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Iwata E, Sugimoto M, Asaoka D, Hojo M, Ito M, Kitazawa N, Kurihara N, Masaoka T, Mizuno S, Mori H, Nagahara A, Niikura R, Ohkusa T, Sano M, Shimada Y, Suzuki H, Takeuchi Y, Tanaka A, Tokunaga K, Ueda K, Sakaki N, Takahashi S, Kawai T. Characteristics of Helicobacter pylori Eradication Therapy in Patients 80 Years or Older Living in a Metropolitan Area: A Multicenter Retrospective Study. Helicobacter 2024; 29:e13125. [PMID: 39152662 DOI: 10.1111/hel.13125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/27/2024] [Accepted: 07/29/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years. METHODS Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated. RESULTS The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment. CONCLUSION After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future.
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Affiliation(s)
- Eri Iwata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
- Division of Genome-Wide Infectious Microbiology, Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University, Oita, Japan
| | - Daisuke Asaoka
- Department of Gastroenterology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
| | - Mariko Hojo
- Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masayoshi Ito
- Department of Gastroenterology, Yotsuya Medical Cube, Tokyo, Japan
| | - Naoko Kitazawa
- Department of Gastroenterology, Foundation for Detection of Early Gastric Carcinoma, Tokyo, Japan
| | - Naoto Kurihara
- Department of Surgery, Nerima General Hospital, Tokyo, Japan
| | - Tatsuhiro Masaoka
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Mita Hospital, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Center for Endoscopy, Kawasaki Municipal Hospital, Kawasaki, Japan
| | | | - Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Ryota Niikura
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Toshifumi Ohkusa
- Department of Internal Medicine, Oriental Ueno Health Checkup Center, Tokyo, Japan
| | - Masaya Sano
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, Shibuya, Japan
| | - Yuji Shimada
- Department of Gastroenterology and Hepatology, Juntendo Shizuoka Hospital, Shizuoka, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Tokai University, Shibuya, Japan
| | | | - Akifumi Tanaka
- Preventive Health Care Center, Kyorin University Suginami Hospital, Tokyo, Japan
| | - Kengo Tokunaga
- Department of Preventive Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Kumiko Ueda
- Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Nobuhiro Sakaki
- Department of Gastroenterology, Foundation for Detection of Early Gastric Carcinoma, Tokyo, Japan
| | - Shin'ichi Takahashi
- Department of Internal Medicine, Kyorin University Suginami Hospital, Tokyo, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
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Sahara S, Sugimoto M, Murata M, Iwata E, Kawai T, Murakami K, Yamaoka Y, Shimoyama T. Eradication Therapy for Helicobacter pylori Infection in Patients Receiving Hemodialysis: Review. Helicobacter 2024; 29:e13106. [PMID: 38984746 DOI: 10.1111/hel.13106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 05/15/2024] [Accepted: 06/05/2024] [Indexed: 07/11/2024]
Abstract
Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2-1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48-1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93-5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23-6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2-1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.
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Affiliation(s)
- Shu Sahara
- Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu, Japan
| | - Mitsushige Sugimoto
- Division of Genome-Wide Infectious Diseases, Research Center for GLOBAL and LOCAL Infectious Disease, Oita University, Yufu, Japan
| | - Masaki Murata
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Eri Iwata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Japan
| | | | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University, Yufu, Japan
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Tsuda M, Watanabe Y, Oikawa R, Watanabe R, Higashino M, Kubo K, Yamamoto H, Itoh F, Kato M. Impact of mixed-infection rate of clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori strains on the success rate of clarithromycin-based eradication treatment. Helicobacter 2024; 29:e13062. [PMID: 38459683 DOI: 10.1111/hel.13062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 02/08/2024] [Accepted: 02/15/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND Clarithromycin (CAM) resistance is a major contributor to the failure to eradicate Helicobacter pylori (H. pylori). The mixed-infection ratio of CAM-susceptible and CAM-resistant H. pylori strains differs among individuals. Pyrosequencing analysis can be used to quantify gene mutations at position each 2142 and 2143 of the H. pylori 23S rRNA gene in intragastric fluid samples. Herein, we aimed to clarify the impact of the rate of mixed infection with CAM-susceptible and CAM-resistant H. pylori strains on the success rate of CAM-containing eradication therapy. MATERIALS AND METHODS Sixty-four H. pylori-positive participants who received CAM-based eradication therapy, also comprising vonoprazan and amoxicillin, were enrolled in this prospective cohort study. Biopsy and intragastric fluid samples were collected during esophagogastroduodenoscopy. H. pylori culture and CAM-susceptibility tests were performed on the biopsy samples, and real-time PCR and pyrosequencing analyses were performed on the intragastric fluid samples. The mutation rates and eradication success rates were compared. RESULTS The overall CAM-based eradication success rate was 84% (54/64): 62% (13/21) for CAM-resistant strains, and 95% (39/41) for CAM-sensitive strains. When the mutation rate of the 23S rRNA gene was 20% or lower for both positions (2142 and 2143), the eradication success rate was 90% or more. However, when the mutation rate was 20% or higher, the eradication success rate was lower (60%). CONCLUSIONS The mutation rate of the CAM-resistance gene was related to the success of eradication therapy, as determined via pyrosequencing analysis.
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Affiliation(s)
- Momoko Tsuda
- Department of Gastroenterology, NHO Hakodate National Hospital, Hakodate, Japan
| | - Yoshiyuki Watanabe
- Department of Internal Medicine, Kawasaki Rinko General Hospital, Kawasaki, Japan
- Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Ritsuko Oikawa
- Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Ryosuke Watanabe
- Department of Gastroenterology, NHO Hakodate National Hospital, Hakodate, Japan
| | - Masayuki Higashino
- Department of Gastroenterology, NHO Hakodate National Hospital, Hakodate, Japan
| | - Kimitoshi Kubo
- Department of Gastroenterology, NHO Hakodate National Hospital, Hakodate, Japan
| | - Hiroyuki Yamamoto
- Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
- Department of Bioinformatics, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
| | - Fumio Itoh
- Division of Gastroenterology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, NHO Hakodate National Hospital, Hakodate, Japan
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Lin K, Huang L, Wang Y, Li K, Ye Y, Yang S, Li A. Efficacy of genotypic susceptibility-guided tailored therapy for Helicobacter pylori infection: A systematic review and single arm meta-analysis. Helicobacter 2023; 28:e13015. [PMID: 37634236 DOI: 10.1111/hel.13015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 07/28/2023] [Accepted: 08/01/2023] [Indexed: 08/29/2023]
Abstract
BACKGROUND AND AIM The prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular-based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single-arm meta-analysis to determine the efficacy of tailored therapy guided by molecular-based AST. METHODS A systematic literature review was performed on multiple databases, and studies on molecular-based TT were included. The eradication rates of TT by intention-to-treat (ITT) and per-protocol (PP) analyses were pooled respectively. RESULTS A total of 35 studies from 31 literature (4626 patients) were included in the single-arm meta-analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%-89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%-93.2%) by PP analysis. The pooled eradication rates of first-line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype-susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%-94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7-day TT or tailored triple therapy without bismuth for genotype-susceptive strains could both reach more than 93.0%. CONCLUSION Tailored therapy guided by molecular-based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7-day duration or without bismuth for genotype-susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth.
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Affiliation(s)
- Kaihao Lin
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lifang Huang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yadong Wang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Gastroenterology, Laboratory Department of Baiyun Branch, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Kangkang Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yuanning Ye
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Siqi Yang
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Aimin Li
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Miri AH, Kamankesh M, Rad-Malekshahi M, Yadegar A, Banar M, Hamblin MR, Haririan I, Aghdaei HA, Zali MR. Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori. Expert Rev Anti Infect Ther 2023; 21:617-639. [PMID: 37171213 DOI: 10.1080/14787210.2023.2203382] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
INTRODUCTION Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).
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Affiliation(s)
- Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Kamankesh
- Polymer Chemistry Department, School of Science, University of Tehran, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Banar
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg Doornfontein, Johannesburg, South Africa
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sholeh M, Khoshnood S, Azimi T, Mohamadi J, Kaviar VH, Hashemian M, Karamollahi S, Sadeghifard N, Heidarizadeh H, Heidary M, Saki M. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. PeerJ 2023; 11:e15121. [PMID: 37016679 PMCID: PMC10066884 DOI: 10.7717/peerj.15121] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/03/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori (H. pylori) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics. METHOD A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance. RESULTS The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41-29.69]). The heterogeneity between reports was significant (I2 = 97.80%, P < 0.01). The resistance rate increased from 24.28% in 2010-2017 to 32.14% in 2018-2021 (P < 0.01). Iran, with 38 articles, has the most report. Nevertheless, Switzerland, Portugal, and Israel had the highest resistance rates (67.16%, 48.11%, and 46.12%, respectively). The heterogeneity between the continents and the antimicrobial susceptibility methods also interpreted standard guidelines and breakpoints was insignificant (P > 0.05). CONCLUSION Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains.
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Affiliation(s)
- Mohammad Sholeh
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Taher Azimi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jasem Mohamadi
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Vahab Hassan Kaviar
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Marzieh Hashemian
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Somayeh Karamollahi
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Hedayat Heidarizadeh
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Tsuda M, Watanabe Y, Oikawa R, Watanabe R, Higashino M, Kubo K, Yamamoto H, Itoh F, Kato M. Clinical evaluation of a novel molecular diagnosis kit for detecting Helicobacter pylori and clarithromycin-resistant using intragastric fluid. Helicobacter 2022; 27:e12933. [PMID: 36263754 PMCID: PMC9788249 DOI: 10.1111/hel.12933] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/23/2022] [Accepted: 09/27/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Although there are many Helicobacter pylori (H. pylori) diagnostic methods, the culture and antibiotic susceptibility test is an important method for selecting the most effective H. pylori eradication regimen. However, this diagnostic method is complicated and takes several days; therefore, the development of a rapid and simple diagnostic method is required. Eradication failure due to clarithromycin (CAM) resistance should also be considered. In this study, we report the clinical evaluation of point-of-care testing (POCT) kit using intragastric fluid, a novel kit for detecting H. pylori and CAM resistance. MATERIALS AND METHODS The study participants were 143 patients suspected of H. pylori infection and had an endoscopic examination. The novel diagnostic kit diagnosed H. pylori infection and CAM resistance-associated mutation using intragastric fluid. To diagnose H. pylori infection, the relationship between the diagnostic kit and conventional diagnostic methods (urea breath test, stool antigen test, culture test, and real-time polymerase chain reaction [PCR]) was evaluated. For CAM resistance-associated mutation detection, the concordance between the diagnostic kit and antibiotic susceptibility test was evaluated. RESULTS The diagnosis of H. pylori infection with the novel molecular diagnostic kit using intragastric fluid showed significant relationship with conventional diagnostic methods. Especially when the culture was control, the sensitivity was 100% (67/67), the specificity was 95.9% (71/74), and the overall concordance was 97.9% (138/141). The detection of CAM resistance-associated mutations had a concordance rate of 97.0% (65/67) when compared with the antibiotic susceptibility test. CONCLUSIONS The H. pylori molecular POCT kit uses intragastric fluid as a sample and can diagnose H. pylori infection and detect CAM resistance-associated mutations within an hour. This novel kit is expected to prove useful in selecting the most effective eradication regimen for H. pylori.
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Affiliation(s)
- Momoko Tsuda
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Yoshiyuki Watanabe
- Department of Internal MedicineKawasaki Rinko General HospitalKawasakiJapan
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Ritsuko Oikawa
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Ryosuke Watanabe
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Masayuki Higashino
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Kimitoshi Kubo
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
| | - Hiroyuki Yamamoto
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
- Department of BioinformaticsSt. Marianna University Graduate School of MedicineKawasakiJapan
| | - Fumio Itoh
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
| | - Mototsugu Kato
- Department of GastroenterologyNational Hospital Organization Hakodate National HospitalHakodateJapan
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Zhao X, Zhang Z, Lu F, Xiong M, Jiang L, Tang K, Fu M, Wu Y, He B. Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis. Front Pharmacol 2022; 13:938419. [PMID: 36278195 PMCID: PMC9582748 DOI: 10.3389/fphar.2022.938419] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 09/12/2022] [Indexed: 11/28/2022] Open
Abstract
Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis. Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16. Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%). Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.
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Affiliation(s)
- Xianghong Zhao
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhongqiu Zhang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Fang Lu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China
| | - Mengqiu Xiong
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liping Jiang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ke Tang
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Min Fu
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yu Wu
- Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- H. pylori Research Key Laboratory, Nanjing Medical University, Nanjing, China
- *Correspondence: Bangshun He,
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9
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Han Y, Long H, Lin Y, He Q, Chen W, Ding X, Zhou L, An P, Wang F, Zhang Z, Hu Y, Li P. Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study. Helicobacter 2022; 27:e12922. [PMID: 35939559 PMCID: PMC9541209 DOI: 10.1111/hel.12922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/09/2022] [Accepted: 07/13/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.
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Affiliation(s)
- Ying‐Ying Han
- Division of GastroenterologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
| | - Hui Long
- Department of GastroenterologyTianyou Hospital Affiliated to Wuhan University of Science and TechnologyWuhanChina
| | - Ya Lin
- Department of GastroenterologyWenchang People's HospitalWenchangChina
| | - Qiong He
- Department of GastroenterologyWuhan Red Cross HospitalWuhanChina
| | - Wei‐Gang Chen
- Department of GastroenterologyThe First Affiliated Hospital of Shihezi University Medical CollegeShiheziChina
| | - Xiang‐Wu Ding
- Department of GastroenterologyWuhan Fourth HospitalWuhanChina
| | - Lin Zhou
- Department of GastroenterologySuizhou Central HospitalSuizhouChina
| | - Ping An
- Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina
| | - Fen Wang
- Department of GastroenterologyThe Third Xiangya Hospital, Central South UniversityChangshaChina
| | - Zhen‐Yu Zhang
- Department of GastroenterologyNanjing First Hospital, Nanjing Medical UniversityNanjingChina
| | - Yun‐Lian Hu
- Department of GastroenterologyHubei Provincial Hospital of Traditional Chinese MedicineWuhanChina
| | - Pei‐Yuan Li
- Division of GastroenterologyTongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina,Department of GastroenterologyWenchang People's HospitalWenchangChina
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10
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Huang Y, Chen J, Ding Z, Liang X, Lu H. Susceptibility testing alone will not reliably achieve high Helicobacter pylori cure rates: A systematic review and meta-analysis. J Gastroenterol Hepatol 2022; 37:1212-1221. [PMID: 35434851 DOI: 10.1111/jgh.15864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/21/2022] [Accepted: 04/09/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Not all the susceptibility-guided therapies for Helicobacter pylori (H. pylori) infection achieve excellent eradication rates. The aim of this study was to perform a systematic review and meta-analysis to identify the optimal regimen for H. pylori treatment based on antibiotic susceptibility. METHODS A systematic search was performed in multiple databases. Studies reporting eradication rates of H. pylori with susceptibility-guided therapies were selected. Meta-analysis was conducted to calculate the pooled eradication rate among the treatment regimens. RESULTS Forty-eight eligible studies with 101 susceptibility-guided treatment arms were included. The overall eradication rate in patients harboring susceptible strains was 95.0% (95% CI, 94.1-95.9%), but only 63.4% of treatment arms (64/101) achieved good eradication rates (≥ 90%). Pooled eradication rates in patients with susceptible strains were: 93.4% (95% CI, 92.0-94.8%) for clarithromycin, 99.0% (95% CI, 98.1-100%) for nitroimidazoles and 95.4% (95% CI, 93.6-97.2%) for fluoroquinolones. Among the arms using a triple therapy, 66.7% (28/42) using clarithromycin, 84.2% (16/19) using nitroimidazoles and 70.8% (17/24) using fluoroquinolones achieved good (≥ 90%) eradication rates. Of 13 arms using sequential therapy, ≥ 90% eradication was achieved in 14.3% (1/7) using clarithromycin, 25.0% (1/4) using nitroimidazoles and both arms (2/2) using fluoroquinolones. CONCLUSIONS Susceptibility testing alone seemed insufficient to reliably attain high H. pylori cure rates. The eradication rate in patients with nitroimidazoles susceptible strains was higher than those of fluoroquinolones and clarithromycin.
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Affiliation(s)
- 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
| | - 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
| | - 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
| | - 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
| | - 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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11
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Nyssen OP, Espada M, Gisbert JP. Empirical vs. Susceptibility-Guided Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Front Microbiol 2022; 13:913436. [PMID: 35774456 PMCID: PMC9237546 DOI: 10.3389/fmicb.2022.913436] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 05/17/2022] [Indexed: 01/30/2023] Open
Abstract
Background Treating Helicobacter pylori infection according to antibiotic resistance has been frequently recommended. However, information on its real effectiveness is scarce. Aim The aim of this study is to perform a meta-analysis comparing empirical vs. susceptibility-guided treatment of H. pylori. Methods Selection of studies: Studies comparing empirical versus susceptibility-guided treatment were selected. Search strategy: electronic and manual up to August 2021. Data synthesis: by intention-to-treat (random-effects model). Results Overall, 54 studies were included (6,705 patients in the susceptibility-guided group and 7,895 in the empirical group). H. pylori eradication rate was 86 vs. 76%, respectively (RR: 1.12; 95% CI: 1.08-1.17; I 2: 83%). Similar results were found when only RCTs were evaluated (24 studies; RR: 1.16; 95% CI: 1.11-1.22; I 2: 71%) and when susceptibility testing was assessed by culture (RR: 1.12; 95% CI: 1.06-1.18) or PCR (RR: 1.14; 95% CI: 1.05-1.23). For first-line treatments (naïve patients; 30 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR: 1.15; 95% CI: 1.11-1.20; I 2: 79%). However, for empirical first-line quadruple regimens, in particular (both with and without bismuth, excluding the suboptimal triple therapies), not based on CYP2C19 gene polymorphism, no differences in efficacy were found compared with the susceptibility-guided group (RR: 1.04; 95% CI: 0.99-1.09); this lack of difference was confirmed in RCTs (RR: 1.05; 95% CI: 0.99-1.12). For rescue therapies (13 studies, most 2nd-line), similar results were demonstrated for both strategies, including all studies (RR: 1.09; 95% CI: 0.97-1.22; I 2: 82%) and when only RCTs were considered (RR: 1.15; 95% CI: 0.97-1.36). Conclusion The benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapies.
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Affiliation(s)
- Olga P. Nyssen
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Marta Espada
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Javier P. Gisbert
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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12
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Morino Y, Sugimoto M, Nagata N, Niikiura R, Iwata E, Hamada M, Kawai Y, Fujimiya T, Takeuchi H, Unezaki S, Kawai T. Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis. Front Pharmacol 2021; 12:759249. [PMID: 34721043 PMCID: PMC8553963 DOI: 10.3389/fphar.2021.759249] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 09/16/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Proton pump inhibitors (PPIs) are the first-line treatment for acid-related diseases. The pharmacokinetics and therapeutic efficacy of PPIs, however, are influenced by genetic factors such as variants in genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19 [CYP2C19]) and drug transporters. We performed a meta-analysis to evaluate the influence of CYP2C19 genotype and PPI class, PPI dose, treatment duration and clarithromycin dose on the cure rate of PPI-containing Helicobacter pylori eradication therapy. Methods: Randomized control trials (RCTs) investigating cure rates using a PPI-amoxicillin-clarithromycin regimen among different CYP2C19 genotypes through May 2021 were included. Results: A total of 25 studies (5,318 patients) were included. The overall eradication rate in the intention-to-treat analysis was 79.0% (3,689/4,669, 95% confidence interval [CI]: 77.8-80.2%), and that in CYP2C19 extensive metabolizers (EMs), intermediate metabolizer (IMs) and poor metabolizers (PMs) was 77.7% (1,137/1,464, 95% CI: 75.3-79.6%), 81.2% (1,498/1,844, 95% CI: 79.3-83.0%) and 86.8% (644/742, 95% CI: 83.9-88.9%), respectively. Meta-analysis showed that the relaTakashitive risk of failed eradication in CYP2C19 EMs compared with IMs and PMs was 1.21 (95% CI: 1.06-1.39, P = 0.006) and 1.57 (95% CI: 1.27-1.94, P < 0.001), respectively, in the fixed-effects model. The cure rate of omeprazole and lansoprazole-containing eradication regimens differed among CYP2C19 genotypes (P < 0.05), while that of rabeprazole and esomeprazole-containing regimens was similar. Conclusion: The cure rates of PPI-amoxicillin-clarithromycin H. pylori eradication regimen, especially those containing omeprazole and lansoprazole, differ among CYP2C19 genotypes. Therefore, selection of a second-generation PPI or tailored treatment may achieve higher eradication rates than first-generation PPI-amoxicillin-clarithromycin triple regimen.
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Affiliation(s)
- Yuko Morino
- Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Naoyoshi Nagata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Ryota Niikiura
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Eri Iwata
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Mariko Hamada
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Yusuke Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Tatsuhiro Fujimiya
- Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Hironori Takeuchi
- Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan
| | - Sakae Unezaki
- Department of Practical Pharmacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
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13
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Choi YI, Chung JW, Kim KO, Kwon KA, Kim YJ, Kim JH, Seo JY, Park DK. Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients. World J Gastroenterol 2021; 27:5247-5258. [PMID: 34497448 PMCID: PMC8384750 DOI: 10.3748/wjg.v27.i31.5247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/09/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Antibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention.
AIM To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen.
METHODS We included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen.
RESULTS Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).
CONCLUSION The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.
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Affiliation(s)
- Youn I Choi
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Jun-Won Chung
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Kyoung Oh Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Kwang An Kwon
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Yoon Jae Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Jung Ho Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Ja Young Seo
- Department of Laboratory Medicine, Gil Medical Center, Gachon University, Inchoen 21565, South Korea
| | - Dong Kyun Park
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
- Health IT Research Center, Gachon University Gil Hospital, Incheon 21565, South Korea
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14
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Fu J, Sun CF, He HY, Ojha SC, Shi H, Deng CL, Sheng YJ. The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis. Pharmacogenomics 2021; 22:859-879. [PMID: 34414773 DOI: 10.2217/pgs-2020-0127] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Premise: The effects of proton pump inhibitors (PPI) depend on metabolic enzyme CYP2C19 that has different activity due to gene polymorphism. The purpose of this meta-analysis is to determine the potential effects of CYP2C19 polymorphism on the efficiency of PPI-based treatment. Materials & methods: The PubMed, EMBASE, Cochrane Library, etc. were searched for relevant articles published in English or Chinese from inception to 31 May 2020. Finally, 26 randomized controlled trials and 15 cohort studies met the inclusion criteria and used for the meta-analysis via STATA version 15. Results: Poor metabolizer (PM) genotype Helicobacter pylori eradication rates were highest for Asian individuals receiving triple or quadruple first-line therapy based on PPIs (p < 0.05). CYP2C19 polymorphism could influence H. pylori eradication rate only in Mainland China and Japan (p < 0.05). Conclusion: PM genotype facilitates the elimination of H. pylori in Asian populations. Rabeprazole-, esomeprazole- and pantoprazole-based eradication program was less affected by the CYP2C19 polymorphism.
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Affiliation(s)
- Juan Fu
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Chang-Feng Sun
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Department of Tuberculosis, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Hong-Yan He
- Experimental Teaching Center, School of Public Health of Southwest Medical University, Luzhou, 646000, China
| | - Suvash Chandra Ojha
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Department of Tuberculosis, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Han Shi
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Cun-Liang Deng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Department of Tuberculosis, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
| | - Yun-Jian Sheng
- Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Department of Tuberculosis, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.,Infection & Immunity Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China
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15
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Zhou JJ, Shi X, Zheng SP, Tang D, Cai T, Yao Y, Wang F. Efficacy of bismuth-based quadruple therapy for eradication of Helicobacter pylori infection based on previous antibiotic exposure: A large-scale prospective, single-center clinical trial in China. Helicobacter 2020; 25:e12755. [PMID: 32914914 DOI: 10.1111/hel.12755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/29/2020] [Accepted: 08/06/2020] [Indexed: 01/30/2023]
Abstract
OBJECTIVE This study aims to evaluate the efficacy and safety of three bismuth-based quadruple regimens for eradication of Helicobacter pylori (H pylori) infection in a large number of H pylori-positive patients with or without previous eradication therapy. METHODS Consecutive adult patients with H pylori infection, regardless of previous eradication therapy, were eligible for the present study. Three bismuth-based quadruple regimens were selected according to the past history of antibiotics use: (A) esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth tartrate; (B) esomeprazole, amoxicillin, furazolidone, and colloidal bismuth tartrate; and (C) esomeprazole, doxycycline, furazolidone, and colloidal bismuth tartrate. All patients received a 14-day course of treatment, and 13 C/14 C urea breath test was utilized at four weeks after the completion of treatment to determine the H pylori eradication. Then, the eradication rates were calculated in terms of intention-to-treat (ITT) and per-protocol (PP) analyses. Adverse events (AEs) were recorded during the treatment. RESULTS Overall, 1,226 patients were recruited, and 331, 57, and 838 patients were allocated to receive regimens A, B, and C, respectively. The H pylori eradication rates were 84.0%, 82.5%, and 82.9% (ITT) and 94.6%, 92.2%, and 93.7% (PP), respectively, in regimens A, B, and C. However, there was no significant difference among these three regimens. The incidence of AEs was 4.6% for all patients during the study, that is, 3.3%, 10.5%, and 4.7% for regimens A, B, and C, respectively. All AEs were mild and recovered at the follow-up visit. CONCLUSION All three bismuth-based quadruple regimens based on the previous antibiotic use can achieve satisfactory eradication rates for H pylori infection and are safe.
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Affiliation(s)
- Jing-Jing Zhou
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Xiao Shi
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Shao-Peng Zheng
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Dan Tang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Ting Cai
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yao Yao
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Fen Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Non-Resolving Inflammation and Cancer, The Third Xiangya Hospital, Central South University, Changsha, China
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16
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Murata M, Sugimoto M. Effect of a rabeprazole half-dose twice daily on acid inhibition in patients with different CYP2C19 alleles. Eur J Clin Pharmacol 2020; 76:1253-1261. [PMID: 32488332 DOI: 10.1007/s00228-020-02917-w] [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: 12/18/2019] [Accepted: 05/25/2020] [Indexed: 10/24/2022]
Abstract
PURPOSE Fractional doses of proton pump inhibitors (PPIs) more often than once daily (qd) inhibit 24-h acid secretion more effectively than an increase in the standard single daily dose. Although rabeprazole 5 mg qd is covered for prevention of aspirin-induced gastric injury under the Japanese insurance system, it is unclear whether rabeprazole 5 mg twice daily (bid) would more effectively inhibit acid secretion. We compared acid inhibition between rabeprazole 10 mg qd and 5 mg bid in healthy volunteers with different alleles of CYP2C19. METHODS Twelve Helicobacter pylori-negative healthy volunteers (CYP2C19 genotypes: extensive metabolizer (EM) (n = 6) and poor metabolizer (PM) (n = 6)) received three kinds of regimen for 7 days under a randomized crossover design: rabeprazole 5 mg qd (5 mg QD), 10 mg qd (10 mg QD), and 5 mg bid (5 mg BID). A 24-hour pH monitoring was conducted before the trial and on day 7 of each regimen. RESULTS No significant differences in median pH values (4.0 (1.9-5.9)) and (4.4 (2.1-6.5)) or percent time of pH ≥ 4 (50.7% (11.9-86.8%) and 56.8% (19.3-83.9%)) were seen between the 10 mg QD and 5 mg BID regimens. Median pHs and percent time of pH ≥ 4 in CYP2C19 PMs were significantly higher than those in EMs. With 5 mg BID, there was no significant difference in percent-time with pH ≥ 4 between daytime and nighttime, but the 10 mg QD showed a significant difference. CONCLUSION Rabeprazole 5 mg bid provided no therapeutic advantage for acid inhibition compared with rabeprazole 10 mg qd, regardless of CYP2C19 genotype status.
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Affiliation(s)
- Masaki Murata
- Department of Gastroenterology, National Hospital Organization, Kyoto Medical Center, Kyoto, 612-8555, Japan
| | - Mitsushige Sugimoto
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
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Valle Muñoz J, Muñoz Gómez P, Sierra Bernal C, de Andrés E, Gómez Hernando C, Gómez Rodríguez R. Tailored Helicobacter pylori eradication based on prior intake of macrolide antibiotics allows the use of triple therapy with optimal results in an area with high clarithromycin resistance. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 111:655-661. [PMID: 31345044 DOI: 10.17235/reed.2019.6198/2019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND the previous intake of macrolide antibiotics is associated with a failure to eradicate Helicobacter pylori (H. pylori) with clarithromycin-containing regimens. However, the standard triple therapy achieves eradication rates of over 90% in patients without a previous use of macrolides in our health area. The aim of this study was to evaluate the efficacy of an H. pylori eradication strategy based on the intake of macrolides by the patient during the previous years. METHODS one hundred and sixty-nine patients with H. pylori infection were prospectively included in the study. The electronic medical record of each patient was reviewed at the time of inclusion. Depending on their previous intake of macrolides, patients were assigned to one of two eradication regimens: group A) patients without a previous intake of macrolides received an optimized triple therapy for 14 days; and group B) patients with a previous intake of macrolides received bismuth quadruple therapy for ten days. RESULTS ninety-one patients (53.84%) without a previous intake of macrolides received an optimized triple therapy (group A) and 78 patients (46.15%) with a previous intake of macrolides received bismuth quadruple therapy (group B). In group A, the H. pylori eradication rates were 90.11% in the intention-to-treat and 95.35% in the per-protocol analysis. In group B, the H. pylori eradication rates were 85.89% in the intention-to-treat and 98.5% in the per-protocol analysis. The overall eradication rates obtained using this strategy were 88.16% (95% CI: 82.32-92.02%) in the intention-to-treat and 96.75% (95% CI: 92.59-98.94%) in the per-protocol analysis. CONCLUSIONS an H. pylori eradication strategy based on the intake of macrolides during the previous years achieves overall eradication rates close to 90% and allows the use of standard triple therapy in more than half of the patients from a health area with a high level of clarithromycin resistance.
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Murata M, Sugimoto M, Mizuno H, Kanno T, Satoh K. Clarithromycin Versus Metronidazole in First-Line Helicobacter Pylori Triple Eradication Therapy Based on Resistance to Antimicrobial Agents: Meta-Analysis. J Clin Med 2020; 9:543. [PMID: 32079208 PMCID: PMC7073899 DOI: 10.3390/jcm9020543] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 02/09/2020] [Accepted: 02/12/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND International treatment guidelines for Helicobacter pylori infection recommend a proton pump inhibitor (PPI)/amoxicillin/clarithromycin (CAM) regimen (PAC) or PPI/amoxicillin/metronidazole (MNZ) regimen (PAM) as first-line therapy based on culture and sensitivity testing. As incidence rates of antimicrobial agent-resistant strains are changing year by year, it is important to reevaluate the efficacy of eradication regimens. We performed a meta-analysis to evaluate the efficacy and safety of PAC and PAM based on different locations categorized by the reported incidence of CAM- and MNZ-resistant strains. METHODS Randomized control trials (RCTs) comparing eradication rates between PAC and PAM first-line treatment up to December 2018 were included. We divided RCTs into four groups based on resistance to CAM (< 15% or ≥ 15%) and MNZ (< 15% or ≥ 15%). RESULTS A total of 27 studies (4825 patients) were included. Overall eradication rates between PAC and PAM were similar (74.8% and 72.5%, relative risk (RR): 1.13, 95% confidence interval (CI): 0.91-1.39, P = 0.27) in the intention-to-treat analysis. In areas with low MNZ- and high CAM-resistance rates, PAM had a significantly higher eradication rate than PAC (92.5% vs. 70.8%, RR: 0.29, 95% CI: 0.13-0.68). In areas with high MNZ- and low CAM-resistance rates, the eradication rate with PAC was only 72.9%. CONCLUSIONS Overall eradication rates with PAC and PAM were equivalent worldwide. In low MNZ-resistance areas, PAM may be recommended as first-line therapy. However, the efficacy of PAC may be insufficient, irrespective of susceptibility to CAM.
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Affiliation(s)
- Masaki Murata
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan;
- Department of Gastroenterology, National Hospital Organization Kyoto Medical Center, Fushimi, Kyoto 612-8555, Japan
| | - Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga 520-2192, Japan
- Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Shinjuku, Tokyo 160-0023, Japan
| | - Hitomi Mizuno
- Toyoda Aoba Clinic, Iwata, Shizuoka 438-0821, Japan;
| | - Takeshi Kanno
- Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyagi 980-8578, Japan;
| | - Kiichi Satoh
- Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara, Tochigi 329-2763, Japan;
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Chang YW, Ko WJ, Oh CH, Park YM, Oh SJ, Moon JR, Cho JH, Kim JW, Jang JY. Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis. Korean J Intern Med 2019; 34:1022-1029. [PMID: 29898576 PMCID: PMC6718756 DOI: 10.3904/kjim.2018.054] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 03/09/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND/AIMS The eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure. METHODS A total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment. RESULTS Of 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CY-P2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication. CONCLUSION Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.
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Affiliation(s)
- Young Woon Chang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Weon Jin Ko
- Department of Internal Medicine, CHA Gumi Medical Center, CHA University School of Medicine, Gumi, Korea
| | - Chi Hyuk Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
- Correspondence to Chi Hyuk Oh, M.D. Division of Gastroenterology and Hepatology, Department of Internal medicine, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea Tel: +82-2-958-8114 Fax: +82-2-958-8147 E-mail:
| | - Yoo Min Park
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Shin Ju Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jung Rock Moon
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jun-Hyung Cho
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jung-Wook Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
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Efficacy of a tailored PCR-guided triple therapy in the treatment of Helicobacter pylori infection. Med Mal Infect 2019; 50:492-499. [PMID: 31257067 DOI: 10.1016/j.medmal.2019.06.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 06/04/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Resistance to clarithromycin and fluoroquinolones is increasing in many countries. We aimed to assess the efficacy of a tailored PCR-guided triple therapy versus an empirical triple therapy in the treatment of H. pylori infection. PATIENTS AND METHODS French multicenter prospective open-label randomized study to assess H. pylori and resistance to clarithromycin and levofloxacin with GenoType HelicoDR® test. Patients of the control group were treated with empirical therapy of proton pump inhibitor (PPI), amoxicillin, and clarithromycin for 7 days. Patients of the experimental group with clarithromycin-susceptible strains, clarithromycin-resistant/levofloxacin-susceptible strains, and with clarithromycin-resistant/levofloxacin-resistant strains received tailored therapy of PPI, amoxicillin, and clarithromycin for 7 days, PPI, amoxicillin, and levofloxacin for 10 days, and PPI, amoxicillin, and metronidazole for 14 days, respectively. H. pylori eradication was assessed by 13C urea breath test at least 28 days after the end of treatment. RESULTS We included 526 patients: 260 (49.4%) were randomly assigned to empirical triple therapy and 266 (50.6%) to tailored therapy. Clarithromycin and levofloxacin resistances were 23.3% and 12.8%, respectively. Follow-up urea breath test was available for 415 (78.9%) patients. Tailored therapy was superior to empirical therapy in terms of eradication (85.5% vs. 73.1%, RR=1.85, 95%CI [1.25-2.78], p=0.003). Findings were consistent in the susceptibility analysis using multiple imputation (RR=1.61, 95%CI [1.14-2.27], P=0.003) and per-protocol analysis (RR=1.89, 95%CI [0.25-2.78], p=0.003). CONCLUSION In a country with a high level of clarithromycin resistance, tailored PCR-guided therapy was superior to empirical triple therapy for H. pylori eradication (https://www.ClinicalTrials.gov: NCT01168063).
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Chen Q, Long X, Ji Y, Liang X, Li D, Gao H, Xu B, Liu M, Chen Y, Sun Y, Zhao Y, Xu G, Song Y, Yu L, Zhang W, Liu W, Graham DY, Lu H. Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment. Aliment Pharmacol Ther 2019; 49:1385-1394. [PMID: 31020673 DOI: 10.1111/apt.15273] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 03/04/2019] [Accepted: 03/29/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. AIM To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. METHODS We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylori eradication. RESULTS Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI -3.1% to 3.2%) and 6.2% intent-to-treat (-0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. CONCLUSIONS Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.
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Eradication Efficacy of Modified Dual Therapy Compared with Bismuth-Containing Quadruple Therapy as a First-Line Treatment of Helicobacter pylori. Am J Gastroenterol 2019; 114:437-445. [PMID: 30807294 DOI: 10.14309/ajg.0000000000000132] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This study assessed the effectiveness, adverse events, patient adherence, and costs of modified dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients. We also sought to determine whether modified dual therapy could be used as an alternative first-line treatment for H. pylori infection. METHODS A total of 232 H. pylori-infected, treatment-naive patients were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day modified dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the 2 groups. RESULTS The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, per-protocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar compared with the bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%. In addition, modified dual therapy ameliorated variations in the CYP2C19, IL-1B-511, and H. pylori VacA genotypes. There were no significant differences in the compliance rates between the 2 groups. The modified dual therapy group exhibited significantly less overall side effects compared with the bismuth-containing quadruple therapy group (P < 0.001). Furthermore, the cost of medications in the modified dual therapy was lower compared with that in the bismuth-containing quadruple therapy. CONCLUSIONS Modified dual therapy at high dose and administration frequency is equally effective and safer and less costly compared with bismuth-containing quadruple therapy.
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Cosme A, Torrente Iranzo S, Montes Ros M, Fernández-Reyes Silvestre M, Alonso Galán H, Lizasoain J, Bujanda L. Helicobacter pylori antimicrobial resistance during a 5-year period (2013-2017) in northern Spain and its relationship with the eradication therapies. Helicobacter 2019; 24:e12557. [PMID: 30460730 DOI: 10.1111/hel.12557] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 10/23/2018] [Accepted: 10/27/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Antibiotic resistance is the main cause for Helicobacter pylori therapy failure. Frequently, empirical regimens have been recommended in patients with various H. pylori eradication failures. In patients with H. pylori-resistant to various families of antibiotics, the treatment guided by antimicrobial susceptibility testing allows the achievement of good eradication rates. AIM To evaluate the effectiveness of susceptibility-guided antimicrobial treatment for H. pylori infection in patients with resistance to one or various families of antibiotics. METHODS A total of 3170 consecutive patients infected by H. pylori during 2013-2017 were tested for antimicrobial susceptibility. 66.6% patients showed resistance to one antimicrobial, 18.9% to two, and 2.4% to three families of antibiotics. A cohort of 162 H. pylori-positive patients were enrolled in this study. Forty-three with single H. pylori resistance to clarithromycin (CLR) were treated with omeprazole (PPI), amoxicillin (AMX), and levofloxacin (LVX)-OAL (31 subjects) or omeprazole, AMX, and metronidazole (MTZ)-OAM (12 patients) and 77 patients with dual H. pylori resistance (51 to CLR and MTZ, 12 to CLR plus LVX, and 14 to MTZ plus LVX) received OAL or OBTM (PPI, bismuth subcitrate, tetracycline, and MTZ), OAM, and OAC, respectively. Other 42 patients with triple H. pylori resistance (CLR, LVX, and MTZ) were treated with PPI, AMX, and rifabutin-OAR (18 subjects), PPI, AMX, and doxycycline-OAD (8), OADB (7), OBTM (6), and ODBR (3). All subjects received standard doses for 10 days. Eradication rate was confirmed by 13 C-UBT. Adverse events were assessed by a questionnaire. RESULTS Intention-to-treat analysis demonstrates that eradication rates using triple therapies in patients with H. pylori resistance to one and to two families of antibiotics were 93% and 94.8%, respectively. In subjects with H. pylori-resistant to three families of antibiotics, cure rate was higher in naïve patients treated with OAR-10 days compared to those treated with bismuth-containing quadruple therapies (90% vs 75%). Adverse events were limited (18 of 162, 11.1%), all of them mild-moderate. CONCLUSIONS The implementation of susceptibility-guided triple therapy for 10 days leads to eradication rate ≥95% in naïve patients with H. pylori resistance to one or two families of antimicrobials. In naïve patients with H. pylori resistance to three families, OAR treatment achieved a 90% of eradication.
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Affiliation(s)
- Angel Cosme
- Department of Gastroenterology, Donostia University Hospital, San Sebastian, Spain
| | | | - Milagrosa Montes Ros
- Department of Microbiology, Donostia University Hospital-IIS Biodonostia, San Sebastian, Spain
- Biomedical Research Center Network for Respiratory Diseases (CIBERES), San Sebastian, Spain
| | | | - Horacio Alonso Galán
- Department of Gastroenterology, Donostia University Hospital, San Sebastian, Spain
| | - Jacobo Lizasoain
- Department of Gastroenterology, Donostia University Hospital, San Sebastian, Spain
| | - Luis Bujanda
- Department of Gastroenterology, Donostia University Hospital, San Sebastian, Spain
- Biodonostia Medical Research Institute, San Sebastian, Spain
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Sugimoto M, Yamaoka Y. Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan. Front Pharmacol 2019; 9:1560. [PMID: 30697158 PMCID: PMC6340927 DOI: 10.3389/fphar.2018.01560] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 12/21/2018] [Indexed: 12/11/2022] Open
Abstract
Complete eradication of Helicobacter pylori is important for preventing the development of gastric cancer. The outcome of H. pylori eradication therapy is mainly dependent on bacterial susceptibility to antimicrobial agents and potent neutralization of intragastric pH across 24 h, especially when using acid-sensitive antimicrobial agents such as clarithromycin (CLR), amoxicillin and sitafloxacin. However, conventional regimens comprising twice-daily doses (bid) of proton pump inhibitors (PPIs) are generally insufficient for maintaining the required gastric acid secretion for 24 h for successful eradication in all H. pylori-positive patients. Further, the increasing prevalence of CLR-resistant strains with each year has led to a decrease in eradication rates of first-line PPI- and CLR-containing therapies in developed countries, including Japan. In 2015, the potassium-competitive acid blocker vonoprazan (VPZ) became clinically available in Japan. VPZ competitively inhibits H+/K+-ATPase activity more potently than PPIs (e.g., omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole). Therefore, a VPZ-containing H. pylori eradication regimen is expected to increase the eradication rate compared with conventional regimens containing a standard dose of PPI. In fact, a recent meta-analysis that investigated the efficacy of first-line eradication therapy showed that a VPZ-containing regimen achieved a higher eradication rate than a PPI-containing regimen. While the Maastricht V/Florence Consensus Report recommends selecting a bismuth or non-bismuth quadruple therapy and concomitant therapy for patients living in areas with high prevalence of CLR resistance, a VPZ-containing regimen demonstrates effectiveness for patients infected with CLR-resistant strains and patients living in areas where the prevalence of CLR-resistant strains is >15%. As a next step, studies are needed to determine the factors affecting the clinical outcome of VPZ-containing therapy and optimal VPZ-containing alternative regimens for tailored treatments. In this review, we summarize the advantages and disadvantages of VPZ in H. pylori eradication therapy.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
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Sugimoto M, Yasuda H, Andoh A. Nutrition status and Helicobacter pylori infection in patients receiving hemodialysis. World J Gastroenterol 2018; 24:1591-1600. [PMID: 29686466 PMCID: PMC5910542 DOI: 10.3748/wjg.v24.i15.1591] [Citation(s) in RCA: 7] [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: 02/23/2018] [Revised: 03/18/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) patients receiving hemodialysis (HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting (PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori (H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mild-to-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga 520-2192, Japan
| | - Hideo Yasuda
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Shiga 520-2192, Japan
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Muñoz-Gómez P, Jordán-Castro JA, Abanades-Tercero M, Blanco-González JJ, Andrés Esteban EM, Valle-Muñoz J. Macrolide use in the previous years is associated with failure to eradicate Helicobacter pylori with clarithromycin-containing regimens. Helicobacter 2018; 23. [PMID: 29178562 DOI: 10.1111/hel.12452] [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] [Indexed: 12/12/2022]
Abstract
BACKGROUND There is some evidence that prior use of macrolide antibiotics is a useful predictor of the likelihood of standard triple therapy failure in Helicobacter pylori eradication. In this study, we have evaluated whether previous intake of macrolides correlates with failure to eradicate H. pylori using two different first-line clarithromycin-containing regimens. MATERIALS AND METHODS Retrospective study of 212 patients with H. pylori infection treated with one of two first-line clarithromycin-containing regimens: 108 patients treated with triple therapy for 10 days and 104 patients treated with concomitant therapy for 10 days. The intake of macrolides (clarithromycin, azithromycin, and other macrolides) prior to the eradication therapy was obtained from the electronic medical record, which contains information regarding all the medication prescribed to the patients since the year 2004. RESULTS One hundred of 212 patients (47.2%) had received at least one treatment with macrolides during the years prior to the eradication therapy. H. pylori eradication rates were significantly lower in patients with previous use compared to patients without previous use of macrolides, both with triple therapy (60.8% vs 92.9%; P < .0001) and with concomitant therapy (85.7% vs 98.2%; P = .024). CONCLUSIONS Previous use of macrolides correlates with a low H. pylori eradication rate with triple and concomitant clarithromycin-containing regimens. In addition, our study shows that in patients without previous use of macrolides, triple therapy achieves per-protocol eradication rates over 90%.
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Affiliation(s)
- Pablo Muñoz-Gómez
- Gastroenterology Department, Complejo Hospitalario de Toledo, Toledo, Spain
| | | | | | | | | | - Julio Valle-Muñoz
- Gastroenterology Department, Complejo Hospitalario de Toledo, Toledo, Spain
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Sahara S, Sugimoto M, Ichikawa H, Kagami T, Sakao Y, Ohashi N, Horio Y, Sugimoto K, Kato A, Furuta T, Yasuda H. Efficacy of Reduced Dosage of Amoxicillin in an Eradication Therapy for Helicobacter pylori Infection in Patients on Hemodialysis: A Randomized Controlled Trial. Digestion 2018; 97:163-169. [PMID: 29310119 DOI: 10.1159/000484981] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Accepted: 11/04/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND An optimum Helicobacter pylori-eradication regimen for hemodialysis patients is yet to be established because of different pharmacokinetics of amoxicillin involved between hemodialysis patients and healthy subjects. We investigated to establish appropriate doses of amoxicillin for H. pylori infection eradication in hemodialysis patients. METHODS Of 409 hemodialysis patients screened for H. pylori infection, 37 H. pylori-positive patients were randomized to different 1-week eradication regimens: esomeprazole 20 mg twice a day (b.i.d.) and clarithromycin 200 mg b.i.d., plus amoxicillin at either 750 mg b.i.d. (group A; conventional) or 250 mg b.i.d. (group B; experimental). Sixty-three patients with normal renal function received the conventional regimen (group C). Successful eradication was confirmed by urea breath testing. RESULTS Eradication rates of group B (reduced amoxicillin-regimen) were 84.2% in intention-to-treat analysis and 88.9% in per-protocol analysis, which were similar with group A (77.8 and 77.8%) and group C (74.6 and 81.0%). However, the incidence of adverse events in group A was significantly higher than that in group C (22.2 vs. 5.1%, p = 0.027). CONCLUSIONS In H. pylori-positive hemodialysis patients, amoxicillin at 250 mg b.i.d. may be an appropriate scheme for eradication with equivalent effects to the conventional therapy and safety effects for adverse events.
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Affiliation(s)
- Shu Sahara
- First Department of Medicine, Hamamatsu, Japan
| | - Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu, Japan
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Japan
| | | | | | | | - Naro Ohashi
- First Department of Medicine, Hamamatsu, Japan
| | - Yoshiaki Horio
- Department of Gastroenterology, Municipal Kosai Hospital, Kosai, Japan
| | | | | | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
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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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Osaki T, Mabe K, Zaman C, Yonezawa H, Okuda M, Amagai K, Fujieda S, Goto M, Shibata W, Kato M, Kamiya S. Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy. Helicobacter 2017; 22. [PMID: 28544222 DOI: 10.1111/hel.12396] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND To prevent Helicobacter pylori infection in the younger generation, it is necessary to investigate the prevalence of antibiotic-resistant H. pylori. OBJECTIVE The aim of this study was to evaluate the method of PCR-based sequencing to detect clarithromycin (CAM) resistance-associated mutations using fecal samples as a noninvasive method. METHODS DNA extracted from fecal specimens and isolates from gastric biopsy specimens were collected from patients with H. pylori infection. Antibiotic resistance to CAM was analyzed by molecular and culture methods. The detection rates of CAM resistance-associated mutations (A2142C or A2143G) were compared before and after eradication therapy. RESULTS With CAM resistance of H. pylori evaluated by antibiotic susceptibility test as a gold standard, the sensitivity and the specificity of gene mutation detection from fecal DNA were 80% and 84.8%, respectively. In contrast, using DNA of isolated strains, the sensitivity and the specificity were 80% and 100%. Of the seven cases in which eradication was unsuccessful by triple therapy including CAM, CAM-resistant H. pylori, and resistance-associated mutations were detected in three cases, CAM-resistant H. pylori without the mutation was detected in two patients, and resistance-associated mutation was only detected in one patient. CONCLUSION PCR-based sequencing to detect CAM resistance-associated mutations using isolates or fecal samples was useful for finding antibiotic-resistant H. pylori infection. Although the specificity of the detection from fecal samples compared with antibiotic susceptibility testing was lower than that from isolates, this fecal detection method is suitable especially for asymptomatic subjects including children. Further improvement is needed before clinical application.
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Affiliation(s)
- Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Hakodate, Japan.,Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan
| | - Cynthia Zaman
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Masumi Okuda
- Department of General Medicine and Community Health Science, Hyogo College of Medicine, Sasayama, Hyogo, Japan
| | - Kenji Amagai
- Ibaraki Prefectural Central Hospital, Ibaraki, Japan
| | | | | | - Wataru Shibata
- Department of Gastroenterology, Yokohama City University, Yokohama, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Hakodate, Japan.,Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
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Arslan N, Yılmaz Ö, Demiray-Gürbüz E. Importance of antimicrobial susceptibility testing for the management of eradication in Helicobacter pylori infection. World J Gastroenterol 2017; 23:2854-2869. [PMID: 28522904 PMCID: PMC5413781 DOI: 10.3748/wjg.v23.i16.2854] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 02/06/2017] [Accepted: 03/30/2017] [Indexed: 02/06/2023] Open
Abstract
The management of Helicobacter pylori (H. pylori) infection treatment differs from the common treatment protocol for other infectious diseases. Because culture- or molecular-guided approaches face several practical issues, such as the invasive procedures required to obtain gastric biopsy specimens and the lack of availability of routine laboratory testing in some places, H. pylori treatment includes the administration of two or three empirically selected antibiotics combined with a proton pump inhibitor rather than evidence-based eradication treatment. The efficacy of empirical therapy is decreasing, mostly due to increasing multiple resistance. Multiresistance to levofloxacin, clarithromycin, and metronidazole, which are commonly used in empirical treatments, appears to have increased in many countries. Mutations play a primary role in the antimicrobial resistance of H. pylori, but many different mechanisms can be involved in the development of antibiotic resistance. Determining and understanding these possible mechanisms might allow the development of new methods for the detection of H. pylori and the determination of antimicrobial resistance. A treatment based on the detection of antimicrobial resistance is usually more effective than empirical treatment. Nevertheless, such an approach before treatment is still not recommended in the Maastricht guidelines due to the difficulty associated with the routine application of available culture- or molecular-based susceptibility tests, which are usually administered in cases of treatment failure. The management of first and rescue treatments requires further research due to the steadily increase in antimicrobial resistance.
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Chunlertlith K, Limpapanasit U, Mairiang P, Vannaprasaht S, Tassaneeyakul W, Sangchan A, Sawadpanich K, Suttichaimongkol T, Pongpit J, Pattarapongsin M. Outcomes of a Randomized Controlled Trial Comparing Modified High Dose Omeprazole and Amoxicillin Triple Therapy with Standard Triple Therapy for Helicobacter Pylori Eradication. ASIAN PACIFIC JOURNAL OF CANCER PREVENTION : APJCP 2017; 18:927-932. [PMID: 28545189 PMCID: PMC5494241 DOI: 10.22034/apjcp.2017.18.4.927] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Background: Helicobacter pylori (H. pylori) infection is related to peptic ulcer diseases and gastric cancer and eradication of H. pylori should be expected to decrease the risk of their development. Factors affecting H. pylori eradication are antibiotic resistance, CYP2C19 genotypes, drug regimen and patient compliance. Increment of omeprazole and amoxicillin dosage in clarithromycin-containing triple therapy regimen may overcome these problems and may be a better choice than the conventional clarithromycin-containing triple therapy regimen. Objective: To compare the eradication rates with modified triple therapy (MTT) and standard triple therapy (STT) as first-line treatment. Materials and Methods: The study was an open label, multicenter, randomized controlled trial. A total of 170 patients infected with H. pylori diagnosed by rapid urease test were randomly assigned into 2 groups. The first was treated with a 14-day MTT (20 mg omeprazole t.i.d., 500 mg amoxicillin t.i.d., and 500 mg clarithromycin b.i.d.) and the second with a 14-day STT (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 500 mg clarithromycin b.i.d.). H. pylori eradication was evaluated by 14C-urea breath test. CYP2C19 genotypes, clarithromycin resistance, side effects and patient compliance were also recorded. Results: There were 85 patients in each group. The H. pylori eradication rate in the MTT group was 84.7% by ITT analysis and 91.1% by PP analysis, compared to the STT group values of 76.5% and 87.8% (p = 0.18 and 0.51), respectively. CYP2C19 genotypes and patient compliance were similar in both groups. Prevalence of clarithromycin resistance was 7.0%. Side effects were all mild with no significant differences between the twogroups. Conclusions: MTT is not superior to STT. From this study, MTT may not be recommended as the first-line treatment for H. pylori infection in Thailand because eradication rates proved to be less than 90% by ITT analysis.
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Affiliation(s)
- Kitti Chunlertlith
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, KhonKaen University, Thailand.
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Clarithromycin resistance in Helicobacter pylori and its molecular determinants in Northern Spain, 2013-2015. J Glob Antimicrob Resist 2017; 9:43-46. [PMID: 28343971 DOI: 10.1016/j.jgar.2016.12.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 11/22/2016] [Accepted: 12/31/2016] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES Clarithromycin resistance (CLR-R) is the main reason for failure of Helicobacter pylori infection treatment, which is frequently empirically prescribed due to the erroneous belief that culture for susceptibility testing is difficult. The aim of this study was to determine CLR-R in a region of southern Europe and to evaluate the utility of a PCR sequencing assay applied on gastroduodenal biopsies in detecting H. pylori and clarithromycin (CLR) susceptibility. METHODS The susceptibility of all H. pylori isolates obtained by culture during 2013-2015 was determined by Etest. During 2014-2015, H. pylori detection and CLR susceptibility were also studied by PCR followed by sequencing performed on gastroduodenal biopsies. Point mutations in the 23S rRNA gene were studied in all CLR-resistant isolates in 2014. RESULTS Of 1986 H. pylori isolates obtained by culture (63 from children and 1923 from adults), 349 (17.6%) were CLR-resistant [21/63 (33.3%) in children and 328/1923 (17.1%) in adults; P<0.001], of which 31.5% were also resistant to levofloxacin. The main mutations detected were A2147G (79.8%), A2146G (17.2%) and A2146C (2%). Concordance between the PCR sequencing assay on biopsies and CLR susceptibility by Etest after culture was 89.8%. CONCLUSIONS CLR-R was high in Gipuzkoa, northern Spain. The molecular PCR method performed directly on biopsies was a good alternative to the traditional Etest susceptibility method and was an aid when culture was non-viable.
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Sugimoto M, Sahara S, Ichikawa H, Kagami T, Ban H, Otsuka T, Andoh A, Furuta T. Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan. Helicobacter 2017; 22. [PMID: 27213463 DOI: 10.1111/hel.12319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. AIM To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. METHODS We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a 13 C-urea breath test. RESULTS Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. CONCLUSION In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q.i.d. and an antibiotic agent (amoxicillin q.i.d. or sitafloxacin b.i.d.) in Japanese patients with metronidazole-resistant strains.
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Affiliation(s)
- Mitsushige Sugimoto
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Shu Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Takuma Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Hiromitsu Ban
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Taketo Otsuka
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science Hospital, Otsu, Shiga, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
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Hu JL, Yang J, Zhou YB, Li P, Han R, Fang DC. Optimized high-dose amoxicillin-proton-pump inhibitor dual therapies fail to achieve high cure rates in China. Saudi J Gastroenterol 2017; 23:275-280. [PMID: 28937021 PMCID: PMC5625363 DOI: 10.4103/sjg.sjg_91_17] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
UNLABELLED Background\Aim: Quadruple daily administration of proton-pump inhibitor (PPI) therapy achieves potent acid inhibition, and combined with amoxicillin, with its pharmacodynamic and pharmacokinetic characteristics, may be efficient for Helicobacter pylori eradication. We compared the efficacy of two optimized high-dose dual therapies with a bismuth-containing quadruple regimen for treating H. pylori infection. Rabeprazole dosages for H. pylori eradication were also evaluated. PATIENTS AND METHODS Treatment-naive and H. pylori-positive subjects were recruited and randomly apportioned to three treatment groups: Group A (n = 87), rabeprazole 10 mg plus amoxicillin 750 mg (4 times/day for 14 days); Group B (n = 87), rabeprazole 20 mg plus amoxicillin 750 mg (4 times/day for 14 days); and Group C (n = 89), bismuth-containing quadruple regimen consisting of rabeprazole 20 mg, bismuth 220 mg, amoxicillin 1000 mg, and clarithromycin 500 mg (2 times/day for 14 days). Four weeks after treatment discontinuation, patients were examined for H. pylori infection by 13C-urea breath test. The rates of adverse effects, compliance, and eradication were evaluated. RESULTS Eradication rates in groups A, B, and C were 78.1, 81.6, and 84.3%, respectively, based on intention-to-treat analysis, or 79.1, 83.5, and 86.2%, according to per-protocol analysis. Rates of adverse events and compliance of the three groups were similar. CONCLUSION For treating H. pylori infection, optimized high-dose amoxicillin-PPI dual therapies failed to achieve high cure rates in China and held no advantage over a bismuth-containing quadruple regimen.
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Affiliation(s)
- Jia-Li Hu
- Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Jun Yang
- Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Yin-Bin Zhou
- Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Ping Li
- Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China
| | - Ran Han
- Department of Gastroenterology, Guizhou Province Hospital, Guiyang, Guizhou Province, People's Republic of China
| | - Dian-Chun Fang
- Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China,Address for correspondence: Dr. Dian-Chun Fang, Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400016, China. E-mail:
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Yamada S, Kawakami T, Nakatsugawa Y, Suzuki T, Fujii H, Tomatsuri N, Nakamura H, Sato H, Okuyama Y, Kimura H, Yoshida N. Usefulness of vonoprazan, a potassium ion-competitive acid blocker, for primary eradication of Helicobacter pylori. World J Gastrointest Pharmacol Ther 2016; 7:550-555. [PMID: 27867688 PMCID: PMC5095574 DOI: 10.4292/wjgpt.v7.i4.550] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 07/28/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate usefulness of triple therapy with vonoprazan, a potassium ion-competitive acid blocker and antibiotics, for Helicobacter pylori (H. pylori) eradication.
METHODS The H. pylori eradication rate was examined in 2507 patients (2055 undergoing primary eradication and 452 undergoing secondary eradication, excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September 2015. For patients treated from March 2013 to February 2015, a proton pump inhibitor (PPI) was used to reduce acid secretion, while vonoprazan was used after March 2015. The success rates of the 2 regimens (PPI + amoxicillin + clarithromycin/metronidazole, or vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared.
RESULTS The success rate of primary H. pylori eradication was significantly higher in the vonoprazan group. When stratified by the underlying disease, a significant increase of the H. pylori eradication rate was observed in patients with chronic gastritis. A significantly lower H. pylori eradication rate was observed in younger patients compared to older patients in the PPI group, but there was no difference according to age in the vonoprazan group. On the other hand, the success rate of secondary eradication was similar at approximately 90% in both groups.
CONCLUSION Vonoprazan is very useful for primary eradication of H. pylori, and may become a first-line acid secretion inhibitor instead of PPIs.
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Puig I, Baylina M, Sánchez-Delgado J, López-Gongora S, Suarez D, García-Iglesias P, Muñoz N, Gisbert JP, Dacoll C, Cohen H, Calvet X. Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment. J Antimicrob Chemother 2016; 71:2740-2753. [PMID: 27342548 DOI: 10.1093/jac/dkw220] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 05/09/2016] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies. OBJECTIVES The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis. METHODS Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates. RESULTS Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies. CONCLUSIONS PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.
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Affiliation(s)
- Ignasi Puig
- Digestive Diseases Unit, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Spain Universitat Internacional de Catalunya, Barcelona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mireia Baylina
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Jordi Sánchez-Delgado
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Sheila López-Gongora
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - David Suarez
- Unitat d'Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain
| | - Pilar García-Iglesias
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Neus Muñoz
- Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain
| | - Cristina Dacoll
- Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Henry Cohen
- Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
| | - Xavier Calvet
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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Talebi Bezmin Abadi A, Lee YY. Chinese Helicobacter pylori vaccine: Solution for an old challenge? World J Gastrointest Pharmacol Ther 2016; 7:412-415. [PMID: 27602242 PMCID: PMC4986397 DOI: 10.4292/wjgpt.v7.i3.412] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 04/09/2016] [Accepted: 05/17/2016] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class I carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase III study of an oral recombinant vaccine (Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children (6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge.
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Hong J, Shu X, Liu D, Zhu Y, Xie C, Xie Y, Zhang K, Wang A, Xiong H, Zeng H, Yu H, Ma J, Chen Y, Zhu X, Lu N. Antibiotic resistance and CYP2C19 polymorphisms affect the efficacy of concomitant therapies for Helicobacter pylori infection: an open-label, randomized, single-centre clinical trial. J Antimicrob Chemother 2016; 71:2280-5. [PMID: 27107097 DOI: 10.1093/jac/dkw118] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 03/09/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated. METHODS In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined. RESULTS A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious. CONCLUSIONS The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy.
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Affiliation(s)
- Junbo Hong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Dongsheng Liu
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Chuan Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yong Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Kunhe Zhang
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Anjiang Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huifang Xiong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huilie Zeng
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Huiqiang Yu
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Jiuhong Ma
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Youxiang Chen
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
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Puig I, López-Góngora S, Calvet X, Villoria A, Baylina M, Sanchez-Delgado J, Suarez D, García-Hernando V, Gisbert JP. Systematic review: third-line susceptibility-guided treatment for Helicobacter pylori infection. Therap Adv Gastroenterol 2016; 9:437-48. [PMID: 27366212 PMCID: PMC4913327 DOI: 10.1177/1756283x15621229] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Susceptibility-guided therapies (SGTs) have been proposed as preferable to empirical rescue treatments after two treatment failures. The aim of this study was to perform a systematic review and meta-analysis evaluating the effectiveness and efficacy of SGT as third-line therapy. METHODS A systematic search was performed in multiple databases. Studies reporting cure rates of Helicobacter pylori with SGT in third-line therapy were selected. A qualitative analysis describing the current evidence and a pooled mean analysis summarizing the cure rates of SGT in third-line therapy was performed. RESULTS No randomized controlled trials or comparative studies were found. Four observational studies reported cure rates with SGT in third-line treatment, and three studies which mixed patients with second- and third-line treatment also reported cure rates with SGT. The majority of the studies included the patients when culture had been already obtained, and so the effectiveness of SGT and empirical therapy has never been compared. A pooled mean analysis including four observational studies (283 patients) showed intention-to-treat and per-protocol eradication rates with SGT of 72% (95% confidence interval 56-87%; I(2) : 92%) and 80% (95% confidence interval 71-90%; I(2) : 80%), respectively. CONCLUSIONS SGT may be an acceptable option as rescue treatment. However, cure rates are, at best, moderate and this approach has never been compared with a well-devised empirical therapy. The evidence in favor of SGT as rescue therapy is currently insufficient to recommend its use.
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Affiliation(s)
| | | | | | - Albert Villoria
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain,Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain,Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Mireia Baylina
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Jordi Sanchez-Delgado
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain,Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain,Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - David Suarez
- Unitat d’Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain
| | | | - Javier P. Gisbert
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain,Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
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Talebi Bezmin Abadi A. Vaccine against Helicobacter pylori: Inevitable approach. World J Gastroenterol 2016; 22:3150-3157. [PMID: 27003991 PMCID: PMC4789989 DOI: 10.3748/wjg.v22.i11.3150] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 01/05/2016] [Accepted: 01/30/2016] [Indexed: 02/06/2023] Open
Abstract
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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Abstract
Many interesting articles have been published from many parts of the world over the last year assessing different issues around Helicobacter pylori eradication therapy. This article will address the published literature over the last year pertaining to the topic of treatment of H. pylori infection. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized nonbismuth- and bismuth-containing quadruple therapies with some promising data also emerging on dual therapy. There was also considerable progress in investigating antibiotic resistance rates with much more data emerging from varied parts of the world compared to recent years. There have also been advances in the use of adjunctive therapies, especially probiotic therapies. Undoubtedly, the eradication of H. pylori remains a worthwhile goal to alleviate the burden of diseases caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer.
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Affiliation(s)
- Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
| | - Javier P Gisbert
- Department of Gastroenterology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Colm O'Morain
- Department of Gastroenterology, Tallaght Hospital/Trinity College Dublin, Dublin, Ireland
| | - Spiros Ladas
- Department of Medicine & Gastroenterology, Medical School, "Laiko" University General Hospital of Athens, University of Athens, Athens, Greece
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Uotani T, Miftahussurur M, Yamaoka Y. Effect of bacterial and host factors on Helicobacter pylori eradication therapy. Expert Opin Ther Targets 2015; 19:1637-50. [PMID: 26245678 DOI: 10.1517/14728222.2015.1073261] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION A clearer understanding of the factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets. AREAS COVERED This review covers two important issues that affect the eradication of H. pylori: bacterial and host factors. Several virulence factors have been shown to be predictors for gastroduodenal diseases. Successful treatment of H. pylori infection also depends on host genetic factors such as CYP2C19 and IL-1B. The latest evidence on host genetic factors is discussed. EXPERT OPINION The authors identify three main targets for achieving effective eradication therapy. The first therapeutic target is to identify counter measures for antibiotic-resistant H. pylori strains. Thus, antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The second therapeutic target is the inhibition of acid suppression. Maintaining a high intragastric pH for 24 h increases the effectiveness of some antibiotics and the eradication effects for H. pylori. The third therapeutic target is to identify high-risk groups; the CYP2C19 and IL-1B polymorphisms are candidates for significant risk factors. A personalized medical approach will likely increase the cure rate of H. pylori infection.
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Affiliation(s)
- Takahiro Uotani
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,b 2 Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Department of Gastroenterology and Hepatology , Houston, TX 77030, USA
| | - Muhammad Miftahussurur
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,c 3 Airlangga University, Institute of Tropical Disease , Surabaya 60115, Indonesia
| | - Yoshio Yamaoka
- a 1 Oita University Faculty of Medicine, Department of Environmental and Preventive Medicine , 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita 879-5593, Japan +81 97 586 5740 ; +81 97 586 5749 ; .,b 2 Baylor College of Medicine and Michael DeBakey Veterans Affairs Medical Center, Department of Gastroenterology and Hepatology , Houston, TX 77030, USA
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Sugimoto M, Sahara S, Ichikawa H, Kagami T, Uotani T, Furuta T. High Helicobacter pylori cure rate with sitafloxacin-based triple therapy. Aliment Pharmacol Ther 2015; 42:477-483. [PMID: 26075959 DOI: 10.1111/apt.13280] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2015] [Revised: 03/09/2015] [Accepted: 05/27/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Bacterial resistance of Helicobacter pylori to antibiotics is increasing and it often leads to failure of antibiotic treatment. A new sitafloxacin-based triple therapy was developed to counter this situation; the fluoroquinolone sitafloxacin has a low minimum inhibitory concentration for H. pylori. AIM To investigate the efficacy in Japanese patients of sitafloxacin-based triple therapy and document its efficacy in relation to anti-microbial susceptibility. METHODS We investigated the efficacy of a 1-week sitafloxicin-based regimen of rabeprazole 10 mg four times daily (q.d.s.), metronidazole 250 mg twice daily (b.d.) and sitafloxacin 100 mg b.d. in 180 H. pylori-positive Japanese patients (first-line treatment: n = 45, second-line; n = 41, third-line: n = 94). At 8 weeks, patients were given the (13) C-urea breath test to assess eradication status. RESULTS Eradication rate was 92.2% [95% confidence interval (CI): 87.3-95.7%, 166/180] in intention-to-treat analysis. Although the eradication rate was higher in patients treated with first-line therapy [45/45 (100%, 95% CI: 83.4-100%)] than in those with second- [38/41 (92.7%, 80.1-98.5%)] or third-line therapy [83/94 (88.3%, 80.0-94.0%)], no significant differences were noted with respect to the number of previous therapy attempts (P = 0.054). Eradication rates in patients infected with sensitive- and resistant strains to metronidazole were 96.6% (28/29) and 96.3% (77/80) (P = 0.941), respectively, while rates were 98.4% (60/61) in sitafloxacin-sensitive and 50.0% (1/2) in sitafloxacin resistant strains (P < 0.001). CONCLUSION Sitofloxacin-based triple therapy with metronidazole b.d. and rabeprazole q.d.s. achieved an eradication rate exceeding 88%, irrespective of eradication history, CYP2C19 genotype, or metronidazole resistance status.
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Affiliation(s)
- M Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
- Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan
| | - S Sahara
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - H Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Kagami
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Uotani
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - T Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan
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Ji YL, Jiang Y, Zhang ZG, Qi FX, Zhang Y. Efficacy of first-line treatment for Helicobacter pylori infection in patients with chronic renal insufficiency. Shijie Huaren Xiaohua Zazhi 2015; 23:3481-3485. [DOI: 10.11569/wcjd.v23.i21.3481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy, compliance and adverse effects of 14-day amoxicillin- and furazolidone-based triple therapy for eradication of Helicobacter pylori (H. pylori) in patients with chronic renal insufficiency.
METHODS: A total of 108 patients with H. pylori positive peptic ulcers and chronic renal insufficiency were enrolled into this retrospective study. Triple therapy (furazolidone, amoxicillin and esomeprazole) was administered for 14 d. The patients' renal function was monitored one week before treatment, one week after drug administration, and one week after treatment. H. pylori status was assessed by 13C-urea breath test at 4 wk after treatment.
RESULTS: A total of 104 patients completed the treatment, and successful eradication was achieved in 91 patients. The H. pylori eradication rates were 87.5% (91/104) and 84.3% (91/108) according to per-protocol (PP) and intention-to-treat (ITT) analyses, respectively. The patients' renal function showed no significant change throughout the treatment process. Mild and moderate adverse effects occurred in 17 (15.7%) patients; four of them had to terminate their treatment due to skin rash and dizziness.
CONCLUSION: The 14-day triple therapy with amoxicillin, furazolidone and esomeprazole may be an effective and safe treatment option for eradication of H. pylori in patients with chronic renal insufficiency.
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Sakurai Y, Nishimura A, Kennedy G, Hibberd M, Jenkins R, Okamoto H, Yoneyama T, Jenkins H, Ashida K, Irie S, Täubel J. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/non-Japanese Subjects. Clin Transl Gastroenterol 2015; 6:e94. [PMID: 26111126 PMCID: PMC4816246 DOI: 10.1038/ctg.2015.18] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 04/20/2015] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES: To evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-438 (vonoprazan, a potassium-competitive acid blocker) in healthy male subjects. METHODS: In two phase I, randomized, double-blind, placebo-controlled, single rising-dose studies, healthy male subjects (Japan N=84; UK N=63) received a single TAK-438 dose (1–120 mg in Japan and 1–40 mg in the UK). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (intragastric pH). RESULTS: Plasma concentration–time profiles of TAK-438 at all dose levels showed rapid absorption (median Tmax up to 2 h). Estimated mean elimination half-life was up to 9 h. Exposure was slightly greater than dose proportional. No clear difference in TAK-438 pharmacokinetics was observed between Japanese and non-Japanese subjects. Acid suppression was dose dependent and similar in both studies. The 24-h intragastric pH ≥4 holding time ratio with 40 mg TAK-438 was 92% in Japan and 87% in the UK. TAK-438 was well tolerated, with no adverse events reported in Japanese subjects; 10 of 63 UK subjects experienced 12 treatment-emergent adverse events (non-serious). Increases in serum gastrin and pepsinogen I and II concentrations were observed at doses ≥10 mg, but there were no changes in alanine aminotransferase concentrations. CONCLUSIONS: Single oral doses of TAK-438 20–120 mg caused rapid, profound, and 24-h suppression of gastric acid secretion in healthy male subjects, regardless of geographical region, and TAK-438 was well tolerated at all doses studied, making it a potential alternative to proton pump inhibitors for the treatment of acid-related disorders.
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Affiliation(s)
| | | | - Gale Kennedy
- Takeda Development Centre Europe Ltd, London, UK
| | - Mark Hibberd
- Takeda Development Centre Europe Ltd, London, UK
| | | | | | | | | | - Kiyoshi Ashida
- Department of Gastroenterology and Hepatology, Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Shin Irie
- Medical Co. LTA Honjo Clinic (current Sumida Hospital), Tokyo, Japan
| | - Jörg Täubel
- 1] Richmond Pharmacology Ltd, London, UK [2] St George's University of London, London, UK
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López-Góngora S, Puig I, Calvet X, Villoria A, Baylina M, Muñoz N, Sanchez-Delgado J, Suarez D, García-Hernando V, Gisbert JP. Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. J Antimicrob Chemother 2015; 70:2447-55. [PMID: 26078393 DOI: 10.1093/jac/dkv155] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Accepted: 05/16/2015] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND The cure rate of standard triple therapy for Helicobacter pylori infection is unacceptably low. Susceptibility-guided therapies (SGTs) have been proposed as an alternative to standard empirical treatments. The aim of this study was to perform a systematic review and meta-analysis evaluating the efficacy of SGTs. METHODS A systematic search was performed in multiple databases. Randomized controlled trials comparing cure rates of SGTs versus those of empirical therapy were selected and analysed separately for first- and second-line treatments. A meta-analysis was performed using risk ratio (RR) and number needed to treat (NNT) to measure the effect. RESULTS Twelve studies were included in the meta-analysis. In first-line treatment, SGT was more efficacious than empirical 7-10 day triple therapy (RR 1.16, 95% CI 1.10-1.23, I (2) = 33%; NNT = 8). Most studies used a 7-10 day triple therapy and randomized the patients after endoscopy and/or culture, thus precluding the comparison of SGT versus non-invasive testing and empirical treatment in clinical practice. For second-line therapy, only four studies were found. Results were highly heterogeneous and no significant differences were found (RR 1.11, 95% CI 0.82-1.51, I (2) = 87%). CONCLUSIONS Once endoscopy and culture have been performed, SGT is superior to empirical 7 or 10 day triple therapy for first-line treatment. Further studies are needed to evaluate the effectiveness of SGT in clinical practice, especially when compared with currently recommended first-line quadruple therapies.
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Affiliation(s)
- Sheila López-Góngora
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Ignasi Puig
- Digestive Diseases Unit, Althaia Xarxa Assistencial, Universitaria de Manresa, Barcelona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Departament de Medicina, Universitat Internacional de Catalunya, Barcelona, Spain
| | - Xavier Calvet
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Albert Villoria
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Mireia Baylina
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Neus Muñoz
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Jordi Sanchez-Delgado
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - David Suarez
- Unitat d'Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain
| | - Victor García-Hernando
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
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Improved allele-specific PCR assays for detection of clarithromycin and fluoroquinolone resistant of Helicobacter pylori in gastric biopsies: identification of N87I mutation in GyrA. Diagn Microbiol Infect Dis 2014; 81:251-5. [PMID: 25600075 DOI: 10.1016/j.diagmicrobio.2014.12.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 12/01/2014] [Accepted: 12/10/2014] [Indexed: 12/18/2022]
Abstract
Molecular testing can rapidly detect Helicobacter pylori susceptibility using gastric biopsies. Allele-specific polymerase chain reaction (ASP-PCR) was used to identify H. pylori 23S rRNA and gyrA mutation using gastric biopsies from Colombian patients and confirmed by PCR and sequencing of the 23S rRNA and gyrA genes. The sensitivity and specificity of ASP-PCR were compared with susceptibilities measured by agar dilution. Samples included gastric biopsies from 107 biopsies with H. pylori infections and 20 H. pylori negative. The sensitivity and specificity of ASP-PCR for the 23S rRNA gene were both 100%. The sensitivity and specificity of ASP-PCR for the gyrA gene, published in 2007 by Nishizawa et al., were 52% and 92.7%, respectively; the lower sensitivity was due to the presence of mutation N87I in our samples, which were not detected by the test. In this study, we designed new primers to detect the mutation N87I in GyrA. The ASP-PCR was performed with the original primers plus the new primers. The molecular test with the new primers improved the sensitivity to 100%. In conclusion, ASP-PCR provides a specific and rapid means of predicting resistance to clarithromycin and levofloxacin in gastric biopsies.
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Abstract
PURPOSE OF REVIEW This review focuses on new treatment options for eradicating Helicobacter pylori that have emerged as a result of decreased efficacy of standard triple therapy due to increasing antibiotic resistance. We also report on new data regarding primary and secondary gastric cancer prevention strategies and the potential role of H. pylori as a risk factor for extragastric malignancies. RECENT FINDINGS Treatment options have shifted from triple to various quadruple modifications. The length of therapy duration has, in general, been extended from 7 to 10 and 14 days. Nonbismuth-based quadruple therapies prescribed as sequential, concomitant, and hybrid have shown superiority as compared to standard triple therapy in the eradication of clarithromycin-resistant H. pylori. Bismuth-based quadruple therapy appears almost totally independent of antibiotic resistance and maintains high eradication rates. Levofloxacin is an adequate substitute for clarithromycin and is recommended in second-line regimens. However, it should be used prudently as H. pylori has developed resistance to levofloxacin in many regions of the world. Strategies for primary gastric cancer prevention by H. pylori eradication are effective, whereas H. pylori eradication for secondary gastric cancer prevention is uncertain. Very recent data implicate H. pylori as a risk factor for extragastric malignancies. SUMMARY H. pylori therapy should be tailored according to local antibiotic resistance patterns. In many regions of the world, H. pylori is becoming increasingly resistant to clarithromycin, metronidazole, and levofloxacin. Gastric cancer prevention by H. pylori eradication is most effective, if implemented early in the course of infection. New data are provided which indicate H. pylori as risk factor for extragastric malignancies.
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Abstract
This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
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Affiliation(s)
- Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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