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Lin Y, Lin X, Suo B, Chen Q, Cheng X, Lin Z, Huang X. Randomized multicenter trial comparing minocycline and ornidazole with classical quadruple therapy in Helicobacter pylori treatment. Sci Rep 2025; 15:16318. [PMID: 40348820 PMCID: PMC12065867 DOI: 10.1038/s41598-025-01117-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 05/05/2025] [Indexed: 05/14/2025] Open
Abstract
This study evaluated the efficacy, safety, and cost of minocycline, ornidazole, esomeprazole, and bismuth (MOEB) therapy versus classical therapy (amoxicillin, clarithromycin, esomeprazole, and bismuth potassium citrate, ACEB) for Helicobacter pylori eradication. In a randomized trial of 390 patients, MOEB demonstrated superior eradication rates (93.2% per-protocol, 78.5% intention-to-treat) compared to ACEB (82.5% per-protocol, 72.8% intention-to-treat). Adverse events were significantly lower with MOEB (19.3% vs. 33.8%, p = 0.0019). MOEB was also more cost-effective, with a direct cost of 675.7 CNY versus 970.1 CNY for ACEB, yielding an incremental cost-effectiveness ratio of -27.5 CNY per eradication rate. MOEB is a safe, effective, and cost-efficient first-line regimen for H. pylori eradication.
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Affiliation(s)
- Yi Lin
- The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China
- Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
- Gastroenterology and Hepatology Department, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Xueyan Lin
- The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China
- Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
- Gastroenterology and Hepatology Department, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Biao Suo
- Department of Gastroenterology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361000, China
| | - Qiuzhao Chen
- Department of Gastroenterology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361000, China
| | - Xianxing Cheng
- Department of Gastroenterology, Wuyishan Municipal Hospital, Nanping, 353000, China
| | - Zhihui Lin
- The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China
- Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China
- Gastroenterology and Hepatology Department, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Xueping Huang
- The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China.
- Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, China.
- Gastroenterology and Hepatology Department, Fujian Provincial Hospital, Fuzhou, 350001, China.
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Cho JH, Jin SY. Efficacy and Safety of Modified Bismuth Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Microorganisms 2025; 13:519. [PMID: 40142411 PMCID: PMC11944862 DOI: 10.3390/microorganisms13030519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 02/21/2025] [Accepted: 02/24/2025] [Indexed: 03/28/2025] Open
Abstract
This study aimed to evaluate the efficacy of adding bismuth to conventional triple therapy (modified bismuth quadruple therapy [mBQT]) for Helicobacter pylori treatment-naïve patients in an era of increasing eradication failure. We performed a comprehensive literature search up to December 2024 using PubMed, Embase, and the Cochrane Library to investigate mBQT's benefits. The comparative treatments were as follows: (1) triple therapy without bismuth (TT), (2) non-BQTs (sequential and concomitant), and (3) classic BQT (cBQT) containing metronidazole and tetracycline. Randomized controlled trials (RCTs) were analyzed to compare eradication rates, adverse drug events, and patient compliance between the mBQT and comparison groups. In total, 9162 and 8449 patients from 43 trials in 35 RCTs were included in the intention-to-treat and per-protocol analyses, respectively. The mBQT group had a superior pooled eradication rate compared to the TT group (84.8% vs. 74.1%, p < 0.00001, and odds ratio [OR] = 2.02 [1.61-2.55]). The mBQT showed a similar eradication rate to the non-BQT and cBQT groups (80.8% vs. 80.2%, p = 0.55, and OR = 1.09 [0.83-1.43] in the non-BQT group; 81.5% vs. 83.0%, p = 0.36, and OR = 0.84 [0.59-1.21] in the cBQT group). Regarding adverse drug events, there was no significant difference between the mBQT and comparison groups (25.4% vs. 27.5%, p = 0.53, and OR = 0.95 [0.80-1.12]). The subgroup analysis showed that patient adherence to mBQT was significantly higher than to cBQT (96.4% vs. 93.3%, p = 0.004, and OR = 1.83 [1.21-2.77]). Our meta-analysis showed that mBQT was an effective and tolerable first-line therapy for H. pylori eradication.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea;
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Valizadeh Toosi SM, Feyzi S, Kazemi A. Comparison of the Efficacy of 12-day Concomitant Quadruple Therapy versus 14-day High dose Dual Therapy as a First-line H. pylori Eradication Regimen. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:150-156. [PMID: 38659251 DOI: 10.4166/kjg.2024.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/01/2024] [Accepted: 04/12/2024] [Indexed: 04/26/2024]
Abstract
Background/Aims Helicobacter pylori (H. pylori) is the most prevalent infection in the world and is strongly associated with gastric adenocarcinoma, lymphoma and gastric or duodenal ulcers. Different regimens have been used for H. pylori eradication. We aimed to compare the efficacy of two different regimens as first-line H. pylori eradication regimens, in an area with high antibiotic resistance. Methods In this RCT, we assigned 223 patients with H. pylori infection, who were naïve to treatment. They were randomly divided into two groups to receive either 12-day concomitant quadruple therapy (consisting of pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg every 12 hours) or 14-day high dose dual therapy (consisting of esomeprazole 40 mg and amoxicillin 1 g TDS). H. pylori eradication was assessed eight weeks after the end of treatment. Results H. pylori eradication rate by PP analysis for 12-day concomitant quadruple therapy and 14-day high dose dual therapy were 90.4% and 79.1%, respectively (p=0.02). According to ITT analysis, the eradication rates were 86.2% and 76.3%, respectively (p=0.06). Adverse drug reactions were 12.3% in high dose dual therapy and 36.8% in concomitant quadruple therapy (p<0.001). Conclusions Twelve-day concomitant therapy seems to be an acceptable regimen for first-line H. pylori eradication in Iran, a country with a high rate of antibiotic resistance. Although, high dose dual therapy did not result in an ideal eradication rate, but it had fewer drug side effects than the 12-day concomitant regimen.
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Affiliation(s)
- Seyed Mohammad Valizadeh Toosi
- Gut and Liver Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Sahar Feyzi
- Medicine faculty, Mazandaran University of Medical Sciences, Sari, Iran
| | - Arash Kazemi
- Gut and Liver Research Center, Non-communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
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Tian XL, Suo BJ, Zhang H, Lu HP, Li CL, Zhang YX, Ren XL, Yao XY, Zhou LY, Song ZQ. Bismuth, esomeprazole, metronidazole and amoxicillin or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial. Helicobacter 2023; 28:e12935. [PMID: 36374159 DOI: 10.1111/hel.12935] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/14/2022] [Accepted: 10/21/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Due to general unavailability and common side effects of tetracycline, the clinical application of bismuth quadruple therapy (BQT) is greatly limited. Whether amoxicillin can replace tetracycline in BQT remains unknown. This study aimed to compare the eradication rate, safety and compliance between amoxicillin-containing and tetracycline-containing BQT as a first-line regimen for Helicobacter pylori eradication. METHODS This randomized trial was conducted on 404 naïve patients for H. pylori eradication. The participants were randomly assigned to 14-day amoxicillin-containing (bismuth potassium citrate 110 mg four times/day, esomeprazole 20 mg twice daily, metronidazole 400 mg four times/day and amoxicillin 500 mg four times/day) and tetracycline-containing (tetracycline 500 mg four times/day and the other three drugs used as above) BQT. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. RESULTS As for the eradication rates of amoxicillin-containing and tetracycline-containing BQT, the results of both intention-to-treat and per-protocol analyses showed that the difference rate of the lower limit of 95% confidence interval was above -10.0% (intention-to-treat analysis: 81.7% vs. 83.2%, with a rate difference of -1.5% [-6.3% to 9.3%]; per-protocol analysis: 89.0% vs. 91.6%, -2.6% [-4.1% to 9.3%]). The incidence of adverse events in amoxicillin-containing BQT was significantly lower than tetracycline-containing BQT (29.5% vs. 39.7%). Both groups achieved relatively good compliance (92.0% vs. 89.9%). CONCLUSION The eradication efficacy of amoxicillin-containing BQT was non-inferior to tetracycline-containing BQT as a first-line regimen for H. pylori eradication with better safety and similar compliance.
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Affiliation(s)
- Xue-Li Tian
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Bao-Jun Suo
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Hua Zhang
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Hao-Ping Lu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Cai-Ling Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yu-Xin Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xin-Lu Ren
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xing-Yu Yao
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Li-Ya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhi-Qiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
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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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Choi YI, Chung JW, Kim KO, Kwon KA, Kim YJ, Kim JH, Seo JY, Park DK. Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients. World J Gastroenterol 2021; 27:5247-5258. [PMID: 34497448 PMCID: PMC8384750 DOI: 10.3748/wjg.v27.i31.5247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/09/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Antibiotic resistance to Helicobacter pylori (H. pylori) infection, which ultimately results in eradication failure, has been an emerging issue in the clinical field. Recently, to overcome this problem, an antibiotic sensitivity-based tailored therapy (TT) for H. pylori infection has received attention.
AIM To investigate the efficacy and safety profiles of TT for H. pylori infection treatment compared to a non-bismuth quadruple therapy, concomitant therapy (CT) regimen.
METHODS We included patients (> 18 years) with an H. pylori infection and without a history of Helicobacter eradication who visited the Gil Medical Center between March 2016 and October 2020. After being randomly assigned to either the TT or CT treatment group in 1 to 1 manner, patient compliance, eradication success rate (ESR), and patient-reported side effects profiles were assessed and compared between the two groups. H. pylori infection was diagnosed using a rapid urease test, Giemsa stain, or dual priming oligonucleotide polymerase chain reaction (DPO-PCR). Tailored eradication strategy based through the presence of a 23S ribosomal RNA point mutation. For the TT group, a DPO-PCR test, which detected A2142G and/or A2143G point mutations, and a clarithromycin resistance test were performed. Patients in the clarithromycin-resistant group were treated with a bismuth-containing quadruple combination therapy, while those with sensitive results were treated with the standard triple regimen.
RESULTS Of the 217 patients with a treatment naive H. pylori infection, 110 patients [mean age: 58.66 ± 13.03, men, n = 55 (50%)] were treated with TT, and 107 patients [mean age: 56.67 ± 10.88, men, n = 52 (48.60%)] were treated with CT. The compliance (TT vs CT, 100% vs 98.13%, P = 0.30), and follow-up loss rates (8.18% vs 9.35%, P = 0.95) were not significantly different between the groups. The ESR after treatment was also not statistically different between the groups (TT vs CT, 82.73% vs 82.24%, P = 0.95). However, the treatment-related and patient-reported side effects were significantly lower in the TT group than in the CT group (22.77% vs 50.52%, P < 0.001).
CONCLUSION The DPO-based TT regimen shows promising results in efficacy and safety profiles as a first-line Helicobacter eradication regimen in Korea, especially when physicians are confronted with increased antibiotic resistance rates.
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Affiliation(s)
- Youn I Choi
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Jun-Won Chung
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Kyoung Oh Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Kwang An Kwon
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Yoon Jae Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Jung Ho Kim
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
| | - Ja Young Seo
- Department of Laboratory Medicine, Gil Medical Center, Gachon University, Inchoen 21565, South Korea
| | - Dong Kyun Park
- Division of Internal Medicine, Department of Gastroenterology, Gachon University College of Medicine, Gil Medical Center, Inchoen 21565, South Korea
- Health IT Research Center, Gachon University Gil Hospital, Incheon 21565, South Korea
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Yozgat A, Kasapoğlu B, Demirci S, Coşkun Sökmen F. Modified quadruple therapy or bismuth-containing quadruple therapy in the first-line treatment of Helicobacter pylori in Turkey. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:490-493. [PMID: 33233910 DOI: 10.17235/reed.2020.7261/2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIM Helicobacter pylori (H. pylori) eradication is still an important issue in countries with high antibiotic resistance. This study aimed to compare the efficacy and safety of two bismuth-containing treatment modalities in H. pylori treatment in Turkey. MATERIAL AND METHODS subjects with H. pylori infection who were treated with either bismuth-containing quadruple therapy (pantoprazole 40 mg bid, tetracycline 500 mg qid, metronidazole 500 mg tid, bismuth subcitrate 262 mg qid daily) (BQT group) or modified quadruple therapy (pantoprazole 40 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 262 mg qid daily) (MBQT group) for 14 days were compared, retrospectively. The eradication success rate, adverse events related to the medications and compliance were investigated. RESULTS a total of 128 patients in the BQT group and 102 patients in the MBQT group completed the treatment. The overall rate of adverse events was significantly higher in the BQT group compared with the MBQT group (39.4 % vs 18.6; p: 0.001). Among the adverse events, nausea-vomiting and abdominal discomfort was significantly more frequent in the BQT group than in the MBQT group (p: 0.001). The adverse events were mild-moderate in both groups and life threatening adverse events were not present in any of the patients. CONCLUSION although both regimens were highly effective and safe in H. pylori eradication, both intention-to-treat (ITT) and per-protocol (PP) eradication rates were higher and adverse events were lower in the modified quadruple therapy group. Modified quadruple therapy should be kept in mind for the first-line treatment of H. pylori in regions with high clarithromycin and metronidazole resistance.
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Affiliation(s)
- Ahmet Yozgat
- Gastroenterology, Ufuk University Hospital, Türkiye
| | - Benan Kasapoğlu
- Gastroenterology, Lokman Hekim Akay Hospital. Lokman Hekim University
| | - Selim Demirci
- Gastroenterology, Abdurrahman Yurtaslan Oncology Training and Research Hospital
| | - Fevzi Coşkun Sökmen
- Internal Medicine, Abdurrahman Yurtaslan Oncology Training and Research Hospital
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Xu H, Wang W, Ma X, Feng R, Su Y, Cheng L, Yang Y, Zhang D. Comparative efficacy and safety of high-dose dual therapy, bismuth-based quadruple therapy and non-bismuth quadruple therapies for Helicobacter pylori infection: a network meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:775-786. [PMID: 32639419 DOI: 10.1097/meg.0000000000001835] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Helicobacter pylori (H. pylori) infection is associated with the development of multiple diseases. The eradication rate of H. pylori has gradually decreased, suggesting the need to discover more effective therapies. This study aimed to compare the effectiveness of first-line treatments including high-dose dual therapy (HDDT), bismuth-based quadruple therapy (BQT), sequential therapy (ST), concomitant therapy (CT) and hybrid therapy (HT) by network meta-analysis (NMA). A comprehensive search on PubMed, Embase, Cochrane Library and Web of Science, was performed from their inception to 1 September 2019. A network analysis of randomized controlled trials (RCTs) comparing first-line therapies were carried out using Stata 14.0 and Revman 5.2. Moreover, a sensitivity analysis was conducted by omitting non-Asian studies. Finally, 41 RCTs with 14 119 patients were included. The NMA showed that, in terms of eradication rate, ST for 10 days (ST-10) was significantly lower than CT for 10 or 14 days (CT ≥ 10). Sensitivity analysis among the Asian population showed that ST-10 denoted the lowest effectiveness among the interventions. The ranking results based on probability showed that HDDT ranked first for the eradication rate. As for adverse events, HDDT was significantly less than BQT and CT regardless of duration, while BQT for 14 days represented higher adverse events than ST, HT and CT ≥ 10. HDDT ranked first among the therapies. In conclusion, HDDT for 14 days appeared to be the most optimal first-line therapy for H. pylori among the Asian population with comparable efficacy and compliance but causing fewer adverse events.
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Affiliation(s)
- Huimei Xu
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Wancong Wang
- Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - Xueni Ma
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Rukun Feng
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Yujing Su
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Long Cheng
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Yifan Yang
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
| | - Dekui Zhang
- Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province
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Ke H, Li J, Lu B, Yang C, Wang J, Wang Z, Liu L, Chen Y. The appropriate cutoff gastric pH value for Helicobacter pylori eradication with bismuth-based quadruple therapy. Helicobacter 2021; 26:e12768. [PMID: 33089598 DOI: 10.1111/hel.12768] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND This study aimed to investigate whether an increased proton pump inhibitor (PPI) dose enhanced the efficacy of Helicobacter pylori (H. pylori) eradication and determine the appropriate cutoff intragastric pH value that could predict H. pylori eradication with bismuth-based quadruple therapy. MATERIALS AND METHODS A total of 207 H. pylori infected, treatment naive patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated into Eso40-group (esomeprazole 40 mg bid) and Eso20-group (esomeprazole 20 mg bid), and their CYP2C19 genotyping status was assessed. The 24-h intragastric pH monitoring on day 7 was performed, and percentage of time gastric pH ≥ 3, ≥4, ≥5, and ≥6 (pH holding time ratios; HTRs) were measured. H. pylori eradication was evaluated using 13 C-urea breath test. RESULTS No significant difference in the eradication rates was observed between two groups. The median 24-h intragastric pH value was not significant different between two groups but the Eso40 Group had a significant higher pH4 HTRs (91.11% [95%CI: 87.50%-95.83%] vs. 95.83% [95.83%-100%]; p = .002). Additionally, the median 24-h intragastric pH value showed significantly difference between two groups in EM genotype (Eso20 Group 6.00 [95%CI; 5.75-6.15] vs. Eso40 Group 6.30 [6.05-6.30]; p = .019). Similar results were observed in pH4 HTRs. There were significant differences in intragastric pH value (6.10 [95%CI: 4.40-7.00] vs. 5.65 [4.85-5.95], p = .038) and in pH4 HTRs (96% [95%CI: 92.00%-96.00%] vs. 87.5% [67.00%-100.0%], p = .019) between eradication-successful and eradication-failed patients. Statistical analysis suggested that the median intragastric pH = 5.7 could identify the success of H. pylori eradication. CONCLUSIONS Bismuth-based quadruple therapy resulted in high H. pylori eradication rates either in PPI standard or double doses. Double dose of esomeprazole is associated with better intragastric acid suppression. A median 24-h intragastric pH of 5.7 could be appropriate cutoff value for predicting the successful H. pylori eradication.
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Affiliation(s)
- Haoran Ke
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jing Li
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Bingyun Lu
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chenghai Yang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jiamin Wang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Gastroenterology, University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, China
| | - Zhiqing Wang
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Le Liu
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ye Chen
- Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Pih GY, Choi KD, Gong EJ, Na HK, Ahn JY, Lee JH, Jung KW, Kim DH, Song HJ, Lee GH, Jung HY. Modified bismuth quadruple therapy with low-dose metronidazole as first-line therapy for Helicobacter pylori infection. Helicobacter 2021; 26:e12759. [PMID: 33113240 DOI: 10.1111/hel.12759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/30/2020] [Accepted: 09/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Bismuth-containing quadruple therapy is an effective alternative first-line therapy for Helicobacter pylori infection. We evaluated the efficacy and safety of a modified twice-a-day bismuth quadruple regimen (BQT-2) with low-dose (1000 mg total) metronidazole as first-line therapy for the eradication of H pylori. MATERIALS AND METHODS In this prospective pilot study, patients diagnosed with H pylori infection and naïve to eradication therapy were included. The modified BQT-2 therapy consisted of rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily, given 30 minutes before morning and evening meals for 14 days. H pylori eradication was assessed by 13 C-urea breath test conducted at least 4 weeks after therapy completion. RESULTS In 66 patients who received the modified BQT-2 regimen, the compliance rate was 100% and the H pylori eradication rate was 77.3%. H pylori was successfully cultured in 50 (75.8%) patients. The resistance rates to metronidazole and clarithromycin were 30.0% and 22.0%, respectively. Eradication rates were not significantly different according to the resistance to metronidazole (metronidazole-susceptible: 74.3% [26/35], metronidazole-resistant: 73.3% [11/15]; P > .99). Most of the adverse events were mild, with 20 (30%) patients developing nausea, epigastric soreness, loose stool, asthenia, skin rash, dizziness, taste perversion, headache, or dyspepsia. CONCLUSIONS Twice-a-day modified BQT-2 regimen with low-dose metronidazole was suboptimal as an alternative first-line therapy for eradicating H pylori, despite high patient compliance.
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Affiliation(s)
- Gyu Young Pih
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Mestrovic A, Perkovic N, Bozic J, Pavicic Ivelja M, Vukovic J, Kardum G, Puljiz Z, Tonkic A. Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection. PLoS One 2020; 15:e0244500. [PMID: 33378403 PMCID: PMC7773256 DOI: 10.1371/journal.pone.0244500] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 12/09/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. MATERIALS AND METHODS In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. RESULTS Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. CONCLUSION Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Split, Croatia
- * E-mail:
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split, Croatia
| | | | - Jonatan Vukovic
- Department of Gastroenterology, University Hospital of Split, Split, Croatia
| | - Goran Kardum
- Department of Psychology, Faculty of Humanities and Social Sciences, University of Split, Split, Croatia
| | - Zeljko Puljiz
- Department of Gastroenterology, University Hospital of Split, Split, Croatia
- Department of Internal Medicine, University of Split School of Medicine, Split, Croatia
| | - Ante Tonkic
- Department of Gastroenterology, University Hospital of Split, Split, Croatia
- Department of Internal Medicine, University of Split School of Medicine, Split, Croatia
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Park JH, Kim D, Choe JW, Kim SY, Jung SW, Hyun JJ, Jung YK, Koo JS, Yim HJ, Lee SW. First-line Helicobacter pylori Eradication Rate of the 10-day Hybrid Therapy. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2020. [DOI: 10.7704/kjhugr.2020.0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background/Aims: To improve the eradication rate of a first-line therapy for Helicobacter pylori infection, alternate regimens such as sequential, concomitant, and hybrid therapies have been tried. The aim of this study was to evaluate the eradication rate of the 10-day hybrid therapy as a first-line therapy.Materials and Methods: This retrospective study enrolled 124 patients from the Korea University Ansan Hospital between April 2016 and December 2019. The 10-day hybrid therapy comprised 5 days of dual therapy (proton pump inhibitor [PPI] standard dose and amoxicillin 1 g, twice daily) followed by 5 days of quadruple therapy (PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily). We compared the 10-day hybrid therapy with the 10-day concomitant therapy comprising PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily. Eradication was assessed by a <sup>13</sup>C-urea breath test or gastroscopic biopsy at least 4 weeks after treatment completion.Results: The eradication rates of the 10-day hybrid and concomitant therapies were 74.2% (46/62) and 67.7% (42/62), respectively, in the intention-to-treat (ITT) analysis and 88.5% (46/52) and 82.4% (42/51), respectively, in the per-protocol (PP) analysis. There was no significant difference in the eradication rates between the two groups in the ITT (P=0.429) and PP analysis (P=0.380). Adverse events developed in 75.0% and 70.6% of patients in the hybrid and concomitant groups, respectively, but there was no significant difference (P=0.615).Conclusions: The 10-day hybrid therapy can be an option for a first-line therapy of Helicobacter pylori infection.
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Ma X, You P, Xu Y, Ye X, Tu Y, Liu Y, Yang M, Liu D. Anti-Helicobacter pylori-associated gastritis effect of the ethyl acetate extract of Alpinia officinarum Hance through MAPK signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2020; 260:113100. [PMID: 32531409 DOI: 10.1016/j.jep.2020.113100] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 06/02/2020] [Accepted: 06/07/2020] [Indexed: 06/11/2023]
Affiliation(s)
- Xiaoqing Ma
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Pengtao You
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Yan Xu
- Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
| | - Xiaochuan Ye
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Yijun Tu
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Yanwen Liu
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Min Yang
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
| | - Dan Liu
- Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
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Bang CS, Lim H, Jeong HM, Shin WG, Choi JH, Soh JS, Kang HS, Yang YJ, Hong JT, Shin SP, Suk KT, Lee JJ, Baik GH, Kim DJ. Amoxicillin or tetracycline in bismuth-containing quadruple therapy as first-line treatment for Helicobacter pylori infection. Gut Microbes 2020; 11:1314-1323. [PMID: 32362221 PMCID: PMC7524369 DOI: 10.1080/19490976.2020.1754118] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/17/2020] [Accepted: 03/30/2020] [Indexed: 02/08/2023] Open
Abstract
AIM To compare the efficacy and safety between modified quadruple- and bismuth-containing quadruple therapy as first-line eradication regimen for Helicobacter pylori infection. METHODS This study was a multicenter, randomized-controlled, non-inferiority trial. Subjects endoscopically diagnosed with H. pylori infection were randomly allocated to receive modified quadruple- (rabeprazole 20 mg bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid [elemental bismuth 480 mg]; PAMB) or bismuth-containing quadruple therapy (rabeprazole 20 mg bid, bismuth subcitrate 300 mg qid, metronidazole 500 mg tid, tetracycline 500 mg qid; PBMT) for 14 days. Rates of eradication success and adverse events were investigated. Antibiotic resistance was determined using the agar dilution and DNA sequencing of the clarithromycin resistance point mutations in the 23 S rRNA gene of H. pylori. RESULTS In total, 233 participants were randomized, 27 were lost to follow-up, and four violated the protocol. Both regimens showed an acceptable eradication rate in the intention-to-treat (PAMB: 87.2% vs. PBMT: 82.8%, P = .37), modified intention-to-treat (96.2% vs. 96%, P > .99), and per-protocol (96.2% vs. 96.9%, P > .99) analyses. Non-inferiority in the eradication success between PAMB and PBMT was confirmed. The amoxicillin-, metronidazole-, tetracycline-, clarithromycin-, and levofloxacin-resistance rates were 8.3, 40, 9.4, 23.5, and 42.2%, respectively. Antimicrobial resistance did not significantly affect the efficacy of either therapy. Overall compliance was 98.1%. Adverse events were not significantly different between the two therapies. CONCLUSION Modified quadruple therapy comprising rabeprazole, amoxicillin, metronidazole, and bismuth is an effective first-line treatment for the H. pylori infection in regions with high clarithromycin and metronidazole resistance.
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Affiliation(s)
- Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
| | - Hyun Lim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Hae Min Jeong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Jae Ho Choi
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
| | - Jae Seung Soh
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ho Suk Kang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Young Joo Yang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ji Taek Hong
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Suk Pyo Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Jae Jun Lee
- Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
- Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
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Bari Z, Fakheri H, Taghvaei T, Yaghoobi M. A Comparison between 10-day and 12-day Concomitant Regimens for Helicobacter Pylori Eradication: A Randomized Clinical Trial. Middle East J Dig Dis 2020; 12:106-110. [PMID: 32626563 PMCID: PMC7320987 DOI: 10.34172/mejdd.2020.169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is one of the most common bacterial infections worldwide, which is associated with peptic ulcer disease and gastric cancer. In this study, we compared the efficacy of 10-day versus 12-day concomitant therapy as the first-line treatment for H. pylori eradication in Iran. METHODS 218 patients with peptic ulcer disease and naïve H. pylori infection, were randomly divided into two groups to receive either 10-day or 12-day concomitant regimens, composed of pantoprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily. Eight weeks after treatment, H. pylori eradication was assessed by 14C- urea breath test. The trial was registered in the Iranian Registry of Clinical Trials (code: IRCT20170521034070N2). RESULTS 212 patients completed the study. According to the intention to treat analysis, the eradication rates were 83.6% (95% CI: 76.6-90.5) and 88.8% (95% CI: 82.8-94.7) in 10-day and 12-day concomitant therapy groups, respectively (p = 0.24). Per-protocol eradication rates were 85.9% (95% CI: 79.3–92.4) and 92.6% (95% CI: 87.6–97.5), respectively (p = 0.19). The rates of severe side effects were not statistically different between the two groups (3.6% vs. 8.1%; p = 0.428). CONCLUSION 12-day concomitant therapy could achieve ideal eradication rates by both intention to treat and perprotocol analyses. In order to reduce the cost of drugs and the rate of adverse effects of therapy, among 10-day and 12day regimens, 12-day concomitant therapy seems to be a good alternative to 14-day concomitant therapy that has been suggested by international guidelines.
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Affiliation(s)
- Zohreh Bari
- Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hafez Fakheri
- Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Tarang Taghvaei
- Gut and Liver Research Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Mohammad Yaghoobi
- Associate Professor of Gastroenterology, Division of Gastroenterology, Deartment of Medicine, McMaster University Medical Center, Hamiton, Ontarion, Canada
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Cho JH, Jin SY. Optimized diagnosis of Helicobacter pylori and tailored eradication therapy for preventing gastric cancer: a proposal for SHAKE strategy. Expert Rev Gastroenterol Hepatol 2020; 14:553-564. [PMID: 32410515 DOI: 10.1080/17474124.2020.1770594] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION To decrease gastric cancer-related mortality, the Korean National Cancer Screening Program provides biennial screening gastroscopy to all individuals aged >40 years. However, a test-and-treat strategy of Helicobacter pylori for preventing gastric cancer has not been established. AREAS COVERED In this review, we present up-to-date results of endoscopic findings of H. pylori gastritis, optimal sites for H. pylori detection, gastric cancer risk assessment using serum pepsinogen, tailored eradication based on the antimicrobial resistance against H. pylori, and post-eradication surveillance. EXPERT OPINION Here we propose approaches to H. pylori diagnosis and treatment for preventing gastric cancer, termed 'Screening for H. pylori in Korea and Eradication (SHAKE)' strategy. This strategy consists of the following: (1) optimized H. pylori diagnosis, (2) individualized management based on the H. pylori infection status, and (3) tailored eradication therapy. H. pylori gastritis can be diagnosed by endoscopic observation of the gastric mucosal pattern at the greater curvature of the corpus. Measurement of the serum pepsinogen I/II ratio is useful for assessing the risk of gastric cancer. As a first-line treatment, tailored eradication based on the results of molecular testing is effective in a country with a high rate of clarithromycin-resistant H. pylori.
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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
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17
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Suzuki S, Gotoda T, Kusano C, Ikehara H, Ichijima R, Ohyauchi M, Ito H, Kawamura M, Ogata Y, Ohtaka M, Nakahara M, Kawabe K. Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan. Gut 2020; 69:1019-1026. [PMID: 31915235 PMCID: PMC7282559 DOI: 10.1136/gutjnl-2019-319954] [Citation(s) in RCA: 164] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/04/2019] [Accepted: 12/25/2019] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy. DESIGN This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori-positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. RESULTS Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups. CONCLUSION The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance. TRIAL REGISTRATION NUMBER UMIN000034140.
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Affiliation(s)
- Sho Suzuki
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Department of Gastroenterology, Yuri Kumiai General Hospital, Yurihonjo, Akita, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Chika Kusano
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hisatomo Ikehara
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ryoji Ichijima
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Motoki Ohyauchi
- Department of Gastroenterology, Osaki Citizen Hospital, Osaki, Miyagi, Japan
| | - Hirotaka Ito
- Department of Gastroenterology, Osaki Citizen Hospital, Osaki, Miyagi, Japan
| | - Masashi Kawamura
- Department of Gastroenterology, Sendai City Hospital, Sendai, Miyagi, Japan
| | - Yohei Ogata
- Department of Gastroenterology, Sendai City Hospital, Sendai, Miyagi, Japan
| | - Masahiko Ohtaka
- Yamanashi Koseiren Health Care Center, Kofu, Yamanashi, Japan
| | - Moriyasu Nakahara
- Department of Gastroenterology, Chichibu Municipal Hospital, Chichibu, Saitama, Japan
| | - Koichi Kawabe
- Department of Gastroenterology, Fukaya Red Cross Hospital, Fukaya, Saitama, Japan
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Kim SJ, Chung JW, Woo HS, Kim SY, Kim JH, Kim YJ, Kim KO, Kwon KA, Park DK. Two-week bismuth-containing quadruple therapy and concomitant therapy are effective first-line treatments for Helicobacter pylori eradication: A prospective open-label randomized trial. World J Gastroenterol 2019; 25:6790-6798. [PMID: 31857780 PMCID: PMC6920663 DOI: 10.3748/wjg.v25.i46.6790] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 12/01/2019] [Accepted: 12/06/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Increasing levels of antibiotic resistance have reduced the Helicobacter pylori (H. pylori) eradication rates afforded by the standard triple therapy. Thus, 2-wk first-line four-drug regimens must be considered.
AIM To analyze the eradication rates of modified bismuth-containing quadruple therapy (mBCQT) and concomitant therapy (CT), the associated adverse events, and compliance.
METHODS Patients infected with H. pylori were prospectively randomized to receive mBCQT or CT for 2 wk. mBCQT featured a proton pump inhibitor (PPI), bismuth, metronidazole, and tetracycline, taken twice daily. CT included a PPI, clarithromycin, metronidazole, and amoxicillin, taken twice daily. The 13C-urea breath test was performed no earlier than 4 wk after therapy concluded to confirm eradication. If either the histological or rapid urease test was positive, H. pylori infection was diagnosed.
RESULTS The demographic characteristics of 68 patients who received mBCQT and 68 who received CT did not differ significantly. On intention-to-treat analysis, the eradication rate was 88.2% (60/68) in the mBCQT group and 79.4% (54/68) in the CT group (P = 0.162). By per-protocol analysis, the respective eradication rates were 98.4% (60/61) and 93.1% (54/58) (P = 0.199). More CT than mBCQT patients experienced adverse events [33.8% (23/68) mBCQT vs 51.5% (35/58) CT patients, respectively, P = 0.037]. All patients showed good compliance [85.3% (58/68) mBCQT vs 82.4% (56/68) CT patients, P = 0.641].
CONCLUSION The H. pylori eradication rates of the 2-wk mBCQT and CT regimens are high. Most patients show good compliance, and more CT than mBCQT patients experience adverse events.
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Affiliation(s)
- So Jeong Kim
- College of Medicine, Gachon University Graduate School of Medicine, Incheon 21936, South Korea
| | - Jun-Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Hyun Sun Woo
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, South Korea
| | - Jung Ho Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Yoon Jae Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Kyoung Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Kwang An Kwon
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
| | - Dong Kyun Park
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
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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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20
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Kim BJ, Lee H, Lee YC, Jeon SW, Kim GH, Kim HS, Sung JK, Lee DH, Kim HU, Park MI, Choi IJ, Yoon SM, Kim SW, Baik GH, Lee JY, Kim JI, Kim SG, Kim J, Lee J, Kim JG, Kim JJ. Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea. Gut Liver 2019; 13:531-540. [PMID: 31505907 PMCID: PMC6743805 DOI: 10.5009/gnl19136] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/10/2019] [Accepted: 07/19/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIMS This nationwide, multicenter prospective randomized controlled trial aimed to compare the efficacy and safety of 10-day concomitant therapy (CT) and 10-day sequential therapy (ST) with 7-day clarithromycin-containing triple therapy (TT) as first-line treatment for Helicobacter pylori infection in the Korean population. METHODS Patients with H. pylori infection were assigned randomly to 7d-TT (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for 7 days), 10d-ST (lansoprazole 30 mg and amoxicillin 1 g twice daily for the first 5 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for the remaining 5 days), or 10d-CT (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 10 days). The primary endpoint was eradication rate by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS A total of 1,141 patients were included. The 10d-CT protocol achieved a markedly higher eradication rate than the 7d-TT protocol in both the ITT (81.2% vs 63.9%) and PP analyses (90.6% vs 71.4%). The eradication rate of the 10d-ST protocol was superior to that of the 7d-TT protocol (76.3% vs 63.9%, ITT analysis; 85.0% vs 71.4%, PP analysis). No significant differences in adherence or serious side effects were found among the three treatment arms. CONCLUSIONS The 10d-CT and 10d-ST regimens were superior to the 7d-TT regimen as standard first-line treatment in Korea.
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Affiliation(s)
- Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul,
Korea
| | - Seong Woo Jeon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu,
Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan,
Korea
| | - Hyun-Soo Kim
- 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
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju,
Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan,
Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang,
Korea
| | - Soon Man Yoon
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju,
Korea
| | - Sang Wook Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju,
Korea
| | - Gwang Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon,
Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Dongsan Medical Center, Keimyung University School of Medicine, Daegu,
Korea
| | - Jin Il Kim
- Department of Internal Medicine, Yeouido St. Mary Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Jayoun Kim
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul,
Korea
| | - Joongyup Lee
- Department of Prevention and Management, Inha University Hospital, Inha University School of Medicine, Incheon,
Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Jae J. Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
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21
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Yu L, Luo L, Long X, Liang X, Ji Y, Chen Q, Song Y, Li X, Graham DY, Lu H. Susceptibility-guided therapy for Helicobacter pylori infection treatment failures. Therap Adv Gastroenterol 2019; 12:1756284819874922. [PMID: 31523279 PMCID: PMC6734621 DOI: 10.1177/1756284819874922] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 07/30/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Empirical therapy of Helicobacter pylori frequently results in treatment failure due to unrecognized antimicrobial resistance. The aim of this study was to investigate the effectiveness of susceptibility-guided therapy for rescue treatment of H. pylori infection in China. METHODS This was a prospective study of consecutive 200 patients infected with H. pylori with one or more treatment failures. The therapy chosen was susceptibility based using the most effective, best-tolerated regimens first and a locally proven, reliably effective regimen for multidrug-resistant infections. All patients received 14-day triple therapy, i.e. esomeprazole 20 mg and amoxicillin 1 g twice a day plus clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, or levofloxacin 500 mg daily, or, for multidrug-resistant infections, amoxicillin-containing bismuth quadruple therapy with esomeprazole 20 mg twice a day, bismuth 220 mg twice a day, amoxicillin 1 g three times a day, and metronidazole 400 mg four times a day. Antibiotic resistance was determined by agar dilution. RESULTS The eradication rate of susceptibility-guided therapy overall was 94.5% (189/200, 95% confidence interval: 90.4-97.2%). Around 28% (56/200) of patients carried strains susceptible to one of the tested antibiotics and were prescribed the triple therapy. A total of 144 multidrug-resistant patients received bismuth quadruple therapy. The eradication rates were all greater than 90%, i.e. 91.7% (11/12), 92.3% (12/13), and 93.5% (29/31) in those who received clarithromycin, metronidazole, and levofloxacin-containing triple therapy and 95.1% (137/144) for the bismuth quadruple therapy. There were no differences in eradication rates between the subgroups. CONCLUSIONS Although susceptibility-guided therapy proved high efficacious despite the high proportion of multidrug-resistant strains, the strategy suggested the best approach for this population would be empirical amoxicillin-containing bismuth quadruple therapy. ClinicalTrials.gov identifier: NCT03413020.
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Affiliation(s)
- Lou Yu
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Laisheng Luo
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Xiaohua Long
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Liang
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Yingjie Ji
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Qi Chen
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - Yanyan Song
- Department of Biostatistics, Institute of
Medical Sciences, Shanghai Jiao Tong University School of Medicine,
Shanghai, China
| | - Xiaobo Li
- Division of Gastroenterology and Hepatology, Key
Laboratory of Gastroenterology & Hepatology, Ministry of Health,
Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine,
Shanghai Jiao Tong University, Shanghai, China
| | - David Y. Graham
- Department of Medicine, Michael E DeBakey
Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX,
USA
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22
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Jun JS, Seo JH, Park JS, Rhee KH, Youn HS. Changes in the Treatment Strategies for Helicobacter pylori Infection in Children and Adolescents in Korea. Pediatr Gastroenterol Hepatol Nutr 2019; 22:417-430. [PMID: 31555566 PMCID: PMC6751106 DOI: 10.5223/pghn.2019.22.5.417] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Revised: 08/29/2019] [Accepted: 08/30/2019] [Indexed: 12/13/2022] Open
Abstract
The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive non-invasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.
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Affiliation(s)
- Jin-Su Jun
- Department of Pediatrics, Gyeongsang National Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Ji-Hyun Seo
- Department of Pediatrics, Gyeongsang National Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Ji-Sook Park
- Department of Pediatrics, Gyeongsang National Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Kwang-Ho Rhee
- Department of Microbiology, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Hee-Shang Youn
- Department of Pediatrics, Gyeongsang National Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
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23
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Chen Q, Long X, Ji Y, Liang X, Li D, Gao H, Xu B, Liu M, Chen Y, Sun Y, Zhao Y, Xu G, Song Y, Yu L, Zhang W, Liu W, Graham DY, Lu H. Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment. Aliment Pharmacol Ther 2019; 49:1385-1394. [PMID: 31020673 DOI: 10.1111/apt.15273] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 03/04/2019] [Accepted: 03/29/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness. AIM To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. METHODS We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s. Primary outcome was H pylori eradication. RESULTS Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4% (82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI -3.1% to 3.2%) and 6.2% intent-to-treat (-0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates. CONCLUSIONS Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy.
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24
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Macías-García F, Bastón-Rey I, de la Iglesia-García D, Calviño-Suárez C, Nieto-García L, Domínguez-Muñoz JE. Bismuth-containing quadruple therapy versus concomitant quadruple therapy as first-line treatment for Helicobacter Pylori infection in an area of high resistance to clarithromycin: A prospective, cross-sectional, comparative, open trial. Helicobacter 2019; 24:e12546. [PMID: 30346636 DOI: 10.1111/hel.12546] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/14/2018] [Accepted: 09/18/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance. AIM To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. METHODS A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. CONCLUSION The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.
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Affiliation(s)
- Fernando Macías-García
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Iria Bastón-Rey
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Daniel de la Iglesia-García
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Cristina Calviño-Suárez
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Laura Nieto-García
- Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Juan Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
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25
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Park JY, Kim JG. [New Helicobacter pylori Eradication Therapies]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 72:237-244. [PMID: 30642139 DOI: 10.4166/kjg.2018.72.5.237] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 10/20/2018] [Accepted: 10/29/2018] [Indexed: 12/13/2022]
Abstract
While the prevalence of Helicobacter pylori (H. pylori) infection is decreasing in Korea, the incidence of gastric cancer remains high, emphasizing the importance of H. pylori eradication. A new treatment strategy is needed as the eradication rate with standard triple therapy, which is currently the standard first-line regimen for H. pylori infection, has decreased below the optimum level. The major cause of eradication failure is increased antibiotic resistance. Sequential, concurrent, and hybrid therapies that include clarithromycin produce higher eradication rates than conventional standard triple therapy. However, the effectiveness of these treatments is limited in regions where the resistance rate to various antibiotics is high. Bismuth quadruple therapy is another alternative therapy, but again the eradication rate is not sufficiently high. Tailored therapy based on individual characteristics, including antibiotic susceptibility, may be ideal, but there are several limitations for clinical application and further research is needed. New potassium-competitive acid blocker-based therapies could emerge as effective alternatives in the near future. A consensus is needed to establish a strategy for applying new eradication therapies in Korea.
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Affiliation(s)
- Jae Yong Park
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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26
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Lim H, Bang CS, Shin WG, Choi JH, Soh JS, Kang HS, Yang YJ, Hong JT, Shin SP, Suk KT, Lee JJ, Baik GH, Kim DJ. Modified quadruple therapy versus bismuth-containing quadruple therapy in first-line treatment of Helicobacter pylori infection in Korea; rationale and design of an open-label, multicenter, randomized controlled trial. Medicine (Baltimore) 2018; 97:e13245. [PMID: 30431605 PMCID: PMC6257664 DOI: 10.1097/md.0000000000013245] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 10/22/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Clarithromycin-containing triple regimen for eradication of Helicobacter pylori is no longer acceptable in Korea due to high clarithromycin resistance. Concomitant therapy or bismuth-containing quadruple therapy is recommended as an alternative regimen. A recent study in Korea has shown that modified quadruple therapy has comparable efficacy and safety to concomitant therapy as a first-line regimen. However, there has been no comparative study of modified quadruple therapy with bismuth-containing quadruple therapy. The aim of this study is to compare the efficacy and safety of modified quadruple therapy with those of bismuth-containing quadruple therapy as a first-line regimen and to present the phenotypic and genotypic antibiotic resistance profile of H pylori. METHODS This study is an open-label, multicenter, randomized controlled trial. We are recruiting subjects endoscopically diagnosed with H pylori infection from 2 hospitals in Korea. Subjects will be randomly allocated either to modified quadruple therapy (proton-pump inhibitor bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) or bismuth-containing quadruple therapy (proton-pump inhibitor bid, tetracycline 500 mg qid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) for 14 days. The rate of eradication success and adverse events will be checked at least 4 weeks after the treatment. Antibiotic resistance will be established using both a bacterial culture with agar dilutions and DNA sequencing of the clarithromycin resistance point mutations in the 23S rRNA gene of H pylori. CONCLUSION The results of this study will provide solid evidence for determining the optimal treatment regimen for first-line H pylori eradication in Korea.
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Affiliation(s)
| | - Chang Seok Bang
- Department of Internal Medicine
- Institute of New Frontier Research
| | | | | | | | | | - Young Joo Yang
- Department of Internal Medicine
- Institute of New Frontier Research
| | | | | | | | - Jae Jun Lee
- Institute of New Frontier Research
- Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon, Korea
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27
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O'Morain NR, Dore MP, O'Connor AJP, Gisbert JP, O'Morain CA. Treatment of Helicobacter pylori infection in 2018. Helicobacter 2018; 23 Suppl 1:e12519. [PMID: 30203585 DOI: 10.1111/hel.12519] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.
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Affiliation(s)
- Neil R O'Morain
- Department of Gastroenterology & Clinical Medicine, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland
| | - Maria P Dore
- Department of Medical, Surgical and Experimental Science, University of Sassari, Sassari, Italy
| | - Anthony J P O'Connor
- Department of Gastroenterology & Clinical Medicine, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Colm A O'Morain
- Department of Gastroenterology & Clinical Medicine, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland
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28
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Graham DY, Dore MP, Lu H. Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies. Expert Rev Anti Infect Ther 2018; 16:679-687. [PMID: 30102559 DOI: 10.1080/14787210.2018.1511427] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Recent Helicobacter pylori treatment guidelines recommend the 4-drug combinations bismuth quadruple therapy and concomitant therapy. Areas covered: We review antimicrobial therapy for H. pylori in the context of antimicrobial therapy in general and specifically in relation to good antimicrobial stewardship (defined as optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance). Expert commentary: The lack of regional and local H. pylori susceptibility data prevents implementation of susceptibility-based antimicrobial therapy and forces compromises. Bismuth quadruple therapy employing at least 1,500 mg of metronidazole for 14 days is effective despite metronidazole resistance. The main drawback is side effects causing reduced adherence. Versions where amoxicillin replaces metronidazole or tetracycline also appear effective. It is likely that bismuth quadruple therapy can be simplified by giving bismuth and possibly tetracycline b.i.d., possibly with fewer side effects. Concomitant therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is ineffective with dual clarithromycin-metronidazole resistance and all patients receive at least one unnecessary antibiotic thus promoting antimicrobial resistance worldwide. Concomitant therapy should be abandoned when susceptibility testing becomes widespread or an alternate becomes available.
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Affiliation(s)
- David Y Graham
- a Department of Medicine , Michael E. DeBakey VA Medical Center and Baylor College of Medicine , Houston , TX , USA
| | - Maria Pina Dore
- b Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica , University of Sassari , Sassari , Italy
| | - Hong Lu
- c Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, GI Division, Ren Ji Hospital, School of medicine , Shanghai Jiao Tong University, Shanghai Institution of Digestive Disease , Shanghai , China
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