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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 I, Shin YR, Kim JS, Kim BW, Maeng LS, Kim JM. Detection of Clarithromycin Resistance in Helicobacter pylori Using MmaxSure™ H. pylori & ClaR Assay. Dig Dis 2024; 42:292-298. [PMID: 38599188 PMCID: PMC11250404 DOI: 10.1159/000538655] [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: 12/16/2023] [Accepted: 03/27/2024] [Indexed: 04/12/2024]
Abstract
INTRODUCTION Clarithromycin resistance is a crucial factor in the eradication of Helicobacter pylori. This study aimed to evaluate the performance of MmaxSure™ H. pylori & ClaR Assay (MmaxSure™) in the diagnosis and detection of clarithromycin resistance in H. pylori. METHODS Subjects who underwent esophagogastroduodenoscopy between April 2020 and October 2022 were enrolled. The diagnostic performances of MmaxSure™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with the rapid urease test and culture. Secondary gene sequencing analysis was performed in discordant cases of PCR tests. RESULTS A total of 156 gastric biopsy samples were analyzed. In H. pylori detection, MmaxSure™ showed a 95.9% sensitivity (95% CI: 90.6-98.6), a 42.7% specificity (95% CI: 26.3-60.7), and a kappa value of 0.457. For the detection of A2143G mutation samples, MmaxSure™ showed a 91.2% sensitivity (95% CI: 76.3-98.1), a 93.4% specificity (95% CI: 87.5-97.1), and a kappa value of 0.804. There were a total of 10 discordant cases compared to gene sequencing in A2143G mutation detection for MmaxSure™. CONCLUSION In this study, MmaxSure™ showed comparable diagnostic performance to DPO-PCR in the detection of the H. pylori and A2143G mutation. Further research is needed to confirm the clinical effectiveness of the MmaxSure™ assay in H. pylori eradication.
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Affiliation(s)
- Ilsoo Kim
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea,
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea,
| | - Yu Ri Shin
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Wook Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Lee-So Maeng
- Department of Hospital Pathology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Min Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Nguyen TC, Le GKN, Pham DTH, Pham BV, Nguyen LTH, Che TH, Nguyen HT, Truong DQ, Robert A, Bontems P, Nguyen PNV. Antibiotic resistance and heteroresistance in Helicobacter pylori isolates from symptomatic Vietnamese children: A prospective multicenter study. Helicobacter 2023; 28:e13009. [PMID: 37497797 DOI: 10.1111/hel.13009] [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: 04/18/2023] [Revised: 06/26/2023] [Accepted: 07/19/2023] [Indexed: 07/28/2023]
Abstract
BACKGROUND Antibiotic resistance of Helicobacter pylori (H. pylori) is increasing worldwide, with geographical variations, impacting the treatment outcomes. This study assessed the antibiotic resistance patterns of H. pylori in Vietnamese children. MATERIALS AND METHODS Symptomatic children undergoing gastroduodenoscopy at two tertiary Children's Hospitals in Ho Chi Minh City were recruited. Antral and corpus biopsies were obtained and cultured separately. Susceptibility to amoxicillin (AMO), clarithromycin (CLA), metronidazole (MET), levofloxacin (LEV), and tetracycline (TET) was determined using E-test. Polymerase chain reaction was performed on another antral biopsy to detect the urease gene, cytotoxin-associated gene A (cagA), vacuolating cytotoxin A (vacA) genotypes, and 23S rRNA mutations conferring CLA resistance. RESULTS Among 123 enrolled children, a high primary resistance rate was found for CLA (68.5%, 61/89), followed by LEV (55.1%), MET (31.5%), AMO (25.8%), and TET (1.1%). Secondary resistance rates were 82.1% (7/28), 71.4%, 53.6%, and 3.6% for CLA, LEV, MET, and TET, respectively. Multidrug resistance was frequent (67.7%), with common patterns including CLA + LEV (20.3%) and CLA + MTZ + LEV (15.2%). Heteroresistance was detected in eight children (6.5%). The A2143G mutation was detected in 97.5% (119/122) of children. 86.1% of children had positive cagA strains and 27.9% had multiple vacA genotypes. No factor was significantly associated with antibiotic resistance. CONCLUSIONS The alarming rate of antibiotic resistance for H. pylori, especially for CLA, with emerging multi- and hetero-resistant strains, pose a major treatment challenge that precludes CLA use as empirical therapy. Biopsies from both antrum and corpus can improve H. pylori culture, allowing tailored treatment based on antimicrobial susceptibility.
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Affiliation(s)
- Tu Cam Nguyen
- Department of Gastroenterology, City Children's Hospital, Ho Chi Minh City, Vietnam
- Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Giao Kim Ngoc Le
- Department of Microbiology and Parasitology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Dao Thi Hong Pham
- Department of Genetics, University of Science - Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Bao Van Pham
- Department of Microbiology and Parasitology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Loan Thi Hong Nguyen
- Department of Gastroenterology, Children's Hospital 2, Ho Chi Minh City, Vietnam
| | - Thai Hoang Che
- Department of Biostatistics and Informatics, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Hiep Thanh Nguyen
- Faculty of Public Health, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Dinh Quang Truong
- Department of Surgery, City Children's Hospital, Ho Chi Minh City, Vietnam
| | - Annie Robert
- Institut de recherche expérimentale et clinique, Pôle d'épidémiologie et Biostatistique, Université catholique de Louvain, Brussels, Belgium
| | - Patrick Bontems
- Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium
- Department of Gastroenterology, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium
| | - Phuong Ngoc Van Nguyen
- Department of Biostatistics and Informatics, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
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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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Karmakar BC, Paul S, Basak S, Ghosh M, Mukherjee P, Das R, Chaudhuri S, Dutta S, Mukhopadhyay AK. Development and evaluation of a simple PCR assay and nested PCR for rapid detection of clarithromycin-resistant Helicobacter pylori from culture and directly from the biopsy samples in India. Gut Pathog 2023; 15:7. [PMID: 36782212 PMCID: PMC9925366 DOI: 10.1186/s13099-023-00530-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/23/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Eradication of Helicobacter pylori provides the most effective treatment for gastroduodenal diseases caused by H. pylori infection. Clarithromycin, a member of the macrolide family, still remains the most important antibiotic used in H. pylori eradication treatment. But the increasing prevalence of clarithromycin resistant H. pylori strains due to point mutations in the V region of the 23S rRNA, poses a great threat in treating the ailing patients. So, we aimed for PCR-mediated rapid detection of the point mutation at 2143 position of 23S rRNA gene in H. pylori that is relevant to clarithromycin resistance from culture and simultaneously from biopsy specimens to avoid the empirical treatment. RESULTS Newly developed PCR assay using DNA of pure culture detected point mutation in 23S rRNA gene in 21 (8.04%) of 261 clinical strains tested. The agar dilution method showed that all these 21 strains were resistant to clarithromycin indicating the perfect match of the PCR based results. Additionally, the sequencing study also identified the A to G mutation at 2143 position in 23S rRNA gene of the resistant strains only. Consequently, the newly developed Nested-ASP-PCR dealing directly with 50 biopsy specimens demonstrated 100% sensitivity and specificity with the findings of agar dilution method taken as Gold standard. Bioinformatics based analysis such as accessibility analysis and dot plot clearly stated that the base pairing probability has increased due to mutation. Computational studies revealed that the point mutation confers more stability in secondary structure due to conversion of loop to stem. Furthermore, interaction studies showed binding affinity of the CLR to the mutant type is weaker than that to the wild type. CONCLUSION This assay outlines a rapid, sensitive and simple approach to identify point mutation that confers clarithromycin resistance as well as clarithromycin sensitive strains, providing rapid initiation of effective antibiotic treatment. Additionally, it is simple to adopt for hospital based diagnostic laboratories to evaluate the degree of regional clarithromycin resistance from biopsy specimens itself. Furthermore, in silico studies provide evidence or a signal that the prevalence of clarithromycin resistance may rise in the near future as a result of this point mutation.
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Affiliation(s)
- Bipul Chandra Karmakar
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Sangita Paul
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Surajit Basak
- Division of Bioinformatics, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Manisha Ghosh
- Division of Bioinformatics, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Piyali Mukherjee
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Rajashree Das
- Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | | | - Shanta Dutta
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India
| | - Asish Kumar Mukhopadhyay
- Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, 700010, India.
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Chang YW, Shin GY, Kim JW, Moon JC, Chang EJ, Oh CH, Jang JY. Cost-Effectiveness of Empirical Bismuth-Based Quadruple Therapy and Tailored Therapy After Clarithromycin Resistance Tests for Helicobacter pylori Eradication. Dig Dis Sci 2022; 67:1222-1230. [PMID: 33755825 DOI: 10.1007/s10620-021-06938-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 03/05/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND The eradication rate of clarithromycin-based standard triple therapy (STT) for Helicobacter pylori infection has decreased due to clarithromycin resistance (CR). We evaluated the cost-effectiveness of tailored therapy according to CR test results, and compared the results of STT with those of empirical bismuth quadruple therapy (BQT). METHODS The prospectively collected data of 490 H. pylori-positive patients with chronic gastritis or peptic ulcer disease were retrospectively analyzed. Among them, 292 patients underwent CR testing using dual-priming oligonucleotide-based polymerase chain reaction. The tailored group (n = 292) consisted of patients treated with STT for 7 days and BQT for 10 days as per their CR test results. The remaining patients were assigned to the empirical group (n = 198) and received BQT for 10 days without a CR test. The eradication rate, adverse events and medical costs associated with H. pylori eradication therapy were investigated. RESULTS In the tested patients (tailored group), the CR-positive rate was 32.2% (n = 94/292). The eradication rate according to an intention-to-treat analysis was 87.7% in the tailored group and 91.8% in the empirical group (P = 0.124); the respective rates were 94.4% and 97.9% by per-protocol analysis (P = 0.010). The frequency of adverse events was lower in the empirical group than the tailored group (35.1% vs. 52.7%, P < 0.001). Total per capita medical costs were $406.50 and $503.50, respectively. CONCLUSIONS Ten-day empirical BQT was more effective, safer, and less expensive than tailored therapy based on a CR test for H. pylori eradication.
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Affiliation(s)
- Young Woon Chang
- Department of Internal Medicine, Cheonan-Woori Hospital, Cheonan, Korea
| | - Ga Young Shin
- Department of Gastroenterology, Kyung Hee University College of Medicine, 23 Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Korea
| | - Jung-Wook Kim
- Department of Gastroenterology, Kyung Hee University College of Medicine, 23 Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Korea.
| | - Jin-Chang Moon
- Department of Internal Medicine, Cheonan-Woori Hospital, Cheonan, Korea
| | - Eun Jee Chang
- Department of Preventive Medicine, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Chi Hyuk Oh
- Department of Gastroenterology, Kyung Hee University College of Medicine, 23 Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Korea
| | - Jae-Young Jang
- Department of Gastroenterology, Kyung Hee University College of Medicine, 23 Kyung Hee Dae-ro, Dongdaemun-gu, Seoul, 02447, Korea
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Seo SI, Lim H, Bang CS, Yang YJ, Baik GH, Lee SP, Jang HJ, Kae SH, Kim J, Kim HY, Shin WG. Bismuth-Based Quadruple Therapy versus Metronidazole-Intensified Triple Therapy as a First-Line Treatment for Clarithromycin-Resistant Helicobacter pylori Infection: A Multicenter Randomized Controlled Trial. Gut Liver 2022; 16:697-705. [PMID: 35145043 PMCID: PMC9474493 DOI: 10.5009/gnl210365] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 11/02/2021] [Accepted: 11/17/2021] [Indexed: 11/16/2022] Open
Abstract
Background/Aims Clarithromycin resistance is a main factor for treatment failure in the context of Helicobacterpylori infection. However, the treatment regimen for clarithromycin-resistant H. pylori infection has not yet been determined. We aimed to compare the efficacy and cost-effectiveness of 14-day bismuth-based quadruple therapy versus 14-day metronidazole-intensified triple therapy for clarithromycin-resistant H. pylori infection with genotypic resistance. Methods This was a multicenter, randomized, controlled trial. A total of 782 patients with H. pylori infection examined using sequencing-based clarithromycin resistance point mutation tests were recruited between December 2018 and October 2020 in four institutions in Korea. Patients with significant point mutations (A2142G, A2142C, A2143G, A2143C, and A2144G) were randomly assigned to receive either 14-day bismuth-based quadruple therapy (n=102) or 14-day metronidazole-intensified triple therapy (n=99). Results The overall genotypic clarithromycin resistance rate was 25.7% according to the sequencing method. The eradication rate of 14-day bismuth-based quadruple therapy was not significantly different in the intention-to-treat analysis (80.4% vs 69.7%, p=0.079), but was significantly higher than that of 14-day metronidazole-intensified triple therapy in the per-protocol analysis (95.1% vs 76.4%, p=0.001). There were no significant differences in the incidence of side effects. In addition, the 14-day bismuth-based quadruple therapy was more cost-effective than the 14-day metronidazole-intensified triple therapy. Conclusions Fourteen-day bismuth-based quadruple therapy showed comparable efficacy with 14-day metronidazole-intensified triple therapy, and it was more cost-effective in the context of clarithromycin-resistant H. pylori infection.
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Affiliation(s)
- Seung In Seo
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Hyun Lim
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Chang Seok Bang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Young Joo Yang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ho Baik
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Korea
| | - Sang Pyo Lee
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Hyun Joo Jang
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Sea Hyub Kae
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea.,Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Jinseob Kim
- Department of Epidemiology, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Hak Yang Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.,Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
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8
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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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9
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Kim YJ, Chung WC. Bismuth-containing Standard Triple Therapy the First-line Eradication Therapy for Helicobacter pylori. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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10
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Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial. Clin Transl Gastroenterol 2021; 11:e00194. [PMID: 33094958 PMCID: PMC7494145 DOI: 10.14309/ctg.0000000000000194] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
We investigated to compare the effect of empirical therapy vs clarithromycin resistance–guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori.
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11
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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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Moghadam MT, Chegini Z, Norouzi A, Dousari AS, Shariati A. Three-Decade Failure to the Eradication of Refractory Helicobacter pylori Infection and Recent Efforts to Eradicate the Infection. Curr Pharm Biotechnol 2021; 22:945-959. [PMID: 32767919 DOI: 10.2174/1389201021666200807110849] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/30/2020] [Accepted: 07/04/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. METHODS Thus, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and address new therapeutic methods that may be effective in controlling this bacterium in the future. RESULTS Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in the failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccines can be helpful in the treatment and eradication of H. pylori infections. CONCLUSION Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.
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Affiliation(s)
- Majid T Moghadam
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Chegini
- Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
| | - Amin Norouzi
- Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Aref Shariati
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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13
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Choe AR, Shim KN, Park Y, Song EM, Tae CH, Jung SA. Cost-Effectiveness, Efficacy, and Safety Analysis of Tailored Therapy in Patients with Helicobacter pylori Infection. J Clin Med 2021; 10:jcm10122619. [PMID: 34198677 PMCID: PMC8232140 DOI: 10.3390/jcm10122619] [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] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/06/2021] [Accepted: 06/11/2021] [Indexed: 12/14/2022] Open
Abstract
Recently in Korea, where triple therapy is accepted as the first-line Helicobacter pylori (H. pylori) eradication treatment, antibiotic resistance to clarithromycin has increased considerably, resulting in eradication rates of less than 80%. We investigated the efficacy of tailored therapy after a clarithromycin resistance test compared with empirical therapy for H. pylori eradication. The cost-effectiveness of H. pylori eradication success was evaluated according to the average medical cost per patient. A total of 364 patients were enrolled in the study. The first-line H. pylori eradication rate was significantly higher in patients who received tailored therapy than in those who received empirical therapy. The total medical costs for the tailored and empirical groups were 46,374 Won and 53,528 Won. The total treatment period for each ultimately successful eradication in the tailored group was 79.8 ± 2.8 days, which is shorter than that of the empirical group (99.2 ± 7.4 days). The rate of eradication-related adverse events for the tailored group and empirical group was 12.9% and 14.8%, respectively. Tailored therapy could be a useful option to achieve a higher successful eradication rate, shorter treatment periods, and lower medical costs than empirical therapy in the era of increasing antibiotic resistance.
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Affiliation(s)
| | - Ki-Nam Shim
- Correspondence: ; Tel.: +82-2-6986-3122; Fax: +82-6986-3129
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14
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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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Kang S, Kim Y, Ahn JY, Jung HY, Kim N, Na HK, Lee JH, Jung KW, Kim DH, Choi KD, Song HJ, Lee GH. Role of Antimicrobial Susceptibility Testing before First-Line Treatment Containing Clarithromycin for Helicobacter pylori Eradication in the Clinical Setting. Antibiotics (Basel) 2021; 10:214. [PMID: 33669969 PMCID: PMC7924850 DOI: 10.3390/antibiotics10020214] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/14/2021] [Accepted: 02/18/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Checking Helicobacter pylori susceptibility tests in the clinical setting before first-line treatment is considered difficult. We compared susceptibility-guided therapy (SGT) with empirical therapy (ET) as a first-line treatment containing clarithromycin and investigated the eradication rate using antimicrobial susceptibility testing (AST). METHODS 257 patients with H. pylori infection, with AST, performed before the eradication of clarithromycin-containing regimens were enrolled and divided into two groups: the SGT and ET groups. RESULTS Eradication rates in the SGT and ET groups were 85.4% and 58.4% (P < 0.01), respectively. In triple therapy (TT), eradication rates of the SGT and ET groups were 85.1% and 56.6% (P < 0.01), respectively. In sequential therapy (SET), eradication rates of the SGT and ET groups were 86.2% and 65.6% (P = 0.06), respectively. According to AST, TT had an eradication rate of 84.6% with strains susceptible to clarithromycin and amoxicillin and 11.1% with strains resistant to both. SET had an eradication rate of 89.5% with strains susceptible to clarithromycin, amoxicillin, and metronidazole, whereas it was 0% with strains resistant to clarithromycin and metronidazole. CONCLUSIONS SGT as first-line treatment improved eradication rates of TT and SET by 28.5 (P < 0.01) and 20.6 (P = 0.06) percent points, respectively, compared with ET.
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Affiliation(s)
- Seokin Kang
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Yuri Kim
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Ji Yong Ahn
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Hwoon-Yong Jung
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Nayoung Kim
- Asan Medical Center, Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Seoul 05505, Korea;
| | - Hee Kyong Na
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Jeong Hoon Lee
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Kee Wook Jung
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Do Hoon Kim
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Kee Don Choi
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Ho June Song
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
| | - Gin Hyug Lee
- Asan Medical Center, Department of Gastroenterology, University of Ulsan College of Medicine, Seoul 05505, Korea; (S.K.); (Y.K.); (H.K.N.); (J.H.L.); (K.W.J.); (D.H.K.); (K.D.C.); (H.J.S.); (G.H.L.)
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16
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Lee JW, Kim N, Nam RH, Yu JE, Son JH, Lee SM, Lee DH. Efficacy of Tegoprazan for Improving the Susceptibility of Antimicrobial Agents against Antibiotic-Resistant Helicobacter pylori. Gut Liver 2021; 15:53-60. [PMID: 33191308 PMCID: PMC7817939 DOI: 10.5009/gnl20247] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 10/04/2020] [Accepted: 10/05/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Favorable outcomes of potassium-competitive acid blocker (PCAB)-containing eradication therapy have been reported. In fact, tegoprazan, a recently developed PCAB, was presumed to show good eradication efficacy even for resistant Helicobacter pylori. We aimed to investigate the anti-H. pylori efficacy of tegoprazan compared with that of vonoprazan. Methods A total of 220 resistant clinical H. pylori isolates were utilized. The anti-H. pylori efficacy of PCABs was determined by evaluating the minimum inhibitory concentrations (MICs) of clarithromycin, fluoroquinolone, metronidazole, and amoxicillin in combination with vonoprazan or tegoprazan by the agar dilution method. The impact of the mutations responsible for resistance development, such as 23S rRNA, gyrA, rdxA, frxA, and pbp1 mutations, was also analyzed. Results H. pylori growth was significantly inhibited in a medium containing 1 μg/mL clarithromycin with tegoprazan (128 μg/mL). The MICs of clarithromycin (46.3%), fluoroquinolone (46.7%), metronidazole (55.6%), and amoxicillin (34.5%) against resistant H. pylori isolates improved after tegoprazan administration. Tegoprazan demonstrated more frequent susceptibility acquisition with metronidazole than with vonoprazan (20.6% vs 4.7%, p=0.014). However, there were no significant differences depending on the mutational status of each antimicrobial agent. Conclusions Tegoprazan administration may improve the susceptibility of antimicrobial-resistant H. pylori, independent of acid suppression.
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Affiliation(s)
- Jung Won Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joo Hee Son
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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17
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Wu D, Sun Z, Li T, Tan Q, Sun Y, Chen T, Liu Y, Li J, Jiang H, Yuan Z, Zhao Y, Chen W. Efficacy of quadruple regimen with polaprezinc for gastric Helicobacter pylori infection eradication: protocol for a single-centre, single-blind, non-inferiority, randomised clinical trial. BMJ Open 2020; 10:e037182. [PMID: 33203625 PMCID: PMC7674085 DOI: 10.1136/bmjopen-2020-037182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) is the most well-known risk factor for gastric cancer. At present, H. pylori shows varying levels of resistance to different treatments, leading to a lower rate of H. pylori eradication. The aim of this study is to evaluate the efficacy of polaprezinc-containing quadruple therapy (PQT) for the eradication of H. pylori infection and, thus, to provide more evidence to inform the clinical treatment of H. pylori infection in China. METHODS AND ANALYSIS This is a single-centre, single-blind, non-inferiority, randomised controlled trial, enrolling 158 patients with H. pylori infection. Patients are randomised (1:1) to the two groups for a 14-day therapy. Treatment group: PQT (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, polaprezinc 75 mg) two times per day; control group: bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, bismuth potassium citrate 220 mg) two times per day. The primary outcome is the rate of H. pylori eradication. Secondary outcomes are the incidence of adverse events and the gastrointestinal microbiota distribution. The 16S ribosomal RNA (16S rRNA) next-generation sequencing (NGS) is used to evaluate the effect of two different therapies on the distribution of the gastrointestinal microbiota. ETHICS AND DISSEMINATION This study was approved by the Ethics Committee of Sichuan Cancer Center & Hospital (No. SCCHEC-02-2019-015). Any amendment to the research protocol will be submitted for ethical approval. All participants must provide informed consent. On completion, the results of the study will be published in the appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER ChiCTR1900025800; preresults.
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Affiliation(s)
- Dingkun Wu
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhen Sun
- Department of Gastroenterology, Jilin People's Hospital, Jilin, China
| | - Tingyuan Li
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qinwen Tan
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Chongqing Medical University, Chongqing, China
| | - Yue Sun
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Tingting Chen
- West China School of Public Health/West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Yujing Liu
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Li
- Cancer Prevention and Treatment Office, Yanting Cancer Hospital, Mianyang, China
| | - Haidong Jiang
- Cancer Prevention and Treatment Office, Yanting Cancer Hospital, Mianyang, China
| | - Zhiqiang Yuan
- Cancer Prevention and Treatment Office, Yanting Cancer Hospital, Mianyang, China
| | - Yuqian Zhao
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wen Chen
- Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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18
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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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19
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Kim SY, Chung JW. Best Helicobacter pylori Eradication Strategy in the Era of Antibiotic Resistance. Antibiotics (Basel) 2020; 9:antibiotics9080436. [PMID: 32717826 PMCID: PMC7459868 DOI: 10.3390/antibiotics9080436] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/11/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
Antibiotic resistance is the major reason for Helicobacter pylori treatment failure, and the increasing frequency of antibiotic resistance is a challenge for clinicians. Resistance to clarithromycin and metronidazole is a particular problem. The standard triple therapy (proton pump inhibitor, amoxicillin, and clarithromycin) is no longer appropriate as the first-line treatment in most areas. Recent guidelines for the treatment of H. pylori infection recommend a quadruple regimen (bismuth or non-bismuth) as the first-line therapy. This treatment strategy is effective for areas with high resistance to clarithromycin or metronidazole, but the resistance rate inevitably increases as a result of prolonged therapy with multiple antibiotics. Novel potassium-competitive acid blocker-based therapy may be effective, but the data are limited. Tailored therapy based on antimicrobial susceptibility test results is ideal. This review discussed the current important regimens for H. pylori treatment and the optimum H. pylori eradication strategy.
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Affiliation(s)
- Su Young Kim
- Divison of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju 26426, Korea;
| | - Jun-Won Chung
- Divison of Gastroenterology, Department of Internal Medicine, Gachon University, Gil Medical Center, 21, Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea
- Correspondence: ; Tel.: +82-32-460-3778; Fax: +82-32-460-3408
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Gong EJ, Ahn JY, Kim JM, Lee SM, Na HK, Lee JH, Jung KW, Choi KD, Kim DH, Song HJ, Lee GH, Kim SW, Jung HY. Genotypic and Phenotypic Resistance to Clarithromycin in Helicobacter pylori Strains. J Clin Med 2020; 9:1930. [PMID: 32575584 PMCID: PMC7356929 DOI: 10.3390/jcm9061930] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 06/10/2020] [Accepted: 06/17/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The increasing prevalence of antimicrobial resistance, together with the lack of novel treatment options, negatively affects successful eradication of Helicobacter pylori. The aim of this study was to investigate genetic mutations in the 23S rRNA genes, which is associated with clarithromycin resistance, and to determine the clinical impact of genotype on phenotypic antimicrobial resistance. METHODS A total of 46 H. pylori strains were obtained from 13 patients, before and after unsuccessful eradication with clarithromycin-based triple therapy. The phenotypic resistance of each H. pylori strain was determined by minimum inhibitory concentration against clarithromycin using the serial two-fold agar dilution method. The genomic sequences of 23S rRNA genes were identified through next-generation sequencing, and nucleotide variants were determined based on comparison with genome sequences of the reference strain H. pylori 26695. RESULTS Clarithromycin resistance was found in 9 of 13 subjects before treatment and all subjects after unsuccessful eradication. Whole-genome sequencing of the 23S rRNA genes detected 42 mutations on 40 nonidentical loci, including 2147A>G (formerly 2143A>G) and 2146A>G (formerly 2142A>G). All strains with clarithromycin-resistant phenotype had either 2147A>G or 2146A>G mutation. When comparing genotype and phenotype for clarithromycin resistance, there was a significant association between 2147A>G mutation and clarithromycin-resistant phenotype. CONCLUSIONS All clarithromycin-resistant strains had either 2146A>G or 2147A>G mutation, suggesting that tests targeting these two mutations may be enough for the prediction of clarithromycin resistance in this population.
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Affiliation(s)
- Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung 25440, Korea;
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Jung Mogg Kim
- Department of Microbiology, Hanyang University College of Medicine, Seoul 04763, Korea;
| | - Sun Mi Lee
- Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea;
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
| | - So Won Kim
- Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (J.Y.A.); (H.K.N.); (J.H.L.); (K.W.J.); (K.D.C.); (D.H.K.); (H.J.S.); (G.H.L.)
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Yoon K, Kim N, Lee JW, Yoon H, Shin CM, Park YS, Lee DH. Annual eradication rate of bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: A 15-year prospective study at a tertiary hospital in Korea. Helicobacter 2020; 25:e12685. [PMID: 32141173 DOI: 10.1111/hel.12685] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 02/09/2020] [Accepted: 02/10/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Bismuth-containing quadruple therapy is widely used as second-line treatment for Helicobacter pylori infection. This prospective study investigated the changes in the annual H. pylori eradication rates of quadruple therapy. METHODS This study included an intention-to-treat (ITT) population of 452 subjects who failed first-line eradication therapy for H. pylori between 2003 and 2018. All subjects received a 14-day course of bismuth-containing quadruple therapy consisting of esomeprazole (40 mg twice daily), metronidazole (500 mg thrice daily), bismuth subcitrate (120 mg four times daily), and tetracycline (500 mg four times daily). Per-protocol (PP) analysis of data was performed in subjects who followed up with strict treatment adherence. Eradication was confirmed based on the results of the 13 C-urea breath test, rapid urease test (CLOtest® ), and histopathologic evaluation. Compliance and adverse effects were also investigated. A minimal inhibitory concentration test was performed on tissue samples obtained from 103 subjects. RESULTS The overall eradication rates following ITT and PP analyses were 78.8% (356/452) and 89.5% (314/351), respectively. The annual eradication success rate did not show significant changes (P = .062 [ITT], P = .857 [PP]) over the 15-year study period. Adverse events were reported in 57.3% of the ITT population. The rates of resistance to metronidazole and tetracycline were 44.7% and 18.4%, respectively. CONCLUSIONS Despite high antibiotic resistance rates, no significant reduction in annual eradication rates was observed during the study period.
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Affiliation(s)
- Kichul Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jung Won Lee
- Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Young Soo Park
- 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
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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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Ong S, Kim SE, Kim JH, Yi NH, Kim TY, Jung K, Park MI, Jung HY. Helicobacter pylori eradication rates with concomitant and tailored therapy based on 23S rRNA point mutation: A multicenter randomized controlled trial. Helicobacter 2019; 24:e12654. [PMID: 31411793 DOI: 10.1111/hel.12654] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 07/01/2019] [Accepted: 07/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND We evaluated the efficacy of tailored therapy based on point mutation presence identified with the dual-priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) method compared with concomitant therapy. MATERIALS AND METHODS Subjects were randomly assigned concomitant therapy (amoxicillin 1 g, clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days) or tailored therapy (amoxicillin 1 g, clarithromycin 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-negative subjects; and amoxicillin 1 g, metronidazole 500 mg, and lansoprazole 30 mg twice/day for 14 days in point mutation-positive subjects). RESULTS A total of 397 and 352 subjects were included in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. Point mutations were identified in 25.9% of the subjects. The overall eradication rate was not significantly different between the groups by ITT (86.2% vs 81.6%, P = .132) and PP analyses (90.2% vs 86.5%, P = .179). There was no significant difference in the eradication rates between the groups in both the point mutation-negative subjects (91.7% vs 87.3%, P = .154) and the point mutation-positive subjects (71.2% vs 64.7%, P = .312). The eradication rates were significantly lower in the point mutation-positive subjects than in the point mutation-negative subjects in both the concomitant and tailored therapy groups. CONCLUSIONS Tailored therapy based on point mutation presence identified with the DPO-based multiplex PCR method was as effective as concomitant therapy. The eradication rates of both therapy regimens were suboptimal in point mutation-positive subjects.
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Affiliation(s)
- Sungmoon Ong
- Department of Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Ji Hyun Kim
- Department of Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Nam Hee Yi
- Department of Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Young Kim
- Department of Gastroenterology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Kyoungwon Jung
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Kim BJ, Yang C, Song HJ, Jeon SW, Kim GH, Kim H, Kim TH, Shim K, Chung I, Park MI, Choi IJ, Kim JH, Kim B, Baik GH, Han SW, Seo HE, Jung WT, Hwan Oh J, Kim SG, Lee JH, Park SK, Park B, Yang BR, Lee J, Kim JG. Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success. Helicobacter 2019; 24:e12646. [PMID: 31368629 PMCID: PMC6790945 DOI: 10.1111/hel.12646] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 06/18/2019] [Accepted: 06/26/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION There was no relationship between the eradication rate and antibiotic use density in Korea.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal MedicineChung‐Ang University College of MedicineSeoulKorea
| | - Chang‐Hun Yang
- Department of Internal MedicineDongguk University College of Medicine Gyeongju HospitalGyeongjuKorea
| | - Hyun Joo Song
- Department of Internal MedicineJeju National University School of MedicineJejuKorea
| | - Seong Woo Jeon
- Department of Internal Medicine, School of MedicineKyungpook National UniversityDaeguKorea
| | - Gwang Ha Kim
- Department of Internal MedicinePusan National University School of MedicineBusanKorea
| | - Hyun‐Soo Kim
- Department of Internal MedicineChonnam National University Medical SchoolGwangjuKorea
| | - Tae Ho Kim
- Department of Gastroenterology, Bucheon St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaBucheonKorea
| | - Ki‐Nam Shim
- Department of Internal MedicineEwha Womans University School of MedicineSeoulKorea
| | - Il‐Kwun Chung
- Department of Internal Medicine, Cheonan HospitalSoon Chun Hyang University College of MedicineCheonanKorea
| | - Moo In Park
- Department of Internal Medicine, Kosin University Gospel HospitalKosin University College of MedicineBusanKorea
| | - Il Ju Choi
- Center for Gastric CancerNational Cancer CenterGyeonggiKorea
| | - Ji Hyun Kim
- Department of Internal MedicinePusan Paik Hospital, Inje University College of MedicineBusanKorea
| | - Byung‐Wook Kim
- Department of Internal Medicine, College of MedicineThe Catholic University of KoreaIncheonKorea
| | - Gwang Ho Baik
- Department of Internal MedicineHallym University College of MedicineSeoulKorea
| | - Sok Won Han
- Department of Gastroenterology, Bucheon St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaBucheonKorea
| | - Hyang Eun Seo
- Department of Internal MedicineDaegu Fatima HospitalDaeguKorea
| | - Woon Tae Jung
- Department of Internal MedicineGyeongsang National University School of MedicineJinjuKorea
| | - Jung Hwan Oh
- Department of Internal Medicine, St. Paul's Hospital, College of MedicineThe Catholic University of KoreaSeoulKorea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research InstituteSeoul National University College of MedicineSeoulKorea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
| | - Sue K. Park
- Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
- Department of Biomedical ScienceSeoul National University Graduate SchoolSeoulKorea
- Cancer Research InstituteSeoul National UniversitySeoulKorea
| | - Byung‐Joo Park
- Department of Preventive MedicineSeoul National University College of MedicineSeoulKorea
| | - Bo Ram Yang
- Department of Biomedical ScienceSeoul National University Graduate SchoolSeoulKorea
| | - Joongyub Lee
- Department of Prevention and Management, Inha University Hospital, School of MedicineInha UniversityIncheonKorea
| | - Jae G. Kim
- Department of Internal MedicineChung‐Ang University College of MedicineSeoulKorea
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Chang YW, Ko WJ, Oh CH, Park YM, Oh SJ, Moon JR, Cho JH, Kim JW, Jang JY. Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis. Korean J Intern Med 2019; 34:1022-1029. [PMID: 29898576 PMCID: PMC6718756 DOI: 10.3904/kjim.2018.054] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 03/09/2018] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND/AIMS The eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure. METHODS A total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment. RESULTS Of 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CY-P2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication. CONCLUSION Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.
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Affiliation(s)
- Young Woon Chang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Weon Jin Ko
- Department of Internal Medicine, CHA Gumi Medical Center, CHA University School of Medicine, Gumi, Korea
| | - Chi Hyuk Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
- Correspondence to Chi Hyuk Oh, M.D. Division of Gastroenterology and Hepatology, Department of Internal medicine, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea Tel: +82-2-958-8114 Fax: +82-2-958-8147 E-mail:
| | - Yoo Min Park
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Shin Ju Oh
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jung Rock Moon
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jun-Hyung Cho
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jung-Wook Kim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
| | - Jae-Young Jang
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
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Lee JH, Ahn JY, Choi KD, Jung HY, Kim JM, Baik GH, Kim BW, Park JC, Jung HK, Cho SJ, Shin CM, Choi YJ, Lee SH, Kim JH, Lee WS, Sung JK, Chung JW, Cheung DY, Lee H, Min YW, Kim JJ, Kim SY. Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study. Helicobacter 2019; 24:e12592. [PMID: 31111572 DOI: 10.1111/hel.12592] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 04/14/2019] [Accepted: 04/16/2019] [Indexed: 12/22/2022]
Abstract
INTRODUCTION The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea. MATERIALS AND METHODS Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate. RESULTS The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate. CONCLUSION The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.
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Affiliation(s)
- Jeong Hoon Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Jung Mogg Kim
- Department of Microbiology, Hanyang University College of Medicine, Seoul, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
| | - Jun Chul Park
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Soo Jeong Cho
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Si Hyung Lee
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Wan Sik Lee
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Jae Kyu Sung
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Jun-Won Chung
- Department of Internal Medicine, Gil Medical Center, Gachon University, Incheon, Korea
| | - Dae Young Cheung
- Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Young Kim
- Department of Internal Medicine, Ansan Hospital, Korea University College of Medicine, Ansan, Korea
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27
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Wang D, Guo Q, Yuan Y, Gong Y. The antibiotic resistance of Helicobacter pylori to five antibiotics and influencing factors in an area of China with a high risk of gastric cancer. BMC Microbiol 2019; 19:152. [PMID: 31272365 PMCID: PMC6611032 DOI: 10.1186/s12866-019-1517-4] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 06/17/2019] [Indexed: 12/18/2022] Open
Abstract
Background H. pylori exhibits antibiotic resistance with regional differences. In this paper, we explored antibiotic resistance of H. pylori to five antibiotics in an area with a high risk of gastric cancer. Results H. pylori resistance rates to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were 78.0, 56.0, 31.0, 9.0, and 15.0%, respectively. Double, triple, quadruple, and quintuple resistance rates were 23, 20, 6, and 4%, respectively. The clarithromycin and multidrug resistance rates were significantly higher in males than females (clarithromycin: 44.4% vs 15.2%, respectively, P = 0.002; multidrug: 75.5% vs 37.2%, respectively; P < 0.001). During the three periods of 1998–1999, 2002–2004 and 2016–2017, the resistance rates to levofloxacin and amoxicillin were increasing (OR: 2.089, 95%CI: 1.142–3.821, P = 0.017; and OR: 5.035, 95%CI: 1.327–19.105, P = 0.018, respectively). The antibiotic resistance rates were unassociated with the host disease state. Metronidazole resistance was lower in the vacAs1m1/m2 group than the vacAs1m1m2 group (65% vs 85.7%, respectively; P = 0.026). As for levofloxacin resistance, it was higher with cagA+ than cagA− (60.9% vs 23.1%, respectively; P = 0.020) but lower with slyD+ than slyD− (41.4% vs 68.5%, respectively; P = 0.009). Clarithromycin had a lower resistance rate with iceA++ than iceA−+ (19.7% vs 52.4%, respectively; P = 0.017). For amoxicillin, the iceA++ group had a lower resistance rate than the iceA−− group (1.6% vs 27.8%, respectively; P = 0.009). Conclusions The total resistance rates of H. pylori to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were high in Zhuanghe. The resistanc rates to levofloxacin and amoxicillin increased over time. Clarithromycin resistance was associated with male and iceA. The resistance of metronidazole was related to vacA. Levofloxacin resistance was concerned with cagA and slyD and amoxicillin resistance was concerned with iceA. While, the antibiotic resistance of H. pylori had nothing to do with the status of gastric disease.
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Affiliation(s)
- Dan Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surger, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Qianqian Guo
- Tumor Etiology and Screening Department of Cancer Institute and General Surger, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surger, the First Hospital of China Medical University, Shenyang, 110001, China. .,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, 110001, China. .,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China.
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General Surger, the First Hospital of China Medical University, Shenyang, 110001, China. .,Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, 110001, China. .,Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China.
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Helicobacter pylori Mutations Detected by Next-Generation Sequencing in Formalin-Fixed, Paraffin-Embedded Gastric Biopsy Specimens Are Associated with Treatment Failure. J Clin Microbiol 2019; 57:JCM.01834-18. [PMID: 31068413 DOI: 10.1128/jcm.01834-18] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 05/02/2019] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori antibiotic resistance is widespread and increasing worldwide. Routine detection of H. pylori mutations that invoke antimicrobial resistance may be a useful approach to guide antimicrobial therapy and possibly avert treatment failure. In this study, formalin-fixed, paraffin-embedded (FFPE) gastric biopsy specimens from a cohort of individuals from northern Ohio in the United States were examined using a next-generation sequencing (NGS) assay to detect H. pylori mutations that are known to confer resistance to clarithromycin, levofloxacin, and tetracycline. From January 2016 to January 2017, 133 H. pylori-infected gastric biopsy specimens were identified histologically and subsequently analyzed by NGS to detect mutations in gyrA, 23S rRNA, and 16S rRNA genes. The method successfully detected H. pylori in 126 of 133 cases (95% sensitivity). Mutations conferring resistance were present in 92 cases (73%), including 63 cases with one mutation (50%) and 29 cases with mutations in multiple genes (23%). Treatment outcomes were available in 58 cases. Sixteen of the 58 cases failed therapy (28%). Therapy failure correlated with the number of mutated genes: no failure in cases with no mutations (0/15), 19% (5/27) failure in cases with one gene mutation, and 69% (11/16) failure in cases with more than one mutated gene. Common 23S rRNA mutations (A2142G or A2413G) were present in 88% (14/16) of failed cases as opposed to in only 10% (4/42) of eradicated cases (P < 0.001). This NGS assay can be used on remnant specimens collected during standard-of-care testing to detect mutations that correlate with increased risk of treatment failure. A prospective study is needed to determine if the risk of treatment failure can be decreased by using this assay to guide antibiotic therapy.
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Cho JH, Jeon SR, Kim HG, Jin SY, Park S. Cost-effectiveness of a tailored Helicobacter pylori eradication strategy based on the presence of a 23S ribosomal RNA point mutation that causes clarithromycin resistance in Korean patients. J Gastroenterol Hepatol 2019; 34:700-706. [PMID: 30011083 DOI: 10.1111/jgh.14383] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 07/03/2018] [Accepted: 07/05/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM The Helicobacter pylori eradication rate using conventional triple therapy has decreased due to clarithromycin (CAM) resistance in H. pylori. Recently, dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) can be used to detect H. pylori and point mutations in the 23S ribosomal RNA gene causing CAM resistance. This study aimed to evaluate the success rate and cost-effectiveness of tailored H. pylori eradication using DPO-PCR. METHODS The H. pylori-positive patients diagnosed by a rapid urease test or DPO-PCR were enrolled from a single academic hospital. The patients with positive rapid urease test results received a CAM-based triple regimen. In the tailored therapy group that underwent DPO-PCR testing, patients with A2142G and/or A2143G point mutations were treated with a bismuth-containing quadruple regimen. The cost-effectiveness of H. pylori eradication success was evaluated according to the average cost per patient and the incremental cost-effectiveness ratio. RESULTS A total of 243 patients were allocated to the triple therapy group and 124 patients to the tailored therapy group. The first-line eradication rate of H. pylori was significantly higher in the tailored therapy group than in the conventional triple therapy group (92.7% vs 76.5%, P < 0.001). The average costs per patient for tailored therapy were $307.37 and $299.59 for first-line and second-line treatments, respectively. Compared with triple therapy, the incremental cost-effectiveness ratios of tailored therapy were $3.96 and -$3.81 per patient for first-line and second-line treatments, respectively. CONCLUSION In Korea, tailored H. pylori eradication using DPO-PCR may be more cost-effective than conventional triple therapy.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, Korea
| | - Seong Ran Jeon
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, Korea
| | - Hyun Gun Kim
- 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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Hashemi SJ, Sheikh AF, Goodarzi H, Yadyad MJ, Seyedian SS, Aslani S, Assarzadegan MA. Genetic basis for metronidazole and clarithromycin resistance in Helicobacter pylori strains isolated from patients with gastroduodenal disorders. Infect Drug Resist 2019; 12:535-543. [PMID: 30881059 PMCID: PMC6404679 DOI: 10.2147/idr.s192942] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The aim of this study was to evaluate the antimicrobial resistance and genetic basis for metronidazole (Mtz) and clarithromycin (Cla) resistance in strains of Helicobacter pylori, isolated from patients with gastroduodenal disorders. PATIENTS AND METHODS A total of 157 H. pylori isolates (from 22 gastric cancer, 38 peptic ulcer disease, and 97 non-ulcer dyspepsia patients) were analyzed for drug susceptibility to Mtz and Cla, by gradient diffusion test (E-test, MAST). The PCR and sequence analysis of the rdxA and frxA for Mtz-resistant strains and the 23S rRNA for Cla-resistant strains were used to determine the genetic basis of drug resistance in H. pylori strains. Increased expression of TolC homologous genes (hefA) that upregulates efflux pump activity was determined in multidrug-resistant (MDR) strain of H. pylori by real-time PCR technique. RESULTS Among 157 H. pylori isolates, 32 (20.4%) strains were resistant to at least one of the antimicrobial agents. The highest resistance rate was attributed to Mtz (n=69, 43.94%). Among the resistant strains of H. pylori, 15 cases (9.55%) were detected as MDR. Mutations in the rdxA (85.5%) and A2143G point mutations (63.1%) in the 23S rRNA were the most common cause of resistance to Mtz and Cla in strains of H. pylori, respectively. In MDR strains, the rdxA mutation and A2143G-point mutation in the 23S rRNA were the most abundant mutations responsible for drug resistance. The relative expression of hefA in MDR strains (mean 3.706) was higher than the susceptible strains (mean 1.07). CONCLUSION Mutational inactivation and efflux pump overexpression are two mechanisms that increase the resistance to H. pylori antimicrobial agents and the rate of MDR strains. In Iran, the mutations of rdxA and frxA in Mtz-resistant strains and A2143G and A2142G of the 23S rRNA in Cla-resistant strains were significant. The screening for these mutations could help to prevent antibiotic resistance, and to determine the most effective anti-H. pylori drugs.
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Affiliation(s)
- Seyed Jalal Hashemi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
- Research Institute for Infectious Diseases of the Digestive System, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Division of Gastroenterology and Hepatology, Ahvaz Jundishapur University of Medical Sciences, Ahwaz, Iran
| | - Ahmad Farajzadeh Sheikh
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
- Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
| | - Hamed Goodarzi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
- Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
- Molecular Biology Research Center, Baqiyatallah University of Medical Science, Tehran, Iran,
| | - Mohammad Jaafar Yadyad
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,
| | - Seyed Saeid Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sajad Aslani
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
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Morovic W, Roos P, Zabel B, Hidalgo-Cantabrana C, Kiefer A, Barrangou R. Transcriptional and Functional Analysis of Bifidobacterium animalis subsp. lactis Exposure to Tetracycline. Appl Environ Microbiol 2018; 84:e01999-18. [PMID: 30266728 PMCID: PMC6238047 DOI: 10.1128/aem.01999-18] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 09/25/2018] [Indexed: 12/11/2022] Open
Abstract
Commercial probiotic bacteria must be tested for acquired antibiotic resistance elements to avoid potential transfer to pathogens. The European Food Safety Authority recommends testing resistance using microdilution culture techniques previously used to establish inhibitory thresholds for the Bifidobacterium genus. Many Bifidobacterium animalis subsp. lactis strains exhibit increased resistance to tetracycline, historically attributed to the ribosomal protection gene tet(W). However, some strains that harbor genetically identical tet(W) genes show various inhibition levels, suggesting that other genetic elements also contribute to observed differences. Here, we adapted several molecular assays to confirm the inhibition of B. animalis subsp. lactis strains Bl-04 and HN019 and employed RNA sequencing to assess the transcriptional differences related to genomic polymorphisms. We detected specific stress responses to the antibiotic by correlating ATP concentration to number of viable genome copies from droplet digital PCR and found that the bacteria were still metabolically active in high drug concentrations. Transcriptional analyses revealed that several polymorphic regions, particularly a novel multidrug efflux transporter, were differentially expressed between the strains in each experimental condition, likely having phenotypic effects. We also found that the tet(W) gene was upregulated only during subinhibitory tetracycline concentrations, while two novel tetracycline resistance genes were upregulated at high concentrations. Furthermore, many genes involved in amino acid metabolism and transporter function were upregulated, while genes for complex carbohydrate utilization, protein metabolism, and clustered regularly interspaced short palindromic repeat(s) (CRISPR)-Cas systems were downregulated. These results provide high-throughput means for assessing antibiotic resistances of two highly related probiotic strains and determine the genetic network that contributes to the global tetracycline response.IMPORTANCEBifidobacterium animalis subsp. lactis is widely used in human food and dietary supplements. Although well documented to be safe, B. animalis subsp. lactis strains must not contain transferable antibiotic resistance elements. Many B. animalis subsp. lactis strains have different resistance measurements despite being genetically similar, and the reasons for this are not well understood. In the current study, we sought to examine how genomic differences between two closely related industrial B. animalis subsp. lactis strains contribute to different resistance levels. This will lead to a better understanding of resistance, identify future targets for analysis of transferability, and expand our understanding of tetracycline resistance in bacteria.
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Affiliation(s)
- Wesley Morovic
- Genomics & Microbiome Science, DuPont Nutrition & Health, Madison, Wisconsin, USA
| | - Paige Roos
- Genomics Laboratory, DuPont Pioneer, Johnston, Iowa, USA
| | - Bryan Zabel
- Genomics & Microbiome Science, DuPont Nutrition & Health, Madison, Wisconsin, USA
| | - Claudio Hidalgo-Cantabrana
- Department of Food, Processing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina, USA
| | - Anthony Kiefer
- Probiotic Development, DuPont Nutrition & Health, Madison, Wisconsin, USA
| | - Rodolphe Barrangou
- Department of Food, Processing and Nutrition Sciences, North Carolina State University, Raleigh, North Carolina, USA
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Jung DH, Kim JH, Jeong SJ, Park SY, Kang IM, Lee KH, Song YG. Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori. Gut Liver 2018; 12:641-647. [PMID: 30037168 PMCID: PMC6254629 DOI: 10.5009/gnl18111] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/17/2018] [Accepted: 06/10/2018] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important. Methods We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing. Results Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (κ-value=0.990; standard error, 0.010). Conclusions H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.
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Affiliation(s)
- Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Jie-Hyun Kim
- Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Su Jin Jeong
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Soon Young Park
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Il-Mo Kang
- Korea Institute of Geoscience and Mineral Resources, Daejeon,
Korea
| | - Kyoung Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Young Goo Song
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
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Gweon TG, Kim JS, Kim BW. An Economic Modeling Study of Helicobacter pylori Eradication: Comparison of Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction and Empirical Treatment. Gut Liver 2018; 12:648-654. [PMID: 30037167 PMCID: PMC6254616 DOI: 10.5009/gnl18079] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 05/16/2018] [Accepted: 06/18/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-based PCR) can detect the presence of clarithromycin resistance without culture. The aim of this study was to investigate the cost-effectiveness of DPO-based PCR for Helicobacter pylori eradication. METHODS From 2015 to 2016, medical records of patients who received H. pylori eradication therapy were analyzed. Patients were divided into two groups: tailored group patients who were treated based on DPO-based PCR and empirical group patients. Eradication rate and medical cost, including diagnostic tests, eradication regimens, and 13C-urea breath tests, were compared between the two groups. Cost for one successful eradication was calculated in each group. The expected cost of eradication for empirical treatment was investigated by varying the treatment duration and eradication rate. RESULTS A total of 527 patients were analyzed (tailored group 208, empirical group 319). The eradication success rate of the first-line therapy was higher in the tailored group compared to that in the empirical group (91.8% vs 72.1%, p＜0.01). The total medical cost for each group was 114.8±14.1 U.S. dollars (USD) and 85.8±24.4 USD, respectively (p＜0.01). The total medical costs for each ultimately successful eradication in the tailored group and in the empirical group were 120.0 USD and 92.4 USD, respectively. The economic modeling expected cost of a successful eradication after a 7- or 14-day empirical treatment was 93.8 to 111.4 USD and 126.3 to 149.9 USD, respectively. CONCLUSIONS Based on economic modeling, the cost for a successful eradication using DPO-based PCR would be similar or superior to the expected cost of a successful eradication with a 14-day empirical treatment when the first-line eradication rate is ≤80%.
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Affiliation(s)
- Tae-Geun Gweon
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Byung-Wook Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155:1372-1382.e17. [PMID: 29990487 PMCID: PMC6905086 DOI: 10.1053/j.gastro.2018.07.007] [Citation(s) in RCA: 793] [Impact Index Per Article: 113.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 06/27/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. METHODS We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. RESULTS We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). CONCLUSIONS Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
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Affiliation(s)
- Alessia Savoldi
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany
| | - Elena Carrara
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Michela Conti
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany; Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy.
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Park CG, Kim S, Lee EJ, Jeon HS, Han S. Clinical relevance of point mutations in the 23S rRNA gene in Helicobacter pylori eradication: A prospective, observational study. Medicine (Baltimore) 2018; 97:e11835. [PMID: 30113472 PMCID: PMC6112885 DOI: 10.1097/md.0000000000011835] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Clarithromycin-based triple therapy is prescribed worldwide for Helicobacter pylori eradication. However, increases in the clarithromycin resistance of H pylori are thought to be responsible for eradication failure. Here, we studied whether point mutations in domain V of the 23S rRNA gene can affect H pylori eradication failure in a prospective, open-label, observational study. Of the 755 enrolled patients, 299 patients (39.6%) had positive Campylobacter-like organism (CLO) tests. DNA sequencing analysis of H pylori 23S rRNA in 295 patients revealed that 2143G was the most frequent point mutation (24.7% of patients), followed by the 2182T mutation (11.5%). The overall eradication failure rate was 20.9% (42/201) in clarithromycin-based triple therapy. Patients with the 2143G had an approximately 60% eradication failure rate, which suggested that 2143G was a high-risk genotype for eradication failure. Patients with the 2182C genotype without 2143G had an 8.7% failure rate, and patients without 2143G or 2182C had only a 4.3% failure rate. The presence of 2143G, which was associated with previous eradication history and female sex, was an independent risk factor for eradication failure. In conclusion, the 2143G point mutation in the 23S rRNA of H pylori was an independent risk factor for eradication failure in clarithromycin-based triple therapy. Personalized tailored therapy based on the genotypes of 23S rRNA can increase eradication success rates in H pylori infections.
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Affiliation(s)
| | | | - Eun-Ju Lee
- Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital
| | | | - Seungwoo Han
- Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Daegu Fatima Hospital
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
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Park JS, Park JE, Oh BS, Yoon BW, Kim HK, Lee JW, Kim NH, Cho WS, Woo YS, Jahng J, Kim YS. [Trend in the Eradication Rates of Helicobacter pylori Infection Over the Last 10 Years in West Gyeonggi-do, Korea: A Single Center Experience]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 70:232-238. [PMID: 29161792 DOI: 10.4166/kjg.2017.70.5.232] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background/Aims The eradication rate of Helicobacter pylori (H. pylori) has been decreasing recently in Korea due to antibiotics resistance. The aim of this study was to investigate the trend of eradication rate and clinical factors affecting the eradication rate of H. pylori in the last 10 years in west Gyeonggi-do, Korea. Methods The trends of eradication rate of H. pylori, gender, age, concomitant mediations, and clinical factors were retrospectively evaluated in patients with H. pylori infection between 2006 and 2015 (n=2,485). Results The overall H. pylori eradication rate for the standard triple therapy was 82.5%. The annual eradication rates from 2006 to 2015 were 90%, 77.9%, 75.8%, 83.2%, 85.6%, 90.1%, 81.3%, 81.1%, 78.7%, and 78.8%, respectively, showing a significant decrement during the last five years (p<0.001). Higher eradication rate was observed in males than in females (p<0.001). Esomeprazole showed a higher eradication rate compared with pantoprazole between 2006 and 2010 (p<0.022). Age and the use of probiotics and mucosal protective agents played no significant role in the H. pylori eradication rate. The overall eradication rate for bismuth-based quadruple therapy was 94.4%. Conclusions The eradication rate of H. pylori over the last 10 years for first-line therapy ranged from 75.8 to 90.1%; the eradication rate for triple therapy has declined. However, the eradication rate for quadruple therapy has remained unchanged over the last 10 years.
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Affiliation(s)
- Jong Seol Park
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Ji Eun Park
- Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Byoung Soo Oh
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Byung Wook Yoon
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Hyun Ki Kim
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Jae Won Lee
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Nam Ho Kim
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Won Seok Cho
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Young Sik Woo
- Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Jaehoon Jahng
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
| | - Yong Sung Kim
- Department of Internal Medicine and Wonkwang Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Korea
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Matta AJ, Zambrano DC, Pazos AJ. Punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori in Colombian populations. World J Gastroenterol 2018; 24:1531-1539. [PMID: 29662291 PMCID: PMC5897857 DOI: 10.3748/wjg.v24.i14.1531] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 02/25/2018] [Accepted: 03/18/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize punctual mutations in 23S rRNA gene of clarithromycin-resistant Helicobacter pylori (H. pylori) and determine their association with therapeutic failure.
METHODS PCR products of 23S rRNA gene V domain of 74 H. pylori isolates; 34 resistant to clarithromycin (29 from a low-risk gastric cancer (GC) population: Tumaco-Colombia, and 5 from a high-risk population: Tuquerres-Colombia) and 40 from a susceptible population (28 from Tumaco and 12 from Túquerres) were sequenced using capillary electrophoresis. The concordance between mutations of V domain 23S rRNA gene of H. pylori and therapeutic failure was determined using the Kappa coefficient and McNemar’s test was performed to determine the relationship between H. pylori mutations and clarithromycin resistance.
RESULTS 23S rRNA gene from H. pylori was amplified in 56/74 isolates, of which 25 were resistant to clarithromycin (20 from Tumaco and 5 from Túquerres, respectively). In 17 resistant isolates (13 from Tumaco and 4 from Túquerres) the following mutations were found: A1593T1, A1653G2, C1770T, C1954T1, and G1827C in isolates from Tumaco, and A2144G from Túquerres. The mutations T2183C, A2144G and C2196T in H. pylori isolates resistant to clarithromycin from Colombia are reported for the first time. No association between the H. pylori mutations and in vitro clarithromycin resistance was found. However, therapeutic failure of eradication treatment was associated with mutations of 23S rRNA gene in clarithromycin-resistant H. pylori (κ = 0.71).
CONCLUSION The therapeutic failure of eradication treatment in the two populations from Colombia was associated with mutations of the 23S rRNA gene in clarithromycin-resistant H. pylori.
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Affiliation(s)
- Andrés Jenuer Matta
- Registro Poblacional de Cáncer de Cali, Department of Pathology, School of Medicine, Universidad del Valle, Cali 760043, Colombia
- Faculty of Education and Sports Sciences, Institución Universitaria Escuela Nacional del Deporte, Cali 760043, Colombia
| | - Diana Carolina Zambrano
- Faculty of Education and Sports Sciences, Institución Universitaria Escuela Nacional del Deporte, Cali 760043, Colombia
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Gong EJ, Ahn JY. Antimicrobial Resistance ofHelicobacter pyloriIsolates in Korea. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2018. [DOI: 10.7704/kjhugr.2018.18.2.82] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, Gangneung, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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40
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Kwon YH, Kim JY, Kim N, Park JH, Nam RH, Lee SM, Kim JW, Kim JM, Park JY, Lee DH. Specific mutations of penicillin-binding protein 1A in 77 clinically acquired amoxicillin-resistant Helicobacter pylori strains in comparison with 77 amoxicillin-susceptible strains. Helicobacter 2017; 22. [PMID: 28840971 DOI: 10.1111/hel.12437] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Amoxicillin (Amx) is one of the most important antibiotics for eradication of Helicobacter pylori (H. pylori). Main determinants of genetically stable Amx resistance are mutations in the C-terminus of penicillin-binding protein 1A (pbp1A). However, contribution of individual mutation remains unclear. METHODS 77 Amx-resistant (AmxR ) and 77 Amx-susceptible (AmxS ) H. pylori strains were isolated from gastric tissues, and DNA sequencing was performed to compare C-terminus sequences of pbp1A gene between AmxR and AmxS strains. Natural transformation of these mutated genes into amoxicillin-susceptible strains was performed. RESULTS Among many mutations in pbp1A, D479E (OR: 37.4, 95% CI: 5.53-252.49, P < .001), and T593 mutation (OR: 32.0, 95% CI: 4.04-252.86, P < .001) independently contributed to Amx resistance in H. pylori strains. In the transformation experiment, T593 mutations were identified in their transformants showing Amx resistance. However, PCR product of D479E was not inserted into recipient (ATCC 43504) resulting in transformation failure. CONCLUSION Amx resistance is associated with various substitutions in pbp1A and T593 mutation contributes to Amx resistance of H. pylori.
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Affiliation(s)
- Yong Hwan Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Ji Yeon Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 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
| | - Ji Hyun Park
- 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
| | - Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jin-Wook 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
| | - Jung Mogg Kim
- Department of Microbiology, Hanyang University School of Medicine, Seoul, 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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41
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Kwon S, Lee DH, Kang JB, Kim N, Park YS, Shin CM, Yoon H, Choi YJ. [The Efficacy of Moxifloxacin-containing Triple Therapy after Hybrid Therapy Failure in Helicobacter pylori Eradication]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 70:72-80. [PMID: 28830132 DOI: 10.4166/kjg.2017.70.2.72] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background/Aims Hybrid therapy was successful in eradicating Helicobacter pylori (H. pylori) according to previous reports. However, to the best of our knowledge, there have only been a few studies evaluating the optimal choice after hybrid failure. Hence, we aimed to evaluate the efficacy of moxifloxacin-containing triple therapy after hybrid therapy failure in H. pylori eradication. Methods Between January 2013 and March 2016, we retrospectively reviewed patients who underwent failed hybrid therapy, as first line treatment, in eradicating H. pylori (rabeprazole and amoxicillin b.i.d for 14 days, in addition to clarithromycin and metronidazole b.i.d for final 7 days). Then, we investigated the eradication rates of moxifloxacin-containing triple therapy (rabeprazole, amoxicillin b.i.d and moxifloxacin qd) as the second line of treatment. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to determine the eradication rate. We evaluated the status of H. pylori by using 13C-urea breath test 6 weeks after the final treatment. Moreover, compliance and adverse effects of each patient were analyzed. Results Among those who failed the initial hybrid therapy, 11 patients received moxifloxacin-containing triple therapy. The overall eradication rates, as determined by ITT and PP, were 72.7% (n=8/11) and 80% (n=8/10), respectively. The compliance rate was 100%, and there were no serious adverse effects. Conclusions Moxifloxacin-containing triple therapy can be used as a second line therapy in case of hybrid therapy failure. A large scale study is necessary to confirm the findings of this study and establish clinical evidence.
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Affiliation(s)
- Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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42
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Chang JY, Shim KN, Tae CH, Lee KE, Lee J, Lee KH, Moon CM, Kim SE, Jung HK, Jung SA. Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication. BMC Gastroenterol 2017; 17:16. [PMID: 28109257 PMCID: PMC5251227 DOI: 10.1186/s12876-017-0579-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 01/18/2017] [Indexed: 12/20/2022] Open
Abstract
Background The eradication rate of Helicobacter pylori (H. pylori) with triple therapy which was considered as standard first-line treatment has decreased to 70–85%. The aim of this study is to compare 7-day triple therapy versus 10-day sequential therapy as the first line treatment. Methods Data of 1240 H. pylori positive patients treated with triple therapy or sequential therapy from January 2013 to December 2015 were analyzed retrospectively. The patients who had undertaken previous H. pylori eradication therapy or gastric surgery were excluded. Results There were 872 (74.3%) patients in the triple therapy group, and 302 (25.7%) patients in the sequential therapy group. There was no significant difference between the two groups regarding age, residence, comorbidities or drug compliance, but several differences were noted in endoscopic characteristics and indication for the treatment. The eradication rate of H. pylori by intention to treat analysis was 64.3% in the triple therapy group, and 81.9% in the sequential therapy group (P = 0.001). In per protocol analysis, H. pylori eradication rate in the triple therapy and sequential therapy group was 81.9 and 90.3%, respectively (P = 0.002). There was no significant difference in overall adverse events between the two groups (P = 0.706). For the rescue therapy, bismuth-containing quadruple therapy showed comparable treatment efficacy after sequential therapy, as following triple therapy. Conclusions The eradication rate of triple therapy was below the recommended threshold. Sequential therapy could be effective and tolerable candidate for the first-line H. pylori eradication therapy.
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Affiliation(s)
- Ji Young Chang
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea.
| | - Chung Hyun Tae
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Ko Eun Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Jihyun Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Kang Hoon Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Chang Mo Moon
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 158-710, South Korea
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43
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Jung YD, Kim YJ, Chung WC. A Pilot Study of Helicobacter pylori Eradication Using a Polymerase Chain Reaction-based Test for Clarithromycin Resistance. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2017. [DOI: 10.7704/kjhugr.2017.17.4.200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Yun Duk Jung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeon-Ji Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Sung J, Kim N, Park YH, Hwang YJ, Kwon S, Na G, Choi JY, Kang JB, Kim HR, Kim JW, Lee DH. Rifabutin-based Fourth and Fifth-line Rescue Therapy in Patients with forHelicobacter pyloriEradication Failure. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 69:109-118. [DOI: 10.4166/kjg.2017.69.2.109] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Jihee Sung
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yo Han Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Jae Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Soohoon Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Gyeongjae Na
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joon Young Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jae Bin Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Rang Kim
- Hospital Health Promotion Center, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea
| | - Jin-Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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45
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Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies. Gastroenterol Res Pract 2016; 2016:9086581. [PMID: 28070184 PMCID: PMC5187483 DOI: 10.1155/2016/9086581] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 10/15/2016] [Accepted: 11/03/2016] [Indexed: 01/06/2023] Open
Abstract
A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin resistance, bismuth quadruple therapy and so-called nonbismuth quadruple therapies (sequential, concomitant, and sequential-concomitant hybrid) are some first-line regimen options. However, more research is needed regarding appropriate second-line treatments after first-line treatment failure. Tailored therapy, which is based on antibiotic sensitivity testing, would be optimal but has several limitations for clinical use, and an alternative technique is required. A novel potassium-competitive acid blocker-based eradication regimen could be a valuable eradication option in the near future.
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46
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Matsumoto H, Shiotani A, Nishibayashi H, Kamada T, Kimura T, Fujimura Y, Nakato R, Murao T, Fujita M, Haruma K. Molecular Detection of H. pylori Using Adherent Gastric Mucous to Biopsy Forceps. Helicobacter 2016; 21:548-553. [PMID: 27061611 DOI: 10.1111/hel.12310] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIM We assessed whether adherent gastric mucous to biopsy forceps instead of biopsy samples was suitable for the diagnosis of H. pylori infection. We confirmed the PCR methods to improve the diagnosis of H. pylori infection and clarithromycin (CAM) susceptibility. METHODS Gastric mucous was obtained by gently scraping gastric mucosa using biopsy forceps in patients undergoing upper gastrointestinal (GI) endoscopy for PCR and rapid urease test (RUT). DNA was extracted from gastric mucous present within the gel of RUT. H. pylori status and CAM susceptibility were evaluated using H. pylori-specific PCR amplification for 23S rRNA using 4 different primer sets and 16S rRNA. H. pylori positive was defined as two of the three tests (serum antibody, histology, and RUT or PCR) were positive. CAM susceptibility was evaluated by point mutations (A 2142G and A 2143G of 23S rRNA). RESULTS Samples taken from 494 subjects were evaluated: 300 H. pylori-positive patients and 194 negative patients. The results of PCR using DNA extracted from gastric mucous present within the RUT gel were consistent with those within water. The accuracy of 23S rRNA PCR for H. pylori detection using RUT samples was superior to the other tests. The frequency of CAM resistance was 38.9%, and eradication rate was 91.3% in the patients with wild-type and 47.0% in the patients with the mutant strains. CONCLUSION Adherent gastric mucous to biopsy forceps in RUT gel can be used for molecular testing to confirm the diagnosis of H. pylori infection and for CAM susceptibility.
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Affiliation(s)
- Hiroshi Matsumoto
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Akiko Shiotani
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Hiroyuki Nishibayashi
- Department of Gastroenterology and Hepatology, Kawanishi Municipal Hospital, Hyogo, Japan
| | - Tomoari Kamada
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Tomonari Kimura
- Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama, Japan
| | - Yoshinori Fujimura
- Department of Gastroenterology, Sakakibara Heart Institute of Okayama, Okayama, Japan
| | - Rui Nakato
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Takahisa Murao
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Minoru Fujita
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Ken Haruma
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
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47
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Kim BJ, Kim HS, Song HJ, Chung IK, Kim GH, Kim BW, Shim KN, Jeon SW, Jung YJ, Yang CH, Kim JH, Kim TH, Kim SG, Shin WG, Kim SM, Han SW, Lee JH, Kim KH, Park SK, Park BJ, Lee J, Kim JG. Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis. J Korean Med Sci 2016; 31:1246-1253. [PMID: 27478335 PMCID: PMC4951554 DOI: 10.3346/jkms.2016.31.8.1246] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Accepted: 04/09/2016] [Indexed: 12/14/2022] Open
Abstract
Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Joo Song
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Il-Kwun Chung
- Department of Internal Medicine, Cheonan Hospital, Soon Chun Hyang University College of Medicine, Cheonan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University Medical Center, Daegu, Korea
| | - Yun Jin Jung
- Department of Internal Medicine, Daegu Fatima Hospital, Daegu, Korea
| | - Chang-Hun Yang
- Department of Internal Medicine, Dongguk University College of Medicine Gyeongju Hospital, Gyeongju, Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Pusan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Ho Kim
- Department of Gastroenterolgy, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Sun Moon Kim
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Sok Won Han
- Department of Gastroenterolgy, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyung Ho Kim
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Sue K. Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
- Cancer Research Institute, Seoul National University, Seoul, Korea
| | - Byung-Joo Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Joongyub Lee
- Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea
| | - Jae G. Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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48
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Shin WG, Lee SW, Baik GH, Huh KC, Lee SI, Chung JW, Jung WT, Park MI, Jung HK, Kim HU, Kim JH, Seol SY, Yoon SM, Jeon SW, Hong SJ, Kim GH, Lee DH, Kim HS, Choi SC, Kang HM, Lee J, Kim JG, Kim JJ. Eradication Rates of Helicobacter pylori in Korea Over the Past 10 years and Correlation of the Amount of Antibiotics Use: Nationwide Survey. Helicobacter 2016; 21:266-278. [PMID: 26470999 DOI: 10.1111/hel.12279] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The efficacy of proton-pump inhibitor-amoxicillin-clarithromycin therapy for H. pylori eradication has decreased over time. OBJECTIVE We assessed the trend of H. pylori eradication rates over the last 10 years and the relationship between the eradication rates and the amount of macrolide antibiotic use in a country with a high prevalence of H. pylori infection. METHODS This vast nationwide multicenter study was conducted with 34,139 adults treated for H. pylori infection from January 2001 to December 2010. The defined daily dose per km(2) (DSD) of macrolide antibiotics was calculated (n = 141,019) using the Health Insurance Review & Assessment data base from 2008 to 2010 in the two cities which had the lowest (Jeju city) or highest (Chuncheon city) eradication rate. RESULTS The eradication rates of proton-pump inhibitor-amoxicillin-clarithromycin therapy ranged 84.9-87.5% from 2001 to 2007, and those of 2008 to 2010 ranged 80.0-81.4% with a decreasing trend (p < 0.0001). The decreasing trend of eradication rates for the overall first-line therapy was observed only in three of the seven geographic areas in Korea (p < 0.0001). The DSD of macrolide antibiotics was significantly higher in Jeju than Cheunchon city (0.85 vs 0.52, p < 0.0001). CONCLUSIONS H. pylori eradication rates with clarithromycin-containing triple therapy in Korea showed a decreasing trend over the past 10 years, although the trend varied among geographic areas. This difference may be associated with the amount of macrolide antibiotic use.
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Affiliation(s)
- Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
| | - Sang Woo Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
| | - Kyu Chan Huh
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Sang In Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun-Won Chung
- Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea
| | - Woon Tae Jung
- Department of Internal Medicine and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Jeong Hwan Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Sang Young Seol
- Department of Internal Medicine, Inje University College of Medicine, Busan, Korea
| | - Soon Man Yoon
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Su Jin Hong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Soo Kim
- Department of Internal Medicine, Chonnam National University School of Medicine, Gwangju, Korea
| | - Suck Chei Choi
- Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea
| | - Hee Mo Kang
- Department of Finance and Information Statistics, Hallym University College of Natural Science, Chuncheon, Korea
| | - Joongyub Lee
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jae J Kim
- Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
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49
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Ji Z, Han F, Meng F, Tu M, Yang N, Zhang J. The Association of Age and Antibiotic Resistance of Helicobacter Pylori: A Study in Jiaxing City, Zhejiang Province, China. Medicine (Baltimore) 2016; 95:e2831. [PMID: 26937912 PMCID: PMC4779009 DOI: 10.1097/md.0000000000002831] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The antibiotic resistance of Helicobacter pylori (H pylori) is steadily increasing worldwide, resulting in the low efficiency of the current therapeutic approaches for eradication. In this study, we investigated the relationship between antibiotic resistances, the year of sample collection, and the ages of the infected individuals.A total of 29,034 gastric mucosa biopsy samples were randomly collected from January 1, 2009 to December 9, 2014 in Jiaxing City, Zhejiang Province, China. An antibiotic susceptibility testing was determined using an agar-dilution method. The statistical significance was tested using the chi-squared (χ) test.A total of 9687 strains were isolated. The resistance rate to clarithromycin, levofloxacin, and metronidazole were 17.76%, 19.66%, and 95.5%, respectively. Resistance was rare against amoxicillin, gentamicin, and furazolidone. The metronidazole resistance rate stayed at a consistently high level. In contrast, the resistance rates of clarithromycin and levofloxacin increased rapidly from 2009 to 2011, gradually decreased from 2012 to 2013, and then increased again in 2014. Although patients ages 31 to 50 and 71 to 80 years had lower infection rates of H pylori, they also had higher resistance rates to clarithromycin and levofloxacin. The highest antibiotic resistance rate was observed in patients' ages 71 to 80 years old. Younger patients (below 30 years old) had a lower resistance to levofloxacin. Patients' ages 51 to 60 years old may thus represent an important category for the future study of H pylori infection.Age plays a key element in H pylori resistance to clarithromycin and levofloxacin. It is therefore necessary to consider individualized therapy for the optimized treatment of H pylori-infected patients.
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Affiliation(s)
- Zizhong Ji
- From the First Hospital of Jiaxing (ZJ, FH), Zhiyuan Inspection Medical Institute (FM, MT), Zhiyuan Medical Inspection Institute Co., LTD (NY), and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (JZ), Hangzhou, Zhejiang, China and State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (JZ)
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50
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Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, Valasek MA. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016; 43:514-33. [PMID: 26694080 PMCID: PMC5064663 DOI: 10.1111/apt.13497] [Citation(s) in RCA: 540] [Impact Index Per Article: 60.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/04/2015] [Accepted: 11/19/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. AIM To review recent trends in H. pylori antibiotic resistance rates, and to discuss diagnostics and treatment paradigms. METHODS A PubMed literature search using the following keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. RESULTS The prevalence of bacterial antibiotic resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other antibiotics show similar trends, although less pronounced. CONCLUSIONS Since the choice of empiric therapies should be predicated on accurate information regarding antibiotic resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric antibiotic therapy but also inform the development of better methods to identify H. pylori antibiotic resistance at diagnosis. Patient-specific tailoring of effective antibiotic treatment strategies may lead to reduced treatment failures and less antibiotic resistance.
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Affiliation(s)
- I. Thung
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - H. Aramin
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - V. Vavinskaya
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
| | - S. Gupta
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - J. Y. Park
- Department of Pathology and the Eugene McDermott Center for Human Growth and DevelopmentUniversity of Texas Southwestern Medical Center and Children's Medical CenterDallasTXUSA
| | - S. E. Crowe
- Division of GastroenterologyDepartment of MedicineUniversity of California San Diego Medical CenterLa JollaCAUSA
| | - M. A. Valasek
- Division of Anatomic PathologyDepartment of PathologyUniversity of California San Diego Medical CenterSan DiegoCAUSA
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