention-to-treat eradication rates were 50% (37/74) for the sequential treatment group and 52.7% (39/74) for the standard triple treatment group (P=0.87). A total of 136 children completed the study. The per-protocol eradication rates were 56% (37/66) and 55.7% (39/70) for sequential and standard triple therapy groups, respectively. CLA resistance was assessed and 113 children were included in the final analysis. Of 113 participants, 53 were in the sequential treatment group and 60 were in the standard triple treatment group. The success rates of the respective therapies (29/53=54.7% in sequential, 33/60=55% in standard therapy) were similar (P=0.98). CLA resistance was detected in 29 (25.7%) of the patients. Eradication rates with sequential therapy in CLA susceptible and resistant cases were 60.5% (23/38) and 40% (6/15), respectively (P=0.23). The corresponding figures for the standard triple treatment group were 63% (29/46) and 28.6% (4/14) (P=0.033). Although a higher eradication rate was observed in CLA-resistant cases with sequential therapy, the difference did not reach statistical significance (P=0.69). CONCLUSION In this study, standard triple treatment failed to eradicate H. pylori infection in the majority of the children, and sequential therapy offered only a small advantage over standard triple therapy in the eradication of CLA-resistant strains.
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Lee JW, Kim N, Nam RH, Park JH, Choi YJ, Kim JM, Kim JS, Jung HC. GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea. Scand J Gastroenterol 2014; 49:1058-67. [PMID: 24957849 DOI: 10.3109/00365521.2014.894117] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Antimicrobial resistance of Helicobacter pylori is most important factor in eradication success. GenoType HelicoDR test has been developed for rapid detection of antimicrobial resistance. The present study evaluated the clinical usefulness of GenoType HelicoDR test in Korea. MATERIALS AND METHODS To detect 23S rRNA for clarithromycin resistance and gyrA mutations for fluoroquinolone resistance, both DNA sequencing after minimal inhibitory test (MIC) and GenoType HelicoDR test were performed in H. pylori isolates from the gastric mucosa of 101 patients. The eradication results of clarithromycin and moxifloxacin-containing triple therapy were evaluated by the 23S rRNA and gyrA mutations. RESULTS For 42 isolates with A2143G mutation by GenoType HelicoDR, 83.3% (35/42) of concordance rate was estimated with DNA sequencing method and 85.7% (36/42) for MIC test. For 43 isolates with N87K mutation by GenoType HelicoDR, 71.1% (31/43) of concordance rate was estimated with DNA sequencing and 88.4% (38/43) for MIC test. The sensitivity and specificity of GenoType HelicoDR test in determination of 23S rRNA mutation were 94.9% and 87.1%, and those of gyrA 98.2% and 80.0%. The sensitivity and specificity of GenoType HelicoDR test in determination of clarithromycin resistance based on MIC test were 55.0% and 80.0%, for fluoroquinolone 74.4% and 70.0%. CONCLUSION GenoType HelicoDR test is useful to determine mutations responsible for clarithromycin or fluoroquinolone-containing eradication failure but has a limitation for the clinical applicability in determination of resistance.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Gyeonggi-do , Korea
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Boyanova L, Davidkov L, Gergova G, Kandilarov N, Evstatiev I, Panteleeva E, Mitov I. Helicobacter pylori susceptibility to fosfomycin, rifampin, and 5 usual antibiotics for H. pylori eradication. Diagn Microbiol Infect Dis 2014; 79:358-61. [DOI: 10.1016/j.diagmicrobio.2014.03.028] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Revised: 03/25/2014] [Accepted: 03/29/2014] [Indexed: 12/14/2022]
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Zhou L, Zhang J, Chen M, Hou X, Li Z, Song Z, He L, Lin S. A comparative study of sequential therapy and standard triple therapy for Helicobacter pylori infection: a randomized multicenter trial. Am J Gastroenterol 2014; 109:535-541. [PMID: 24642580 DOI: 10.1038/ajg.2014.26] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 12/19/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Studies conducted in large populations of patients and providing full information on Helicobacter pylori (H. pylori) antibiotic resistance are needed to determine the efficacy of sequential therapy (SQT) against this pathogen. This study compared eradication rates with SQT and standard triple therapy (STT), and evaluated the impact of antibiotic resistance on outcomes. METHODS The study population included adults with positive H. pylori culture presenting at four centers in China between March 2008 and December 2010. Patients were randomly assigned to 10 days of treatment with esomeprazole, amoxicillin, and clarithromycin (STT; n=140) or to 5 days of treatment with esomeprazole and amoxicillin, followed by 5 days of esomeprazole, clarithromycin, and tinidazole (SQT; n=140). Eradication was assessed 8-12 weeks after treatment. RESULTS There was no significant difference between the eradication rates achieved with STT (66.4% (95% confidence interval (CI) 59.3-74.3)) and SQT (72.1% (65.0-79.3); P=0.300) in either the intention-to-treat analysis or the per-protocol analysis (72.7% (65.6-79.7) and 76.5% (69.7-83.3), respectively; P=0.475). Clarithromycin resistance (CLA-R, odds ratio (OR)=8.34 (3.13-22.26), P<0.001) and metronidazole resistance (MET-R, OR=7.14 (1.52-33.53), P=0.013) both independently predicted treatment failure in the SQT group. Patients in the SQT group with dual CLA-R and MET-R had a lower eradication rate (43.9%) than those with isolated CLA-R (88.9%, P=0.024) or isolated MET-R (87.8%, P<0.001). CONCLUSIONS H. pylori eradication rates with STT and SQT were compromised by antibiotic resistance. SQT may be suitable in regions with high prevalence of isolated CLA-R, but it is unsatisfactory when both CLA-R and MET-R are present.
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Affiliation(s)
- Liya Zhou
- 1] Department of Gastroenterology, Peking University Third Hospital, Beijing, China [2] These authors contributed equally to this work
| | - Jianzhong Zhang
- 1] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China [2] These authors contributed equally to this work
| | - Minhu Chen
- Department of Gastroenterology, First Affiliated Hospital of SunYat-sen University, Guangzhou, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Technology and Science, Wuhan, China
| | - Zhaoshen Li
- Department of Digestive Diseases, Changhai Hospital of Second Military Medical University, Shanghai, China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Lihua He
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Sanren Lin
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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Wu JY, Wang SSW, Lee YC, Yamaoka Y, Graham DY, Jan CM, Wang WM, Wu DC. Detection of genotypic clarithromycin-resistant Helicobacter pylori by string tests. World J Gastroenterol 2014; 20:3343-9. [PMID: 24695835 PMCID: PMC3964405 DOI: 10.3748/wjg.v20.i12.3343] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 09/17/2013] [Accepted: 10/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR)-restriction fragment length polymorphism. METHODS Patients undergoing endoscopic examinations were enrolled in the present study. String tests were done on the next day of endoscopy. Segments of 23S rRNA were amplified from DNA obtained from string tests. PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143 or at 2142 of 23S rRNA domain V, respectively. RESULTS One hundred and thirty-four patients with H. pylori infection underwent string tests. To compare phenotypic resistance, 43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified. Of five patients with clarithromycin-resistant H. pylori, 23S rRNA of H. pylori isolates from four patients could be digested by BsaI. In 38 susceptible isolates, 23S rRNA of H. pylori isolates from 36 patients could not be digested by either BsaI or BbsI. The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7% and 97.3%, respectively. Positive and negative predictive values were 80% and 94.7%, respectively. CONCLUSION String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment. Further large-scale investigations are necessary to confirm our results.
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Seo JH, Woo HO, Youn HS, Rhee KH. Antibiotics resistance of Helicobacter pylori and treatment modalities in children with H. pylori infection. KOREAN JOURNAL OF PEDIATRICS 2014; 57:67-71. [PMID: 24678329 PMCID: PMC3965796 DOI: 10.3345/kjp.2014.57.2.67] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Accepted: 01/24/2014] [Indexed: 01/23/2023]
Abstract
Pediatric infection with Helicobacter pylori may occur early in childhood and persist lifelong. Global pediatric clinical studies have reported a decreasing tendency in the overall rate of H. pylori eradication. In pediatric patients with H. pylori infection, pediatric patients with peptic ulcer, and the first-degree relatives of patients with a history of gastric cancer, it is commonly recommended that H. pylori strains be eradicated. Antibiotic drug resistance to H. pylori, which has been reported to vary widely between geographic regions, is mainly associated with treatment failure in these patients. It is therefore imperative that the antibiotic resistance rates of H. pylori in children and adolescents be meticulously monitored across countries and throughout geographic regions. This paper particularly focuses on the antibiotic drug resistance of H. pylori and the thearpy of pediatric H. pylori infection cases.
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Affiliation(s)
- Ji-Hyun Seo
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Hyang-Ok Woo
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Hee-Shang Youn
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Kwang-Ho Rhee
- Department of Microbiology, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
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