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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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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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Ishibashi F, Suzuki S, Nagai M, Mochida K, Morishita T. Optimizing Helicobacter pylori Treatment: An Updated Review of Empirical and Susceptibility Test-Based Treatments. Gut Liver 2023; 17:684-697. [PMID: 36843419 PMCID: PMC10502504 DOI: 10.5009/gnl220429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/07/2022] [Accepted: 11/20/2022] [Indexed: 02/28/2023] Open
Abstract
As the rate of discovery of drug-resistant Helicobacter pylori cases increases worldwide, the relevant societies have updated their guidelines for primary eradication regimens. A promising strategy against drug-resistant H. pylori is tailored therapy based on the results of an antibiotic susceptibility test; however, it is difficult to apply this strategy to all cases. Although culture-based antibiotic susceptibility tests can assess resistance to any antimicrobial agent, their greatest disadvantage is the time required to draw a conclusion. In contrast, molecular-based methods, such as polymerase chain reaction, can rapidly determine the presence of resistance, although a single test can only test for one type of antimicrobial agent. Additionally, the limited availability of facilities for molecular-based methods has hindered their widespread use. Therefore, low-cost, minimally invasive, simple, and effective primary regimens are needed. Several studies have compared the efficacy of the latest primary eradication regimens against that of tailored therapies, and their results have shaped guidelines. This article reviews the latest research on empirical and tailored treatments for H. pylori infections. Evidence for the superiority of tailored therapy over empirical therapy is still limited and varies by region and treatment regimen. A network meta-analysis comparing different empirical treatment regimens showed that vonoprazan triple therapy provides a superior eradication effect. Recently, favorable results towards vonoprazan dual therapy have been reported, as it reached eradication levels similar to those of vonoprazan triple therapy. Both vonoprazan dual therapy and tailored therapy based on antibiotic susceptibility tests could contribute to future treatment strategies.
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Affiliation(s)
- Fumiaki Ishibashi
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Sho Suzuki
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Mizuki Nagai
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Kentaro Mochida
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Tetsuo Morishita
- Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
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Noiri Y, Nagata R. Current status of gastric and oral infection/diseases caused by Helicobacter pylori. ORAL SCIENCE INTERNATIONAL 2023; 20:182-189. [DOI: 10.1002/osi2.1172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 01/17/2023] [Indexed: 01/06/2025]
Abstract
AbstractHelicobacter pylori is found in the stomach, which is its optimal habitat, and is considered an important factor in various serious diseases, including stomach cancer. The World Health Organization has identified H. pylori as a causative agent of gastric cancer, as confirmed by animal experiments in rodents. The fact that H. pylori can live in the harsh environment of stomach acid was the greatest hindrance to the discovery of H. pylori. It was not so long ago, in 1983, that it was successfully isolated and cultured. Subsequently, H. pylori eradication therapy was established, and it became possible to control gastric cancer to some extent. However, the mechanism, route, and mode of H. pylori infection still remain unclear. Furthermore, currently, the prevention of first‐episode gastric cancer and control of recurrent gastric cancer are not perfect. One of the reasons for this may be that the status of H. pylori in the oral cavity, which is the entry point for the organism (the beginning of the digestive system: the first route of infection), is still unknown. Therefore, we reviewed the current status of H. pylori infection in the stomach and oral cavity, focusing on (1) the mechanism of infection, (2) pathogenic factors, (3) the actual status of eradication therapy, and (4) control strategies.
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Affiliation(s)
- Yuichiro Noiri
- Division of Cariology, Operative Dentistry and Endodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences Niigata University Niigata Japan
| | - Ryoko Nagata
- Division of Cariology, Operative Dentistry and Endodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences Niigata University Niigata Japan
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Li M, Wang X, Meng W, Dai Y, Wang W. Empirical versus tailored therapy based on genotypic resistance detection for Helicobacter pylori eradication: a systematic review and meta-analysis. Therap Adv Gastroenterol 2023; 16:17562848231196357. [PMID: 37667805 PMCID: PMC10475236 DOI: 10.1177/17562848231196357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/04/2023] [Indexed: 09/06/2023] Open
Abstract
Background The eradication rate of Helicobacter pylori infection with empirical therapy has decreased due to increased drug resistance. The latest guidelines recommend genotypic resistance-guided therapy, but its clinical efficacy remains unclear. Objectives The purpose of our study was to evaluate whether tailored therapy based on genotypic resistance is superior to empirical therapy for H. pylori infection. Design A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing tailored therapy based on genotypic resistance with empirical therapy was performed. Sources and methods We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate and the adverse events (AEs) was the secondary outcome. A random-effect model was applied to compare pooled risk ratios (RRs) with related 95% confidence intervals (CIs). Results A total of 12 qualified RCTs containing 3940 patients were identified in our systematic review and meta-analysis. The pooled eradication rates of tailored therapy based on the detection of genotypic resistance were consistently higher than those in the empirical treatment group, with no statistical significance. In triple therapy, the eradication rate was significantly higher in the tailored group than in the empirical group by intention-to-treat analysis (ITT) and per-protocol analysis (PP) analysis (p < 0.0001, RR: 1.20; 95% CI: 1.12-1.29; p < 0.0001, RR: 1.20; 95% CI: 1.15-1.25). In quadruple therapy, the eradication rate was higher in the empirical group (p = 0.001, RR: 0.93; 95% CI: 0.89-0.97; p = 0.009, RR: 0.95; 95% CI: 0.92-0.99). And this result was true for both bismuth quadruple therapy (BQT) and non-BQT. Regarding total AEs, the pooled rate was 34% in the tailored group and 37% in the empirical group, and no difference between the two groups was found (p = 0.17, RR: 0.88; 95% CI: 0.74-1.06). Conclusion In conclusion, tailored therapy based on molecular methods may offer better efficacy than empirical triple therapy, but it may not be superior to empirical quadruple therapy in eradicating H. pylori infection. Larger and more individualized RCTs are needed to aid clinical decision-making. Registration PROSPERO CRD42023408688.
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Affiliation(s)
- Meng Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiaolei Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wenting Meng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Weihong Wang
- Department of Gastroenterology, Peking University First Hospital, No. 8 Xishiku Street, Beijing 100034, China
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Sue S, Suzuki Y, Sasaki T, Kaneko H, Irie K, Komatsu K, Maeda S. Prospective Study of Vonoprazan-Based First-Line Triple Therapy with Amoxicillin and Metronidazole for Clarithromycin-Resistant Helicobacter pylori. J Clin Med 2023; 12:5443. [PMID: 37685510 PMCID: PMC10488100 DOI: 10.3390/jcm12175443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/16/2023] [Accepted: 08/16/2023] [Indexed: 09/10/2023] Open
Abstract
AIM This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). METHODS We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. RESULTS The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0-100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9-84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7-85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. CONCLUSIONS The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.
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Affiliation(s)
- Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
| | - Yuichi Suzuki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
- Department of Gastroenterology, Yokosuka City Hospital, Yokosuka 240-0195, Japan
| | - Tomohiko Sasaki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
| | - Hiroaki Kaneko
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
| | - Kuniyasu Irie
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
| | - Kazuto Komatsu
- Department of Gastroenterology, Yokosuka City Hospital, Yokosuka 240-0195, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; (S.S.); (Y.S.); (T.S.)
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Rokkas T, Ekmektzoglou K, Graham DY. Current role of tailored therapy in treating Helicobacter pylori infections. A systematic review, meta-analysis and critical analysis. Helicobacter 2023; 28:e12936. [PMID: 36458328 DOI: 10.1111/hel.12936] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 10/17/2022] [Accepted: 10/21/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND AND AIMS Recent guidelines dictate that all Helicobacter pylori (H. pylori) infected subjects should receive curative therapy. The efficacy of empirical regimens for H. pylori eradication might decline with bacterial, drug, and host factors. The necessity of a tailored therapy still remains controversial. Here we provide a meta-analysis of the current status of susceptibility-based (tailored) therapy in which susceptibility-based therapies were compared to the currently accepted choice of empiric therapy. In this rapidly closing era, neither the susceptibility nor empiric therapies were routinely optimized, such that we report the outcome of comparisons on the efficacy of unoptimized tailored vs. locally preferred empiric treatments. METHODS PubMed, Medline, and Embase databases were searched using suitable keywords. Individual and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity was calculated employing the Cochrane Q test and I2 values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed. RESULTS Thirty-four studies were included with a total of 9613 patients. Tailored therapy proved superior to empiric treatment [OR 2.07 (95% CI 1.53-2.79)]. However, tailored therapy achieved eradication rates >90% in only 15 (44%) studies and >95% in only 6 (17.6%). CONCLUSIONS Although tailored therapy performed better than empiric treatment, the lack of optimization of therapies failed to reliably achieve high cure rates (>90%). These results emphasize that H. pylori infection, like other infectious diseases, should utilize the principles of antimicrobial stewardship in relation to treatment guidance.
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Affiliation(s)
- Theodore Rokkas
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.,Medical School, European University of Cyprus, Nicosia, Cyprus
| | - Konstantine Ekmektzoglou
- Gastroenterology Clinic, Henry Dunant Hospital, Athens, Greece.,Medical School, European University of Cyprus, Nicosia, Cyprus
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, USA
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Ji YH, Shi YM, Hei QW, Sun JM, Yang XF, Wu T, Sun DL, Qi YX. Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection. Helicobacter 2023; 28:e12937. [PMID: 36408808 DOI: 10.1111/hel.12937] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 10/11/2022] [Accepted: 10/31/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines. METHODS Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations. RESULTS A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved. CONCLUSION There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future.
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Affiliation(s)
- Yan-Hong Ji
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Yan-Mei Shi
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Qian-Wen Hei
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Jin-Min Sun
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Xiao-Feng Yang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Tao Wu
- Department of infectious diseases, The First People's Hospital of Kunming, Kunming, China
| | - Da-Li Sun
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Yu-Xing Qi
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
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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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10
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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: 14] [Impact Index Per Article: 3.5] [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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11
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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: 11] [Impact Index Per Article: 2.8] [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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12
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Park H, Lee JH. Recent Trends in Tailored Treatments for Helicobacter pylori Infection. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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13
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Georgopoulos S, Papastergiou V. An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection. Expert Opin Pharmacother 2020; 22:729-741. [PMID: 33131337 DOI: 10.1080/14656566.2020.1845649] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Eradication of Helicobacter pylori (H. pylori) becomes more challenging due to increasing antimicrobial resistance. Consequently, the performance of clarithromycin-containing triple therapies is now declining to unacceptable levels and should be abandoned unless a prior susceptibility test precludes clarithromycin resistance.Areas covered: This review summarizes updated evidence concerning new and advancing pharmacotherapy options for H. pylori eradication.Expert opinion: Due to the declining efficacy of legacy triple therapies, most guidelines recommend bismuth quadruple therapy as the best initial empiric treatment. Concomitant, sequential and hybrid therapies are remarkable bismuth-free quadruple options, provided that dual clarithromycin-metronidazole resistance is low. Levofloxacin-, rifabutin-, furazolidone- and sitafloxacin-containing regimens remain useful, particularly as salvage options. To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation. Molecular testing methods promise convenient characterization of H. pylori antibiotic susceptibility. High-dose dual therapy (proton-pump-inhibitor plus amoxicillin) and vonoprazan, a more potent acid inhibitor that likely enhances the activity of amoxicillin, are promising alternatives that could decrease misuse of antibiotics. Addition of certain probiotics could somewhat increase the performance of H. pylori eradication regimens, while improving tolerability.
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Affiliation(s)
- Sotirios Georgopoulos
- Department of Gastroenterology, Athens Medical P. Faliron General Hospital, Athens, Greece
| | - Vasilios Papastergiou
- Department of Gastroenterology, "Konstantopoulion-Patision" General Hospital, Athens, Greece
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14
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Gisbert JP. Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review. Therap Adv Gastroenterol 2020; 13:1756284820968736. [PMID: 33240392 PMCID: PMC7675893 DOI: 10.1177/1756284820968736] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023] Open
Abstract
Although susceptibility-guided therapy is frequently recommended for Helicobacter pylori infection, the evidence available to date supporting this strategy is limited. The aim of the present article is to review the advantages and limitations of the susceptibility-guided and the empirical strategies to treat this infection. We performed a bibliographic search to identify studies investigating H. pylori susceptibility-guided therapy. Culture is not the only way to assess antibiotic resistance, as different polymerase chain reaction-based approaches have been developed as alternative methods. For detecting H. pylori antimicrobial resistance, a molecular approach based on a stool sample might enable more convenient, time-saving methods. Unfortunately, the antimicrobial susceptibility cannot be obtained in all cases. Furthermore, antibiotic susceptibility testing in clinical practice yields useful information only for a few antibiotics: clarithromycin, metronidazole, and quinolones. In addition, susceptibility towards clarithromycin and metronidazole in vitro does not necessarily lead to eradication in vivo. In the case of H. pylori therapy failure, we should not re-administer any of the antibiotics against which H. pylori has probably become resistant. Our updated meta-analysis showed that susceptibility-guided treatment is not better than empirical treatment of H. pylori infection in first-line therapy if the most updated quadruple regimens are empirically prescribed, and similar efficacy results were also demonstrated with the two strategies for second-line therapy. Cumulative H. pylori eradication rate with several successive rescue therapies empirically prescribed reaches almost 100%. Finally, the studies that have evaluated the cost-effectiveness of the susceptibility-guided treatment have achieved contradictory results. In summary, we can conclude that the evidence is too limited to support the generalized use of susceptibility-guided therapy for H. pylori treatment in routine clinical practice, either as first-line or as rescue treatment. Nevertheless, it would be recommended that susceptibility tests are performed routinely, even before prescribing first-line treatment, in specialized centers with an interest in H. pylori management.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La
Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad
Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, Madrid, 28006, Spain
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15
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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:jcm9020543. [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
- Correspondence: ; Tel.: +81-3-3342-6111; Fax: +81-3-3345-5359
| | - 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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16
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Kato M, Ota H, Okuda M, Kikuchi S, Satoh K, Shimoyama T, Suzuki H, Handa O, Furuta T, Mabe K, Murakami K, Sugiyama T, Uemura N, Takahashi S. Guidelines for the management of Helicobacter pylori infection in Japan: 2016 Revised Edition. Helicobacter 2019; 24:e12597. [PMID: 31111585 DOI: 10.1111/hel.12597] [Citation(s) in RCA: 190] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 04/08/2019] [Accepted: 04/14/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years. METHODS The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method. RESULTS There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication. CONCLUSION We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.
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Affiliation(s)
- Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, Hakodate, Hokkaido, Japan
| | - Hiroyoshi Ota
- Department of Clinical Laboratory Sciences, Shinshu University School of Medicine, Nagano, Hyogo, Japan
| | - Masumi Okuda
- Department of Pediatrics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Shogo Kikuchi
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Kiichi Satoh
- Department of Gastroenterology, International University of Health and Welfare Hospital, Nasushiobara, Tochigi, Japan
| | | | - Hidekazu Suzuki
- Fellowship Training Center, Medical Education Center, Keio University School of Medicine, Tokyo, Japan
| | - Osamu Handa
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate National Hospital, Hakodate, Hokkaido, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Faculty of Medicine, Oita University, Oita, Japan
| | - Toshiro Sugiyama
- Department of Cancer Prevention and Therapeutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Naomi Uemura
- Department of Gastroenterology, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan
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17
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Kwon YH, Jeon SW, Nam SY, Lee HS, Park JH. Efficacy of tailored therapy for Helicobacter pylori eradication based on clarithromycin resistance and survey of previous antibiotic exposure: A single-center prospective pilot study. Helicobacter 2019; 24:e12585. [PMID: 30969459 DOI: 10.1111/hel.12585] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/14/2019] [Accepted: 02/20/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND As the prevalence of antibiotic resistance is increasing, the effectiveness of traditional Helicobacter pylori (H pylori) therapies is gradually declining. We aimed to evaluate the efficacy of tailored therapy (dual priming oligonucleotide [DPO]-based multiplex PCR) and previous antibiotic exposure survey predicting for antibiotic resistance. MATERIALS AND METHODS Patients with H pylori infection who did not receive previous treatment were enrolled. The patients were divided into four groups (no resistance [NR] group, clarithromycin resistance [CLA-R] group, metronidazole-resistant [MET-R] group, and CLA- and MET-resistant [Dual-R] group) based on the results of dual priming oligonucleotide (DPO) polymerase chain reaction (PCR) and previous antibiotic exposure survey, and they were treated with tailored therapy based on antibiotic susceptibility. RESULTS Consecutive patients were distributed in the NR (n = 36, 70.6%), CLA-R (n = 9, 17.6%), and suspected MET-R (n = 6, 11.8%) group. The overall intention-to-treat/per-protocol eradication rate (ITT/PP) was 92.2%/94.0%. In the subgroup analysis, the ITT and PP of the NR, CLA-R, and MET-R groups were 94.4%/94.4%, 77.8%/87.5%, and 100.0%/100.0%, respectively. Total of 31 patients in all subgroups were evaluated for antibiotic resistance; five (16.1%), two (6.5%), and three (9.7%) participants showed CLA, MET, and dual resistance in culture-based susceptibility test. Compared with culture-based MIC test, the accuracy of DPO-based multiplex PCR in determining CLA resistance was 90.3%, while the accuracy of survey in determining MET resistance was only 77.4%. CONCLUSION A tailored therapy based on DPO-PCR and history of previous antibiotic use is useful in clinical practice and well correlated with culture-based susceptibility test.
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Affiliation(s)
- Yong Hwan Kwon
- School of Medicine, Kyungpook National University, Daegu, South Korea.,Department of Internal medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Seong Woo Jeon
- School of Medicine, Kyungpook National University, Daegu, South Korea.,Department of Internal medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Su Youn Nam
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Hyun Suk Lee
- School of Medicine, Kyungpook National University, Daegu, South Korea.,Department of Internal medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Ji Hey Park
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, South Korea
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18
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Yokota N, Ae R, Amenomori M, Kitagawa K, Nakamura T, Yokota T, Masato K, Sasahara T, Matsubara Y, Kosami K, Nakamura Y. Clinical background factors affecting outcomes of Helicobacter pylori eradication therapy in primary care. J Gen Fam Med 2019; 20:139-145. [PMID: 31312580 PMCID: PMC6612770 DOI: 10.1002/jgf2.245] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 02/27/2019] [Accepted: 03/06/2019] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Few studies have reported the influence of clinical background factors on the outcome of Helicobacter pylori eradication therapy in primary care practice. We aimed to determine which clinical background factors influence the outcome of eradication therapy in a primary care setting. METHODS This was a retrospective study of patients who received H pylori eradication therapy at Higashiohmi City Gamo Medical Center, Shiga, Japan, from January 2012 to December 2015. We investigated clinical background factors associated with success, failure, and self-interruption of H pylori eradication therapy: patients' age, gender, first- or second-line treatment, reasons for receiving gastroenterological endoscopic examination, method of drug administration, and attending physicians' age and their specialties. RESULTS There were 369 patients (208 females, 161 male), with a mean age of 59 years (range 30-88 years). The middle-aged group (50-69 years) was associated with successful eradication therapy compared with the young group (30-49 years). The elderly group (>70 years) was associated with eradication therapy failure compared with the middle-aged group. The young group was associated with self-interruption of eradication therapy. There was a marginally significant association between male patients and self-interruption. Older attending physicians (>50 years) were also associated with failure compared with younger physicians. There was no difference in outcome of eradication therapy between generalists and gastroenterology specialists. CONCLUSION We have identified clinical factors associated with success, failure, and self-interruption of H pylori eradication therapy in a primary care setting.
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Affiliation(s)
- Nozomi Yokota
- Shiga Center for Family Medicine Yuge Medical ClinicShigaJapan
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
| | - Ryusuke Ae
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
| | | | - Koji Kitagawa
- Shiga Center for Family Medicine Yuge Medical ClinicShigaJapan
| | - Takuya Nakamura
- Shiga Center for Family Medicine Yuge Medical ClinicShigaJapan
| | | | - Kato Masato
- Higashiomi city Gamo Medical CenterShigaJapan
| | - Teppei Sasahara
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
| | - Yuri Matsubara
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
| | - Koki Kosami
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
| | - Yoshikazu Nakamura
- Division of Public HealthCenter for Community MedicineJichi Medical UniversityTochigiJapan
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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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Arévalo Galvis A, Trespalacios Rangel AA, Otero Regino W. Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first-line triple therapy. Helicobacter 2019; 24:e12574. [PMID: 30859680 DOI: 10.1111/hel.12574] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Triple therapy efficacy against Helicobacter pylori is low worldwide, and thus, alternatives must be sought to improve eradication. The aim of the present study was to determine CYP2C19 genetic polymorphism effect on H pylori eradication. METHODS A randomized, single-blinded clinical trial including 133 participants was carried out. H pylori infection was confirmed by histologic and microbiologic test. Antibiotic susceptibility to amoxicillin and clarithromycin was performed. CYP2C19 polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche ®), and nested PCR for CYP2C19*17 polymorphisms. Participants were randomized into two groups for different H pylori therapies, one with standard omeprazole doses and another with omeprazole doses depending on CYP2C19 polymorphism. H pylori eradication was verified by stool antigen tests (Meridian ®). RESULTS The most common CYP2C19 polymorphism was *1/*1 in 54.9% of the participants followed by *17/*17 in 21.1%. Triple therapy efficacy with standard omeprazole doses versus personalized therapy based on CYP2C19 polymorphism by ITT analysis was 84% (95% CI: 0.73-0.91) vs 92.2% (95% CI: 0.82-0.97) (P = 0. 14), respectively. The efficacy by PP analysis was 92.1% (95% CI: 0.82-0.97) vs 100% (95% CI: 0.92-0.01) (P = 0.027), respectively. CONCLUSIONS The most frequent polymorphism was extensive PPI metabolizers (62.4%). Effectiveness of guided therapies by susceptibility test was good, yet they can be further improved by customized therapy based on CYP genotype. Therefore, high PPI (80 mg/d) doses are recommended for H pylori eradication therapies in Colombia. ClinicalTrials.gov ID: NCT03650543.
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Affiliation(s)
- Azucena Arévalo Galvis
- Laboratorio de Bacteriología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - Alba Alicia Trespalacios Rangel
- Laboratorio de Bacteriología Especial, Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, Colombia
| | - William Otero Regino
- Unidad de Gastroenterología, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.,Unidad de Gastroenterología Clínica Fundadores, Bogotá, Colombia
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21
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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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22
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Sue S, Ogushi M, Arima I, Kuwashima H, Nakao S, Naito M, Komatsu K, Kaneko H, Tamura T, Sasaki T, Kondo M, Shibata W, Maeda S. Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: A multicenter, prospective, randomized trial. Helicobacter 2018; 23:e12456. [PMID: 29271026 DOI: 10.1111/hel.12456] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The eradication rate of vonoprazan-based first-line triple therapy (combined with clarithromycin and amoxicillin) (V-AC) was reported to be 97.6% in patients with clarithromycin (CAM)-susceptible Helicobacter pylori in a phase III study, whereas our real-world, prospective, multicenter cohort study yielded an eradication rate <90%. OBJECTIVE To validate the eradication rate of V-AC using CAM-susceptible testing in a multicenter, prospective, randomized trial. METHODS We included 147 treatment-naïve H. pylori-positive patients [41 with CAM-resistant infections and 106 with CAM-susceptible infections]. The CAM-susceptible group patients were randomized to either the V-AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI-AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). All CAM-resistant H. pylori were eradicated by V-AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires. RESULTS The intention-to-treat and per-protocol eradication rates of V-AC in the CAM-susceptible H. pylori-infected patients were 87.3% (95% confidence interval 75.5%-94.7%) and 88.9% (77.4%-95.8%). The respective eradication rates of PPI-AC were 76.5% (62.5%-87.2%) and 86.7% (73.2%-94.9%). No significant difference was observed between the V-AC and PPI-AC regimes in terms of the intention-to-treat (P = .21) or per-protocol (P = .77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention-to-treat and per-protocol eradication rates of V-AC in the CAM-resistant patients were 82.9% (67.9%-92.8%). CONCLUSION The eradication rate of V-AC treatment in the CAM-susceptible H. pylori-infected patients was <90%, as was that by PPI-AC, thus V-AC is not ideal regimen in CAM-susceptible H. pylori. However, the 82.9% eradication rate of V-AC in the CAM-resistant infections may indicate the potential of V-AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).
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Affiliation(s)
- Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Marina Ogushi
- Department of Gastroenterology, Yokohama Hodogaya Central Hospital, Yokohama, Japan
| | - Isao Arima
- Department of Gastroenterology, Yokosuka City Hospital, Yokosuka, Kanagawa, Japan
| | - Hirofumi Kuwashima
- Department of Gastroenterology, Yokohama Hodogaya Central Hospital, Yokohama, Japan
| | - Satoshi Nakao
- Department of Gastroenterology, Yokosuka City Hospital, Yokosuka, Kanagawa, Japan
| | - Makoto Naito
- Department of Gastroenterology, Yokohama Hodogaya Central Hospital, Yokohama, Japan
| | - Kazuo Komatsu
- Department of Gastroenterology, Yokosuka City Hospital, Yokosuka, Kanagawa, Japan
| | - Hiroaki Kaneko
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Toshihide Tamura
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tomohiko Sasaki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masaaki Kondo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Wataru Shibata
- Advanced Medical Research Center, Yokohama City University, Yokohama, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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23
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Sue S, Suzuki N, Shibata W, Sasaki T, Yamada H, Kaneko H, Tamura T, Ishii T, Kondo M, Maeda S. Response to: Comment on "First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin". Gastroenterol Res Pract 2018; 2018:8046838. [PMID: 29767036 PMCID: PMC5885344 DOI: 10.1155/2018/8046838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 02/20/2018] [Indexed: 12/14/2022] Open
Affiliation(s)
- Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nobumi Suzuki
- Department of Gastroenterology, Institute for Adult Disease, Asahi Life Foundation, Tokyo, Japan
| | - Wataru Shibata
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Advanced Medical Research Center, Yokohama City University, Yokohama, Japan
| | - Tomohiko Sasaki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hiroaki Yamada
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hiroaki Kaneko
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Toshihide Tamura
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tomohiro Ishii
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Masaaki Kondo
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Gastroenterology, Institute for Adult Disease, Asahi Life Foundation, Tokyo, Japan
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Papastergiou V, Mathou N, Licousi S, Evgenidi A, Paraskeva KD, Giannakopoulos A, Stavrou PZ, Platsouka E, Karagiannis JA. Seven-day genotypic resistance-guided triple Helicobacter pylori eradication therapy can be highly effective. Ann Gastroenterol 2018; 31:198-204. [PMID: 29507466 PMCID: PMC5825949 DOI: 10.20524/aog.2017.0219] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 10/30/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The efficacy and applicability of molecular testing to guide the selection of antibiotics in triple Helicobacter pylori (H. pylori) eradication regimens have not been reported. We tested a 7-day, genotypic resistance-guided triple H. pylori eradication therapy in a high-resistance setting. METHODS Consecutive dyspeptic patients with H. pylori infection were prospectively enrolled. Genotypic resistances to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) were determined from gastric biopsy specimens using a commercially available molecular assay (GenoTypeâ HelicoDR). A tailored genotypic resistance-guided 7-day triple therapy comprised esomeprazole, amoxicillin, and either clarithromycin (wild-type 23SrRNA), levofloxacin (23SrRNA mutated/wild-type gyrA) or rifabutin (both 23SrRNA/gyrA mutated). H. pylori eradication was confirmed by 13C-urea breath test. RESULTS Of 148 subjects screened, 51 patients were enrolled (male/female: 27/24, mean age: 50.7±11.4 years, treatment-naïve/-experienced: 32/19). The molecular kit was easily implemented, allowing for rapid (within 24 h) and relatively inexpensive determination of H. pylori resistance (clarithromycin: 47.1%, fluoroquinolones: 15.7%, dual clarithromycin/fluoroquinolones: 7.8%). For patients who received clarithromycin-, levofloxacin- and rifabutin-containing triple therapy, the respective eradication rates were 24/27, 20/20, and 2/4 by intention-to-treat (ITT); and 24/24, 19/19 and 2/3 by per-protocol (PP) analysis. Overall eradication rates were 90.2% (95% confidence interval [CI] 77.8-96.3%) by ITT and 97.8% (95%CI 87-99.8%) by PP analysis, showing no significant difference between treatment-naïve and -experienced patients (ITT: 87.5% vs. 94.7%, P=0.64; PP: 96.4% vs. 100%, respectively, P=1.00). CONCLUSIONS Regardless of prior treatment history, a genotypic resistance-guided 7-day triple therapy, based on a simple molecular assay, achieved a high H. pylori eradication rate.
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Affiliation(s)
- Vasilios Papastergiou
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Nicoletta Mathou
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Sophia Licousi
- Department of Microbiology (Sophia Licousi, Evangelia Platsouka), General Hospital of Nea Ionia “Konstantopouleio-Patission”, Athens, Greece
| | - Aikaterini Evgenidi
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Konstantina D. Paraskeva
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Athanasios Giannakopoulos
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Pinelopi-Zoi Stavrou
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
| | - Evangelia Platsouka
- Department of Microbiology (Sophia Licousi, Evangelia Platsouka), General Hospital of Nea Ionia “Konstantopouleio-Patission”, Athens, Greece
| | - John A. Karagiannis
- Department of Gastroenterology (Vasilios Papastergiou, Nicoletta Mathou, Aikaterini Evgenidi, Konstantina D. Paraskeva, Athanasios Giannakopoulos, Pinelopi-Zoi Stavrou, John A. Karagiannis), Athens, Greece
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25
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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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26
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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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27
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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] [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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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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Abstract
Failed eradication of Helicobacter pylori occurs when the antibiotic concentration at the site where H. pylori is located is lower than the minimal inhibitory concentration of the antibiotic for this bacterium. The main reason for this is the acquisition of resistance; and in the context of the most common treatment, the main reason is the acquisition of resistance to clarithromycin. Several options can then be followed. The most rational option is to use a tailored therapy, that is, to look for clarithromycin resistance either by culture plus antibiogram or by a molecular method. The standard triple therapy is used only in the case of clarithromycin susceptibility. In case of resistance or if an empiric treatment must be given, a good option is to use a bismuth-based quadruple therapy. If unavailable, clarithromycin-based quadruple therapies can be used either as sequential or 'concomitant' or hybrid. The limit, especially for concomitant therapy, is the use of clarithromycin, which will be inactive in about 2/3 of the cases, adding to cost and adverse events. Recently, the dual therapy proton pump inhibitor-amoxicillin has been revisited especially in the Far East, and increasing the dose and the frequency of administration gives excellent results.
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Affiliation(s)
- Francis Mégraud
- Inserm U853, Université de Bordeaux and Laboratoire de Bactériologie, CHU Pellegrin, Bordeaux, France
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Chen H, Dang Y, Zhou X, Liu B, Liu S, Zhang G. Tailored Therapy Versus Empiric Chosen Treatment for Helicobacter pylori Eradication: A Meta-Analysis. Medicine (Baltimore) 2016; 95:e2750. [PMID: 26886617 PMCID: PMC4998617 DOI: 10.1097/md.0000000000002750] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Although various regimens are empirically accepted for Helicobacter pylori eradication, the efficacy might be declined by multiple individual factors. The necessity of a personalized eradication therapy still remains controversial. The aim of the study was to compare tailored therapy with empiric chosen regimens. Databases of PUBMED, EMBASE, and MEDLINE were searched for eligible studies, published up to October 2015. All relevant controlled clinical trials were included. A random-effect model was applied to compare pooled relative risk (RR) with related 95% confidence intervals (CIs).Thirteen controlled clinical trials integrating 3512 participants were assessed. Overall, the pooled eradication rates of tailored groups were higher than those of empiric ones (intention-to-treat: RR = 1.16, 95% CI 1.10-1.22; preprotocol: RR = 1.14, 95% CI 1.08-1.21). In subgroup analysis, tailored therapy was superior to 7-day standard triple therapy (RR = 1.22, 95% CI 1.16-1.29) and bismuth-quadruple therapy (RR = 1.14, 95% CI 1.07-1.22) on eradication rates; first-line tailored therapy achieved higher eradication rates than first-line empirical regimens (pooled RR = 1.18, 95%CI 1.14-1.22), whereas tailored rescue regimen showed no difference with empirical ones (pooled RR = 1.16, 95% CI 0.96-1.39). Moreover, among different tailored designs, susceptibility-guided tailored therapy obtained higher eradication rates than empiric groups, independent of CYP2C19 genotype detection (with CYP: RR = 1.16, 95% CI 1.09-1.23; without CYP: RR = 1.14, 95% CI 1.01-1.28). Both molecular test-based and culture-based tailored groups were better on eradication rates than empiric groups (molecular: RR = 1.23, 95% CI 1.11-1.35; culture: RR = 1.13, 95% CI 1.06-1.20). Compared with empiric chosen treatments, tailored therapy is a better alternative for H pylori eradication.
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Affiliation(s)
- Han Chen
- From the Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, First Clinical Medical College of Nanjing Medical University, Nanjing, China
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31
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Graham DY. Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants. Helicobacter 2015; 20:321-5. [PMID: 26123529 PMCID: PMC5098213 DOI: 10.1111/hel.12244] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics.
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Affiliation(s)
- David Y. Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, 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; 42:477-83. [PMID: 26075959 DOI: 10.1111/apt.13280] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [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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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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34
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Choi KD. Current Trends ofHelicobacter pyloriEradication in Korea. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2015. [DOI: 10.7704/kjhugr.2015.15.3.147] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Kawai T, Takahashi S, Suzuki H, Sasaki H, Nagahara A, Asaoka D, Matsuhisa T, Masaoaka T, Nishizawa T, Suzuki M, Ito M, Kurihara N, Omata F, Mizuno S, Torii A, Kawakami K, Ohkusa T, Tokunaga K, Mine T, Sakaki N. Changes in the first line Helicobacter pylori eradication rates using the triple therapy-a multicenter study in the Tokyo metropolitan area (Tokyo Helicobacter pylori study group). J Gastroenterol Hepatol 2014; 29 Suppl 4:29-32. [PMID: 25521730 DOI: 10.1111/jgh.12796] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. METHODS Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg)+amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. RESULTS The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n=242), 71.2%/72.9% (2002, n=208), 67.8%/70.5% (2003, n=183), 75.6%/84.6% (2004, n=131), 56.4%/70.5% (2005, n=114), 70.5%/75.8% (2006, n=271), 67.4%/82.0% (2007, n=135), 64.0%/76.3% (2008, n=261), 60.5%/74.3% (2009, n=329), and 66.5%/78.8% (2010, n=370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. CONCLUSION In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.
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Affiliation(s)
- Takashi Kawai
- Endoscopy Center, Tokyo Medical University, Tokyo, Japan
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: Past, present and future. World J Gastrointest Pathophysiol 2014; 5:392-399. [PMID: 25400982 PMCID: PMC4231503 DOI: 10.4291/wjgp.v5.i4.392] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 04/15/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.
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Lee JW, Kim N, Nam RH, Park JH, Choi YJ, Kim JM, Kim JS, Jung HC. GenoType HelicoDR test in the determination of antimicrobial resistance of Helicobacter pylori in Korea. Scand J Gastroenterol 2014; 49:1058-67. [PMID: 24957849 DOI: 10.3109/00365521.2014.894117] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Antimicrobial resistance of Helicobacter pylori is most important factor in eradication success. GenoType HelicoDR test has been developed for rapid detection of antimicrobial resistance. The present study evaluated the clinical usefulness of GenoType HelicoDR test in Korea. MATERIALS AND METHODS To detect 23S rRNA for clarithromycin resistance and gyrA mutations for fluoroquinolone resistance, both DNA sequencing after minimal inhibitory test (MIC) and GenoType HelicoDR test were performed in H. pylori isolates from the gastric mucosa of 101 patients. The eradication results of clarithromycin and moxifloxacin-containing triple therapy were evaluated by the 23S rRNA and gyrA mutations. RESULTS For 42 isolates with A2143G mutation by GenoType HelicoDR, 83.3% (35/42) of concordance rate was estimated with DNA sequencing method and 85.7% (36/42) for MIC test. For 43 isolates with N87K mutation by GenoType HelicoDR, 71.1% (31/43) of concordance rate was estimated with DNA sequencing and 88.4% (38/43) for MIC test. The sensitivity and specificity of GenoType HelicoDR test in determination of 23S rRNA mutation were 94.9% and 87.1%, and those of gyrA 98.2% and 80.0%. The sensitivity and specificity of GenoType HelicoDR test in determination of clarithromycin resistance based on MIC test were 55.0% and 80.0%, for fluoroquinolone 74.4% and 70.0%. CONCLUSION GenoType HelicoDR test is useful to determine mutations responsible for clarithromycin or fluoroquinolone-containing eradication failure but has a limitation for the clinical applicability in determination of resistance.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital , Seongnam, Gyeonggi-do , Korea
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance. World J Gastroenterol 2014; 20:9898-911. [PMID: 25110420 PMCID: PMC4123371 DOI: 10.3748/wjg.v20.i29.9898] [Citation(s) in RCA: 75] [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: 11/01/2013] [Revised: 01/27/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.
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Sugimoto M, Uotani T, Sahara S, Ichikawa H, Yamade M, Sugimoto K, Furuta T. Efficacy of tailored Helicobacter pylori eradication treatment based on clarithromycin susceptibility and maintenance of acid secretion. Helicobacter 2014; 19:312-8. [PMID: 24690010 DOI: 10.1111/hel.12128] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Insufficient acid inhibition during Helicobacter pylori eradication treatment and bacterial resistance to antibiotics often causes eradication failure. Four times daily dosing (q.i.d.) of a proton-pump inhibitor (PPI) achieves potent acid inhibition, suggesting its potential usefulness as a regimen for eradicating H. pylori infection. Therefore, a tailored eradication regimen based on antibiotic susceptibility and maintenance of acid inhibition should have a high success rate. We investigated the efficacy of such treatment based on clarithromycin (CAM) susceptibility. METHODS Using 153 H. pylori-positive Japanese patients, we investigated the efficacy of tailored eradication strategy: (1) Patients infected with CAM-sensitive H. pylori were treated with a PPI (rabeprazole 10 mg q.i.d.), amoxicillin 500 mg q.i.d., and CAM 200 mg b.i.d. (n = 89), and (2) patients infected with CAM-resistant were given the same doses of rabeprazole and amoxicillin and metronidazole 250 mg b.i.d. (n = 64) for 1 week. RESULTS In the tailored regimen group, the overall eradication rate was 96.7% (95% CI: 92.5-98.9%, 148/153) in the intention-to-treat (ITT) analysis and 97.4% (93.4-99.3%, 148/152) in the PP analysis. The eradication rates for the CAM- and metronidazole-based treatments were similar (95.5% and 98.4%, respectively, p = .400). The tailored treatment achieved a high eradication rate in CYP2C19 rapid metabolizers who were a resistance genotype for PPI treatment (94.3% (86.0-98.4%, 66/70)). DISCUSSION A tailored H. pylori eradication regimen based on CAM susceptibility and maintaining acid secretion (rabeprazole 10 mg q.i.d.) is useful because it can achieve an eradication rate exceeding 95%, irrespective of eradication history, thus overcoming differences among CYP2C19 genotypes.
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Affiliation(s)
- Mitsushige Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
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Sugimoto M, Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol 2014; 20:6400-6411. [PMID: 24914361 PMCID: PMC4047325 DOI: 10.3748/wjg.v20.i21.6400] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Revised: 12/18/2013] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
The cure rates of Helicobacter pylori (H. pylori) eradication therapy using a proton pump inhibitor (PPI) and antimicrobial agents such as amoxicillin, clarithromycin, and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion. Annual cure rates have gradually decreased because of the increased prevalence of H. pylori strains resistant to antimicrobial agents, especially to clarithromycin. Alternative regimens have therefore been developed incorporating different antimicrobial agents. Further, standard PPI therapy (twice-daily dosing) often fails to induce a long-term increase in intragastric pH > 4.0. Increasing the eradication rate requires more frequent and higher doses of PPIs. Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes (e.g., cytochrome P450 2C19, CYP2C19), drug transporters (e.g., multidrug resistance protein-1; ABCB1), and inflammatory cytokines (e.g., interleukin-1β). For example, quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h, irrespective of CYP2C19 genotype. Therefore, tailored H. pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.
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Mégraud F. Current recommendations for Helicobacter pylori therapies in a world of evolving resistance. Gut Microbes 2013; 4:541-8. [PMID: 23929066 PMCID: PMC3928164 DOI: 10.4161/gmic.25930] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Occurrence of resistance, especially to clarithromycin, renders the standard triple therapy used to cure Helicobacter pylori infection ineffective. This review presents the bacteriological and pharmacological basis for H. pylori therapy and the current recommendations. The third-line treatment must be based on clarithromycin susceptibility testing. If the bacteria are still susceptible, failure may come from problems of compliance, hyperacidity or high bacterial load which can be overcome. If the bacteria are resistant, different regimens must be considered, including bismuth and non-bismuth-based quadruple therapies (sequential or concomitant), as well as triple therapies where amoxicillin is administered several times a day to obtain an optimal concentration at the gastric mucosal level. The treatments are becoming more and more complex and ecologically unsatisfactory, waiting for new agents or vaccines.
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Affiliation(s)
- Francis Mégraud
- INSERM U853; Bordeaux, France,Université de Bordeaux; Laboratoire de Bactériologie; Bordeaux, France,Correspondence to: Francis Mégraud,
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Furuta T, Sugimoto M, Yamade M, Uotani T, Sahara S, Ichikawa H, Yamada T, Osawa S, Sugimoto K, Watanabe H, Umemura K. Effect of dosing schemes of amoxicillin on eradication rates ofHelicobacter pyloriwith amoxicillin-based triple therapy. J Clin Pharmacol 2013; 54:258-66. [PMID: 24122836 DOI: 10.1002/jcph.195] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2013] [Accepted: 09/22/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Mitsushige Sugimoto
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Mihoko Yamade
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Takahiro Uotani
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Shu Sahara
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Hitomi Ichikawa
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Takanori Yamada
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Satoshi Osawa
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Ken Sugimoto
- First Department of Medicine; Hamamatsu University School of Medicine; Hamamatsu Japan
| | - Hiroshi Watanabe
- Center for Clinical Research; Hamamatsu University School of Medicine; Hamamatsu Japan
- Department of Clinical Pharmacology and Therapeutics; Hamamatsu University School of Medicine
| | - Kazuo Umemura
- Center for Clinical Research; Hamamatsu University School of Medicine; Hamamatsu Japan
- Department of Pharmacology; Hamamatsu University School of Medicine
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Liou JM, Chen CC, Chang CY, Chen MJ, Fang YJ, Lee JY, Chen CC, Hsu SJ, Hsu YC, Tseng CH, Tseng PH, Chang L, Chang WH, Wang HP, Shun CT, Wu JY, Lee YC, Lin JT, Wu MS. Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother 2012; 68:450-6. [PMID: 23099849 DOI: 10.1093/jac/dks407] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.
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Affiliation(s)
- Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Helicobacter pylori eradication: can't we do better? J Pediatr Gastroenterol Nutr 2011; 53:468; author reply 468-9. [PMID: 21734603 DOI: 10.1097/mpg.0b013e31822b5f0d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Lee JW, Kim N, Nam RH, Park JH, Kim JM, Jung HC, Song IS. Mutations of Helicobacter pylori associated with fluoroquinolone resistance in Korea. Helicobacter 2011; 16:301-10. [PMID: 21762270 DOI: 10.1111/j.1523-5378.2011.00840.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations on second-line H. pylori eradication therapy. METHODS After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of the QRDR of gyrA was performed in 89 fluoroquinolone-resistant and 27 fluoroquinolone-susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin-containing triple therapy were evaluated depending on the resistance of fluoroquinolone. RESULTS The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp-91 (36.0%) and Asn-87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone-resistant strains received moxifloxacin-containing triple therapy as the second-line therapy, and two of three patients with Asn-87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp-91 mutations had successful eradication treatment. CONCLUSIONS Fluoroquinolone resistance of H. pylori was caused by gyrA Asn-87 and Asp-91 point mutations. The Asn-87 mutation seems to be an important determinant of failure of fluoroquinolone-containing triple eradication therapy based on eradication results.
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Affiliation(s)
- Jung W Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
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Helicobacter pylori eradication rates in children upon susceptibility testing based on noninvasive stool polymerase chain reaction versus gastric tissue culture. J Pediatr Gastroenterol Nutr 2011; 53:65-70. [PMID: 21694538 DOI: 10.1097/mpg.0b013e318210586d] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND OBJECTIVES In children with clarithromycin-resistant Helicobacter pylori, clarithromycin-containing therapies often fail. The present study aimed to assess the outcome of tailored therapy upon noninvasive versus invasive H pylori susceptibility testing. PATIENTS AND METHODS A retrospective cohort study was conducted in a pediatric outpatient clinic located in a region where H pylori clarithromycin resistance is highly prevalent. Between June 2007 and September 2009, 96 infected children (mean age 10.8 years), naïve to H pylori eradication treatment, were prescribed triple eradication therapies. These therapies were individually tailored upon susceptibility testing performed either noninvasively using stool polymerase chain reaction (stool PCR group) or invasively using endoscopy, biopsy, and culturing of gastric biopsies (gastric biopsy group). Eradication was defined by negative results upon noninvasive testing including stool PCR at least 5 weeks after the end of treatment. RESULTS H pylori was eradicated in 43 of 55 stool PCR group versus 30 of 41 gastric biopsy group children (78.2% vs 73.2%, P = 0.63). Of those H pylori strains with pretherapeutic clarithromycin susceptibility, 78.8% were eradicated in the stool PCR group and 69.2% in the gastric biopsy group (P = 0.41) following clarithromycin-containing therapy; clarithromycin resistance was acquired by 4.1% of strains in the former group versus 12% in the latter (P = 0.33). CONCLUSIONS Stool PCR is as effective as the invasive approach of H pylori susceptibility testing for targeting resistance-guided eradication treatments in children. Furthermore, stool PCR is a useful tool for tracking the emergence of clarithromycin resistance following eradication treatment.
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Boyanova L, Mitov I. Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. Expert Rev Anti Infect Ther 2010; 8:59-70. [PMID: 20014902 DOI: 10.1586/eri.09.113] [Citation(s) in RCA: 86] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Antibiotic resistance in Helicobacter pylori is the major cause of eradication failure. Primary H. pylori susceptibility patterns, however, are becoming less predictable. Currently, high (> or =20%) clarithromycin resistance rates have been observed in the USA and in developed countries in Europe and Asia, while the highest (> or =80%) metronidazole-resistance rates have been reported in Africa, Asia and South America. Primary quinolone-resistance rates of 10% or more have already been reported in developed countries in Europe and Asia. Primary amoxicillin resistance has been low (0 to <2%) in Europe but higher (6-59%) in Africa, Asia and South America. Similarly, tetracycline resistance has been absent or low (<5%) in most countries and higher (9-27%) in Asia and South America. The increasing clarithromycin and quinolone resistance, and multidrug resistance detected in 0 to less than 5% in Europe and more often (14.2%) in Brazil are worrying. Growing resistance often parallels national antibiotic consumption and may vary within patient groups according to the geographic region, patient's age and sex, type of disease, birthplace, other infections and other factors. The geographic map and evolution of primary H. pylori resistance are clinically important, should be considered when choosing eradication regimens, and should be monitored constantly at national and global levels in an attempt to reach the recently recommended goal of eradication of more than 95%.
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Affiliation(s)
- Lyudmila Boyanova
- Department of Medical Microbiology, Medical University of Sofia, Zdrave street 2, 1431 Sofia, Bulgaria.
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Yoon H, Kim N, Lee BH, Hwang TJ, Lee DH, Park YS, Nam RH, Jung HC, Song IS. Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate. Helicobacter 2009; 14:77-85. [PMID: 19751431 DOI: 10.1111/j.1523-5378.2009.00709.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to evaluate the efficacy of a moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection. We also investigated the effect of treatment duration and antibiotic resistance on the eradication rate of this therapy. METHODS We prospectively enrolled patients found to have persistent H. pylori infections after failure of first-line proton-pump inhibitor-based triple therapy. Patients took moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.). The eradication rate, drug compliance, and adverse event rates were evaluated. Minimal inhibitory tests were performed for moxifloxacin and amoxicillin by the agar dilution method. RESULTS In 2004, 41 patients were treated for 7 days. The intention-to-treat and per-protocol eradication rates (ITT/PP) were 75.6/83.8%. Moxifloxacin resistance was 5.6%. Therapy was extended to 10 days during 2005-2006 and 139 patients were treated. The ITT/PP eradication rates were 71.9/82.6%; moxifloxacin resistance had increased to 12%. The final group of 181 patients in 2007-2008 who were treated for 14 days also had low eradication rates (68/79.9%), but there was no statistical significance in the efficacy among the treatment periods. Moxifloxacin resistance in 2007-2008 was 28.2%. Side-effect increased with treatment duration (i.e., 9.8, 12.2, and 25.4% at 7, 10, and 14 days, respectively, p = .001). CONCLUSION The 7-day moxifloxacin-containing triple therapy produced an unacceptably low eradication rate. Increasing the duration of therapy was expected to increase the eradication rate, but the expected increased did not materialize, most likely because of coincident marked increase in the prevalence of resistance to moxifloxacin. Tailored treatment based on antibiotic susceptibility testing might be more effective in the achievement of high eradication rate when rapid antibiotic resistance such as moxifloxacin is occurring.
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Affiliation(s)
- Hyuk Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Abstract
The articles published this last year in the field of Helicobacter pylori diagnosis reported the development of in vivo histology, small improvements in some invasive methods (urease test, culture, and histology) and new kits for the stool antigen tests. They also contributed to increasing our knowledge, by further exploration into specific conditions for the urea breath test and into the significance of cagA antibodies. The role of serum markers of atrophy was also confirmed. Molecular methods are still being developed for direct genotyping, detection of H. pylori and its clarithromycin resistance, either by polymerase chain reaction or fluorescent in-situ hybridization. For the first time, there was a report on a possible interest of magnetic resonance spectroscopy.
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Affiliation(s)
- Lurdes Monteiro
- Departamento de Doenças Infecciosas, Instituto Nacional Saúde Dr Ricardo Jorge, Lisbon, Portugal
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