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Mori H, Nishizawa T, Morioka K, Kato M, Kanai T. Should Metronidazole Be Included in Second-Line Treatment After Standard Triple Therapy for Helicobacter pylori?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Helicobacter 2025; 30:e70010. [PMID: 39868753 PMCID: PMC11771550 DOI: 10.1111/hel.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/06/2025] [Accepted: 01/11/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND AND AIM Although standard triple therapy remains the first-line eradication treatment for H. pylori worldwide, it is unclear whether metronidazole should be included empirically in second-line eradication treatments. The aim of this study was to compare the efficacy of metronidazole-containing regimens with that of metronidazole-free regimens after failure of first-line eradication using standard triple therapy. METHODS PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify RCTs eligible for inclusion in this systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Thirteen eligible RCTs were included, with a total of 2039 patients assigned to metronidazole-containing (975 patients) or metronidazole-free (1064 patients) regimens. Metronidazole-containing regimens had significantly lower eradication failure rates than regimens without metronidazole (OR 0.55; 95% CI, 0.39-0.78). Subgroup analysis based on the regional risk of metronidazole resistance demonstrated that metronidazole-containing regimens had lower eradication failure rates not only in low-risk regions but also in high-risk regions (OR, 0.29; 95% CI, 0.11-0.74 and OR, 0.66; 95% CI, 0.49-0.91, respectively). CONCLUSION After failure of standard triple therapy, secondary eradication treatment regimens containing metronidazole demonstrate higher eradication rates than those without metronidazole.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Toshihiro Nishizawa
- Department of Gastroenterology and HepatologyInternational University of Health and Welfare, Narita HospitalNaritaJapan
| | - Kohei Morioka
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Center for Diagnostic and Therapeutic EndoscopyKeio University School of MedicineTokyoJapan
| | - Motohiko Kato
- Center for Diagnostic and Therapeutic EndoscopyKeio University School of MedicineTokyoJapan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
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Jung YS, Jung BW, Park CH. Comparative efficacy of Helicobacter pylori eradication therapy between tegoprazan-based concomitant and bismuth quadruple therapies: A real-world evidence. J Gastroenterol Hepatol 2025; 40:159-165. [PMID: 39557599 DOI: 10.1111/jgh.16798] [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: 08/31/2024] [Revised: 10/07/2024] [Accepted: 10/20/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND AND AIM Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies. METHODS We retrospectively analyzed data from patients with H. pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H. pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates. RESULTS Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P = 0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P = 0.424). The overall adverse event rates (49.6% vs 39.2%, P = 0.001) and insufficient medication rates (4.8% vs 2.4%, P = 0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group. CONCLUSIONS The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance.
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Affiliation(s)
- Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Wook Jung
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
- Department of Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Chung-Ang University H.C.S. Hyundae Hospital, Namyangju, Korea
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Cho JH. Bismuth add-on improves the efficacy of 2-week tegoprazan-based triple therapy for first-line Helicobacter pylori eradication: a real-world evidence study. Expert Rev Anti Infect Ther 2024; 22:793-799. [PMID: 38459869 DOI: 10.1080/14787210.2024.2329251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/12/2024] [Indexed: 03/11/2024]
Abstract
BACKGROUND This study aimed to investigate the efficacy of bismuth added to a 2-week triple therapy consisting of tegoprazan (TPZ), amoxicillin, and clarithromycin for first-line Helicobacter pylori eradication. RESEARCH DESIGN AND METHODS We reviewed the retrospective data of patients who received a 2-week TPZ-based triple therapy with or without 300 mg bismuth twice daily. The primary endpoint was the H. pylori eradication rate of adding bismuth to the TPZ-based triple regimen (TAC-B group), compared to no bismuth added (TAC group). RESULTS In total, 306 and 256 patients were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. The eradication success rates were significantly higher in the TAC-B group than in the TAC group (ITT, 82.9% vs. 71.8%, p = 0.029; PP, 95.8% vs. 87.5%, p = 0.027, respectively). The adherence rate to the eradication regimen was 100% in the TAC-B group and 97.0% in the TAC group. The adverse drug event rate in the TAC-B group was comparable to that in the TAC group (29.2% vs. 27.3%, p = 0.742). No use of bismuth was significantly associated with eradication failure (p = 0.038). CONCLUSIONS The bismuth add-on increased the first-line H. pylori eradication rate of 2-week TPZ-based triple therapy. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov identifier is NCT05453994.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, Korea
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Min BJ, Seo ME, Bae JH, Kim JW, Kim JH. Development and validation of next-generation sequencing panel for personalized Helicobacter pylori eradication treatment targeting multiple species. Front Cell Infect Microbiol 2024; 14:1379790. [PMID: 39268485 PMCID: PMC11390507 DOI: 10.3389/fcimb.2024.1379790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 07/03/2024] [Indexed: 09/15/2024] Open
Abstract
Introduction The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
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Affiliation(s)
- Byung-Joo Min
- Forensic DNA Division, National Forensic Service Seoul Institute, Seoul, Republic of Korea
| | - Myung-Eui Seo
- Seoul National University Biomedical Informatics (SNUBI), Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung Ho Bae
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ji Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ju Han Kim
- Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea
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Kim JS, Kim BW, Kim JI, Chung WC, Jung SW, Bang CS, Kim GH, Jeon SW, Joo MK, Lee SH, Lim YJ, Sung JK, Seo SY, Park SY, Lee WS, Lee HL, Kim KB, Kim HU. Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study. Helicobacter 2024; 29:e13126. [PMID: 39143948 DOI: 10.1111/hel.13126] [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: 06/14/2024] [Revised: 07/28/2024] [Accepted: 07/31/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.
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Affiliation(s)
- Joon Sung Kim
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Il Kim
- Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Woo Jung
- Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University College of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Seon Woo Jeon
- Department of Gastroenterology, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Chilgok, Korea
| | - Moon Kyoung Joo
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Si Hyung Lee
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Yun Jeong Lim
- Department of Internal Medicine, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Korea
| | - Jae Kyu Sung
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Seung Young Seo
- Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
| | - Sun Young Park
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Wan Sik Lee
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea
| | - Hang Lak Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Ki Bae Kim
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Korea
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Kim JY, Kim SG, Cho SJ. Optimal treatment duration of bismuth-containing quadruple therapy in Helicobacter pylori infection: A retrospective study. Medicine (Baltimore) 2023; 102:e36310. [PMID: 38050196 PMCID: PMC10695568 DOI: 10.1097/md.0000000000036310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Accepted: 11/03/2023] [Indexed: 12/06/2023] Open
Abstract
The use of bismuth-containing quadruple therapy (BQT) in Helicobacter pylori eradication has been increasing. Although the recommended treatment length for BQT is 14 days, longer durations may be associated with higher rates of adverse events. The aim of this study was to evaluate the optimal duration of BQT by comparing eradication rates and adverse events among 7, 10, and 14-day regimens. A total of 328 patients treated with BQT at Seoul National University Hospital from January 2010 to May 2022 were retrospectively evaluated. The eradication rates of different treatment groups were compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Baseline characteristics of the enrolled patients and adverse events were also analyzed. A total of 74, 177, and 77 patients were included in the 7-, 10-, and 14-day groups, respectively. Forty-one patients were lost during the follow-up. The eradication rates were 71.6%, 84.2%, and 80.5% (P = .106) by ITT, and 84.1%, 94.9%, and 92.5% (P = .028) by PP analysis in the 7-, 10-, and 14-day groups, respectively. The 10-day regimen showed significantly higher eradication rates than the 7-day regimen in both ITT (P = .024) and PP (P = .018) analyses. However, there were no significant differences in eradication rates between the 10- and 14-day groups in either ITT (P = .667) or PP (P = .537) analysis. Adverse event incidence was comparable among the groups (P = .835). Treatment with BQT for 10 days was as effective as 14 days without increasing the adverse events.
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Affiliation(s)
- Ji Yoon Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Gyun Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo-Jeong Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
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Hoang T, Woo H, Cho S, Lee J, Kazmi SZ, Shin A. Descriptive Analysis of Gastric Cancer Mortality in Korea, 2000-2020. Cancer Res Treat 2023; 55:603-617. [PMID: 36097804 PMCID: PMC10101797 DOI: 10.4143/crt.2022.307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 09/02/2022] [Indexed: 11/21/2022] Open
Abstract
PURPOSE This study aimed to examine secular trends, age-period-cohort effects, and geographical differences in gastric cancer (GC) mortality in Korea. Materials and Methods Using cause of death data from the Korean Statistical Information Service for GC from 2000 to 2020, we calculated average annual percentage changes (AAPCs) in the age-standardized mortality of GC in 17 cities and provinces through joinpoint regression. Decomposition of age, period, and cohort effects on GC mortality were elucidated by applying a log-linear model and an intrinsic estimate method. Spatial patterns and the degree of spatial clustering in 250 administrative regions were explored via Moran's I statistics. Stratification by sex was performed for all analyses. RESULTS The age-standardized mortality of GC per 100,000 persons declined from 29.0 in 2000 to 7.9 in 2020 (AAPC, -6.28%). Age-period-cohort analyses of GC mortality showed a downward trend among five-year age groups from age 20-89 years across five-year periods from 2005-2020 and five-year birth cohorts from 1920-2000. Overall, the younger birth cohort showed lower mortality rates than the older cohort within the same period. In 2020, clusters of high GC mortality were observed in the central area for men (Chungcheongbuk, Jeollabuk, Gyeongsangbuk, and Gyeongsangnam) and in the eastern area for women (Gyeongsangbuk). CONCLUSION This study identified a downward trend in GC mortality among men and women from 2000 to 2020 in Korea. This trend was mainly attributed to birth cohort rather than period effects. Spatial analysis showed high GC mortality in the Chungcheong and Gyeongsangbuk areas.
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Affiliation(s)
- Tung Hoang
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul,
Korea
| | - Hyeongtaek Woo
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Department of Preventive Medicine, Keimyung University School of Medicine, Daegu,
Korea
| | - Sooyoung Cho
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Jeeyoo Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Sayada Zartasha Kazmi
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul,
Korea
- Cancer Research Institute, Seoul National University, Seoul,
Korea
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Matta AJ, Zambrano DC, Martínez YC, Fernández FF. Point mutations in the glycosyltransferase domain of the pbp1a gene in amoxicillin-resistant Helicobacter pylori isolates. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:100-106. [PMID: 35661638 DOI: 10.1016/j.rgmxen.2021.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 05/14/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) eradication treatment includes a proton pump inhibitor and two antibiotics: amoxicillin and clarithromycin. The goal of that treatment is to eradicate the infection in at least 90% of the patients. Failure to eradicate the infection can have multiple causes, among which is the presence of point mutations in the antimicrobial target genes. OBJECTIVE To characterize the mutations present in the pbp1a gene and their possible association with resistance to amoxicillin in vitro. METHODOLOGY Susceptibility to amoxicillin was evaluated in 147 isolates of H. pylori from the Colombian municipality of Túquerres. PCR amplification and sequencing of the glycosyltransferase domain of the pbp1a gene were carried out on Túquerres isolates, and the association between mutations and resistance was evaluated. RESULTS A total of 5.4% (8/147) Túquerres isolates were resistant to amoxicillin in vitro. PCR amplification of the glycosyltransferase domain of the pbp1A gene was performed on 87.5% of the amoxicillin-resistant isolates in vitro, and in the DNA sequencing analysis, a total of 2 changes of amino acids from 3 DNA mutations that encoded the PBP1A-1 protein were observed. CONCLUSION The present study is the first report on pbp1a gene mutations in H. pylori isolates coming from a population in Túquerres. Mutations that have not been reported in previous studies were found.
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Affiliation(s)
- A J Matta
- Facultad de Ciencias de la Educación y el Deporte, Escuela Nacional del Deporte, Cali, Colombia
| | - D C Zambrano
- Facultad de Ciencias de la Educación y el Deporte, Escuela Nacional del Deporte, Cali, Colombia
| | - Y C Martínez
- Facultad de Salud, Escuela de Medicina, Corporación Universitaria Rafael Núñez, Cartagena de Indias, Colombia
| | - F F Fernández
- Facultad de Ciencias, Universidad San Buenaventura, Cali, Colombia.
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Sholeh M, Khoshnood S, Azimi T, Mohamadi J, Kaviar VH, Hashemian M, Karamollahi S, Sadeghifard N, Heidarizadeh H, Heidary M, Saki M. The prevalence of clarithromycin-resistant Helicobacter pylori isolates: a systematic review and meta-analysis. PeerJ 2023; 11:e15121. [PMID: 37016679 PMCID: PMC10066884 DOI: 10.7717/peerj.15121] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/03/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Knowledge of global clarithromycin (CLA)-resistant rates of Helicobacter pylori (H. pylori) is crucial for decision of the most appropriate eradication therapies with good clinical outcomes. Therefore, this review and meta-analysis aimed to evaluate the global prevalence of the CLA resistance in H. pylori to provide some guidance for selecting the first-line antibiotics. METHOD A comprehensive search was performed for relevant literature until April 2021 in PubMed, Embase, and Web of Science databases. Freeman-Tukey double arcsine transformation was performed to estimate the weighted pooled prevalence of resistance. RESULTS The meta-analysis included 248 articles. The prevalence of CLA-resistant H. pylori was 27.53% (95% CI [25.41-29.69]). The heterogeneity between reports was significant (I2 = 97.80%, P < 0.01). The resistance rate increased from 24.28% in 2010-2017 to 32.14% in 2018-2021 (P < 0.01). Iran, with 38 articles, has the most report. Nevertheless, Switzerland, Portugal, and Israel had the highest resistance rates (67.16%, 48.11%, and 46.12%, respectively). The heterogeneity between the continents and the antimicrobial susceptibility methods also interpreted standard guidelines and breakpoints was insignificant (P > 0.05). CONCLUSION Overall CLA resistance rate was 27.53%, worldwide. The difference in CLA resistance rate among the included studies can be due to several reasons such as differences in antibiotic prescription rates in various geographic areas, use of different breakpoints or inaccurate criteria in performed studies, and the emergence of multidrug-resistant (MDR) strains.
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Affiliation(s)
- Mohammad Sholeh
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Taher Azimi
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jasem Mohamadi
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Vahab Hassan Kaviar
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Marzieh Hashemian
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Somayeh Karamollahi
- Department of Microbiology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Nourkhoda Sadeghifard
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Hedayat Heidarizadeh
- Department of Pediatrics, School of Medicine, Emam Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
| | - Mohsen Heidary
- Department of Laboratory Sciences, School of Paramedical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran
- Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Morteza Saki
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Gong Y, Zhai K, Sun L, He L, Wang H, Guo Y, Zhang J. RdxA Diversity and Mutations Associated with Metronidazole Resistance of Helicobacter pylori. Microbiol Spectr 2023; 11:e0390322. [PMID: 36943041 PMCID: PMC10100817 DOI: 10.1128/spectrum.03903-22] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 02/15/2023] [Indexed: 03/23/2023] Open
Abstract
Metronidazole (MNZ) is administered as first-line antibiotic for Helicobacter pylori eradication therapy; however, increasing resistance to MNZ impaired the efficacy. Increasing the dose of MNZ was recommended to overcome low-level resistance, but it was difficult to determine MNZ resistance level simply based on the rdxA gene mutation. In this study, the rdxA sequences of 511 clinical H. pylori strains were analyzed to assess the genotypes associated with MNZ resistance. We observed that the prevalences of rdxA sequences with missense, nonsense, and frameshift mutations were 70.25, 11.35, and 17.03%, respectively. Regarding the amino acid substitutions, T31E, H53R, D59N, L62V, S88P, G98S/N, R131K, and V172I were present in most strains regardless of the resistance phenotype. The correlation analysis showed R16H/C, Y47C, A67V/T, and V204I substitutions were associated with MNZ resistance. The mutation resulting in RdxA truncation was observed in 36.29% of the resistant strains, and 83.45% of these strains displayed high-level MNZ resistance (MIC > 256 μg/mL). Moreover, all strains with truncated mutation positions before amino acid 70 expressed high-level MNZ resistance. Our results indicated that most amino acid mutations probably contributed to the sequence diversity of RdxA, while R16H/C, Y47C, A67V/T, and V204I were potentially helpful to identify resistant strains. Although it was difficult to determine the mutations associated with MNZ resistance, the prediction of high-level resistance based on truncated characteristics of RdxA might be an important approach, which can effectively avoid H. pylori eradication therapy with unreasonable of MNZ dose increases for patients with high-level drug resistance. IMPORTANCE The increasing resistance to metronidazole impaired the efficacy of Helicobacter pylori eradication, and increasing the dose of metronidazole was recommended to overcome low-level resistance. For patients infected with highly resistant strains, the current empirical treatments, which generally used metronidazole in double doses or more, appeared impossibly to overcome the resistance and would only increase the incidence of adverse effects. Our results indicated that high-level metronidazole resistance was predominant, and almost half of the patients with high-level drug resistance could avoid usage of metronidazole based on the truncated mutations of RdxA sequences, which can effectively avoid H. pylori eradication therapy with unreasonable increases in the metronidazole dose.
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Affiliation(s)
- Yanan Gong
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Kangle Zhai
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lu Sun
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Lihua He
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Hairui Wang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Yahui Guo
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Jianzhong Zhang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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11
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Lee JW, Kim N, Choi SI, Jang JY, Song CH, Nam RH, Lee DH. Prevalence and trends of multiple antimicrobial resistance of Helicobacter pylori in one tertiary hospital for 20 years in Korea. Helicobacter 2023; 28:e12939. [PMID: 36478622 DOI: 10.1111/hel.12939] [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: 04/30/2022] [Revised: 09/26/2022] [Accepted: 10/21/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Soo In Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Chin Hee Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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12
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Lee JW. Fluoroquinolone and Rifabutin-Containing Therapy. HELICOBACTER PYLORI 2023:587-594. [DOI: 10.1007/978-981-97-0013-4_49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Lee JY. Triple Therapy. HELICOBACTER PYLORI 2023:541-552. [DOI: 10.1007/978-981-97-0013-4_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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14
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Kwon YH. Tailored Therapy Based on Antibiotic Resistance. HELICOBACTER PYLORI 2023:575-586. [DOI: 10.1007/978-981-97-0013-4_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Park CH, Song MJ, Jung BW, Park JH, Jung YS. Comparative Efficacy of 14-Day Tegoprazan-Based Triple vs. 10-Day Tegoprazan-Based Concomitant Therapy for Helicobacter pylori Eradication. J Pers Med 2022; 12:1918. [PMID: 36422094 PMCID: PMC9695183 DOI: 10.3390/jpm12111918] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/09/2022] [Accepted: 11/15/2022] [Indexed: 11/18/2022] Open
Abstract
Tegoprazan, a novel potassium-competitive acid blocker, is currently available for the treatment of Helicobacter pylori infection. We compared the efficacies of tegoprazan-based triple and concomitant therapies in a real-world practice. Data of patients treated with a 14-day tegoprazan-based triple therapy (50 mg of tegoprazan + 1000 mg of amoxicillin + 500 mg of clarithromycin twice daily) or 10-day tegoprazan-based concomitant therapy (50 mg of tegoprazan + 1000 mg of amoxicillin + 500 mg of clarithromycin + 500 mg of metronidazole twice daily) were retrospectively reviewed. Primary endpoint was eradication rate in the intention-to-treat (ITT) population. Of the 928 included patients, 551 and 377 were treated with triple and concomitant therapies, respectively. Eradication rate from ITT analysis was 76.4% (95% confidence interval [CI], 72.7−79.8%) in the triple therapy group and 85.9% (95% CI, 82.2−89.2%) in the concomitant therapy group (p < 0.001). Eradication rate in the per-protocol analysis was also higher in the concomitant therapy group than in the triple therapy group (triple vs. concomitant therapy: 84.5% [81.1−87.5%] vs. 91.1% [87.8−93.8%]). Overall adverse event rate was 29.0% in the triple therapy group and 45.9% in the concomitant therapy group (p < 0.001). Adherence rate was similar between the two groups (triple vs. concomitant therapy: 90.0 vs. 92.6%, p = 0.180). Overall, the 10-day tegoprazan-based concomitant therapy had superior efficacy than the 14-day tegoprazan-based triple therapy for H. pylori eradication. Although concomitant therapy showed common adverse events, adherence was comparable between the two therapies.
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Affiliation(s)
- Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Republic of Korea
| | - Myung Jin Song
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Republic of Korea
| | - Byung Wook Jung
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Republic of Korea
| | - Jung Ho Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
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16
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Zhong Z, Zhan B, Xu B, Gao H. Achieving Helicobacter pylori eradication in the primary treatment requires a deep integration of personalization and standardization. Helicobacter 2022; 27:e12916. [PMID: 35939537 DOI: 10.1111/hel.12916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/18/2022] [Accepted: 07/08/2022] [Indexed: 12/09/2022]
Affiliation(s)
- Zishao Zhong
- Tongji Hospital, Institute of Digestive Disease, School of Medicine, Tongji University, Shanghai, China.,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bingjie Zhan
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
| | - Baohui Xu
- China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
| | - Hengjun Gao
- Tongji Hospital, Institute of Digestive Disease, School of Medicine, Tongji University, Shanghai, China.,China Center for Helicobacter pylori Molecular Medicine, Shanghai, China
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17
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He XJ, Zeng XP, Jiang CS, Liu G, Li DZ, Wang W. Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China. Dig Dis Sci 2022; 67:208-215. [PMID: 33559090 DOI: 10.1007/s10620-021-06856-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 01/17/2021] [Indexed: 02/08/2023]
Abstract
AIMS Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.
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Affiliation(s)
- Xiao-Jian He
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Xiang-Peng Zeng
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Chuan-Shen Jiang
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Gang Liu
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Da-Zhou Li
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China
| | - Wen Wang
- Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, 156 North Road of West No.2 Ring, Fuzhou, 350025, China.
- Fuzhou General Clinical Medical College, Fujian Medical University, Fuzhou, China.
- Oriental Hospital Affiliated To Xiamen University, Fuzhou, China.
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18
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Cho JH, Jin SY, Park S. Comparison of tailored Helicobacter pylori eradication versus modified bismuth quadruple therapy in Korea: a randomized controlled trial. Expert Rev Anti Infect Ther 2021; 20:923-929. [PMID: 34883037 DOI: 10.1080/14787210.2022.2017280] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to compare the success rate, adverse drug events, and cost-effectiveness of tailored Helicobacter pylori eradication and modified bismuth-containing quadruple therapy. METHODS The diagnosis of H. pylori infection was randomly based on either rapid urease test (RUT) or dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) in 1:1 ratio. According to the presence of point mutations that cause clarithromycin resistance, patients in the tailored therapy (TT) group received standard triple therapy or classic bismuth quadruple therapy. Patients with positive RUT results received 40 mg pantoprazole, 1000 mg amoxicillin, 750 mg metronidazole, and 600 mg bismuth subcitrate twice daily for 14 days (PAM-B therapy). RESULTS Between the TT (n = 141) and PAM-B groups (n = 141), H. pylori eradication rate did not differ significantly according to intention-to-treat (TT: 80.9% vs. PAM-B: 85.8%, P = 0.262), modified intention-to-treat (TT: 89.1% vs. PAM-B: 91.0%, P = 0.606), and per-protocol (TT: 89.0% vs. PAM-B: 93.5%, P = 0.198) analyses. The average cost for successful eradication was higher in the TT group than in the PAM-B group ($340.7 vs. $263.9 per patient). CONCLUSION PAM-B therapy exhibits similar efficacy and improved cost-effectiveness compared to TT based on the results of DPO-PCR tests. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov identifier is NCT05002595.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, Korea
| | - So Young Jin
- Department of Pathology, Soonchunhyang University Hospital, Seoul, Korea
| | - Suyeon Park
- Department of Medical Biostatistics, Soonchunhyang University Hospital, Seoul, Korea
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19
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Lee JW, Kim N, Nam RH, Jang JY, Choi Y, Lee DH. Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance. Helicobacter 2021; 26:e12844. [PMID: 34382277 DOI: 10.1111/hel.12844] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Failure of second or third-line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. AIMS To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment. METHODS Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. RESULTS A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). CONCLUSIONS As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Nayoung Kim
- Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ryoung Hee Nam
- Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jae Young Jang
- Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yonghoon Choi
- Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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20
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Yoon JY, Kwak MS, Jeon JW, Cha JM. Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study. TOHOKU J EXP MED 2021; 255:41-48. [PMID: 34526429 DOI: 10.1620/tjem.255.41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.
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Affiliation(s)
- Jin Young Yoon
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong
| | - Min Seob Kwak
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong
| | - Jung Won Jeon
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong
| | - Jae Myung Cha
- Department of Internal Medicine, Division of Gastroenterology, Kyung Hee University Hospital at Gang Dong
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21
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Seo JH, Park JS, Youn HS. Recent Changes in the Treatment of Helicobacter pylori Infection in Children and Adolescents. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Treatments aimed at eradicating Helicobacter pylori (H. pylori) infections in children and adolescents should be clearly beneficial. According to the updated guidelines, a 14-day triple therapy or bismuth-based triple therapy is the first choice for treatment of children based on the results of antimicrobial sensitivity testing. Though culturing H. pylori using biopsy specimens is not always feasible, it should be performed for establishing empirical rescue therapy for patients not responding to first-line eradication therapy. The European and North American therapeutic strategies for children and adolescents with H. pylori infections may not be appropriate for treating children and adolescents in other countries owing to regional differences in epidemiological characteristics of H. pylori. The existence of clarithromycin-resistant H. pylori is an important factor involved in eradication failure. The development of new treatment-related allergies, treatment failure, side effects, and alteration of the gut microbiome have been highlighted as factors potentially outweighing the possible benefit of preventing future peptic ulcers or gastric cancer. Drug compliance can be improved by providing a detailed explanation of the reason for therapy, duration, and routes of drug administration. Physicians should understand the mechanisms underlying eradication treatment and explain drug prescriptions in detail to both parents and children to increase compliance. Herein, we reviewed the indications for and various modalities of eradication treatment in children with H. pylori infections in accordance with a review of recently published articles.
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22
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Huang X, Liu Y, Lin Z, Wu B, Nong G, Chen Y, Lu Y, Ji X, Zhou X, Suo B, Chen Q, Wei J. Minimum inhibitory concentrations of commonly used antibiotics against Helicobacter Pylori: A multicenter study in South China. PLoS One 2021; 16:e0256225. [PMID: 34473713 PMCID: PMC8412354 DOI: 10.1371/journal.pone.0256225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/02/2021] [Indexed: 01/10/2023] Open
Abstract
Aim To determine the minimum inhibitory concentrations (MICs) of commonly used antibiotics against Helicobacter Pylori (H. pylori) in South China and compare their resistance rates by using EUCAST breakpoints and other breakpoints. Methods Patients who had not previously received H. pylori treatment in clinical centers in South China were enrolled in this study from 2017 to 2020. Gastric biopsies were obtained for H. pylori culture. The MICs of amoxicillin (AMX), clarithromycin (CLA), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET) and furazolidone (FZD) were tested by broth microdilution method and assessed by two different breakpoints. ATCC43504 standard strain served as a control. Results A total of 208 H. pylori strains were isolated from patients’ biopsy samples. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for H. pylori were 0.0156-256mg/L (MIC50 0.125mg/L, MIC90 4mg/L), 0.0156- >256 mg/L (MIC50 0.0312mg/L, MIC90 64mg/L), 0.0156- >256mg/L (MIC50 8mg/L, MIC90 256mg/L), 0.0156-256mg/L (MIC50 0.25mg/L, MIC90 16mg/L), 0.0156-256mg/L (MIC50 0.0625mg/L, MIC90 4mg/L), and 0.0156- >256mg/L (MIC50 0.0312mg/L, MIC90 2mg/L), respectively. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for ATCC43504 strain were 0.25mg/L, 0.0625mg/L, 64mg/L, 0.5mg/L, 1mg/L and 0.25mg/L, respectively. The resistance rate of FZD was 11.05%. The overall resistance rates according to EUCAST breakpoints and other breakpoints were 57.21% and 14.90% for AMX (p<0.001), 38.94% and 38.94% for CLA (p = 1), 39.42% and 50.96% for MTZ (p<0.001), 12.98% and 10.58% for TET (p = 0.025), 35.10% and 35.10% for LEV (p = 1), respectively. Conclusions Our results demonstrate that AMX, FZD, and TET, but not MTZ, CLR or LEV, showed good anti-H. pylori activity in vitro in South China. When different breakpoints were used, similar results were found with CLA, and LEV, but not with AMX, MTZ, or TET.
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Affiliation(s)
- Xueping Huang
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, Fujian, China
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Yuan Liu
- Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Zhihui Lin
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, Fujian, China
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Baihe Wu
- Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
| | - Gaohui Nong
- Department of Microbiology, Zhuhai Health School, Zhuhai, Guangdong, China
| | - Yushan Chen
- Department of Gastroenterology, Fuzhou First Hospital, Fuzhou, Fujian, China
| | - Yuping Lu
- Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, Fujian, China
- Department of Gastroenterology, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Xinhua Ji
- Department of Gastroenterology, Pucheng Hospital, Nanping, Fujian, China
| | - Xiang Zhou
- Department of Gastroenterology, Pucheng Hospital, Nanping, Fujian, China
| | - Biao Suo
- Department of Gastroenterology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Qiuzhao Chen
- Department of Gastroenterology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian, China
| | - Jinqi Wei
- Department of Gastroenterology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China
- * E-mail:
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23
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Cha B, Bang BW, Shin JB, Ko EJ, Ko W, Kwon KS, Shin YW, Suh YJ, Kim H. Bismuth containing quadruple therapy versus tailored therapy as first-line treatments for Helicobacter pylori infection in a high clarithromycin resistance area. Scand J Gastroenterol 2021; 56:1017-1022. [PMID: 34369255 DOI: 10.1080/00365521.2021.1948606] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Increasing clarithromycin resistance has led to the need for an alternative first-line therapy for the eradication of Helicobacter pylori (H. pylori) in Korea, and bismuth containing quadruple therapy (BQT) and tailored therapy (TT) have been proposed as alternative regimens. The aim of this study was to compare the eradication rates of BQT and TT as first-line H. pylori eradication therapies. METHODS H. pylori infection was diagnosed using the rapid urease test or dual-priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) during endoscopy. Patients positive for H. pylori were divided into two groups; those tested using the rapid urease test received empirical BQT (the BQT group) whereas those tested by DPO-PCR received TT (the TT group). Eradication rates, adverse events, and overall medical costs, which included diagnostic test and eradication regimen costs, were compared. RESULTS Three hundred and sixty patients were included in the study (TT group 178, BQT group 182). The modified intention-to-treat eradication rates of BQT and TT were 88.2% (142/161) and 80.3% (118/147), respectively (p = .055), and corresponding eradication rates in the per-protocol population were 88.8% (142/160) and 81.4% (118/145) (p = .07). Compliance and adverse event rates were similar in the two groups. Average medical costs were $90.3 per patient in the TT group and $75.5 in the BQT group (p = .000). CONCLUSIONS Empirical BQT and tailored therapy were similar in terms of H. pylori eradication rate, safety, and tolerability, but BQT was more cost-effective.
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Affiliation(s)
- Boram Cha
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Byoung Wook Bang
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Jong Beom Shin
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Eun Jung Ko
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Weonjin Ko
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Kye Sook Kwon
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Yong Woon Shin
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
| | - Young Ju Suh
- Department of Biostatistics, Inha University College of Medicine, Incheon, Republic of Korea
| | - Hyungkil Kim
- Department of Internal Medicine, Division of Gastroenterology, Inha University College Medicine, Incheon, Republic of Korea
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24
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Singh SP, Ahuja V, Ghoshal UC, Makharia G, Dutta U, Zargar SA, Venkataraman J, Dutta AK, Mukhopadhyay AK, Singh A, Thapa BR, Vaiphei K, Sathiyasekaran M, Sahu MK, Rout N, Abraham P, Dalai PC, Rathi P, Sinha SK, Bhatia S, Patra S, Ghoshal U, Poddar U, Mouli VP, Kate V. Management of Helicobacter pylori infection: The Bhubaneswar Consensus Report of the Indian Society of Gastroenterology. Indian J Gastroenterol 2021; 40:420-444. [PMID: 34219211 DOI: 10.1007/s12664-021-01186-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 04/20/2021] [Indexed: 02/04/2023]
Abstract
The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.
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Affiliation(s)
- Shivaram Prasad Singh
- Department of Gastroenterology, Srirama Chandra Bhanja Medical College and Hospital, Cuttack, 753 007, India.
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Showkat Ali Zargar
- Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190 011, India
| | - Jayanthi Venkataraman
- Department of Hepatology, Sri Ramachandra Medical Centre, No. 1 Ramachandra Nagar, Porur, Chennai, 600 116, India
| | - Amit Kumar Dutta
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore, 632 004, India
| | - Asish K Mukhopadhyay
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, 700 010, India
| | - Ayaskanta Singh
- Department of Gastroenterology, IMS and Sum Hospital, Bhubaneswar, 756 001, India
| | - Babu Ram Thapa
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Kim Vaiphei
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160 012, India
| | - Malathi Sathiyasekaran
- Department of Pediatric Gastroenterology, Kanchi Kamakoti Childs Trust Hospital, Chennai, 600 034, India
| | - Manoj K Sahu
- Department of Gastroenterology, IMS and Sum Hospital, Bhubaneswar, 756 001, India
| | - Niranjan Rout
- Department of Pathology, Acharya Harihar Post Graduate Institute of Cancer, Manglabag, Cuttack, 753 007, India
| | - Philip Abraham
- P D Hinduja Hospital and Medical Research Centre, Veer Savarkar Marg, Cadel Road, Mahim, Mumbai, 400 016, India
| | - Prakash Chandra Dalai
- Gastro and Kidney Care Hospital, IRC Village, Nayapalli, Bhubaneswar, 751 015, India
| | - Pravin Rathi
- Department of Gastroenterology, Topiwala National Medical College and B Y L Nair Charitable Hospital, Dr Anandrao Laxman Nair Marg, Mumbai, 400 008, India
| | - Saroj K Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Shobna Bhatia
- Department of Gastroenterology and Hepatobiliary Sciences, Sir HN Reliance Foundation Hospital and Research Centre, Raja Rammohan Roy Road, Prarthana Samaj, Girgaon, Mumbai, 400 004, India
| | - Susama Patra
- Department of Pathology, All India Institute of Medical Sciences, Patrapada, Bhubaneswar, 751 019, India
| | - Ujjala Ghoshal
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226 014, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Vikram Kate
- Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, 605 006, India
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25
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Li SY, Li J, Dong XH, Teng GG, Zhang W, Cheng H, Gao W, Dai Y, Zhang XH, Wang WH. The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: A retrospective study over 8 years in Beijing. Helicobacter 2021; 26:e12804. [PMID: 33860967 DOI: 10.1111/hel.12804] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/23/2021] [Accepted: 03/17/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.
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Affiliation(s)
- Si-Yu Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Jiang Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xin-Hong Dong
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Gui-Gen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Hong Cheng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wen Gao
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiao-He Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei-Hong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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26
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Kim SY, Park JM, Lim CH, Lee HA, Shin GY, Choe Y, Cho YK, Choi MG. Types of 23S Ribosomal RNA Point Mutations and Therapeutic Outcomes for Helicobacter pylori. Gut Liver 2021; 15:528-536. [PMID: 33376228 PMCID: PMC8283296 DOI: 10.5009/gnl20225] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 09/21/2020] [Accepted: 09/21/2020] [Indexed: 12/11/2022] Open
Abstract
Background/Aims Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori clarithromycin resistance. This study aimed to detect the prevalence of these point mutations and to investigate the role of different point mutations in the success of eradication therapy. Methods We retrospectively investigated a total of 464 consecutive patients who underwent an endoscopic examination and dual-priming oligonucleotide-based multiplex polymerase chain reaction for H. pylori between June 2014 and October 2019. For 289 patients with negative point mutations, standard triple therapy was used in 287 patients, and the bismuth-quadruple regimen was used in two patients. For 175 patients with positive point mutations (A2142G, A2143G, and both mutations), standard triple and bismuth-quadruple therapies were used in 37 patients and 138 patients, respectively. Results The eradication rates of standard triple and bismuth-quadruple therapies showed no significant difference in mutation-negative patients or those with the A2142G point mutation. However, the eradication rate with bismuth-quadruple therapy was significantly higher than that with standard triple therapy in the group with the A2143G mutation or with the double mutation. The eradication rates for standard triple and bismuth-quadruple therapies, respectively, were 25.8% and 92.1% in the per-protocol group (p<0.001) and 24.2% and 85.2% in the intention-totreat analysis (p<0.001). Conclusions The A2143G point mutation is the most prevalent cause of clarithromycin resistance. Bismuth-quadruple therapy is superior to standard triple therapy in patients with the A2143G or double point mutation.
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Affiliation(s)
- Sang Yoon Kim
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Jae Myung Park
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.,Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Ga-Yeong Shin
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Younghee Choe
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Yu Kyung Cho
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea
| | - Myung-Gyu Choi
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea.,Catholic Photomedicine Research Institute, College of Medicine, The Catholic University of Korea
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27
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence based guidelines for the treatment of Helicobacter pylori infection in Korea 2020. Korean J Intern Med 2021; 36:807-838. [PMID: 34092054 PMCID: PMC8273819 DOI: 10.3904/kjim.2020.701] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 05/06/2021] [Indexed: 01/10/2023] Open
Abstract
Helicobacter pylori infection is one of the most common infectious diseases worldwide. H. pylori is responsible for substantial gastrointestinal morbidity with a high disease burden. Since the revision of the H. pylori Clinical Practice Guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin based triple therapy. According to a nationwide randomized controlled study by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance to clarithromycin. The clinical practice guidelines for treatment of H. pylori were updated based on evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines were designed to provide clinical evidence for the treatment of H. pylori to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards, and will be revised if more evidence emerges in the future.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul,
Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul,
Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju,
Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan,
Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin,
Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Su Youn Nam
- Center for Gastric Cancer, Kyungpook National University Chilgok Hospital, Daegu,
Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon,
Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang,
Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul,
Korea
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28
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Kim YJ, Chung WC, Kim DB. Efficacy of bismuth added to standard triple therapy as the first-line eradication regimen for Helicobacter pylori infection. Helicobacter 2021; 26:e12792. [PMID: 33650225 DOI: 10.1111/hel.12792] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/04/2021] [Accepted: 02/05/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Addressing the increasing antibiotic resistance, including clarithromycin resistance, which affects Helicobacter pylori eradication therapy, is a challenge for clinicians. The objective of this study was to determine the efficacy of bismuth added to standard triple therapy as a first-line treatment regimen for Helicobacter pylori infection. The secondary outcome was the treatment efficacy for clarithromycin-resistant strains. MATERIAL AND METHODS A prospective study was undertaken from January to December 2019. A total of 107 patients with Helicobacter pylori infection were enrolled and received Helicobacter pylori eradication therapy with bismuth added to standard triple therapy for 14 days. We also evaluated the clarithromycin resistance rate by dual-priming oligonucleotide-based multiplex PCR and treatment efficacy. RESULTS A total of 104 patients completed standard triple therapy with bismuth added for Helicobacter pylori eradication. The eradication rates in the intention to treat and per-protocol analyses were 87.9% and 90.4%, respectively. The frequency of clarithromycin resistance was 33.6% (35/104), and the eradication rate was 77.1% in resistant strains (27/35). CONCLUSION Bismuth added to standard triple therapy could be acceptable as a first-line treatment regimen for Helicobacter pylori eradication in patients with clarithromycin-resistant strains. In particular, in areas with high clarithromycin tolerance, it is advisable to consider bismuth add-on therapy as the first-line treatment regimen.
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Affiliation(s)
- Yeon-Ji Kim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea
| | - Woo Chul Chung
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea
| | - Dae Bum Kim
- Department of Internal Medicine, St. Vincent Hospital, The Catholic University of Korea College of Medicine, Seoul, South Korea
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29
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Lee JW, Kim SJ, Choi CW, Kim HJ, Kang DH, Kim HW, Park SB, Nam HS, Ryu DG. Seven-day triple therapy is sufficient to eradicate infection caused by Helicobacter pylori without 23S rRNA point mutation. Medicine (Baltimore) 2021; 100:e26133. [PMID: 34032763 PMCID: PMC8154452 DOI: 10.1097/md.0000000000026133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 01/25/2021] [Accepted: 05/05/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Tailored therapy based on dual priming oligonucleotide-based polymerase chain reaction (DPO-PCR) can be considered an alternative to overcome the low eradication rate in high clarithromycin-resistance areas. The triple therapy (TT) duration of the tailored approach in most studies was 7 days for patients without point mutation. However, recent western guidelines have recommended a treatment duration of 14 days. The aim of this study was to compare the success rate of 7 and 14 days of TT for eradicating Helicobacter pylori without point mutation, as determined by DPO-PCR.Between Feb 2016 and Feb 2019, medical records of patients who underwent DPO-PCR were reviewed. Patients without point mutation as determined by DPO-PCR were enrolled in this study. The eradication success rate and adverse events were evaluated.A total of 366 patients without A2142G and A2143G point mutation were enrolled. The success rates of 7-day and 14-day TT were 88.4% (168/190) and 85.9% (151/176) by intention to treat analysis (P = .453) and 90.8% (168/185) and 90.4% (151/167) by per-protocol analysis (P = .900), respectively. The adverse event rates showed no significant difference between the 2 groups.In patients without point mutation based on DPO-PCR results, 7-day TT is as effective as 14-day TT. Therefore, 7 days may be considered as a cost-effective treatment duration in Korea.
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30
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020. Gut Liver 2021; 15:168-195. [PMID: 33468712 PMCID: PMC7960974 DOI: 10.5009/gnl20288] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/14/2020] [Accepted: 10/20/2020] [Indexed: 01/10/2023] Open
Abstract
Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world's population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Su Youn Nam
- Center for Gastric Cancer, Kyungpook National University Hospital Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
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Jeon JY, Kim SY, Moon SJ, Oh K, Lee J, Kim B, Song GS, Kim MG. Pharmacokinetic Interactions between Tegoprazan and Metronidazole/Tetracycline/Bismuth and Safety Assessment in Healthy Korean Male Subjects. Clin Ther 2021; 43:722-734. [PMID: 33637332 DOI: 10.1016/j.clinthera.2021.01.026] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth. METHODS An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed. FINDINGS Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUCτ and Cmax at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild. IMPLICATIONS Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.
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Affiliation(s)
- Ji-Young Jeon
- Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Sun-Young Kim
- Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Seol Ju Moon
- Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Kyeongmin Oh
- Division of Clinical Development, HK Inno.N Corp., Seoul, Republic of Korea
| | - Jiwon Lee
- Division of Clinical Development, HK Inno.N Corp., Seoul, Republic of Korea
| | - Bongtae Kim
- Division of Clinical Development, HK Inno.N Corp., Seoul, Republic of Korea
| | - Geun Seog Song
- Division of Clinical Development, HK Inno.N Corp., Seoul, Republic of Korea
| | - Min-Gul Kim
- Center for Clinical Pharmacology and Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, Republic of Korea; Department of Pharmacology, School of Medicine, Jeonbuk National University, Jeonju, Republic of Korea.
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Pih GY, Choi KD, Gong EJ, Na HK, Ahn JY, Lee JH, Jung KW, Kim DH, Song HJ, Lee GH, Jung HY. Modified bismuth quadruple therapy with low-dose metronidazole as first-line therapy for Helicobacter pylori infection. Helicobacter 2021; 26:e12759. [PMID: 33113240 DOI: 10.1111/hel.12759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/30/2020] [Accepted: 09/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Bismuth-containing quadruple therapy is an effective alternative first-line therapy for Helicobacter pylori infection. We evaluated the efficacy and safety of a modified twice-a-day bismuth quadruple regimen (BQT-2) with low-dose (1000 mg total) metronidazole as first-line therapy for the eradication of H pylori. MATERIALS AND METHODS In this prospective pilot study, patients diagnosed with H pylori infection and naïve to eradication therapy were included. The modified BQT-2 therapy consisted of rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily, given 30 minutes before morning and evening meals for 14 days. H pylori eradication was assessed by 13 C-urea breath test conducted at least 4 weeks after therapy completion. RESULTS In 66 patients who received the modified BQT-2 regimen, the compliance rate was 100% and the H pylori eradication rate was 77.3%. H pylori was successfully cultured in 50 (75.8%) patients. The resistance rates to metronidazole and clarithromycin were 30.0% and 22.0%, respectively. Eradication rates were not significantly different according to the resistance to metronidazole (metronidazole-susceptible: 74.3% [26/35], metronidazole-resistant: 73.3% [11/15]; P > .99). Most of the adverse events were mild, with 20 (30%) patients developing nausea, epigastric soreness, loose stool, asthenia, skin rash, dizziness, taste perversion, headache, or dyspepsia. CONCLUSIONS Twice-a-day modified BQT-2 regimen with low-dose metronidazole was suboptimal as an alternative first-line therapy for eradicating H pylori, despite high patient compliance.
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Affiliation(s)
- Gyu Young Pih
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence-based Guidelines for the Treatment of Helicobacter pylori Infection in Korea: 2020 Revised Edition. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2020. [DOI: 10.7704/kjhugr.2020.0045] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is one of the most common infectious diseases worldwide. Although its incidence is gradually decreasing, about half of the world's population still get infected. H. pylori infection is responsible for substantial gastrointestinal morbidity worldwide. It is the most common cause of gastric and duodenal ulcers as well as gastric cancer. Since the revision of the H. pylori Clinical Practice Guidelines in 2013, the eradication rate of H. pylori has gradually decreased with the use of classical triple therapy, wherein amoxicillin, clarithromycin, and proton pump inhibitors are administered, for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was due to increased antimicrobial resistance induced by the use of antibiotics, especially clarithromycin. The update of clinical practice guideline for treatment of H. pylori was developed based on evidence-based medicine by conducting a meta-analysis. The draft recommendations were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines are designed to provide patients, nurses, medical school students, policymakers, and clinicians with clinical evidence to guide primary care and treatment of H. pylori infection. These may differ from current medical insurance standards and will be revised further, if necessary, based on research-based evidence.
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Joo MK, Park CH, Kim JS, Park JM, Ahn JY, Lee BE, Lee JH, Yang HJ, Cho YK, Bang CS, Kim BJ, Jung HK, Kim BW, Lee YC. Clinical Guidelines for Drug-Related Peptic Ulcer, 2020 Revised Edition. Gut Liver 2020; 14:707-726. [PMID: 33191311 PMCID: PMC7667931 DOI: 10.5009/gnl20246] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/31/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023] Open
Abstract
Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer were previously developed in 2009 with the collaboration of the Korean College of Helicobacter and Upper Gastrointestinal Research and Korean Society of Gastroenterology. However, the previous guidelines were based mainly upon a review of the relevant literature and expert opinion. Therefore, the guidelines need to be revised. We organized a guideline Development Committee for drug-related peptic ulcer under the auspices of the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017 and developed nine statements, including four for NSAIDs, three for aspirin and other antiplatelet agents, and two for anticoagulants through a de novo process founded on evidence-based medicine that included a literature search and a meta-analysis, A consensus was reached through the application of the modified Delphi method. The primary target of these guidelines is adult patients undergoing long-term treatment with NSAIDs, aspirin or other antiplatelet agents and anticoagulants. The revised guidelines reflect the expert consensus and is intended to assist clinicians in the management and prevention of druginduced peptic ulcer and associated conditions.
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Affiliation(s)
- Moon Kyung Joo
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joon Sung Kim
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Myung Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, Asan Digestive Disease Research Institute, University of Ulsan College of Medicine, Seoul, Korea
| | - Bong Eun Lee
- Departments of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, Asan Digestive Disease Research Institute, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yu Kyung Cho
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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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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36
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Gudra D, Pupola D, Skenders G, Leja M, Radovica-Spalvina I, Gorskis H, Vangravs R, Fridmanis D. Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori-infected subjects before and 2 years after a single eradication event. Helicobacter 2020; 25:e12748. [PMID: 32776403 DOI: 10.1111/hel.12748] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 07/13/2020] [Accepted: 07/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND According to recent estimates 80% of Latvian population is infected with Helicobacter pylori thus their susceptibility to numerous gastric tract diseases is increased. The 1st line H. pylori eradication therapy includes treatment with clarithromycin in combination with amoxicillin or metronidazole and a proton pump inhibitor. However, potential adverse events caused by such therapies to microbiome are insufficiently studied. OBJECTIVE This study aimed to evaluate the long-term effect of H. pylori eradication on human gastrointestinal tract (GIT) microbiome. METHODS The assessment of H pylori eradication impact on GIT microbiome was done by analyzing 120 samples acquired from 60 subjects. Each individual was prescribed the following 10-day eradication regimen: Esomeprazolum 40 mg, Clarithromycinum 500 mg, and Amoxicillinum 1000 mg, BID. Samples from each individual were collected before starting H pylori eradication therapy, and 2 years after the completion of the therapy in OC-Sensor (Eiken Chemical Co.) sample collection containers and stored at -86°C. Prior to DNA extraction, the samples were lyophilized, and total DNA was extracted using FastDNA Spin Kit for Soil. 16S V3 rRNA gene sequencing was done employing Ion Torrent PGM, and the obtained raw sequences were analyzed using vsearch and R (phyloseq, cluster packages). RESULTS Alpha diversity measurements-observed OTUs, Chao1 and Shannon index did not differ significantly between the pre- and post-eradication states (two-tailed paired t test: P = .95; P = .71, P = .24, respectively). Unweighted and weighted UniFrac distances of beta diversity analysis indicated a non-specific pattern of sample clustering. Enterotype shift was observed for the majority of individuals comparing pre- and post-eradication study groups. Association analysis revealed that certain bacterial genera significantly correlated with age (eg, Dialister, Paraprevotella, Bifidobacterium), individual (eg, Thermotunica, Streptomyces, Faecalibacterium), and history of respiratory and/or allergic diseases (eg, Colinsella, Faecalibacterium). Redundancy analysis confirmed that the individual was a significant determinant of the subject's microbial community composition (ANOVA, 999 perm., P = .001) with the further lower impact of subject-specific medical history (eg, medication used as prescribed: P = .005, history of cardiovascular diseases: P = .005, history of respiratory, and/or allergic diseases: P = .015) and physiological (eg, age: P = .005, gender: P = .02) parameters. In the post-eradication study group, number of influential genera (n = 260) was increased compared to the pre-eradication study group (n = 209). CONCLUSION Modest global differences at the community level exist between individuals before and after the eradication therapy; however, the microbiome structure is more related to the subject-specific parameters rather than by the eradication therapy itself.
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Affiliation(s)
- Dita Gudra
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Darta Pupola
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Girts Skenders
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.,Faculty of Medicine, University of Latvia, Riga, Latvia
| | | | - Henrihs Gorskis
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Reinis Vangravs
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
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The Prevalence of Multidrug Resistance of Helicobacter pylori and Its Impact on Eradication in Korea from 2017 to 2019: A Single-Center Study. Antibiotics (Basel) 2020; 9:antibiotics9100646. [PMID: 32992624 PMCID: PMC7601770 DOI: 10.3390/antibiotics9100646] [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: 09/08/2020] [Revised: 09/21/2020] [Accepted: 09/26/2020] [Indexed: 01/10/2023] Open
Abstract
Antimicrobial resistance is one of the major factors determining the efficacy of Helicobacter pylori eradication therapy. This study aimed to estimate the recent prevalence of multidrug resistance of H. pylori and its impact on eradication in Korea. A total of 174 patients were prospectively enrolled at Chung-Ang University Hospital from 2017 to 2019. H. pylori strains were isolated from the gastric body and antrum. The minimum inhibitory concentrations of antibiotics were determined by the serial twofold agar dilution method. Eradication results were reviewed and analyzed in connection with antibiotic resistance. The prevalence of H. pylori infection was 51.7% (90/174). The culture success rate was 77.8% (70/90). The resistance rates for clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and moxifloxacin were 28.6% (20/70), 27.1% (19/70), 20.0% (14/70), 18.6% (13/70), 42.9% (30/70), and 42.9% (30/70), respectively. The multidrug resistance (resistance to two or more classes of antimicrobials) rate was 42.9% (30/70). Dual resistance to clarithromycin and metronidazole was confirmed in 8.6% (6/70). Eradication with a first-line treatment was successful in 75% (36/48), and those who received second-line treatment all achieved successful eradication. The rate of multidrug resistance is increasing, and standard triple therapy (STT) is no longer an acceptable first-line option for H. pylori eradication in Korea.
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38
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Joo MK, Park CH, Kim JS, Park JM, Ahn JY, Lee BE, Lee JH, Yang HJ, Cho YK, Bang CS, Kim BJ, Jung HK, Kim BW, Lee YC. [Clinical Guidelines for Drug-induced Peptic Ulcer, 2020 Revised Edition]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2020; 76:108-133. [PMID: 32969360 DOI: 10.4166/kjg.2020.76.3.108] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/08/2020] [Accepted: 07/08/2020] [Indexed: 12/18/2022]
Abstract
The Korean guidelines for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers were previously developed under co-work with the Korean College of Helicobacter and Upper Gastrointestinal Research and Korean Society of Gastroenterology at 2009. On the other hand, the previous guidelines were based mainly on a literature review and expert opinions. Therefore, the guidelines need to be revised. In this study, a guideline development committee for drug-induced peptic ulcers was organized under the Korean College of Helicobacter and Upper Gastrointestinal Research in 2017. Nine statements were developed, including four for NSAID, three for aspirin and other antiplatelet agents, and two for anticoagulants through de novo processes based on evidence-based medicine, such as a literature search, meta-analysis, and the consensus was established using the modified Delphi method. The primary target of this guideline was adult patients taking long-term NSAIDs, aspirin, or other antiplatelet agent and anticoagulants. The revised guidelines reflect the consensus of expert opinions and are intended to assist relevant clinicians in the management and prevention of drug-induced peptic ulcers and associated conditions.
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Affiliation(s)
- Moon Kyung Joo
- Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Joon Sung Kim
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Myung Park
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yu Kyung Cho
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Woman's University, Seoul, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Bang CS, Lim H, Jeong HM, Shin WG, Choi JH, Soh JS, Kang HS, Yang YJ, Hong JT, Shin SP, Suk KT, Lee JJ, Baik GH, Kim DJ. Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection. Gut Microbes 2020; 11:1314-1323. [PMID: 32362221 PMCID: PMC7524369 DOI: 10.1080/19490976.2020.1754118] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/17/2020] [Accepted: 03/30/2020] [Indexed: 02/08/2023] Open
Abstract
AIM To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
| | - Hyun Lim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Hae Min Jeong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Jae Ho Choi
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
| | - Jae Seung Soh
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ho Suk Kang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Young Joo Yang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ji Taek Hong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Suk Pyo Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Jae Jun Lee
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
- Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
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Lee GH, Lee KM, Shin SJ, Kang JK, Noh CK, Kim JH, Lim SG. Impact of previous metronidazole exposure on metronidazole-based second-line quadruple therapy for Helicobacter pylori infection. Korean J Intern Med 2020; 35:1094-1103. [PMID: 32921010 PMCID: PMC7487300 DOI: 10.3904/kjim.2020.174] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 07/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS The negative effects on the eradication success of Helicobacter pylori infection after previous exposure to macrolides, including clarithromycin on clarithromycin-based first-line therapy have been demonstrated. However, whether this is true for metronidazole-based second-line quadruple therapy remains unclear. We investigated the relationship between past administration of metronidazole and the failure of metronidazole-based second-line quadruple therapy in patients with H. pylori infection. METHODS Patients over 20 years of age who were diagnosed with H. pylori infection between January 1998 and March 2016 were enrolled in this study. The relationship between the clinical parameters and the results of a C13-urea breath test after metronidazole-based second-line quadruple therapy was analyzed in patients for whom clarithromycin-based triple therapy failed to eradicate H. pylori. RESULTS The H. pylori eradication failure rate was significantly higher in patients with a history of metronidazole use than in patients without a history of metronidazole use (p = 0.011). Multivariable analysis showed that the odds ratio of previous metronidazole use for eradication failure was 3.468 (95% confidence interval, 1.391 to 8.649; p = 0.008). In the subgroup analysis of patients with a history of metronidazole use, the duration of metronidazole use and interval between its use and eradication therapy did not significantly affect H. pylori eradication failure. CONCLUSION Previous exposure to metronidazole was a significant risk factor for treatment failure of metronidazole-based second-line quadruple therapy; therefore, this should be considered when establishing a treatment strategy for patients with H. pylori infection.
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Affiliation(s)
- Gil Ho Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Kee Myung Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Jae Shin
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Joon Koo Kang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jin Hong Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sun Gyo Lim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
- Correspondence to Sun Gyo Lim, M.D. Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro,
Yeongtong-gu, Suwon 16499, Korea Tel: +82-31-219-6939 Fax: +82-31-219-5999 E-mail:
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Kong S, Huang K, Wang J, Wang X, Yang N, Dong Y, Zhuang Y, Dang Y, Zhang G, Ye F. Efficacy of tailored second-line therapy of Helicobacter pylori eradication in patients with clarithromycin-based treatment failure: a multicenter prospective study. Gut Pathog 2020; 12:39. [PMID: 32874206 PMCID: PMC7456506 DOI: 10.1186/s13099-020-00378-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Accepted: 08/19/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. METHODS Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. RESULTS From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n = 182) than in the LBQT group (n = 182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P < 0.001) and per protocol (PP) analysis (91.1% vs. 67.8%, P < 0.001). Among patients in the TBQT group with levofloxacin susceptibility, eradication rates were similar in the ALEB (n = 51) and AFEB (n = 50) subgroups according to both the ITT (86.3% vs. 90.0%, P = 0.56) and PP (88.0% vs. 90.0%, P = 0.75) analyses. Isolated clarithromycin and levofloxacin resistance rates were 57.7% and 44.5%, respectively. The total clarithromycin and levofloxacin resistance rate in strains with dual or triple resistance was 35.7%. CONCLUSIONS TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance.Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR1900027743.
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Affiliation(s)
- Siya Kong
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Keting Huang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Jun Wang
- Department of Gastroenterology and Hepatology, Jinhu County People’s Hospital, Huaian, China
| | - Xiaoyong Wang
- Department of Gastroenterology, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou, China
| | - Ningmin Yang
- Jiangsu Zhiyuan Inspection Medical Institute, Nanjing, China
| | - Yu Dong
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
| | - Ya Zhuang
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Yini Dang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Guoxin Zhang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Feng Ye
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, 210029 Nanjing, China
- First Clinical Medical College of Nanjing Medical University, Nanjing, China
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Dang NQH, Ha TMT, Nguyen ST, Le NDK, Nguyen TMT, Nguyen TH, Pham TTH, Tran VH. High rates of clarithromycin and levofloxacin resistance of Helicobacter pylori in patients with chronic gastritis in the south east area of Vietnam. J Glob Antimicrob Resist 2020; 22:620-624. [PMID: 32590188 DOI: 10.1016/j.jgar.2020.06.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 04/12/2020] [Accepted: 06/10/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The increasing rates of clarithromycin (CLR)- and levofloxacin (LVX)-resistant Helicobacter pylori are the main causes of the considerable decrease in the eradication rates of triple therapy and LVX-based regimens. The aims of this study were to determine the rates of CLR- and LVX-resistant H. pylori by the Epsilometer test and to assess the risk factors for this antibiotic resistance among patients with chronic gastritis in the south east area of Vietnam. METHODS Gastric biopsy specimens were obtained from 153 patients with H. pylori-positive chronic gastritis for use in culture and in the Epsilometer test to determine CLR and LVX susceptibilities. RESULTS The rates of H. pylori resistance to CLR and LVX were 72.6% and 40.5%, respectively. Dual-resistant H. pylori (to both CLR and LVX) accounted for 30.7% of patients. The rates of high-level resistance to CLR and LVX were 18.9% and 83.9%, respectively. Multivariate analysis showed that age older than 30 years (odds ratio [OR] = 3.80, 95% confidence interval [CI] 1.61-8.97) and history of H. pylori treatment (OR = 8.72, 95% CI 1.90-39.91) were independent risk factors for CLR resistance, whereas only age older than 35 years (OR = 2.42, 95% CI 1.23-4.76) was an independent risk factor for LVX resistance. CONCLUSIONS These results revealed high rates of resistance of H. pylori to CLR and LVX in patients with chronic gastritis in the south east area of Vietnam. This suggests that CLR-based triple therapy should not be used for the eradication treatment of H. pylori, and LVX susceptibility testing of H. pylori strains should be performed before choosing alternative regimens.
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Affiliation(s)
- Ngoc Quy Hue Dang
- Department of Gastroenterology, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Thi Minh Thi Ha
- Department of Medical Genetics, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; Institute of Biomedicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam.
| | - Si-Tuan Nguyen
- Department of Microbiology, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Nguyen Dang Khoa Le
- Department of Endoscopy, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Thi Minh Thi Nguyen
- Department of Endocrinology, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Thanh Hai Nguyen
- Department of Pathology, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Thi Thu Hang Pham
- Department of Microbiology, Thong Nhat General Hospital, Bien Hoa City, Dong Nai Province, Vietnam.
| | - Van Huy Tran
- Department of Internal Medicine, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam.
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Kasahun GG, Demoz GT, Desta DM. Primary Resistance Pattern of Helicobacter pylori to Antibiotics in Adult Population: A Systematic Review. Infect Drug Resist 2020; 13:1567-1573. [PMID: 32547126 PMCID: PMC7266407 DOI: 10.2147/idr.s250200] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Helicobacter pylori is a spiral-shaped gram-negative bacteria associated with peptic ulcer, gastritis and gastric cancer. The global burden and occurrence of H. pylori infection remains prevalent and worldwide. Despite this, the trend of the bacterial resistance is not recently studied which can help in the adoption of global, regional and local prevention strategies. Objective The aim of the study was to systematically review the existing published literature that presents the estimate of H. pylori antibiotic resistance. Methods A protocol was primarily registered in PROSPERO International prospective register of systematic reviews and has given a registration number CRD42017068710. It was registered after checking whether there was similar study being conducted. A database search (PubMed/Medline and Google scholar) was used to collect relevant articles. A standardized form was prepared for the extraction of relevant data from studies which fulfilled the eligibility criteria. A National Institute for Health research (NIH)-based quality assessment tool was utilized to assess the quality of studies included in the study. Results Our searching process has retrieved a total of 288 publications which later resulted in 38 articles for full-text review. Among the 38 articles reviewed in full text, 14 studies were included which fulfilled the inclusion criteria. H.pylori-pooled overall prevalence rate of antibiotic resistance was found to be 4.55% (95% confidence interval (CI): 3.96–5.22%) to amoxicillin, 27.22% (95% CI: 25.89–28.58%) to clarithromycin, 39.66% (95% CI: 38.20–41.15%) to metronidazole, and 22.48% (95% CI: 21.24–23.76%) to levofloxacin. Conclusion The primary antibiotic resistance pattern of H. pylori is increasing worldwide. Thus, implementation of local drug susceptibility surveillance program, rational prescribing and use of antibiotics are necessary.
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Affiliation(s)
| | - Gebre Teklemariam Demoz
- Clinical Pharmacy Unit, School of Pharmacy, College of Health Science, Aksum University, Aksum, Ethiopia
| | - Desilu Mahari Desta
- Clinical Pharmacy Unit, School of Pharmacy, College of Health Science, Mekelle University, Mekelle, Ethiopia
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Chang YW, Park YM, Oh CH, Oh SJ, Cho JH, Kim JW, Jang JY. Effects of probiotics or broccoli supplementation on Helicobacter pylori eradication with standard clarithromycin-based triple therapy. Korean J Intern Med 2020; 35:574-581. [PMID: 31830776 PMCID: PMC7214376 DOI: 10.3904/kjim.2019.139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 07/31/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS The eradication failure rate of standard triple therapy (proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has increased owing to antibiotic resistance in Korea. We assessed whether Saccharomyces boulardii probiotic or broccoli sprout extract sulforaphane supplementation could increase the H. pylori eradication rate and/or reduce antibiotic-associated adverse events. METHODS A total of 217 patients with H. pylori-positive chronic gastritis or peptic ulcer disease were recruited. Clarithromycin resistance was assessed in all patients by testing for A2142G and A2143G point mutations in H. pylori 23S rRNA using a dual-priming polymerase chain reaction (PCR) oligonucleotide. Thirty-four patients (17.3%) were clarithromycin-resistant and were excluded from the study. Finally, 183 patients with infections not resistant to clarithromycin were randomly assigned to triple therapy only (group A, n = 61), triple therapy plus probiotics (group B, n = 61), or triple therapy plus sulforaphane (group C, n = 61) groups. CYP2C19 polymorphisms were examined at position G681A of exon 5 and G636A of exon 4 by PCR with restriction fragment length polymorphism (PCR-RFLP) analysis. H. pylori eradication was assessed by 13C-urea breath test 4 weeks after treatment completion. RESULTS The eradication rates were similar among the groups both in the intention- to-treat (A = 85.2%, B = 89.6%, and C = 81.6%) and per-protocol (A = 89.2%, B = 86.8%, and C = 96.3%) analyses. The frequencies of overall adverse events in the groups also did not differ (A vs. B: p = 0.574; A vs. C: p = 1.000). CONCLUSION Probiotic or sulforaphane with triple therapy for H. pylori infection neither increased the eradication rate nor reduced the occurrence of adverse events.
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Affiliation(s)
- Young Woon Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
| | - Yoo Min Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
| | - Chi Hyuk Oh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
- Correspondence to Chi Hyuk Oh, M.D. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, 23 Kyungheedae-ro, Dongdaemungu, Seoul 02447, Korea Tel: +82-2-958-8114 Fax: +82-2-958-8147 E-mail:
| | - Shin Ju Oh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
| | - Jun-Hyung Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jung-Wook Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
| | - Jae-Young Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea
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Mori H, Suzuki H. Update on quinolone-containing rescue therapies for Helicobacter pylori infection. World J Gastroenterol 2020; 26:1733-1744. [PMID: 32351290 PMCID: PMC7183861 DOI: 10.3748/wjg.v26.i15.1733] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/05/2020] [Accepted: 04/04/2020] [Indexed: 02/06/2023] Open
Abstract
Third generation of quinolones, such as levofloxacin and moxifloxacin, -containing regimens are often used in second-line or rescue treatment of Helicobacter pylori infection. However, the increasing antibiotic resistance to quinolones affects the efficacies of quinolones-containing therapies in recent years. Therefore, there is a need to enhance the effectiveness of quinolones-containing therapies. Sitafloxacin, a fourth-generation quinolone, and vonoprazan, a novel potassium-competitive acid blocker, are now available as more effective treatment options. The aim of this paper is to summarize the current evidence of quinolone-containing therapies in rescue treatments, and to discuss the importance of drug sensitivity tests or analysis of gyrA mutation before treatments.
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Affiliation(s)
- Hideki Mori
- Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven 3000, Belgium
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan
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Khien VV, Thang DM, Hai TM, Duat NQ, Khanh PH, Ha DT, Binh TT, Dung HDQ, Trang TTH, Yamaoka Y. Management of Antibiotic-Resistant Helicobacter pylori Infection: Perspectives from Vietnam. Gut Liver 2020; 13:483-497. [PMID: 31009957 PMCID: PMC6743798 DOI: 10.5009/gnl18137] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 11/13/2018] [Accepted: 11/27/2018] [Indexed: 12/15/2022] Open
Abstract
Antibiotic resistance is the most important factor leading to the failure of eradication regimens. This review focuses on the prevalence of Helicobacter pylori primary and secondary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and multidrug in Vietnam. We searched the PubMed, EMBASE, Vietnamese National Knowledge Infrastructure, and Vietnamese Biomedical databases from January 2000 to December 2016. The search terms included the following: H. pylori infection, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and multidrug) resistance in Vietnam. The data were summarized in an extraction table and analyzed manually. Finally, Excel 2007 software was used to create charts. Ten studies (three studies in English and seven in Vietnamese) were included in this review. A total of 308, 412, 523, 408, 399, and 268 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and multidrug resistance, respectively. Overall, the primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and multidrug resistance were 15.0%, 34.1%, 69.4%, 27.9%, 17.9% and 48.8%, respectively. Secondary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and multidrug resistance were 9.5%, 74.9%, 61.5%, 45.7%, 23.5% and 62.3%, respectively. In Vietnam, primary and secondary resistance to H. pylori is increasing over time and affects the effectiveness of H. pylori eradication.
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Affiliation(s)
- Vu Van Khien
- Departments of GI Endoscopy, 108 Central Hospital, Hanoi, Vietnam
| | - Duong Minh Thang
- Departments of GI Endoscopy, 108 Central Hospital, Hanoi, Vietnam
| | - Tran Manh Hai
- Departments of Molecular Biology, 108 Central Hospital, Hanoi, Vietnam.,University of Science and Technology of Hanoi, Hanoi, Vietnam
| | | | - Pham Hong Khanh
- Department of Gastroenterology, 103 Hospital, Hanoi, Vietnam
| | - Dang Thuy Ha
- Department of Gastroenterology, National Children Hospital, Hanoi, Vietnam
| | - Tran Thanh Binh
- Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | - Ho Dang Quy Dung
- Department of Endoscopy, Cho Ray Hospital, Ho Chi Minh City, Vietnam
| | | | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Oita, Japan
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Kim TH, Park JM, Cheung DY, Oh JH. Comparison of 7- and 14-Day Eradication Therapy for Helicobacter pylori with First- and Second-Line Regimen: Randomized Clinical Trial. J Korean Med Sci 2020; 35:e33. [PMID: 32030921 PMCID: PMC7008067 DOI: 10.3346/jkms.2020.35.e33] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 12/24/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Although Helicobacter pylori is a key cause of gastric cancer development, its eradication rate has been decreasing by standard regimens. For successful eradication, duration of treatment has been issued for overcoming antibiotics resistance. We were to compare the eradication rate of 7-day vs. 14-day treatment in first- and second-line regimens. METHODS This study was an open-label randomized controlled trial. A total of 369 H. pylori-infected patients were enrolled and assigned either to 7-day or 14-day proton pump inhibitor (PPI)-based standard triple therapy (STT; PPI-clarithromycin-amoxicillin). Bismuth-containing quadruple therapy was used as second-line therapy. Eradication success was defined as a negative 13C-urea breath test. RESULTS In first-line treatment, eradication rate was 78.5% (106/135) and 78.6% (114/143) in the 7-day and 14-day treatment in per-protocol (PP) analysis (P = 0.805). In intention-to-treat (ITT) analysis, eradication rate was 64.0% (114/178) and 66.0% (126/191), respectively (P = 0.924). There was no significant difference in drug compliance (81.5% vs. 84.3%, P = 0.320). In second-line therapy, eradication rate was not significantly different in both treatments of PP analysis (91.7% [33/36] vs. 100% [45/45], P = 0.084). In the ITT analysis, eradication rate was 79.6% (35/44) and 90.4% (47/52), respectively (P = 0.080). Drug compliances were not significantly different between the two groups (95.5% vs. 98.1%, P = 0.728). CONCLUSION PPI-based STT for H. pylori is not efficient as a first-line therapy both in 7 days and 14 days in Korea. Although bismuth-containing quadruple therapy for 14 days as a second line therapy tend to show higher eradication rate compared to 7-day therapy, this should be elucidated by further larger scaled studies. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02487511.
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Affiliation(s)
- Tae Ho Kim
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Myung Park
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dae Young Cheung
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Hwan Oh
- Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Helicobacter pylori Eradication According to Sequencing-Based 23S Ribosomal RNA Point Mutation Associated with Clarithromycin Resistance. J Clin Med 2019; 9:jcm9010054. [PMID: 31881688 PMCID: PMC7019680 DOI: 10.3390/jcm9010054] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 12/19/2019] [Accepted: 12/23/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS Clarithromycin resistance in Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. We investigated the point mutations in the 23S rRNA genes of patients with clarithromycin-resistant H. pylori and compared the H. pylori eradication rates based on the point mutations. METHODS A total of 431 adult patients with H. pylori infection were recruited in Kangdong Sacred Heart Hospital in 2017 and 2018. Patients who did not have point mutations related to clarithromycin resistance and/or had clinically insignificant point mutations were treated with PAC (proton pump inhibitor, amoxicillin, clarithromycin) for seven days, while patients with clinically significant point mutations were treated with PAM (proton pump inhibitor, amoxicillin, metronidazole) for seven days. H. pylori eradication rates were compared. RESULTS Sequencing-based detection of point mutations identified four mutations that were considered clinically significant (A2142G, A2142C, A2143G, A2143C). The clarithromycin resistance rate was 21.3% in the overall group of patients. A2143G was the most clinically significant point mutation (84/431, 19.5%), while T2182C was the most clinically insignificant point mutation (283/431, 65.7%). The overall H. pylori eradication rate was 83.7%, and the seven-day PAM-treated clarithromycin-resistance group showed a significantly lower eradication rate than the seven-day PAC-treated nonresistance group (ITT; 55.4% (51/92) vs. 74.3% (252/339), p = 0.001, PP; 66.2% (51/77) vs. 88.4% (252/285), p = 0.0001). CONCLUSIONS There were significantly lower eradication rates in the patients with clarithromycin-resistant H. pylori when treated with PAM for seven days. A future study comparing treatment regimens in clarithromycin-resistant H. pylori-infected patients may be necessary.
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Lee JY, Kim N, Nam RH, In Choi S, Lee JW, Lee DH. Primary and secondary antibiotic resistance of Helicobacter pylori in Korea from 2003 to 2018. Helicobacter 2019; 24:e12660. [PMID: 31507036 DOI: 10.1111/hel.12660] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 08/07/2019] [Accepted: 08/08/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Antimicrobial resistance of Helicobacter pylori (H pylori) affects the efficacy of eradication therapy. The aim of this study was to estimate the prevalence of primary and secondary resistance of H pylori isolates to antibiotics in Korea. METHODS The present study was performed from 2003 to 2018. Primary resistance was evaluated in 591 patients without any history of eradication and secondary resistance in 149 patients from whom Helicobacter pylori was cultured after failure of eradication. A minimal inhibitory concentration test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin using the agar dilution method. RESULTS An increase in the primary resistance rate was found in clarithromycin (P < .001), metronidazole (P < .001), and both levofloxacin (P < .001) during the study period. The primary resistance rates of amoxicillin and tetracycline were low and stable during the study period. The secondary resistance rate significantly increased in metronidazole and levofloxacin (P = .022 and .039, respectively). CONCLUSIONS The primary and secondary resistance rates of clarithromycin, metronidazole, and levofloxacin for Helicobacter pylori in Korea were high and increased over time. However, the primary and secondary resistance rates of amoxicillin and tetracycline were low and stable over time. These results will help in selecting effective eradication regimens of H pylori in Korea in the future.
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Affiliation(s)
- Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.,Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - Soo In Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea
| | - Jung Won Lee
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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Farzi N, Yadegar A, Sadeghi A, Asadzadeh Aghdaei H, Marian Smith S, Raymond J, Suzuki H, Zali MR. High Prevalence of Antibiotic Resistance in Iranian Helicobacter pylori Isolates: Importance of Functional and Mutational Analysis of Resistance Genes and Virulence Genotyping. J Clin Med 2019; 8:2004. [PMID: 31744181 PMCID: PMC6912791 DOI: 10.3390/jcm8112004] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/11/2019] [Accepted: 11/14/2019] [Indexed: 12/14/2022] Open
Abstract
The high prevalence of antibiotic resistance in Helicobacter pylori has become a great challenge in Iran. The genetic mutations that contribute to the resistance have yet to be precisely identified. This study aimed to investigate the prevalence of antibiotic resistance and virulence markers in Iranian H. pylori isolates and to analyze if there is any association between resistance and genotype. Antibiotic susceptibility patterns of 68 H. pylori isolates were investigated against metronidazole, clarithromycin, amoxicillin, rifampicin, ciprofloxacin, levofloxacin, and tetracycline by the agar dilution method. The frxA, rdxA, gyrA, gyrB, and 23S rRNA genes of the isolates were sequenced. The virulence genotypes were also determined using PCR. Metronidazole resistance was present in 82.4% of the isolates, followed by clarithromycin (33.8%), ciprofloxacin (33.8%), rifampicin (32.4%), amoxicillin (30.9%), levofloxacin (27.9%), and tetracycline (4.4%). Overall, 75% of the isolates were resistant to at least two antibiotics tested and considered as a multidrug resistance (MDR) phenotype. Most of the metronidazole-resistant isolates carried frameshift mutations in both frxA and rdxA genes, and premature termination occurred in positions Q5Stop and Q50Stop, respectively. Amino acid substitutions M191I, G208E, and V199A were predominantly found in gyrA gene of fluoroquinolone-resistant isolates. A2143G and C2195T mutations of 23S rRNA were found in four clarithromycin-resistant isolates. Interestingly, significant associations were found between resistance to metronidazole (MNZ) and cagA-, sabA-, and dupA-positive genotypes, with p = 0.0002, p = 0.0001, and p = 0.0001, respectively. Furthermore, a significant association was found between oipA "on" status and resistance to amoxicillin (AMX) (p = 0.02). The prevalence of H. pylori antibiotic resistance is high in our region, particularly that of metronidazole, clarithromycin, ciprofloxacin, and MDR. Simultaneous screening of virulence and resistance genotypes can help clinicians to choose the appropriate therapeutic regime against H. pylori infection.
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Affiliation(s)
- Nastaran Farzi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran; (A.S.); (M.R.Z.)
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran;
| | - Sinéad Marian Smith
- School of Medicine & School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland;
| | - Josette Raymond
- Bacteriology, University of Paris-Descartes, Cochin Hospital, 75006 Paris, France;
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan;
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran; (A.S.); (M.R.Z.)
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