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Umar Z, Tang JW, Marshall BJ, Tay ACY, Wang L. Rapid diagnosis and precision treatment of Helicobacter pylori infection in clinical settings. Crit Rev Microbiol 2025; 51:369-398. [PMID: 38910506 DOI: 10.1080/1040841x.2024.2364194] [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: 02/28/2024] [Revised: 05/08/2024] [Accepted: 05/25/2024] [Indexed: 06/25/2024]
Abstract
Helicobacter pylori is a gram-negative bacterium that colonizes the stomach of approximately half of the worldwide population, with higher prevalence in densely populated areas like Asia, the Caribbean, Latin America, and Africa. H. pylori infections range from asymptomatic cases to potentially fatal diseases, including peptic ulcers, chronic gastritis, and stomach adenocarcinoma. The management of these conditions has become more difficult due to the rising prevalence of drug-resistant H. pylori infections, which ultimately lead to gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. In 1994, the International Agency for Research on Cancer (IARC) categorized H. pylori as a Group I carcinogen, contributing to approximately 780,000 cancer cases annually. Antibiotic resistance against drugs used to treat H. pylori infections ranges between 15% and 50% worldwide, with Asian countries having exceptionally high rates. This review systematically examines the impacts of H. pylori infection, the increasing prevalence of antibiotic resistance, and the urgent need for accurate diagnosis and precision treatment. The present status of precision treatment strategies and prospective approaches for eradicating infections caused by antibiotic-resistant H. pylori will also be evaluated.
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Affiliation(s)
- Zeeshan Umar
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jia-Wei Tang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
| | - Barry J Marshall
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
- Marshall International Digestive Diseases Hospital, Zhengzhou University, Zhengzhou, Henan Province, China
- Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Alfred Chin Yen Tay
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong Province, China
- The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Crawley, Western Australia, China
- Marshall International Digestive Diseases Hospital, Zhengzhou University, Zhengzhou, Henan Province, China
- Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Liang Wang
- Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
- Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, China
- Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, China
- School of Agriculture and Food Sustainability, University of Queensland, Brisbane, Queensland, Australia
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Hasanuzzaman M, Bang CS, Gong EJ. Antibiotic Resistance of Helicobacter pylori: Mechanisms and Clinical Implications. J Korean Med Sci 2024; 39:e44. [PMID: 38288543 PMCID: PMC10825452 DOI: 10.3346/jkms.2024.39.e44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
Helicobacter pylori is a pathogenic bacterium associated with various gastrointestinal diseases, including chronic gastritis, peptic ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The increasing rates of H. pylori antibiotic resistance and the emergence of multidrug-resistant strains pose significant challenges to its treatment. This comprehensive review explores the mechanisms underlying the resistance of H. pylori to commonly used antibiotics and the clinical implications of antibiotic resistance. Additionally, potential strategies for overcoming antibiotic resistance are discussed. These approaches aim to improve the treatment outcomes of H. pylori infections while minimizing the development of antibiotic resistance. The continuous evolution of treatment perspectives and ongoing research in this field are crucial for effectively combating this challenging infection.
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Affiliation(s)
- Md Hasanuzzaman
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
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Chen J, Guo Y, Huang Y, Ding Z, Wang J, Liang X, Xu P, Han Y, Lu H. Rifabutin-Containing Triple Therapy Versus Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Multicenter, Randomized Controlled Trial. J Infect Dis 2023; 228:511-518. [PMID: 37079894 DOI: 10.1093/infdis/jiad114] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/09/2023] [Accepted: 04/19/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND We compared the efficacy and safety of rifabutin-containing triple therapy with bismuth quadruple therapy for rescue treatment of Helicobacter pylori. METHODS This was a noninferiority study trial of H. pylori treatment for subjects who had failed at least 2 prior treatments. Subjects were randomly assigned to receive rifabutin triple therapy with 14-day esomeprazole (20 mg), amoxicillin (1.0 g), and rifabutin (150 mg) twice a day; or bismuth quadruple therapy with esomeprazole (20 mg) and bismuth (220 mg) twice a day, plus metronidazole (400 mg) and tetracycline (500 mg) 4 times a day. Antimicrobial susceptibility was assessed by agar dilution and E-test. RESULTS From May 2021 to October 2022, a total of 364 subjects were randomized. The eradication rates by intention-to-treat, per-protocol, and modified intention-to-treat were 89.0% (162/182; 95% confidence interval [CI], 83.6%-92.8%), 94.0% (157/167; 95% CI, 89.3%-96.7%), and 93.6% (162/173; 95% CI, 89.0%-96.4%) for rifabutin triple group. For bismuth quadruple group, they were 89.6% (163/182; 95% CI, 84.3%-93.2%), 95.3% (143/150; 95% CI, 90.7%-97.7%), and 93.7% (163/174; 95% CI, 89.0%-96.4%). CONCLUSIONS The rifabutin triple therapy is an alternative to classical bismuth quadruple therapy for the rescue treatment of H. pylori with fewer side effects and higher compliance. CLINICAL TRIALS REGISTRATION NCT04879992.
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Affiliation(s)
- Jinnan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yixian Guo
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Huang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhaohui Ding
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Wang
- Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Xiao Liang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ping Xu
- Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Yaohua Han
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University school of Medicine, Hangzhou, China
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Lee JW. Fluoroquinolone and Rifabutin-Containing Therapy. HELICOBACTER PYLORI 2023:587-594. [DOI: 10.1007/978-981-97-0013-4_49] [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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Yang T, Liu B, Zhou J, Shen Y, Song X, Tang X, Benghezal M, Marshall BJ, Tang H, Li H. The Inappropriateness of Using Rifampicin E-Test to Predict Rifabutin Resistance in Helicobacter pylori. J Infect Dis 2022; 226:S479-S485. [PMID: 36478247 DOI: 10.1093/infdis/jiac417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the rifamycin cross-resistance in Helicobacter pylori, and whether the use of rifampicin E-test strips to screen H. pylori rifabutin resistance is appropriate. METHODS A total of 89 H. pylori isolates were included. Rifampicin minimum inhibitory concentrations (MICs) were obtained by E-test, while the MICs for rifapentine, rifaximin, and rifabutin were determined by agar dilution method. The rifamycin resistance rates based on different breakpoints were compared. Isolates with high-level rifampicin resistance were subjected to whole-genome sequencing. RESULTS A wide distribution of MICs (mostly in the range 0.125-8 mg/L) was observed for rifampicin, rifapentine, and rifaximin. Using MIC >1, ≥ 4, and > 4 mg/L as the breakpoints, resistance rates to rifampicin/rifapentine/rifaximin were 60.4%/48.3%/38.2%, 28.1%/25.8%/23.6%, and 15.7%/16.9%/7.9%, respectively. However, the rifabutin MICs of all the tested H. pylori isolates were extremely low (≤0.016 mg/L). Applying MIC ≥ 0.125 mg/L as the breakpoint, rifabutin resistance was nil. No mutation was found in the rpoB gene sequences of the 2 isolates with high-level rifampicin resistance. CONCLUSIONS There is a lack of cross-resistance between rifabutin and other rifamycins in H. pylori. The use of rifampicin E-test to predict H. pylori rifabutin resistance is inappropriate.
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Affiliation(s)
- Tiankuo Yang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Aviation Medical Appraisal Center, Civil Aviation Flight University of China, Guanghan, China
| | | | - Junpeng Zhou
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaona Song
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Barry James Marshall
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia.,School of Biomedical Engineering, Marshall Laboratory of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, China
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China 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.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Borraccino AV, Celiberto F, Pricci M, Girardi B, Iannone A, Rendina M, Ierardi E, Di Leo A, Losurdo G. Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties. World J Gastroenterol 2022; 28:6356-6362. [PMID: 36533106 PMCID: PMC9753051 DOI: 10.3748/wjg.v28.i45.6356] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 10/25/2022] [Accepted: 11/17/2022] [Indexed: 12/02/2022] Open
Abstract
When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch's bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.
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Affiliation(s)
- Antonia Valeria Borraccino
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Francesca Celiberto
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | | | | | - Andrea Iannone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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Ansari S, Yamaoka Y. Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance. Clin Microbiol Rev 2022; 35:e0025821. [PMID: 35404105 PMCID: PMC9491184 DOI: 10.1128/cmr.00258-21] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Despite the recent decrease in overall prevalence of Helicobacter pylori infection, morbidity and mortality rates associated with gastric cancer remain high. The antimicrobial resistance developments and treatment failure are fueling the global burden of H. pylori-associated gastric complications. Accurate diagnosis remains the opening move for treatment and eradication of infections caused by microorganisms. Although several reports have been published on diagnostic approaches for H. pylori infection, most lack the data regarding diagnosis from a clinical perspective. Therefore, we provide an intensive, comprehensive, and updated description of the currently available diagnostic methods that can help clinicians, infection diagnosis professionals, and H. pylori researchers working on infection epidemiology to broaden their understanding and to select appropriate diagnostic methods. We also emphasize appropriate diagnostic approaches based on clinical settings (either clinical diagnosis or mass screening), patient factors (either age or other predisposing factors), and clinical factors (either upper gastrointestinal bleeding or partial gastrectomy) and appropriate methods to be considered for evaluating eradication efficacy. Furthermore, to cope with the increasing trend of antimicrobial resistance, a better understanding of its emergence and current diagnostic approaches for resistance detection remain inevitable.
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Affiliation(s)
- Shamshul Ansari
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu City, Oita, Japan
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, USA
- Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
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Inokuchi K, Mori H, Matsuzaki J, Hirata K, Harada Y, Saito Y, Suzuki H, Kanai T, Masaoka T. Efficacy and safety of low-dose rifabutin-based 7-day triple therapy as a third- or later-line Helicobacter pylori eradication regimen. Helicobacter 2022; 27:e12900. [PMID: 35644041 PMCID: PMC9539484 DOI: 10.1111/hel.12900] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/30/2022] [Accepted: 05/02/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection. MATERIALS AND METHODS Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using a 13 C urea breath test or the H. pylori stool antigen test. The results obtained from our previous study that reported a 10-day or 14-day esomeprazole based rifabutin-containing triple therapy as a third- or fourth-line rescue therapy treated patients were used as historical control. We determined the minimum inhibitory concentrations of amoxicillin and rifabutin. We also evaluated whether the patients were positive for the mutation of the rpoB gene. RESULTS Intention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%-99% and 92.7%, 95% CI: 86%-100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy. CONCLUSIONS This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.
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Affiliation(s)
- Kazumi Inokuchi
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Translational Research Center for Gastrointestinal Disorders (TARGID)University of LeuvenLeuvenBelgium
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of PharmacotherapeuticsKeio University Faculty of PharmacyTokyoJapan
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Yosuke Harada
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Yoshimasa Saito
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of PharmacotherapeuticsKeio University Faculty of PharmacyTokyoJapan
- Department of Gastroenterology and HepatologyKitasato University Kitasato Institute HospitalTokyoJapan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTokai University School of MedicineIseharaJapan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Department of Gastroenterology and HepatologyInternational University of Health and Welfare, Mita HospitalTokyoJapan
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Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance - from biology to clinical implications. Nat Rev Gastroenterol Hepatol 2021; 18:613-629. [PMID: 34002081 DOI: 10.1038/s41575-021-00449-x] [Citation(s) in RCA: 264] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a major human pathogen for which increasing antibiotic resistance constitutes a serious threat to human health. Molecular mechanisms underlying this resistance have been intensively studied and are discussed in this Review. Three profiles of resistance - single drug resistance, multidrug resistance and heteroresistance - seem to occur, probably with overlapping fundamental mechanisms and clinical implications. The mechanisms that have been most studied are related to mutational changes encoded chromosomally and disrupt the cellular activity of antibiotics through target-mediated mechanisms. Other biological attributes driving drug resistance in H. pylori have been less explored and this could imply more complex physiological changes (such as impaired regulation of drug uptake and/or efflux, or biofilm and coccoid formation) that remain largely elusive. Resistance-related attributes deployed by the pathogen cause treatment failures, diagnostic difficulties and ambiguity in clinical interpretation of therapeutic outcomes. Subsequent to the increasing antibiotic resistance, a substantial drop in H. pylori treatment efficacy has been noted globally. In the absence of an efficient vaccine, enhanced efforts are needed for setting new treatment strategies and for a better understanding of the emergence and spread of drug-resistant bacteria, as well as for improving diagnostic tools that can help optimize current antimicrobial regimens.
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Affiliation(s)
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan. .,Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.
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Gingold-Belfer R, Niv Y, Levi Z, Boltin D. Rifabutin triple therapy for first-line and rescue treatment of Helicobacter pylori infection: A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36:1392-1402. [PMID: 33037845 DOI: 10.1111/jgh.15294] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/18/2020] [Accepted: 10/06/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIM Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection. METHODS We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs). RESULTS Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I2 = 68.1%, P = 0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H. pylori infection (OR 3.78, 95% CI 2.44-5.87, P < 0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P = 0.001) and when daily amoxicillin dose was ≥ 3000 mg or proton pump inhibitor dose was ≥ 80 mg or treatment duration was 14 days (80.6% vs 66.0%, P = 0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I2 = 79.76, P = 0.82). CONCLUSION Evidence for the effectiveness of rifabutin for the first-line treatment of H. pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking.
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Affiliation(s)
- Rachel Gingold-Belfer
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yaron Niv
- Division of Patient Safety and Quality Improvement, Ministry of Health, Jerusalem, Israel
| | - Zohar Levi
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Doron Boltin
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Gisbert JP. Rifabutin for the Treatment of Helicobacter Pylori Infection: A Review. Pathogens 2020; 10:pathogens10010015. [PMID: 33379336 PMCID: PMC7823349 DOI: 10.3390/pathogens10010015] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/17/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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12
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Hirata Y, Yamada A, Niikura R, Shichijo S, Hayakawa Y, Koike K. Efficacy and safety of a new rifabutin-based triple therapy with vonoprazan for refractory Helicobacter pylori infection: A prospective single-arm study. Helicobacter 2020; 25:e12719. [PMID: 32602161 DOI: 10.1111/hel.12719] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/27/2020] [Accepted: 05/29/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND A small proportion of Helicobacter pylori-infected individuals in Japan suffer failure of eradication therapy with third-line regimens containing the potent acid suppressor, vonoprazan, and a quinolone. OBJECTIVES This prospective study evaluated the efficacy and safety of rifabutin-based triple therapy with vonoprazan for refractory H pylori infection. METHODS Patients who failed H pylori eradication by clarithromycin-based first-line, metronidazole-based second-line, and sitafloxacin-based third-line therapies were recruited. After obtaining informed consent, patients received eradication therapy with vonoprazan (20 mg), amoxicillin (750 mg), and rifabutin (150 mg) twice daily for 10 days. Eradication was confirmed by a negative H pylori stool antigen or urea breath test at least 8 weeks after the end of therapy. RESULTS Nineteen patients were included in the study. All of the patients completed the course of medication. Eradication of H pylori was confirmed in all of the patients (19/19; 100%, 95% confidence interval; 83-100%). The most common adverse event was soft stool/diarrhea (4/19, 21%). No severe adverse event was observed. CONCLUSIONS Ten-day rifabutin with amoxicillin and vonoprazan triple therapy appears to be effective and safe for refractory H pylori infections. However, considering the recent publications showing high eradication rates with vonoprazan amoxicillin dual therapy, confirmation will require future studies comparing our new therapy with vonoprazan-amoxicillin dual with similar doses and duration and with vonoprazan-rifabutin dual therapy.
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Affiliation(s)
- Yoshihiro Hirata
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.,Division of Advanced Genome Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Atsuo Yamada
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | - Ryota Niikura
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | - Satoki Shichijo
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.,Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yoku Hayakawa
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
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13
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Tang X, Chen X, Shen Y, Yang T, Hu R, Debowski AW, Stubbs KA, Benghezal M, Marshall BJ, Li H, Tang H. Primary antibiotic resistance of Helicobacter pylori among a Chinese Tibetan population. Future Microbiol 2020; 15:1353-1361. [PMID: 32900223 DOI: 10.2217/fmb-2020-0206] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Aim: To evaluate the primary antibiotic resistance in Helicobacter pylori strains isolated from a Chinese Tibetan population. Methods & materials: Gastric biopsies from 400 H. pylori treatment-naive Tibetan patients were collected for H. pylori isolation. Susceptibility to amoxicillin (AML)/clarithromycin (CLR)/levofloxacin (LEV)/metronidazole (MTZ)/tetracycline (TET)/rifampicin (RIF)/furazolidone (FZD) was determined by E-test or a disk diffusion assay. Results: Biopsies from 117 patients were H. pylori culture positive (29.3%). The primary resistance rates to MTZ, CLR, LEV, RIF, AML, TET and FZD were 90.6, 44.4, 28.2, 69.2, 7.7, 0.8 and 0.8%, respectively. Interestingly, 42.7% of the strains had simultaneous resistance to CLR and MTZ. Conclusion: Among Tibetan strains, primary resistance rates were high for CLR/MTZ/LEV, whereas primary resistance rates to AML/TET/FZD were low. The high resistance to RIF is a concerning finding.
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Affiliation(s)
- Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiaohong Chen
- Department of Digestive Medicine, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, 610041, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tiankuo Yang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Aleksandra W Debowski
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research & Training, University of Western Australia, Nedlands, Perth, 6009, Australia.,School of Molecular Sciences, University of Western Australia, Crawley, Perth, 6009, Australia
| | - Keith A Stubbs
- School of Molecular Sciences, University of Western Australia, Crawley, Perth, 6009, Australia
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Barry J Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research & Training, University of Western Australia, Nedlands, Perth, 6009, Australia
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
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14
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Kim SY, Chung JW. Best Helicobacter pylori Eradication Strategy in the Era of Antibiotic Resistance. Antibiotics (Basel) 2020; 9:antibiotics9080436. [PMID: 32717826 PMCID: PMC7459868 DOI: 10.3390/antibiotics9080436] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/11/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
Antibiotic resistance is the major reason for Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy (proton pump inhibitor, amoxicillin, and clarithromycin) is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.
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Affiliation(s)
- Su Young Kim
- Divison of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 26426, Korea;
| | - Jun-Won Chung
- Divison of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, 21, Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea
- Correspondence: ; Tel.: +82-32-460-3778; Fax: +82-32-460-3408
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15
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Siavoshi F, Saniee P, Malekzadeh R. Effective antimicrobial activity of rifabutin against multidrug-resistant Helicobacter pylori. Helicobacter 2018; 23:e12531. [PMID: 30230637 DOI: 10.1111/hel.12531] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 07/21/2018] [Accepted: 07/21/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Helicobacter pylori resistance to more than one antibiotic is the main reason for failure in bacterial eradication in a considerable number of patients. Rifabutin (RFB) with a broad-spectrum of antimicrobial therapy has been suggested for treatment of refractory multidrug-resistant infections. METHODS Helicobacter pylori isolates from 104 patients were examined for resistance to 5 currently used antibiotics and RFB, using agar dilution method. Twofold serial dilutions of antibiotics were used and MICs (μg/mL) determined as metronidazole (MTZ 8), clarithromycin (CLR 2), amoxicillin (AMX 1), tetracycline (TET 0.5), furazolidone (FRZ 0.5), and RFB (0.06). RESULTS Of 104 H. pylori isolates, only 7 (6.7%) were sensitive to all the 6 antibiotics. However, 30 (28.8%) were resistant to one antibiotic, 28 (26.9%) to two, 19 (18.2%) to three, 14 (13.4%) to four, and 6 (5.7%) to five currently used antibiotics. Overall, 67(64.4%) of isolates were resistant to 2-5 currently used antibiotics and considered as multidrug-resistant (MDR), with 59 (88.1%) showing sensitivity to RFB and 8 (11.9%) resistance (P < 0.05). Of 33 isolates resistant to both MTZ and CLR, 25 (75.7%) were sensitive to RFB and 8 (24.3%) resistant (P < 0.05). DISCUSSION In vitro antimicrobial effectiveness of RFB on MDR H. pylori including those with resistance to both MTZ and CLR was demonstrated. However, RFB efficacy decreased as the number of antibiotics responsible for MDR increased. Considering that RFB inhibits both extra- and intracellular H. pylori, it can be suggested as an effective antibiotic against of MDR H. pylori.
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Affiliation(s)
- Farideh Siavoshi
- Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran
| | - Parastoo Saniee
- Faculty of Life Sciences and Biotechnology, Department of Microbiology, Shahid Beheshti University G.C, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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16
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Kim J, Kim K, Lee JS, Kim SY, Kim KO, Kim YJ, Kwon KA, Park DK, Chung JW. [The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 71:204-212. [PMID: 29684969 DOI: 10.4166/kjg.2018.71.4.204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Background/Aims Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. Methods We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). Results The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00-12.32; p=0.05). Conclusions Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.
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Affiliation(s)
- Joonhwan Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kyungwon Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Jun Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kyung Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Yoon Jae Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kwang An Kwon
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Dong Kyun Park
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Jun Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
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17
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Suzuki H, Mori H. World trends for H. pylori eradication therapy and gastric cancer prevention strategy by H. pylori test-and-treat. J Gastroenterol 2018; 53:354-361. [PMID: 29138921 PMCID: PMC5847180 DOI: 10.1007/s00535-017-1407-1] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 10/25/2017] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies.
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Affiliation(s)
- Hidekazu Suzuki
- Fellowship Training Center, Medical Education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan
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18
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Hays C, Burucoa C, Lehours P, Tran CT, Leleu A, Raymond J. Molecular characterization of Helicobacter pylori resistance to rifamycins. Helicobacter 2018; 23. [PMID: 29168600 DOI: 10.1111/hel.12451] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Antibiotic resistance is a major contributing factor in treatment failure of Helicobacter pylori eradication. Rifabutin (RB) is a rescue treatment and rifampicin (RP) is used to screen RB resistance in vitro. The aim of this study was to evaluate the rate of rifamycins resistance and to determine the mutations in the rpoB gene conferring resistance to discuss the current break point. METHODS Antimicrobial susceptibility to RP was first determined by E-test for 1015 H. pylori isolates. RP and RB MICs were then determined by agar dilution method for strains with MIC of RP > 1 mg/L, and the rpoB gene was sequenced. RESULTS Overall, 54 of 1015 strains exhibited a RP MIC > 1 mg/L by agar dilution method. Among these 54 strains, 10 had MICs of RP > 4 mg/L and RB ≥ 1 mg/L. They all carried at least one mutation in the rpoB gene at codons 530, 538, 540, 525 in the RP resistance-determining region (RRDR). Implication of the mutation L547F was confirmed by site-directed mutagenesis experiment. In contrast, among the 44 H. pylori isolates with a MIC of RP comprised between 2 and 4 mg/L, only 4 of 44 (9%) strains exhibited a mutation in rpoB, but outside RRDR (codons 470, 499, 636, or 657). For 31 of 44 tested strains, the RB MICs were ≤0.064 mg/L. CONCLUSION These results suggest that H. pylori isolates should be classified as resistant to RP for MICs > 4 mg/L. We considered that the optimal cut off for RB was ≥0.125 mg/L. We report a new mutation responsible for rifamycins, resistance, L547F.
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Affiliation(s)
- Constantin Hays
- Bacteriology, University of Paris-Descartes, Cochin Hospital, Paris, France
| | - Christophe Burucoa
- EA 4331 LITEC, Université de Poitiers, Laboratoire de bactériologie, Hygiène, CHU de Poitiers, Poitiers, France
| | - Philippe Lehours
- INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, Bordeaux, France.,French National Reference Centre for Campylobacters and Helicobacter, Bordeaux Hospital, Bordeaux, France
| | - Cong Tri Tran
- EA 4331 LITEC, Université de Poitiers, Laboratoire de bactériologie, Hygiène, CHU de Poitiers, Poitiers, France
| | - Anaïs Leleu
- Bacteriology, University of Paris-Descartes, Cochin Hospital, Paris, France
| | - Josette Raymond
- Bacteriology, University of Paris-Descartes, Cochin Hospital, Paris, France
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19
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Gong Y, Yuan Y. Resistance mechanisms of Helicobacter pylori and its dual target precise therapy. Crit Rev Microbiol 2018; 44:371-392. [PMID: 29293032 DOI: 10.1080/1040841x.2017.1418285] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.
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Affiliation(s)
- Yuehua Gong
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
| | - Yuan Yuan
- a Tumor Etiology and Screening Department of Cancer Institute and General Surgery , the First Hospital of China Medical University , Shenyang , China.,b Key Laboratory of Cancer Etiology and Prevention (China Medical University) Liaoning Provincial Education Department , Shenyang , China.,c National Clinical Research Center for Digestive Diseases , Xi'an , China
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Sung J, Kim N, Park YH, Hwang YJ, Kwon S, Na G, Choi JY, Kang JB, Kim HR, Kim JW, Lee DH. Rifabutin-based Fourth and Fifth-line Rescue Therapy in Patients with forHelicobacter pyloriEradication Failure. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 69:109-118. [DOI: 10.4166/kjg.2017.69.2.109] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Jihee Sung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yo Han Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Jae Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Gyeongjae Na
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joon Young Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Rang Kim
- Hospital Health Promotion Center, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Abstract
Failed eradication of Helicobacter pylori occurs when the antibiotic concentration at the site where H. pylori is located is lower than the minimal inhibitory concentration of the antibiotic for this bacterium. The main reason for this is the acquisition of resistance; and in the context of the most common treatment, the main reason is the acquisition of resistance to clarithromycin. Several options can then be followed. The most rational option is to use a tailored therapy, that is, to look for clarithromycin resistance either by culture plus antibiogram or by a molecular method. The standard triple therapy is used only in the case of clarithromycin susceptibility. In case of resistance or if an empiric treatment must be given, a good option is to use a bismuth-based quadruple therapy. If unavailable, clarithromycin-based quadruple therapies can be used either as sequential or 'concomitant' or hybrid. The limit, especially for concomitant therapy, is the use of clarithromycin, which will be inactive in about 2/3 of the cases, adding to cost and adverse events. Recently, the dual therapy proton pump inhibitor-amoxicillin has been revisited especially in the Far East, and increasing the dose and the frequency of administration gives excellent results.
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Affiliation(s)
- Francis Mégraud
- Inserm U853, Université de Bordeaux and Laboratoire de Bactériologie, CHU Pellegrin, Bordeaux, France
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22
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Mori H, Suzuki H, Matsuzaki J, Tsugawa H, Fukuhara S, Miyoshi S, Hirata K, Seino T, Matsushita M, Nishizawa T, Masaoka T, Kanai T. Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study. United European Gastroenterol J 2016; 4:380-387. [PMID: 27403304 PMCID: PMC4924440 DOI: 10.1177/2050640615618043] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 10/28/2015] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND AND AIM This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. METHODS Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. RESULTS Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. CONCLUSION Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Medical Education Center, Keio University School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hitoshi Tsugawa
- Department of Biochemistry and Integrative Medical Biology, Keio University School of Medicine, Tokyo, Japan
| | - Seiichiro Fukuhara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Sawako Miyoshi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takashi Seino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Misako Matsushita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, Valasek MA. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514-33. [PMID: 26694080 PMCID: PMC5064663 DOI: 10.1111/apt.13497] [Citation(s) in RCA: 538] [Impact Index Per Article: 59.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/04/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. AIM To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms. METHODS A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. RESULTS The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced. CONCLUSIONS Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.
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Affiliation(s)
- I. Thung
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - H. Aramin
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - V. Vavinskaya
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - S. Gupta
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - J. Y. Park
- Department of Pathology and the Eugene McDermott Center for Human Growth and DevelopmentUniversity of Texas Southwestern Medical Center and Children's Medical CenterDallasTXUSA
| | - S. E. Crowe
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - M. A. Valasek
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
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Nishizawa T, Suzuki H. Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing. Front Mol Biosci 2014; 1:19. [PMID: 25988160 PMCID: PMC4428472 DOI: 10.3389/fmolb.2014.00019] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Accepted: 10/04/2014] [Indexed: 12/14/2022] Open
Abstract
Antibiotic resistance in Helicobacter pylori (H.pylori) is the main factor affecting the efficacy of current treatment methods against infection caused by this organism. The traditional culture methods for testing bacterial susceptibility to antibiotics are expensive and require 10–14 days. Since resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be exclusively caused by specific mutations in a small region of the responsible gene, molecular methods offer an attractive alternative to the above-mentioned techniques. The technique of polymerase chain reaction (PCR) is an accurate and rapid method for the detection of mutations that confer antibiotic resistance. This review highlights the mechanisms of antibiotic resistance in H. pylori and the molecular methods for antibiotic susceptibility testing.
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Affiliation(s)
- Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine Tokyo, Japan ; Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine Tokyo, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine Tokyo, Japan
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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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Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol 2014; 20:5283-93. [PMID: 24833858 PMCID: PMC4017043 DOI: 10.3748/wjg.v20.i18.5283] [Citation(s) in RCA: 134] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies.
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Song M, Ang TL. Second and third line treatment options for Helicobacter pylori eradication. World J Gastroenterol 2014; 20:1517-1528. [PMID: 24587627 PMCID: PMC3925860 DOI: 10.3748/wjg.v20.i6.1517] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 10/29/2013] [Accepted: 01/06/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is a highly successful bacterium with a high global prevalence and the infection carries significant disease burden. It is also becoming increasingly difficult to eradicate and the main reason for this is growing primary antibiotic resistance rates in a world where antibiotics are frequently prescribed and readily available. Despite knowing much more about the bacterium since its discovery, such as its genomic makeup and pathogenesis, we have seen declining treatment success. Therefore, clinicians today must be prepared to face one, two or even multiple treatment failures, and should be equipped with sufficient knowledge to decide on the appropriate salvage therapy when this happens. This article discusses the factors contributing to treatment failure and reviews the second and third-line treatment strategies that have been investigated. Established empiric second line treatment options include both bismuth based quadruple therapy and levofloxacin based triple therapy. Antibiotic testing is recommended prior to initiating third line treatment. In the event that antibiotic susceptibility testing is unavailable, third line treatment options include rifabutin, rifaximin and sitafloxacin based therapies.
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Mégraud F. Current recommendations for Helicobacter pylori therapies in a world of evolving resistance. Gut Microbes 2013; 4:541-8. [PMID: 23929066 PMCID: PMC3928164 DOI: 10.4161/gmic.25930] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Occurrence of resistance, especially to clarithromycin, renders the standard triple therapy used to cure Helicobacter pylori infection ineffective. This review presents the bacteriological and pharmacological basis for H. pylori therapy and the current recommendations. The third-line treatment must be based on clarithromycin susceptibility testing. If the bacteria are still susceptible, failure may come from problems of compliance, hyperacidity or high bacterial load which can be overcome. If the bacteria are resistant, different regimens must be considered, including bismuth and non-bismuth-based quadruple therapies (sequential or concomitant), as well as triple therapies where amoxicillin is administered several times a day to obtain an optimal concentration at the gastric mucosal level. The treatments are becoming more and more complex and ecologically unsatisfactory, waiting for new agents or vaccines.
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Affiliation(s)
- Francis Mégraud
- INSERM U853; Bordeaux, France,Université de Bordeaux; Laboratoire de Bactériologie; Bordeaux, France,Correspondence to: Francis Mégraud,
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Recent Insights into Antibiotic Resistance in Helicobacter pylori Eradication. Gastroenterol Res Pract 2012; 2012:723183. [PMID: 22829809 PMCID: PMC3398622 DOI: 10.1155/2012/723183] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2012] [Revised: 06/18/2012] [Accepted: 06/18/2012] [Indexed: 12/13/2022] Open
Abstract
Antibiotics have been useful in the treatment of H. pylori-related benign and malignant gastroduodenal diseases. However, emergence of antibiotic resistance often decreases the eradication rates of H. pylori infections. Many factors have been implicated as causes of treatment failure, but the main antibiotic resistance mechanisms described to date are due to point mutations on the bacterial chromosome, a consequence of a significantly phenotypic variation in H. pylori. The prevalence of antibiotic (e.g., clarithromycin, metronidazole, tetracycline, amoxicillin, and furazolidone) resistance varies among different countries; it appears to be partly determined by geographical factors. Since the worldwide increase in the rate of antibiotic resistance represents a problem of relevance, some studies have been performed in order to identify highly active and well-tolerated anti-H. pylori therapies including sequential, concomitant quadruple, hybrid, and quadruple therapy. These represent a promising alternatives in the effort to overcome the problem of resistance. The aim of this paper is to review the current status of antibiotic resistance in H. pylori eradication, highlighting the evolutionary processes in detail at alternative approaches to treatment in the past decade. The underlying resistance mechanisms will be also followed.
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Nishizawa T, Suzuki H, Maekawa T, Harada N, Toyokawa T, Kuwai T, Ohara M, Suzuki T, Kawanishi M, Noguchi K, Yoshio T, Katsushima S, Tsuruta H, Masuda E, Tanaka M, Katayama S, Kawamura N, Nishizawa Y, Hibi T, Takahashi M. Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction. World J Gastroenterol 2012; 18:2735-8. [PMID: 22690086 PMCID: PMC3370014 DOI: 10.3748/wjg.v18.i21.2735] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Revised: 02/28/2012] [Accepted: 03/29/2012] [Indexed: 02/06/2023] Open
Abstract
We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.
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Abstract
BACKGROUND Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection. AIM To evaluate the role of rifabutin in the treatment of H. pylori infection. METHODS Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin-containing regimens on H. pylori eradication were combined and meta-analysed using the generic inverse variance method. RESULTS Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9-1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post-treatment patients were considered. Overall, mean H. pylori eradication rate (intention-to-treat analysis) with rifabutin-containing regimens (1008 patients) was 73% (67-79%). Respective cure rates for second-line (223 patients), third-line (342 patients) and fourth/fifth-line (95 patients) rifabutin therapies were 79% (67-92%), 66% (55-77%) and 70% (60-79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended. The mean rate of adverse effects was 22% (19-25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it. CONCLUSION Rifabutin-containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain.
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Helicobacter pylori resistance to rifabutin in the last 7 years. Antimicrob Agents Chemother 2011; 55:5374-5. [PMID: 21896915 DOI: 10.1128/aac.05437-11] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
A low rate of resistance (0.24%) to rifabutin was noted in Helicobacter pylori strains isolated from 414 Japanese patients. The only rifabutin-resistant strain detected showed a point mutation in the rpoB gene and was isolated from a patient with a history of rifampin treatment for pulmonary tuberculosis.
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Abstract
It is accepted that the success of Helicobacter pylori eradication treatment using standard triple therapy is declining. Resistance, particularly to clarithromycin, has been shown in numerous countries to be rising to a level where the use of standard triple therapy in its current form may no longer be justified. The two major factors influencing resistance are prior exposure to the antibiotic and compliance with therapy. Regimes based on bismuth and levofloxacin, which had previously been mainly second-line options, are now emerging as superior first-line options. Trials of sequential and concomitant therapies are also showing the usefulness of these treatments in different populations. Options for third and subsequent line therapies include furazolidone and rifabutin-based regimes. Susceptibility testing should be performed to maintain accurate data on resistance levels, and has also clinical utility in difficult to eradicate cases. None of these, however, will be successful unless compliance is improved upon. If compliance is assured and eradication confirmation pursued, it has been repeatedly illustrated that near full eradication is achievable.
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Affiliation(s)
- Anthony O'Connor
- Department of Gastroenterology, Adelaide and Meath Hospital incorporating the National Children's Hospital/Trinity College Dublin, Tallaght, Dublin 24, Ireland.
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Rescue therapy using a rifabutin-based regimen is effective for cure of Helicobacter pylori infection. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2010; 24:303-6. [PMID: 20485704 DOI: 10.1155/2010/637908] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the efficacy of rescue therapy using rifabutin, amoxicillin and a proton pump inhibitor (PPI) in the eradication of Helicobacter pylori in patients who have failed at least one course of PPI-based triple therapy. METHODS The present study was a single-centre case series of 16 consecutive patients who had received at least one course of standard eradication therapy. Pretreatment evaluation included endoscopy with biopsies for histology and culture for H pylori infection. Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR). Post-treatment evaluation consisted of a repeat endoscopy with biopsy for histology and culture, or a validated urea breath test at least four weeks after treatment was completed. Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test. RESULTS Of the 16 patients, four had previously received one course of triple therapy, 10 had received two courses and two had received more than two courses. The overall success rate of PPI-AR was 63% (10 of 16). Resistance to A was 0% (0 of 13), metronidazole 77% (10 of 13), clarithromycin 70% (seven of 10), and both metronidazole and clarithromycin 60% (six of 10). There was no correlation between resistance patterns and cure rate. CONCLUSIONS An R-containing regimen such as PPI-AR is a viable option as rescue therapy for H pylori infection.
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Abstract
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.
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Affiliation(s)
- Hidekazu Suzuki
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
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Matsuzaki J, Suzuki H, Tsugawa H, Nishizawa T, Hibi T. Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy. J Gastroenterol Hepatol 2010; 25 Suppl 1:S7-10. [PMID: 20586870 DOI: 10.1111/j.1440-1746.2010.06245.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Resistance of Helicobacter pylori to the standard therapeutic antimicrobial agents has been demonstrated. Although quinolones are an alternative candidate for third-line eradication therapy, quinolone resistance of H. pylori is also increasing. Quinolone resistance of H. pylori is caused by a point mutation of the DNA gyrase subunit A (GyrA) protein, especially on amino acids 87 and 91. The aim of this study is to surmise the structure of H. pylori GryA. METHODS The modeling of the 3-D structure of H. pylori GyrA was performed by an automated homology modeling program: SWISS-MODEL. The position of amino acids 87 and 91 in H. pylori GyrA was plotted on the homology model. To estimate the function of quinolone resistance-determining region (QRDR), the structure of H. pylori GyrA was compared with Escherichia coli GyrA. RESULTS A molecular model of H. pylori GyrA could be predicted using SWISS-MODEL. The GyrA N- and C-terminal domains closely resembled those of E. coli. The position of amino acids 87 and 91 in H. pylori GyrA was part of the DNA binding region (head dimer interface) on the GyrA N-terminal domain. CONCLUSION Our homology model of H. pylori GryA suggests that the quinolone resistance-determining region is on the head dimer interface of the GyrA N-terminal domain.
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Affiliation(s)
- Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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Abstract
This article aims to examine current best practice in the field reference to first-line, second-line, rescue and emerging treatment regimens for Helicobacter pylori eradication. The recommended first-line treatment in published guidelines in Europe and North American is proton pump inhibitor combined with amoxicillin and clarithromycin being the favoured regimen. Rates of eradication with this regimen however are falling alarmingly due to a combination of antibiotic resistance and poor compliance with therapy. Bismuth based quadruple therapies and levofloxacin based regimes have been shown to be effective second line regimens. Third-line options include regimes based on rifabutin or furazolidone, but susceptibility testing is the most rational option here, but is currently not used widely enough. Sequential therapy is promising but needs further study and validation outside of Italy. Although the success of first line treatments is falling, if compliance is good and a clear treatment paradigm adhered to, almost universal eradication rates can still be achieved. If compliance is not achievable, the problem of antibiotic resistance will continue to beset any combination of drugs used for H. pylori eradication.
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Affiliation(s)
- Anthony O'Connor
- Department of Gastroenterology, Adelaide and Meath Hospital incorporating the National Children's Hospital Tallaght, Trinity College Dublin, Dublin, Ireland
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Suzuki H, Iwasaki E, Hibi T. Helicobacter pylori and gastric cancer. Gastric Cancer 2009; 12:79-87. [PMID: 19562461 DOI: 10.1007/s10120-009-0507-x] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2009] [Accepted: 03/25/2009] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori is now well known as an important pathogen related to the development of gastric cancer. However, some clinicians still doubt the causal association of H. pylori with the development of gastric cancer. To summarize the recent clinical data on the link between H. pylori and gastric cancer, we reviewed related articles published over the past 3 years, after the award of the Nobel Prize for Physiology or Medicine to Drs. J.R. Warren and B.J. Marshall for the first culture and isolation of H. pylori and the investigation of their relevance to peptic ulcer disease. This updated summary of the relationship between H. pylori and gastric cancer highlights the strong link between the organism and the development of gastric cancer, and suggests eradication of this bacterial infection as a possible prophylactic measure against the development of this lethal malignancy. At present, clinicians and researchers in the field emphasize the strong need for H. pylori eradication from the human stomach.
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Affiliation(s)
- Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Nishizawa T, Suzuki H, Hibi T. Quinolone-Based Third-Line Therapy for Helicobacter pylori Eradication. J Clin Biochem Nutr 2009; 44:119-24. [PMID: 19308265 PMCID: PMC2654467 DOI: 10.3164/jcbn.08-220r] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Accepted: 09/11/2008] [Indexed: 12/21/2022] Open
Abstract
Currently, a standard third-line therapy for Helicobacter pylori (H. pylori) eradication remains to be established. Quinolones show good oral absorption, no major side effects, and marked activity against H. pylori. Several authors have studied quinolone-based third-line therapy and reported encouraging results, with the reported H. pylori cure rates ranging from 60% to 84%. Resistance to quinolones is easily acquired, and the resistance rate is relatively high in countries with a high consumption rate of these drugs. We recently reported a significant difference in the eradication rate obtained between patients infected with gatifloxacin-susceptible and gatifloxacin-resistant H. pylori, suggesting that the selection of quinolones for third-line therapy should be based on the results of drug susceptibility testing. As other alternatives of third-line rescue therapies, rifabutin-based triple therapy, high-dose proton pump inhibitor/amoxicillin therapy and furazolidone-based therapy have been suggested.
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Affiliation(s)
- Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
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