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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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Abdulqader AKA, Alamri TA, Alhamad MA, Shehab El‐Deen S, Essa A, Alfayez RA, Albaqshi BM, Almajed AS, Alhassan MY, Essa A, Albadrani AA, Alomair O, Al Jalal BA, Almulhim MY, Alotaibi A, Darwish E. First-Line Levofloxacin-Based Triple Therapy Versus Standard Bismuth-Based Quadruple Therapy for Helicobacter pylori Eradication in Saudi Arabia: A Retrospective Single-Center Study. Health Sci Rep 2025; 8:e70432. [PMID: 39917596 PMCID: PMC11798733 DOI: 10.1002/hsr2.70432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 12/12/2024] [Accepted: 01/23/2025] [Indexed: 02/09/2025] Open
Abstract
Background and Aims Antibiotic resistance in Saudi Arabia has led to decreased efficacy of conventional triple therapy for Helicobacter pylori (H. pylori) eradication, prompting the development of alternative treatments like levofloxacin-based triple and bismuth-based quadruple therapies. However, comparative data regarding its efficacy are lacking. Therefore, this study's goal was to compare the efficacy of levofloxacin-based triple therapy with that of standard bismuth-based quadruple therapy as first-line regimens. Methods This retrospective analysis included 197 treatment-naïve adults with H. pylori infection who received levofloxacin-based triple (levofloxacin + amoxicillin + PPI) therapy (n = 81) or standard bismuth-based quadruple (bismuth + tetracycline + metronidazole + PPI) therapy (n = 116). H. pylori eradication was evaluated 4-8 weeks after medication administration using the 13C-urea breath test, and variables that could affect the rate of success were examined. Results There were no differences between groups in terms of age, sex, nationality, or type of proton pump inhibitor (PPI) used. The bismuth-based quadruple therapy group exhibited a markedly superior success rate compared to the levofloxacin-based triple therapy group when the latter was administered for 7 or 10 days (81.03% vs. 6.66%, p < 0.001, and 81.03% vs. 36.1%, p < 0.001, respectively). However, when the levofloxacin-based triple therapy was extended to 14 days, its H. pylori eradication rate became comparable to that of the 10-day bismuth-based quadruple therapy (81.03% vs. 80%, p = 0.898). Eradication rates for both regimens were similar for patients aged ≥ 60, non-Saudi, when using omeprazole and those treated with levofloxacin-based triple therapy for 14 days. Conclusion Quadruple treatment based on bismuth is superior to triple therapy based on levofloxacin for eradicating H. pylori in Saudi Arabia and should be used as a first-line treatment. However, the 14-day levofloxacin-based triple treatment had an H. pylori eradication rate comparable to that of the 10-day bismuth-based quadruple therapy.
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Affiliation(s)
| | - Turki Abdullah Alamri
- Internal Medicine Department, Gastroenterology UnitKing Fahad University HospitalAl KhobarKingdom of Saudi Arabia
- Imam Abdulrahman Bin Faisal UniversityDammamKingdom of Saudi Arabia
| | | | - Somaia Shehab El‐Deen
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
- Tropical Medicine Department, Faculty of MedicineMenoufia UniversityShebin El‐KomEgypt
| | - Abdallah Essa
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
- Tropical Medicine Department, Faculty of MedicineMenoufia UniversityShebin El‐KomEgypt
| | | | | | | | | | - Ali Essa
- Faculty of Medicine, Menoufia UniversityShebin El‐KomEgypt
| | - Ahmed Abdullah Albadrani
- Internal Medicine DepartmentCollege of Medicine, Prince Sattam Bin Abdulaziz UniversityAl‐KharjKingdom of Saudi Arabia
| | - Omar Alomair
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
| | - Bashaeer Abdullh Al Jalal
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
| | - Mohammed Yousef Almulhim
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
| | - Abdullah Alotaibi
- Internal Medicine Department, Gastroenterology UnitKing Fahad University HospitalAl KhobarKingdom of Saudi Arabia
- Imam Abdulrahman Bin Faisal UniversityDammamKingdom of Saudi Arabia
| | - Ehab Darwish
- Internal Medicine DepartmentCollege of Medicine, King Faisal UniversityAl‐AhsaKingdom of Saudi Arabia
- Hepatology, Gastroenterology and Infectious Diseases Department, Faculty of MedicineZagazig UniversityZagazigEgypt
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Xie J, Peng J, Liu D, Zeng R, Qiu J, Shen L, Gong X, Liu D, Xie Y. Treatment failure is a key factor in the development of Helicobacter pylori resistance. Helicobacter 2024; 29:e13091. [PMID: 38780150 DOI: 10.1111/hel.13091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/11/2024] [Accepted: 05/06/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Helicobacter pylori eradication failure influences its antibiotic resistance. AIMS This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. MATERIALS AND METHODS This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. RESULTS The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. CONCLUSION The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.
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Affiliation(s)
- Jinliang Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Jianxiang Peng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Dingwei Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Rong Zeng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Jiayu Qiu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Liting Shen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Xiaomin Gong
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Dongsheng Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
- Jiangxi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi Province, China
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Tungtrongchitr N, Bongkotvirawan P, Ratana-Amornpin S, Siramolpiwat S, Eiamsitrakoon T, Gamnarai P, Wongcha-Um A, Yamaoka Y, Pawa KK, Vilaichone RK. Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial). Sci Rep 2024; 14:8986. [PMID: 38637591 PMCID: PMC11026498 DOI: 10.1038/s41598-024-59621-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/11/2024] [Indexed: 04/20/2024] Open
Abstract
Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3-94.2 and 94%, 95% CI 87.4-100, respectively (RR difference 0.25, 95% CI 0.03-0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.
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Affiliation(s)
- Nuttapat Tungtrongchitr
- Ramathibodi Medical School, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, Thailand
| | - Phubordee Bongkotvirawan
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand
| | - Sarita Ratana-Amornpin
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand
| | - Sith Siramolpiwat
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12120, Thailand
| | - Thanee Eiamsitrakoon
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12120, Thailand
| | - Pornpen Gamnarai
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand
| | - Arti Wongcha-Um
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12120, Thailand
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Oita, 879-5593, Japan
- Department of Medicine-Gastroenterology, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Kammal Kumar Pawa
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12120, Thailand
| | - Ratha-Korn Vilaichone
- Department of Medicine, Faculty of Medicine, Center of Excellence in Digestive Diseases and Gastroenterology Unit, Thammasat University, Pathum Thani, 12120, Thailand.
- Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12120, Thailand.
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Han YY, Li JY, Guan JL, Liu M, Li PY. Application of furazolidone in Helicobacter pylori infection eradication. J Dig Dis 2024; 25:148-155. [PMID: 38624062 DOI: 10.1111/1751-2980.13265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 03/15/2024] [Accepted: 03/18/2024] [Indexed: 04/17/2024]
Abstract
Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.
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Affiliation(s)
- Ying Ying Han
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ji Yan Li
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Jia Lun Guan
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Mei Liu
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Pei Yuan Li
- Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
- Department of Gastroenterology, Wenchang People's Hospital, Wenchang, Hainan Province, China
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Li J, Shi H, Zhou F, Xie L, Lin R. The Efficacy and Safety of Regimens for Helicobacter pylori Eradication Treatment in China: A Systemic Review and Network Meta-Analysis. J Clin Gastroenterol 2024; 58:12-23. [PMID: 38084866 DOI: 10.1097/mcg.0000000000001902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
BACKGROUND With Helicobacter pylori's increasing antibiotic resistance, evidence of more effective treatments is lacking in China, where H. pylori prevalence is nearly 50%. Thus, we performed a network meta-analysis to compare therapeutic regimens. METHODS Data extracted from eligible randomized controlled trials from January 2000 to September 2021 were entered into a Bayesian hierarchical random-effects model to evaluate the efficacy and safety of H. pylori eradication regimens. RESULTS This study included 101 trials involving 21,745 patients. Vonoprazan-bismuth-containing quadruple therapy (VBQT) ranked the highest [surfaces under cumulative ranking curve (SUCRA), 83.64%], followed by high-dose amoxicillin dual therapy (HDDT) [SUCRA, 79.70%, odds ratio (OR)=1.31, 95% credible interval (CrI) (0.36, 4.72)] and proton pump inhibitor-based bismuth-containing quadruple therapy (BQT) [SUCRA, 63.59%, OR=1.59, 95% CrI (0.48, 5.24)]. HDDT [OR=2.47, 95% CrI (1.51, 4.06)], BQT [OR=2.04, 95% CrI (1.69, 2.47)], concomitant quadruple nonbismuth therapy (CT) [OR=1.93, 95% CrI (1.19, 3.15)], and sequential therapy (ST) [OR=1.86, 95% CrI (1.50, 2.32)] had higher eradication rates than standard triple therapy (TT). ST (SUCRA, 82.52%) and VBQT (SUCRA, 83.89%) had the highest eradication rate before and after 2010 in the effectiveness ranking, respectively. Furthermore, the H. pylori eradication rate of patients receiving 14-day BQT treatment was higher than that of 10-day BQT regimen [OR=2.55, 95% CI (1.84, 3.53)] and 7-day BQT regimen [OR=3.64, 95% CI (2.64, 5.01)]. CONCLUSIONS The TT regimen was not an optimal choice in China for H. pylori eradication; VBQT, HDDT, and BQT showed better efficacy. After 2010, there is a trend toward significance that VBQT provided a higher H. pylori eradication rate in China, but with only 1 randomized controlled trial. Thus, more supportive real-world data are needed to confirm its effectiveness.
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Affiliation(s)
- Jing Li
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Huiying Shi
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Fang Zhou
- Takeda Pharmaceutical Company Ltd., Shanghai
| | - Li Xie
- Takeda Pharmaceutical Company Ltd., Beijing, China
| | - Rong Lin
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
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Liu Z, Xiang L, Tian M, Wang H, Zhao X, Liu K, Yu J, Liu T, Liu S, Mu X, Yang B, Zhang S, Luo J. A Counterion-Free Strategy for Chronic Metabolic Acidosis Based on an Orally Administered Gut-Restricted Inorganic Adsorbent. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2305992. [PMID: 37921507 DOI: 10.1002/adma.202305992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 10/23/2023] [Indexed: 11/04/2023]
Abstract
Chronic metabolic acidosis, arising as a complication of chronic kidney disease (CKD), not only reduces patients' quality of life but also aggravates renal impairment. The only available therapeutic modality, involving intravenous infusion of NaHCO3 , engenders undesirable sodium retention, thereby increasing hemodynamic load and seriously exacerbating the primary disease. This deleterious cascade extends to the development of cardiovascular diseases. Herein, an orally administered, gut-restricted inorganic adsorbent that can effectively alleviate chronic metabolic acidosis without causing any electrolytic derangement or superfluous cardiovascular strain is developed. The genesis of ABC-350 entails the engineering of bismuth subcarbonate via annealing, thereby yielding a partially β-Bi2 O3 -doped (BiO)2 CO3 biphasic crystalline structure framework enriched with atomic vacancies. ABC-350 can selectively remove chloride ions and protons from the gastrointestinal tract, mimicking the physiological response to gastric acid removal and resulting in increased serum bicarbonate. Owing to its gut-restricted nature, ABC-350 exhibits commendable biosafety, averting undue systemic exposure. In two rat models of metabolic acidosis, ABC-350 emerges not only as a potent mitigator of acidosis but also effects discernible amelioration concerning proximal tubular morphology, interstitial fibrosis, and the incendiary cascades incited by metabolic acidosis. ABC-350, as the translationally relevant material, provides a promising strategy for the treatment of metabolic acidosis.
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Affiliation(s)
- Zhen Liu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Liang Xiang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Meng Tian
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Haoyu Wang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Xin Zhao
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Kangfei Liu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jia Yu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Tianzhi Liu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Shangpeng Liu
- School of Materials Science and Engineering, Tongji University, Shanghai, 201384, China
| | - Xin Mu
- School of Biomedical Engineering, ShanghaiTech University, Shanghai, 201210, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Bingxue Yang
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Shiyi Zhang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jie Luo
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
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Gugnani JS, Abhishek F, Agarwal Y, Damera AR, Kaur H, Taleb B, Mane R, Soni U, Nayar KD. Effectiveness of Rifabutin-Based Regimens in Treating Helicobacter pylori Infections. Cureus 2023; 15:e50541. [PMID: 38222127 PMCID: PMC10787902 DOI: 10.7759/cureus.50541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2023] [Indexed: 01/16/2024] Open
Abstract
Helicobacter pylori has been reported as a health problem worldwide, affecting a sizable portion of people. Peptic ulcers, gastric cancer, and various extra gastric conditions are associated with this bacterium. The rampant overprescribing of antibiotics has led to the emergence of H. pylori strains resistant to multiple antibiotics, causing a decline in the effectiveness of current treatments. Recently, there has been growing interest in researching alternative treatment options for H. pylori infections that do not respond to initial therapy. Rifabutin, a rifamycin derivative initially designed for tuberculosis treatment and preventing Mycobacterium avium complex infection, has gained attention as a potential rescue medication. It has shown efficacy against H. pylori and the potential to eradicate the bacterium when combined with other antibiotics. This systematic review article focuses on using rifabutin-based regimens as a treatment option after initial treatments have failed. The authors screened literature published in the last five years, between 2017 and 2022, across various search engines and closely examined relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search covered a variety of electronic databases and focused on H. pylori gastritis, rifabutin-based treatment plans, and in vivo investigations in healthy individuals. The comprehensive review provides convincing evidence that rifabutin-based regimens are effective rescue treatments for H. pylori infections. Multiple studies in various areas consistently demonstrated high eradication rates, ranging from 70% to 90%, when rifabutin-containing regimens were used. The analysis found that only a tiny percentage of H. pylori strains (1%) were resistant to rifabutin therapy, further supporting the viability of Rifabutin as an alternative when other antibiotics failed to eradicate H. pylori. The cost of Rifabutin is a significant factor that may limit its accessibility, particularly in resource-constrained settings where H. pylori infection is common. Moreover, the potential side effects of Rifabutin, such as hematological problems, rashes, and digestive issues, need to be considered. However, these side effects are typically manageable and can be reduced by combining Rifabutin with other antibiotics. In conclusion, this systematic review provides evidence supporting the effectiveness of regimens derived from Rifabutin in eliminating H. pylori infections after initial therapy failure. Due to the observation that Rifabutin effectively eradicates resistant H. pylori infections, it can be considered a suitable choice for rescue therapy. Rifabutin-containing regimens should be reserved as fourth- or later-line therapy options, considering economic factors, the risk of microbial resistance, potential side effects, and the availability of alternative medications. Future research should focus on optimizing rifabutin-based regimens and investigating combination therapies that have better H. pylori eradication rates while also addressing the problem of resistant strains.
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Affiliation(s)
| | - Fnu Abhishek
- Internal Medicine, Government Medical College, Amritsar, IND
| | - Yash Agarwal
- College of Medicine, West Bengal University of Health Sciences, Kolkata, IND
| | - Abhiram Rao Damera
- Internal Medicine, MediCiti Institute of Medical Sciences, Hyderabad, IND
| | | | - Bayan Taleb
- College of Medicine, Acibadem University, Istanbul, TUR
| | - Rohan Mane
- Neurological Surgery, University of Nis, Nis, SRB
| | - Ujjwal Soni
- General Medicine, University College of Medical Sciences, Delhi, IND
| | - Kapil D Nayar
- College of Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, IND
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9
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Chen J, Guo Y, Huang Y, Ding Z, Wang J, Liang X, Xu P, Han Y, Lu H. Rifabutin-Containing Triple Therapy Versus Bismuth Quadruple Therapy for Helicobacter pylori Rescue Treatment: A Multicenter, Randomized Controlled Trial. J Infect Dis 2023; 228:511-518. [PMID: 37079894 DOI: 10.1093/infdis/jiad114] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/09/2023] [Accepted: 04/19/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND We compared the efficacy and safety of rifabutin-containing triple therapy with bismuth quadruple therapy for rescue treatment of Helicobacter pylori. METHODS This was a noninferiority study trial of H. pylori treatment for subjects who had failed at least 2 prior treatments. Subjects were randomly assigned to receive rifabutin triple therapy with 14-day esomeprazole (20 mg), amoxicillin (1.0 g), and rifabutin (150 mg) twice a day; or bismuth quadruple therapy with esomeprazole (20 mg) and bismuth (220 mg) twice a day, plus metronidazole (400 mg) and tetracycline (500 mg) 4 times a day. Antimicrobial susceptibility was assessed by agar dilution and E-test. RESULTS From May 2021 to October 2022, a total of 364 subjects were randomized. The eradication rates by intention-to-treat, per-protocol, and modified intention-to-treat were 89.0% (162/182; 95% confidence interval [CI], 83.6%-92.8%), 94.0% (157/167; 95% CI, 89.3%-96.7%), and 93.6% (162/173; 95% CI, 89.0%-96.4%) for rifabutin triple group. For bismuth quadruple group, they were 89.6% (163/182; 95% CI, 84.3%-93.2%), 95.3% (143/150; 95% CI, 90.7%-97.7%), and 93.7% (163/174; 95% CI, 89.0%-96.4%). CONCLUSIONS The rifabutin triple therapy is an alternative to classical bismuth quadruple therapy for the rescue treatment of H. pylori with fewer side effects and higher compliance. CLINICAL TRIALS REGISTRATION NCT04879992.
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Affiliation(s)
- Jinnan Chen
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yixian Guo
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yu Huang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhaohui Ding
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jing Wang
- Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Xiao Liang
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ping Xu
- Department of Gastroenterology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Yaohua Han
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University school of Medicine, Hangzhou, China
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases; Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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10
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Huang Y, Chen J, Ding Z, Chen X, Liang X, Zeng X, Xu F, Han Y, Lu H. Minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori rescue treatment: a multicentre, randomized controlled trial. J Gastroenterol 2023; 58:633-641. [PMID: 37042991 DOI: 10.1007/s00535-023-01991-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 03/31/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND To compare the efficacy and tolerability of minocycline vs. tetracycline in bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) rescue treatment. METHODS This study was a multi-center, randomized-controlled, non-inferiority trial. Refractory H. pylori-infected subjects with multiple treatment-failure were randomly (1:1) allocated to receive 14-day therapy with esomeprazole 20 mg b.i.d, bismuth 220 mg b.i.d, plus metronidazole 400 mg q.i.d and minocycline 100 mg b.i.d (minocycline group) or tetracycline 500 mg q.i.d (tetracycline group). Primary outcome was H. pylori eradication rate evaluated by 13C-urea breath test at least 6 weeks after the end of treatment. Antibiotic resistance was determined using E test method. RESULTS Three hundred and sixty-eight subjects were randomized. The eradication rates in minocycline group and tetracycline group were 88.0% (162/184, 95% CI 83.3-92.8%) and 88.6% (163/184, 95% CI 83.9-93.2%) in intention-to-treat analysis, 98.0% (149/152, 95% CI 95.8-100%) and 97.4% (150/154, 95% CI 94.9-99.9%) in per-protocol analysis, 93.1% (162/174, 95% CI 89.3-96.9%) and 93.1% (163/175, 95% CI 89.4-96.9%) in modified intention-to-treat analysis. Minocycline, tetracycline and metronidazole resistance rates were 0.7%, 1.4% and 89.6%, respectively. Non-inferiority of minocycline was confirmed (P < 0.025). Metronidazole resistance did not affect the efficacy of either therapy. The two therapies exhibited comparable frequencies of adverse events (55.4% vs. 53.3%); almost half of them were mild. Dizziness was the most common adverse events in the minocycline group. CONCLUSIONS Minocycline can be an alternative for tetracycline in bismuth-containing quadruple therapy for H. pylori empirical rescue treatment, irrespective of metronidazole resistance. However, relatively high incidence of adverse events in both regimens should be emphasized.
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Affiliation(s)
- Yu Huang
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jinnan Chen
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhaohui Ding
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xi Chen
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiao Liang
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xin Zeng
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fei Xu
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuehua Han
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Hong Lu
- NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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Sun YC, Zhu MJ, Chen XQ, Yue L, Zhao YR, Wang XJ, Kim JJ, Du Q, Hu WL. Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: A retrospective single center study. World J Gastroenterol 2023; 29:3508-3518. [PMID: 37389237 PMCID: PMC10303514 DOI: 10.3748/wjg.v29.i22.3508] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/09/2023] [Accepted: 05/15/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.
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Affiliation(s)
- Ying-Chao Sun
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Meng-Jia Zhu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Xue-Qin Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Lei Yue
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yi-Ru Zhao
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Xin-Jie Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - John J Kim
- Division of Gastroenterology, Loma Linda University Health, Loma Linda, CA 92354, United States
| | - Qin Du
- Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou 310009, Zhejiang Province, China
| | - Wei-Ling Hu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
- Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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12
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Wang Y, Li Y, Gong Y, Dong Y, Sun J, Chen M. Antibiotic resistance characteristics and risk factors analysis of Helicobacter pylori strains isolated from patients in Liaoning Province, an area in North China. PeerJ 2023; 11:e15268. [PMID: 37214095 PMCID: PMC10198150 DOI: 10.7717/peerj.15268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/29/2023] [Indexed: 05/24/2023] Open
Abstract
Background The prevalence of Helicobacter pylori (H. pylori) keeps rising while the eradication rate continues to decline due to the increasing antibiotic resistance. Regional variations of antimicrobial resistance to H. pylori have been recommended by guidelines in recent years. This study aims to investigate the antibiotic resistance rate of H. pylori and its association with infected subjects' characteristics in Liaoning Province, an area in north China. Methods Gastric tissues from 178 H. pylori positive participants without previous antibiotic use within four weeks were collected for H. pylori culture. Antibiotic susceptibility to furazolidone (AOZ), tetracycline (TC), levofloxacin (LFX), metronidazole (MET), clarithromycin (CLA), and amoxicillin (AMX) were examined with the agar dilution method. Associations between H. pylori resistance and patient characteristics were further analysed. Results No resistance was observed in AOZ or TC. For LFX, MET, CLA, and AMX, the overall resistance rates were 41.10%, 79.14%, 71.78%, and 22.09% respectively. There were significant differences between resistance to CLA and MALToma (P = 0.021), and between resistance to MET and age (P < 0.001). Conclusions The primary resistant rates of LEX, MET, CLA, and AMX were relatively high in Liaoning. Treatment effectiveness improvement could be achieved by prior antimicrobial susceptibility tests before antibiotic prescription.
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Affiliation(s)
- Yanmeng Wang
- Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yiling Li
- Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yuehua Gong
- Key Laboratory of GI Cancer Etiology and Prevention, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yuzhen Dong
- Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Jing Sun
- Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Moye Chen
- Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, China
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13
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Liu L, Nahata MC. Treatment of Helicobacter pylori Infection in Patients with Penicillin Allergy. Antibiotics (Basel) 2023; 12:737. [PMID: 37107099 PMCID: PMC10135207 DOI: 10.3390/antibiotics12040737] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 03/31/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Helicobacter pylori is among the prevalent causes of infections worldwide, and its resistance rate to antibiotics has been rising over time. Amoxicillin is the cornerstone for the treatment regimen. However, the prevalence of penicillin allergy ranges from 4% to 15%. In patients with true allergy, Vonoprazan-Clarithromycin-Metronidazole and bismuth quadruple therapy have demonstrated excellent eradication and high adherence rates. Vonoprazan-based therapy is administered less frequently and may be better tolerated than bismuth quadruple therapy. Therefore, vonoprazan-based therapy may be considered as a first-line therapy if accessible. Bismuth quadruple therapy can be used as the initial therapy when vonoprazan is unavailable. Levofloxacin or sitafloxacin-based regimens achieve a moderately high eradication rate. However, these are associated with potentially serious adverse effects and should only be used when other effective and safer regimens are unavailable. Cephalosporins such as cefuroxime have been used as an alternative to amoxicillin. Microbial susceptibility studies can guide the selection of appropriate antibiotics. PPI-Clarithromycin-Metronidazole fails to achieve a high eradication rate and should be used as a second-line therapy. PPI-Clarithromycin-Rifabutin should not be used because of low eradication rate and frequent adverse reactions. The choice of the most effective antibiotic regimen can enhance clinical outcomes in patients with H. pylori infection and penicillin allergy.
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Affiliation(s)
- Ligang Liu
- Institute of Therapeutic Innovations and Outcomes (ITIO), College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA;
| | - Milap C. Nahata
- College of Medicine, The Ohio State University, Columbus, OH 43210, USA
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14
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Bordin DS, Voynovan IN, Sarsenbaeva AS, Zaytsev OV, Abdulkhakov RA, Bakulina NV, Bakulin IG, Osipenko MF, Livzan MA, Alekseenko SA, Tarasova LV, Tarasova GN, Bogomolov PO, Maev IV, Andreev DN, Abdulkhakov SR, Starostin BD, Bakanova NV, Kononova AG, Kolbasnikov SV, Bueverova EL, Moreira L, Megraud F, O'Morain C, Perez Nyssen O, Gisbert J. [Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)]. TERAPEVT ARKH 2023; 95:120-129. [PMID: 37167127 DOI: 10.26442/00403660.2023.02.202107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 03/29/2023] [Indexed: 05/13/2023]
Abstract
BACKGROUND First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.
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Affiliation(s)
- D S Bordin
- Loginov Moscow Clinical Scientific Center
- Yevdokimov Moscow State University of Medicine and Dentistry
- Tver State Medical University
| | | | | | | | | | - N V Bakulina
- Mechnikov North-Western State Medical University
| | - I G Bakulin
- Mechnikov North-Western State Medical University
| | | | | | | | | | | | - P O Bogomolov
- Yevdokimov Moscow State University of Medicine and Dentistry
- Private Medical Center "Universal"
- Vladimirsky Moscow Regional Clinical Research Institute
| | - I V Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - D N Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | | | | | | | | | | | - E L Bueverova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - L Moreira
- Hospital Clínic de Barcelona
- Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)
- University of Barcelona
| | | | | | - O Perez Nyssen
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
- Universidad Autónoma de Madrid (UAM)
| | - J Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
- Universidad Autónoma de Madrid (UAM)
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Correia C, Almeida N, Leal C, Branquinho D, Fernandes A, Gravito-Soares E, Calhau C, Bastos I, Vasconcelos H, Figueiredo P. Single-capsule bismuth-based quadruple therapy as a rescue therapy for Helicobacter pylori eradication. Scand J Gastroenterol 2023; 58:227-231. [PMID: 36189844 DOI: 10.1080/00365521.2022.2119097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) infection is highly prevalent in Portugal and its eradication is formally recommended. However, the indiscriminate use of antimicrobials has led to a drastic rise in antibiotic resistance, with the failure of traditional eradication schemes. A single-capsule bismuth-based quadruple therapy became recently available in Portugal. This study aims to evaluate the efficacy and safety of a bismuth-based quadruple therapy as a second-line or rescue therapy. PATIENTS AND METHODS This was a multicentric study. All consecutive patients that were treated with bismuth-based quadruple therapy, as second-line or salvage treatment between July 2017 and April 2019 were enrolled. Their medical records were reviewed and clinical and laboratorial parameters, as well as data on treatment efficacy and adverse events were retrieved. Patients were also contacted by phone after treatment to confirm compliance, adverse events, and global satisfaction with this specific therapy. RESULTS A total of 151 subjects were included (female-68.9%; mean age-56 ± 13.5 years). Patients were previously submitted to 212 eradication schemes (Median-1; 1-5; IQR:4): 33.5% triple clarithromycin-based, 25% sequential, 7.5% concomitant, 5.2% others, and in 28.8% it was not possible to know the previous eradication scheme(s) followed by the patient. The PPI of choice was esomeprazole (39.7%), followed by omeprazole (27.8%). Compliance was achieved in 93.4% and the overall eradication rate was 90.1% (95% CI: 84.6-94.2). Treatment-related adverse effects were experienced by 63 patients (41.7%; 95% CI: 34-49.7), being mild in 29, moderate in 19, and severe in 15. The main drawbacks of the treatment, from the patient's perspective, were the high price (47%) and the adverse effects (16.6%). Failure to eradicate H. pylori was correlated with the following: previous rifabutin-based scheme (0 vs. 100%; p = 0.010) and a higher number of previous treatment schemes (1.5 ± 0.7 vs. 2.3 ± 1.2; p < 0.001). CONCLUSION In this South-European country a single-capsule bismuth-based quadruple therapy is an excellent option as a second-line or rescue therapy, with acceptable compliance and side effects.
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Affiliation(s)
- Catarina Correia
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Nuno Almeida
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Carina Leal
- Gastroenterology Department, Leiria Hospital Centre, Leiria, Portugal
| | - Diogo Branquinho
- Gastroenterology Department, Baixo Vouga Hospital Centre, Aveiro, Portugal
| | | | - Elisa Gravito-Soares
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Carlos Calhau
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Isabel Bastos
- Gastroenterology Department, Baixo Vouga Hospital Centre, Aveiro, Portugal
| | | | - Pedro Figueiredo
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Pimanov SI, Makarenko EV. Updated the Maastricht VI/Florence Consensus recommendations for the treatment of <i>Helicobacter pylori</i> infection: A review. CONSILIUM MEDICUM 2023. [DOI: 10.26442/20751753.2022.12.202045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
The new Maastricht VI/Florence Consensus clarifies a number of provisions that were previously under discussion. It has been postulated that Helicobacter pylori infection always causes gastritis, regardless of symptoms or complications. Before making a convincing diagnosis of functional dyspepsia, it is necessary to exclude Helicobacters gastritis. Some provisions of the consensus, such as the test and treat tactic, require elements of a critical attitude, taking into account Russian regional conditions. About 90% of stomach cancers are due to H. pylori. Eradication of H. pylori makes it possible to prevent gastric cancer at any age in adulthood, but the effectiveness of such cancer prevention decreases with age. Bismuth quadruple therapy is preferred in the eradication therapy algorithm. Decreased value of triple treatment with clarithromycin. There is a rapid increase in H. pylori resistance to fluoroquinolones. Triple therapy with rifabutin is called the final eradication protocol.
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Zhou L, Lu H, Song Z, Lyu B, Chen Y, Wang J, Xia J, Zhao Z. 2022 Chinese national clinical practice guideline on Helicobacter pylori eradication treatment. Chin Med J (Engl) 2022; 135:2899-2910. [PMID: 36579940 PMCID: PMC10106216 DOI: 10.1097/cm9.0000000000002546] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Helicobacter pylori ( H. pylori ) infection is an infectious disease with a prevalence rate of up to 50% worldwide. It can cause indigestion, gastritis, peptic ulcer, and gastric cancer. H. pylori eradication treatment can effectively control disease progression and reduce the risk of the above conditions. However, the escalating trend of antibiotic resistance presents a global challenge for H. pylori eradication. We aim to provide guidance on pharmacological treatment of H. pylori infection. METHODS This clinical practice guideline is developed following the World Health Organization's recommended process, adopting Grading of Recommendations Assessment, Development and Evaluation in assessing evidence quality, and utilizing Evidence to Decision framework to formulate clinical recommendations, minimizing bias and increasing transparency of the clinical practice guideline development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. RESULTS Though decreasing in developed countries, the prevalence of H. pylori remains high in developing countries, causing a major public health burden. This clinical practice guideline contains 12 recommendations concerning pharmacological treatment for H. pylori eradication. Among them, it is worth highlighting that bismuth preparations are inexpensive, safe, and effective, consequently making bismuth quadruple therapy a preferred choice for initial and rescue treatment. In empirical treatment, high-dose dual therapy is equally effective compared with bismuth quadruple therapy. CONCLUSIONS The 12 recommendations in this clinical practice guideline are formed with consideration for stakeholders' values and preferences, resource use, feasibility, and acceptability. Recommendations are generalizable to resource limited settings with similar antibiotic resistance pattern as China, and lower middle-income countries facing comparable sociological and technical challenges. REGISTRATION Guidelines International Network (GIN) website, https://guidelines.ebmportal.com/node/69996 .
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Affiliation(s)
- Liya Zhou
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Hong Lu
- Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Zhiqiang Song
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Bin Lyu
- Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310018, China
| | - Ye Chen
- Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China
| | - Jiyao Wang
- Department of Gastroenterology, Fudan University Affiliated Zhongshan Hospital, Shanghai 200032, China
| | - Jun Xia
- Nottingham Ningbo GRADE Center, Nottingham China Health Institute, University of Nottingham Ningbo China, Ningbo, Zhejiang 315100, China
- Academic Unit of Lifespan and Population Health, School of Medicine, The University of Nottingham, Nottingham, UK
| | - Zhan Zhao
- Systematic Review Solutions Ltd, Shanghai 201403, China
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18
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Sun K, Chen Y, Wang Z, Liu Y, Pan Y, Mao X, Xu L, Jin C, Chen M, Yu C, Li L. Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study. BMC Gastroenterol 2022; 22:520. [PMID: 36522612 PMCID: PMC9756606 DOI: 10.1186/s12876-022-02614-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND To improve the eradication rate of H. pylori, researchers have investigated the role of WeChat-based mini-app as an electronic reminding system in H. pylori treatment. METHODS Subjects from three medical centers were divided into two groups. Patients in the daily mini-app-based notification system group received daily notifications via the WeChat mini-app. Patients in the control group received one-time verbal education on the first clinical visit. Both groups received a 14-day quadruple therapy to eradicate H. pylori infection. Eradication rate, compliance, adverse events and satisfaction were evaluated. RESULTS Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted. The eradication rate in the daily mini-app-based notification system group was slightly higher compared with the control group (ITT analysis: 76.70% vs. 70.73%, p = 0.312; PP analysis: 85.87% vs. 82.86%, p = 0.562). The compliance was significantly higher in the daily mini-app-based notification system group (ITT analysis: 85.52% vs. 70.48%, p = 0.028; PP analysis: 92.39% vs. 81.90%, p = 0.030). The adverse event rates were similar between the two groups (PP analysis: 36.96% vs. 40.95%, p = 0.566). No significant difference in eradication rate was seen in each subgroup analysis by age, place of residence, grade of education, or endoscopic findings. CONCLUSION The study showed that daily mini-app-based notification improved patient compliance but not H. pylori eradication rate. Trial registration The research was registered in the Chinese Clinical Trial Registry (ChiCTR2000031011, 21/03/2020).
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Affiliation(s)
- Kefang Sun
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yishu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhenzhen Wang
- Department of Gastroenterology, Taizhou Hospital, Zhejiang University, Linhai, China
| | - Yi Liu
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, China
| | - Yue Pan
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, China
| | - Xinli Mao
- Department of Gastroenterology, Taizhou Hospital, Zhejiang University, Linhai, China
| | - Lei Xu
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, China
| | - Chaohui Jin
- Hithink RoyalFlush Information Network Co., Ltd., Hangzhou, China
| | - Ming Chen
- Hithink RoyalFlush Information Network Co., Ltd., Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lan Li
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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19
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Chi J, Xu C, Liu X, Wu H, Xie X, Liu P, Li H, Zhang G, Xu M, Li C, Wang C, Song F, Yang M, Wu J. A Comparison of Doxycycline and Amoxicillin Containing Quadruple Eradication Therapy for Treating Helicobacter pylori-Infected Duodenal Ulcers: A Multicenter, Opened, Randomized Controlled Trial in China. Pathogens 2022; 11:1549. [PMID: 36558883 PMCID: PMC9783029 DOI: 10.3390/pathogens11121549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/28/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Background: Increased antibiotic resistance is one of the major factors contributing to the failure of H. pylori eradication. This study aimed to compare the efficacy and safety of doxycycline and amoxicillin, both critical components for bismuth-based quadruple therapy, for the first-line treatment of H. pylori-infected duodenal ulcers. Methods: An open, randomized case-controlled, multicenter trial was conducted in seven hospitals in China. A total of 184 eligible participants were divided into an IDFB (ilaprazole 5 mg, doxycycline 100 mg, furazolidone 100 mg, and bismuth 220 mg bid) or IAFB (ilaprazole 5 mg, amoxicillin 1000 mg, furazolidone 100 mg, and bismuth 220 mg bid) group for 14 days. Both groups were administrated with ilaprazole 5 mg qd for another 14 days. The main outcome was an H. pylori eradication rate; secondary outcomes were ulcer healing, relief of symptoms, and incidence of adverse effects. Results: The H. pylori eradication rates were 85.9% (95% CI 78.6−93.9) in the IDFB vs. 84.8% (95% CI 77.3−92.3) in the IAFB group in ITT analysis (p > 0.05), and 92.9% (95% CI 87.4−98.5) vs. and 91.8% (95% CI 85.8−97.7) in PP analysis (p > 0.05). The overall ulcer healing rates of IDFB and IAFB were 79.1% and 84.7% (p > 0.05), both effective in relieving symptoms. Only nine participants had adverse reactions in this trial (4/92 in IDFB and 5/92 in IAFB). Conclusion: A bismuth quadruple regimen containing doxycycline or amoxicillin could be an effective and safe treatment for H. pylori eradication, while doxycycline replacement is an alternative for participants with penicillin allergy.
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Affiliation(s)
- Jingshu Chi
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Canxia Xu
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Xiaoming Liu
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Hao Wu
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Xiaoran Xie
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Peng Liu
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | - Huan Li
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
| | | | - Meihua Xu
- Department of Gastroenterology, Xiangya Hospital of Central South University, Changsha 410008, China
| | - Chaomin Li
- Shaoyang Central Hospital, Shaoyang 422000, China
| | - Chunlian Wang
- Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, China
| | | | - Ming Yang
- The Affiliated Hospital of Yongzhou Vocational Technical College, Yongzhou 425006, China
| | - Jie Wu
- Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha 410013, China
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20
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Tang X, Shen Y, Song X, Benghezal M, Marshall BJ, Tang H, Li H. Reassessment of the Broth Microdilution Method for Susceptibility Testing of Helicobacter pylori. J Infect Dis 2022; 226:S486-S492. [PMID: 36478248 DOI: 10.1093/infdis/jiac389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Helicobacter pylori infection is an infectious disease and thus the eradication treatment should be guided by susceptibility testing. This study aimed to assess the applicability of broth microdilution as a routine susceptibility testing method for H. pylori. METHODS Susceptibility profiles of clarithromycin (CLR) and levofloxacin (LEV) resistance in 76 clinical H. pylori isolates were simultaneously assessed using agar dilution and broth microdilution methods. The correlation between the minimum inhibitory concentrations (MICs) obtained by the 2 methods was assessed by means of linear regression analysis. RESULTS The correlation between the MICs determined by broth microdilution method and agar dilution method was good for both CLR (r = 0.966) and LEV (r = 0.959). The susceptibility agreement between the 2 methods was 100% for CLR and 96.1% for LEV. Using the broth microdilution method, the false resistance was found in 3.9% (3 of 76) strains for LEV susceptibility testing. No false susceptibility was found for either CLR or LEV, and no false resistance was found for susceptibility testing of CLR. CONCLUSIONS The broth microdilution method is suitable for routine susceptibility testing of clinical H. pylori isolates.
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Affiliation(s)
- Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaona Song
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Barry J Marshall
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia.,School of Biomedical Engineering, Marshall Laboratory of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, China
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.,Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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21
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Hu Y, Zhu Y, Lu NH. The management of Helicobacter pylori infection and prevention and control of gastric cancer in China. Front Cell Infect Microbiol 2022; 12:1049279. [PMID: 36530421 PMCID: PMC9751207 DOI: 10.3389/fcimb.2022.1049279] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 11/14/2022] [Indexed: 12/04/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection, a type-1 carcinogen, was closely associated with gastric cancer (GC). Successfully eradicating H. pylori infection could reduce the incidence of GC. China was a country with high incidence of GC and high prevalence of H. pylori infection. Nearly half of worldwide GC new cases and deaths attributed to H. pylori infection occurred in China. H. pylori prevalence varied over time with the improvement of socioeconomic status and sanitary conditions. The knowledge of antibiotic resistance rate in time was important to guide the clinical choice of antibiotics use in the regimens. With the publication of five Chinese consensus reports on the management of H. pylori infection and the effort of public preach of H. pylori-related knowledge, the standardization of H. pylori diagnosis and treatment by clinicians was improved. Bismuth-containing quadruple therapy was widely applied in clinical practice of H. pylori eradication because of high efficacy and safety. High-dose Proton Pump Inhibitor-amoxicillin dual therapy or vonoprazan-amoxicillin dual therapy showed comparable efficacy and lower side effects than bismuth-containing quadruple therapy, which were the alternative choice. The diagnosis rate of early GC was low and distinguishing Chinese GC risk population for the further endoscopy screening was important. Efforts have been done to establish prediction models to stratify GC risk in the Chinese GC risk population. We reviewed the current situation of the management of H. pylori infection and prevention and control of GC in China here.
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Affiliation(s)
- Yi Hu
- Department Of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China,JiangXi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department Of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China,JiangXi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi, China,*Correspondence: Nong-Hua Lu, ; Yin Zhu,
| | - Nong-Hua Lu
- Department Of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China,JiangXi Clinical Research Center for Gastroenterology, Nanchang, Jiangxi, China,*Correspondence: Nong-Hua Lu, ; Yin Zhu,
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22
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Multiple Bismuth Quadruple Therapy Containing Tetracyclines Combined with Other Antibiotics and Helicobacter pylori Eradication Therapy. J Clin Med 2022; 11:jcm11237040. [PMID: 36498615 PMCID: PMC9741466 DOI: 10.3390/jcm11237040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/24/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Helicobacter pylori (HP) infection is closely associated with the development of chronic gastritis, peptic ulcer, and gastric cancer. However, the resistance rate of H. pylori strains to antibiotics such as clarithromycin, metronidazole, and levofloxacin has increased significantly, resulting in a significant decrease in the eradication efficacy of commonly used regimens. Tetracycline has received the attention of domestic and foreign scholars because of its low resistance. The purpose of this review is to provide an update on the tetracycline-containing bismuth quadruple eradication therapy for H. pylori infection and review the efficacy and safety of the regimens, hoping to provide guidance for clinical practice.
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23
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Nyssen OP, Vaira D, Pérez Aísa Á, Rodrigo L, Castro-Fernandez M, Jonaitis L, Tepes B, Vologzhanina L, Caldas M, Lanas A, Lucendo AJ, Bujanda L, Ortuño J, Barrio J, Huguet JM, Voynovan I, Lasala JP, Sarsenbaeva AS, Fernandez-Salazar L, Molina-Infante J, Jurecic NB, Areia M, Gasbarrini A, Kupčinskas J, Bordin D, Marcos-Pinto R, Lerang F, Leja M, Buzas GM, Niv Y, Rokkas T, Phull P, Smith S, Shvets O, Venerito M, Milivojevic V, Simsek I, Lamy V, Bytzer P, Boyanova L, Kunovský L, Beglinger C, Doulberis M, Marlicz W, Goldis A, Tonkić A, Capelle L, Puig I, Megraud F, Morain CO, Gisbert JP. Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg). Clin Gastroenterol Hepatol 2022; 20:2243-2257. [PMID: 34954341 DOI: 10.1016/j.cgh.2021.12.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 12/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.
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Affiliation(s)
- Olga P Nyssen
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Dino Vaira
- Department of Surgical and Medical Sciences, University of Bologna, Bologna, Italy
| | - Ángeles Pérez Aísa
- Department of Gastroenterology, Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Marbella, Spain
| | - Luis Rodrigo
- Department of Gastroenterology, Hospital de Asturias, Oviedo, Spain
| | | | - Laimas Jonaitis
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Bojan Tepes
- Department of Gastroenterology, AM DC Rogaska, Rogaska Slatina, Slovenia
| | | | - María Caldas
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Angel Lanas
- Department of Gastroenterology, Hospital Clínico Universitario/Instituto de Investigacion Sanitaria Aragón, University of Zaragoza, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Zaragoza, Spain
| | - Alfredo J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain
| | - Luis Bujanda
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Universidad del País Vasco, San Sebastián, Spain
| | - Juan Ortuño
- Department of Gastroenterology, Hospital Universitari i Politècnic, La Fe, Valencia, Spain
| | - Jesús Barrio
- Department of Gastroenterology, Hospital Río Hortega, Valladolid, Spain
| | - Jose M Huguet
- Department of Gastroenterology, Hospital General Universitario de Valencia, Valencia, Spain
| | - Irina Voynovan
- Department of Gastroenterology, A.S. Loginov Moscow Clinical Scientific Center, Moscow, Russia
| | | | | | | | | | | | - Miguel Areia
- Department of Gastroenterology, Portuguese Oncology Institute Coimbra, Coimbra, Portugal
| | - Antonio Gasbarrini
- Medicina Interna, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Juozas Kupčinskas
- Department of Gastroenterology, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Dmitry Bordin
- Department of Gastroenterology, A.S. Loginov Moscow Clinical Scientific Center, Moscow, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Tver State Medical University, Tver, Russia
| | - Ricardo Marcos-Pinto
- Department of Gastroenterology, Centro Hospitalar do Porto Institute of Biomedical Sciences Abel Salazar, Centro de Investigação em Tecnologias e Serviços de Saúde, University of Porto, Porto, Portugal
| | - Frode Lerang
- Department of Gastroenterology, Østfold Hospital Trust, Grålum, Norway
| | - Marcis Leja
- Department of Gastroenterology, Digestive Diseases Centre Gastro, Institute of Clinical and Preventive Medicine and Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Gyorgy M Buzas
- Department of Gastroenterology, Ferencváros Health Centre, Budapest, Hungary
| | - Yaron Niv
- Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Petah Tikva, Israel
| | - Theodore Rokkas
- Department of Gastroenterology, Henry Dunant Hospital, Athens, Greece
| | - Perminder Phull
- Department of Gastroenterology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
| | - Sinead Smith
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Oleg Shvets
- Department of Gastroenterology, Internal Medicine, National Medical University, Kyiv, Ukraine
| | - Marino Venerito
- Department of Gastroenterology, Otto-von-Guericke University, Magdeburg, Germany
| | - Vladimir Milivojevic
- Department of Gastroenterology, Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia
| | - Ilkay Simsek
- Department of Gastroenterology, Internal Medicine, Hacettepe, University School of Medicine, Ankara, Turkey
| | - Vincent Lamy
- Department of Gastroenterology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium
| | - Peter Bytzer
- Department of Gastroenterology, Clinical Medicine, Zealand University Hospital, Copenhagen University, Copenhagen, Denmark
| | - Lyudmila Boyanova
- Department of Gastroenterology, Medical Microbiology, Medical University of Sofia, Sofia, Bulgaria
| | - Lumír Kunovský
- Department of Gastroenterology and Internal Medicine, Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | | | - Michael Doulberis
- Emergency Department, University Hospital Inselspital of Bern, Bern, Switzerland, Second Medical Clinic, School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece, and First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland
| | - Adrian Goldis
- Department of Gastroenterology, Timisoara Hospital, Timisoara, Romania
| | - Ante Tonkić
- Department of Gastroenterology, University Hospital of Split, University of Split School of Medicine, Split, Croatia
| | - Lisette Capelle
- Department of Gastroenterology, Meander Medical Center, Amersfoort, The Netherlands
| | - Ignasi Puig
- Department of Gastroenterology, Althaia Xarxa Assistencial Universitària de Manresa, Universitat de Vic-Universitat Central de Catalunya, Manresa, Spain
| | - Francis Megraud
- Institut national de la santé et de la recherche médicale (INSERM) U1312 BRIC Team 4, University of Bordeaux, Bordeaux, France
| | - Colm O' Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Javier P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Li P, Jin J, Chen Y, Ma J, Du Q, Han Y. Susceptibility-guided vs. empirical 10-day quadruple treatment for Helicobacter pylori-infected patients: A prospective clinical trial of first-line therapy. Front Microbiol 2022; 13:973975. [PMID: 36160235 PMCID: PMC9490362 DOI: 10.3389/fmicb.2022.973975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/04/2022] [Indexed: 11/13/2022] Open
Abstract
Background The increasing antimicrobial resistance of Helicobacter pylori (H. pylori) has resulted in a fall in cure rates. We aimed to assess the effectiveness of first-line susceptibility-guided therapy and furazolidone-based quadruple therapy for H. pylori-infected patients. Methods Subjects with H. pylori-infection were randomly assigned to either 10-day susceptibility-guided treatment or empiric treatment in a 2:1 ratio. Susceptibility-guided therapy was based on susceptibility to clarithromycin, and patients with susceptible strains received clarithromycin 500 mg twice daily and otherwise minocycline 100 mg twice a day was administered. Patients in the empiric therapy group was treated with furazolidone 100 mg twice a day. During treatment, all patients were given esomeprazole 20 mg twice daily, colloidal bismuth pectin 200 mg twice daily, and amoxicillin 1 g twice daily. Results A total of 248 patients were screened and 201 were finally included. Empiric and susceptibility-guided regimens were both successful with per-protocol eradication rates of 90.5% (57/63) vs. 88.5% (108/122) (p = 0.685) and intent-to-treat eradication rates of 85.1% (57/67) vs. 80.6% (108/134) (p = 0.435). No significant difference in eradication rates were observed among the furazolidone group, clarithromycin group and minocycline group. Conclusion Both susceptibility-guided therapy and quadruple therapy containing furazolidone can achieve good eradication rates. For population with a high rate of resistance, quadruple therapy containing furazolidone and bismuth may be a more practical choice for first-line treatment.
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Shi X, Wang C, Meng F, Ma S, Xu G, Liu T, Guo X, Li H, Qi X. Impact of insufficient doses of medications on Helicobacter pylori eradication: a retrospective observational study. Postgrad Med 2022; 134:668-674. [PMID: 35860966 DOI: 10.1080/00325481.2022.2105094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 07/11/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. METHODS We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. RESULTS Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200 mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P = 0.095). Among the patients receiving CBP (200 mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P < 0.0001). Among the patients receiving CBP 200 mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P < 0.0001). CONCLUSION Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication. ABBREVIATIONS H. pylori, Helicobacter pylori; UBT, urea breath test; DPM, disintegrations per minute; BQT, bismuth-containing quadruple therapy; PPI, proton pump inhibitor; CBP, colloidal bismuth pectin; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily.
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Affiliation(s)
- Xiaoye Shi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
- Graduate School, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Chunmei Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
- Graduate School, Jinzhou Medical University, Jinzhou, Liaoning, China
| | - Fanjun Meng
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Shaoze Ma
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Guangqin Xu
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Tingwei Liu
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
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Zhu G, Lin N, Wu X, Shi J, Tong B, Cai Z, Zhi J, Dong Y. Multicomponent Spiropolymerization of Diisocyanides, Activated Alkynes, and Bis-Anhydrides. Macromolecules 2022. [DOI: 10.1021/acs.macromol.2c00994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Guinan Zhu
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Na Lin
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Xinghui Wu
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Jianbing Shi
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Bin Tong
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Zhengxu Cai
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Junge Zhi
- Key Laboratory of Cluster Science of Ministry of Education, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Yuping Dong
- Beijing Key Laboratory of Construction Tailorable Advanced Functional Materials and Green Applications, School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
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Cho JH, Jin SY. Current guidelines for Helicobacter pylori treatment in East Asia 2022: Differences among China, Japan, and South Korea. World J Clin Cases 2022; 10:6349-6359. [PMID: 35979311 PMCID: PMC9294908 DOI: 10.12998/wjcc.v10.i19.6349] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/11/2022] [Accepted: 05/08/2022] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent in East Asia. The overall seroprevalence rate of H. pylori infection is 44.2% in China, 37.6%-43.2% in Japan, and 51.0% in South Korea. H. pylori can cause peptic ulcer disease and gastric cancer. East Asian countries have high rates of gastric cancer (age-standardized incidence rate: 20-30 per 100000). The Kyoto global consensus report emphasized that H. pylori gastritis should be considered the main cause for the development of gastric cancer. H. pylori treatment guidelines in China, Japan, and South Korea have recently been revised according to data from each of those countries. However, emerging antibiotic resistance is an important barrier to H. pylori eradication. The recommended H. pylori treatment regimens differ among those three East Asian countries. In this review, recent guidelines and up-to-date research on H. pylori treatment regimens from China, Japan, and South Korea are discussed.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul 04401, South Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University Hospital, Seoul 04401, South Korea
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Pajares-Chamorro N, Hammer ND, Chatzistavrou X. Materials for restoring lost Activity: Old drugs for new bugs. Adv Drug Deliv Rev 2022; 186:114302. [PMID: 35461913 DOI: 10.1016/j.addr.2022.114302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 04/04/2022] [Accepted: 04/12/2022] [Indexed: 11/01/2022]
Abstract
The escalation of bacterial resistance to conventional medical antibiotics is a serious concern worldwide. Improvements to current therapies are urgently needed to address this problem. The synergistic combination of antibiotics with other agents is a strategic solution to combat multi-drug-resistant bacteria. Although these combinations decrease the required high dosages and therefore, reduce the toxicity of both agents without compromising the bactericidal effect, they cannot stop the development of further resistance. Recent studies have shown certain elements restore the ability of antibiotics to destroy bacteria that have acquired resistance to them. Due to these synergistic activities, organic and inorganic molecules have been investigated with the goal of restoring antibiotics in new approaches that mitigate the risk of expanding resistance. Herein, we summarize recent studies that restore antibiotics once thought to be ineffective, but have returned to our armamentarium through innovative, combinatorial efforts. A special focus is placed on the mechanisms that allow the synergistic combinations to combat bacteria. The promising data that demonstrated restoration of antimicrobials, supports the notion to find more combinations that can combat antibiotic-resistant bacteria.
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Gisbert JP, Alcedo J, Amador J, Bujanda L, Calvet X, Castro-Fernández M, Fernández-Salazar L, Gené E, Lanas Á, Lucendo AJ, Molina-Infante J, Nyssen OP, Pérez-Aisa A, Puig I. V Spanish Consensus Conference on Helicobacter pylori infection treatment. GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:392-417. [PMID: 34629204 DOI: 10.1016/j.gastrohep.2021.07.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/30/2021] [Accepted: 07/16/2021] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Javier Alcedo
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, España
| | - Javier Amador
- Medicina de Familia, Centro de Salud Los Ángeles, Dirección Asistencial Centro, SERMAS, Madrid, España
| | - Luis Bujanda
- Servicio de Aparato Digestivo, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Xavier Calvet
- Servicio de Aparato Digestivo, Hospital Parc Taulí, Universitat Autónoma de Barcelona, CIBEREHD, Sabadell, Barcelona, España
| | | | - Luis Fernández-Salazar
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud (SACYL), Universidad de Valladolid, Valladolid, España
| | - Emili Gené
- Servicio de Urgencias, Hospital Parc Taulí Sabadell, CIBEREHD, Universitat Internacional de Catalunya, Barcelona, España
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), CIBEREHD, Zaragoza
| | - Alfredo J Lucendo
- Servicio de Aparato Digestivo, Hospital General de Tomelloso, CIBEREHD, Ciudad Real, España
| | - Javier Molina-Infante
- Servicio de Aparato Digestivo, Hospital Universitario de Cáceres, CIBEREHD, Cáceres, España
| | - Olga P Nyssen
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - A Pérez-Aisa
- Servicio de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Ignasi Puig
- Servicio de Aparato Digestivo, Althaia Xarxa Assistencial Universitària de Manresa, Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Barcelona, España
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Li H, Shen Y, Song X, Tang X, Hu R, Marshall BJ, Tang H, Benghezal M. Need for standardization and harmonization of Helicobacter pylori antimicrobial susceptibility testing. Helicobacter 2022; 27:e12873. [PMID: 35151236 DOI: 10.1111/hel.12873] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 12/23/2021] [Accepted: 12/27/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIMS As with other infectious diseases, Helicobacter pylori eradication regimens should be guided by susceptibility testing to achieve excellent success rate, especially in the era of high antibiotic resistance. However, susceptibility testing for H. pylori is rarely performed, which can be partly ascribed to the current lack of standardization of testing methods and the lack of unified consensus on the antibiotic resistance breakpoints. The aim of this review was to call for an international consensus on standardization and harmonization of H. pylori susceptibility testing. METHODS We summarize and compare the advantages and disadvantages of four different phenotypic antimicrobial susceptibility testing (AST) methods (agar dilution, E-test, disk diffusion, and broth microdilution) and the molecular susceptibility testing method for H. pylori. RESULTS The standard phenotypic testing methods and the molecular testing methods have their own advantages and disadvantages. Compared to the standard phenotypic methods, the molecular testing method does not require successful H. pylori culture, and therefore, is much more rapid and convenient for clinical use. However, the currently available molecular testing method is only suitable for detecting clarithromycin and quinolone susceptibility profiles in H. pylori. Although the standard AST is time-consuming, it is currently the only way to test the susceptibility of H. pylori to all the commonly used antibiotics. CONCLUSION To make H. pylori susceptibility testing become a clinical routine, an international consensus on standardization and harmonization of H. pylori AST is needed. Future efforts are needed for optimizing broth culture of H. pylori, and developing commercial AST plates for achieving high throughput and automated susceptibility testing for H. pylori.
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Affiliation(s)
- Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaona Song
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Barry James Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands, Australia
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Nyssen OP, Vaira D, Tepes B, Kupcinskas L, Bordin D, Pérez-Aisa Á, Gasbarrini A, Castro-Fernández M, Bujanda L, Garre A, Lucendo A, Vologzhanina L, Jurecic NB, Rodrigo-Sáez L, Huguet JM, Voynovan I, Perez-Lasala J, Romero PM, Vujasinovic M, Abdulkhakov R, Barrio J, Fernandez-Salazar L, Mégraud F, O'Morain C, Gisbert JP. Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg). J Clin Gastroenterol 2022; 56:e98-e108. [PMID: 33405435 DOI: 10.1097/mcg.0000000000001482] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 11/16/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.
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Affiliation(s)
- Olga P Nyssen
- 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)
| | - Dino Vaira
- Department of Surgical and Clinical Sciences, University of Bologna, Bologna
| | - Bojan Tepes
- Gastroenterology Unit, AM DC Rogaska, Rogaska Slatina
| | - Limas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Dmitry Bordin
- Department of Pancreatobiliary and Upper GI Diseases, Moscow Clinical Scientific Center, and A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow
| | - Ángeles Pérez-Aisa
- Digestive Unit, Agencia Sanitaria Costa del Sol, Marbella, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Málaga
| | - Antonio Gasbarrini
- Gastronterology Area, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | | | - Luis Bujanda
- Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Universidad del País Vasco (UPV/EHU), Donostia
| | - Ana Garre
- 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)
| | | | | | | | - Luis Rodrigo-Sáez
- Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo
| | - Jose M Huguet
- Hospital General Universitario de Valencia, Valencia
| | - Irina Voynovan
- Department of Pancreatobiliary and Upper GI Diseases, Moscow Clinical Scientific Center, and A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow
| | | | | | | | | | | | | | - Francis Mégraud
- Laboratoire de Bactériologie, Hôpital Pellegrin, Bordeaux Cedex, France
| | - Colm O'Morain
- Trinity College Dublin, Faculty of Health Sciences, Trinity College Dublin, Dublin/IE, Faculty of Health Sciences, 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)
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Shiotani A, Roy P, Lu H, Graham DY. Helicobacter pylori diagnosis and therapy in the era of antimicrobial stewardship. Therap Adv Gastroenterol 2021; 14:17562848211064080. [PMID: 34987609 PMCID: PMC8721397 DOI: 10.1177/17562848211064080] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/15/2021] [Indexed: 02/04/2023] Open
Abstract
The diagnosis and therapy of Helicobacter pylori infection have undergone major changes based on the use the principles of antimicrobial stewardship and increased availability of susceptibility profiling. H. pylori gastritis now recognized as an infectious disease, as such there is no placebo response allowing outcome to be assessed in relation to the theoretically obtainable cure rate of 100%. The recent recognition of H. pylori as an infectious disease has changed the focus to therapies optimized to reliably achieve high cure rates. Increasing antimicrobial resistance has also led to restriction of clarithromycin, levofloxacin, or metronidazole to susceptibility-based therapies. Covid-19 resulted in the almost universal availability of polymerase chain reaction testing in hospitals which can be repurposed to utilize readily available kits to provide rapid and inexpensive detection of clarithromycin resistance. In the United States, major diagnostic laboratories now offer H. pylori culture and susceptibility testing and American Molecular Laboratories offers next-generation sequencing susceptibility profiling of gastric biopsies or stools for the six commonly used antibiotics without need for endoscopy. Current treatment recommendations include (a) only use therapies that are reliably highly effective locally, (b) always perform a test-of-cure, and (c) use that data to confirm local effectiveness and share the results to inform the community regarding which therapies are effective and which are not. Empiric therapy should be restricted to those proven highly effective locally. The most common choices are 14-day bismuth quadruple therapy and rifabutin triple therapy. Prior guidelines and treatment recommendations should only be used if proven locally highly effective.
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Affiliation(s)
- Akiko Shiotani
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Priya Roy
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Hong Lu
- GI Division, 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 77030, USA
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Ivashkin VT, Maev IV, Lapina TL, Fedorov ED, Sheptulin AA, Trukhmanov AS, Kononov AV, Abdulkhakov RA, Alexeeva OP, Alekseenko SA, Andreev DN, Baranskaya EK, Dekhnich NN, Klyaritskaya IL, Kozlov RS, Kogan EA, Korolev MP, Korochanskaya NV, Kurilovich SA, Livsan MA, Osipenko MF, Pavlov PV, Pirogov SS, Sarsenbaeva AS, Simanenkov VI, Tertychny AS, Tkachev AV, Uspensky YP, Khlynov IB, Tsukanov VV. Clinical Recommendations of Russian Gastroenterological Association and RENDO Endoscopic Society on Diagnosis and Treatment of Gastritis and Duodenitis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2021; 31:70-99. [DOI: 10.22416/1382-4376-2021-31-4-70-99] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Aim.The clinical guidelines are intended to supplement specialty decision-making for improved aid quality in patients with gastritis and duodenitis though acknowledging the latest clinical evidence and principles of evidencebased medicine.Key points.Gastritis is an inflammatory disease of stomach mucosa, with a separate definition of acute and chronic gastritis. Chronic gastritis is a cohort of chronic diseases uniting a typical morphology of persistent inflammatory infiltration, impaired cellular renewal with emergent intestinal metaplasia, atrophy and epithelial dysplasia of gastric mucosa. Oesophagogastroduodenoscopy (OGDS) or high-resolution OGDS with magnified or non-magnified virtual chromoendoscopy, including targeted biopsy for atrophy and intestinal metaplasia grading and neoplasia detection, are recommended to verify gastritis and duodenitis, precancer states and/or gastric mucosal changes. All chronic gastritis patients positive for H. рylori should undergo eradication therapy as aetiological and subsidiary for gastric cancer prevention. Chronic gastritis patients with symptoms of dyspepsia (epigastric pain, burning and congestion, early satiety), also combined with functional dyspepsia, are recommended proton pump inhibitors, prokinetics, rebamipide and bismuth tripotassium dicitrate in symptomatic treatment. With focal restricted intestinal metaplasia, follow-up is not required in most cases, mainly when advanced atrophic gastritis is ruled out in high-quality endoscopy with biopsy. However, a familial history of gastric cancer, incomplete intestinal metaplasia and persistent H. pylori infection render endoscopy monitoring with chromoendoscopy and targeted biopsy desirable once in three years. Patients with advanced atrophic gastritis should have high-quality endoscopy every 3 years, and once in 1–2 years if complicated with a familial history of gastric cancer.Conclusion.The recommendations condense current knowledge on the aetiology and pathogenesis of gastritis and duodenitis, as well as laboratory and instrumental diagnostic techniques, main approaches to aetiological H. pylori eradication and treatment of dyspeptic states.
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Affiliation(s)
- V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - T. L. Lapina
- Sechenov First Moscow State Medical University (Sechenov University)
| | - E. D. Fedorov
- Pirogov Russian National Research Medical University
| | - A. A. Sheptulin
- Sechenov First Moscow State Medical University (Sechenov University)
| | - A. S. Trukhmanov
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | | | - D. N. Andreev
- Yevdokimov Moscow State University of Medicine and Dentistry
| | - E. K. Baranskaya
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - E. A. Kogan
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | - S. A. Kurilovich
- Research Institute of Therapy and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
| | | | - M. F. Osipenko
- Research Institute of Therapy and Preventive Medicine — branch of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences
| | - P. V. Pavlov
- Sechenov First Moscow State Medical University (Sechenov University)
| | - S. S. Pirogov
- Hertsen Moscow Oncology Research Center — Branch of the National Medical Research Radiology Center
| | | | | | - A. S. Tertychny
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | | | | | - V. V. Tsukanov
- Research Institute for Medical Problems in the North — Division of Krasnoyarsk Scientific Centre of Siberian Branch of the RAS
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Dutta AK, Phull PS. Treatment of Helicobacter pylori infection in the presence of penicillin allergy. World J Gastroenterol 2021; 27:7661-7668. [PMID: 34908805 PMCID: PMC8641050 DOI: 10.3748/wjg.v27.i44.7661] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/17/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Therapy of Helicobacter pylori (H.pylori) requires a combination of antibiotics together with an acid suppressing agent; most treatment regimens include Amoxicillin as one of the antibiotics, which is an important constituent as resistance to it is low. However, allergies to the penicillin group of antibiotics are not uncommon, and treating H.pylori infection in such individuals can be challenging due to the restricted choice of regimens. The aim of this review is to summarise the evidence for therapeutic options in patients with H.pylori infection and penicillin allergy. A literature search was conducted in PubMed for English language publications using the key words ‘Helicobacter’ and ‘treatment’ or ‘therapy‘ and ‘penicillin’ or ‘beta-lactam’ and ‘allergy’ or ‘anaphylaxis’. Eighteen studies were identified that specifically evaluated H.pylori treatment success in penicillin allergic patients. The number of subjects in most of them was low and many were retrospective, uncontrolled, single cohort studies. The most effective option for first-line treatment appears to be Bismuth-based quadruple therapy for 10-14 d. The evidence supports second-line treatment with Levoflaxacin-based triple therapy for 10 d. Patients with persistent H.pylori infection after 2 treatment courses should be considered for testing to confirm penicillin allergy. Further treatment should be guided by the results of H.pylori culture and sensitivity testing.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College, Vellore 632004, India
- Department of Digestive Disorders, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, United Kingdom
| | - Perminder Singh Phull
- Department of Digestive Disorders, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, United Kingdom
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Qiao C, Li Y, Liu J, Ji C, Qu J, Hu J, Ji R, Wan M, Lin B, Lin M, Qi Q, Zuo X, Li Y. Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area. J Gastroenterol Hepatol 2021; 36:2383-2388. [PMID: 33691344 DOI: 10.1111/jgh.15468] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 02/01/2021] [Accepted: 02/22/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM The increase in antibiotic resistance makes the eradication of Helicobacter pylori more difficult. Considering the limitations of the application of susceptibility-guided therapy, it is important to find an effective empirical regimen. The aim of the study is to compare the efficacy, safety, and cost-effectiveness of clarithromycin-based bismuth-containing quadruple therapy (C-BQT) and furazolidone-based bismuth-containing quadruple therapy (F-BQT) in naïve H. pylori positive patients. METHODS This was an open-label, randomized controlled, crossover trial. The trial comprised two phases. In C-F group, patients received C-BQT in the first phase; those who were still positive for H. pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment. In F-C group, patients were treated with F-BQT firstly and rescued with C-BQT. RESULTS As first-line treatments, the eradication rates of C-BQT and F-BQT were 89.7% (157/175) and 92.0% (161/175) (P = 0.458) in intention-to-treat analysis and 93.4% (156/167) and 95.8% (161/168) (P = 0.327) in per-protocol analysis, respectively. The cumulative eradication rates of the C-F group and the F-C group were both 94.3% in intention-to-treat analysis (P = 1.000). Cost-effectiveness indexes of F-BQT and C-BQT were 0.54 and 1.24 in first-line treatments. Frequencies of adverse events in F-BQT and C-BQT had no differences (36.0% in C-BQT vs 32.6% in F-BQT, P = 0.499). CONCLUSIONS Furazolidone-based bismuth-containing quadruple therapy should be preferred for its excellent cost-effectiveness and acceptable safety.
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Affiliation(s)
- Chen Qiao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yueyue Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Jing Liu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Chaoran Ji
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Junyan Qu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Junnan Hu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Rui Ji
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Meng Wan
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Boshen Lin
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Minjuan Lin
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Qingqing Qi
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
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Resina E, Gisbert JP. Rescue Therapy with Furazolidone in Patients with at Least Five Eradication Treatment Failures and Multi-Resistant H. pylori infection. Antibiotics (Basel) 2021; 10:antibiotics10091028. [PMID: 34572610 PMCID: PMC8467492 DOI: 10.3390/antibiotics10091028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/12/2021] [Accepted: 08/18/2021] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori infection may persist after multiple eradication treatments. The aim of this study was to evaluate the efficacy and safety of a furazolidone-based rescue regimen in hyper-refractory patients. A unicentre, prospective study was designed. Patients in whom five or more treatments had consecutively failed were included. All patients had previously received bismuth and key antibiotics, such as amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin, and had positive H. pylori culture, demonstrating resistance to clarithromycin, metronidazole, and levofloxacin. A quadruple regimen with furazolidone (200 mg), amoxicillin (1 g), bismuth (240 mg), and esomeprazole (40 mg) was prescribed twice a day for 14 days. Eradication was confirmed by the stool antigen test. Compliance was determined through questioning, and adverse effects using a questionnaire. Eight patients (mean age 56 years, 63% men, 38% peptic ulcer disease, 12% gastric cancer precursor lesions, and 50% functional dyspepsia) were included. Per-protocol and intention-to-treat eradication rates were 63%. Compliance was 100%. Adverse effects were reported in two (25%) patients, and all were mild. Even after five or more previous H. pylori eradication failures, and a multi-resistant infection, rescue treatment with furazolidone may be effective in approximately two-thirds of the cases, constituting a valid strategy after multiple previous eradication failures with key antibiotics such as clarithromycin, metronidazole, tetracycline, levofloxacin, and rifabutin.
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Liu J, Ji CR, Li YY, Qiao C, Hu JN, Wan M, Lin MJ, Lin BS, Wang J, Zha J, Li LX, Zuo XL. Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study. Clin Transl Gastroenterol 2021; 12:e00391. [PMID: 34397042 PMCID: PMC8373551 DOI: 10.14309/ctg.0000000000000391] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 07/09/2021] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection. METHODS Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed. RESULTS Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin). DISCUSSION Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.
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Affiliation(s)
- Jing Liu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Chao-Ran Ji
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Yue-Yue Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Chen Qiao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Jun-Nan Hu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Meng Wan
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Min-Juan Lin
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Bo-Shen Lin
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Juan Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Jing Zha
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Li-Xiang Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
| | - Xiu-Li Zuo
- Department of Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China;
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumor, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Jinan, Shandong, China
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Li SY, Li J, Dong XH, Teng GG, Zhang W, Cheng H, Gao W, Dai Y, Zhang XH, Wang WH. The effect of previous eradication failure on antibiotic resistance of Helicobacter pylori: A retrospective study over 8 years in Beijing. Helicobacter 2021; 26:e12804. [PMID: 33860967 DOI: 10.1111/hel.12804] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/23/2021] [Accepted: 03/17/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.
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Affiliation(s)
- Si-Yu Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Jiang Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xin-Hong Dong
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Gui-Gen Teng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Hong Cheng
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wen Gao
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Yun Dai
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiao-He Zhang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Wei-Hong Wang
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
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Liu C, Wang Y, Shi J, Zhang C, Nie J, Li S, Zheng T. The status and progress of first-line treatment against Helicobacter pylori infection: a review. Therap Adv Gastroenterol 2021; 14:1756284821989177. [PMID: 34262609 PMCID: PMC8243100 DOI: 10.1177/1756284821989177] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 12/30/2020] [Indexed: 02/04/2023] Open
Abstract
Helicobacter pylori (HP) is a major causative agent of chronic gastritis and peptic ulcer. HP is also engaged in the development of gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It is an important pathogenic factor in various other systemic diseases, such as vitamin B12 deficiency, iron deficiency, and idiopathic thrombocytopenia. The current consensus is that unless there is a special reason, eradication therapy should be implemented whenever HP infection is found, and it is ideally successful the first time. International guidelines recommend that under certain conditions, treatment should be personalized based on drug susceptibility testing. However, drug susceptibility testing is often not available because it is expensive, time-consuming, and difficult to obtain living tissue. Each region has separately formulated guidelines or consensuses on empirical therapy. Owing to an increasing drug resistance rate in various places, the eradication rate of proton pump inhibitor (PPI) triple therapy and sequential therapy has been affected. These regimens are rarely used; the PPI triple especially has been abandoned in most areas. Currently, radical treatment regimens for HP involve bismuth-containing quadruple therapy and concomitant therapy. However, quadruple therapy has its own limitations, such as complex drug administration. To improve the effectiveness, safety, and compliance, many clinical studies have proposed useful modified regimens, which mainly include the modified bismuth-containing quadruple regimen, high-dose dual therapy, and vonoprazan-containing regimens. Studies have shown that these emerging regimens have acceptable eradication rates and safety, and are expected to become first-line treatments in empirical therapy. However, the problem of decline in the eradication rate caused by drug resistance has not been fundamentally solved. This review not only summarizes the effectiveness of mainstream regimens in the first-line treatment of HP infection with the currently increasing antibiotic resistance rates, but also summarizes the effectiveness and safety of various emerging treatment regimens.
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Affiliation(s)
- Caiqi Liu
- Harbin Medical University, Harbin, China
| | - Yuan Wang
- Harbin Medical University, Harbin, China
| | - Jiaqi Shi
- Harbin Medical University, Harbin, China
| | | | | | - Shun Li
- Harbin Medical University, Harbin, China
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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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Li J, Deng J, Wang Z, Li H, Wan C. Antibiotic Resistance of Helicobacter pylori Strains Isolated From Pediatric Patients in Southwest China. Front Microbiol 2021; 11:621791. [PMID: 33574804 PMCID: PMC7870467 DOI: 10.3389/fmicb.2020.621791] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/31/2020] [Indexed: 02/05/2023] Open
Abstract
The number of antibiotics that are appropriate for Helicobacter pylori eradication in children is limited. Profiling regional or population-specific antibiotic resistance is essential in guiding the H. pylori eradication treatment in children. The aim of this study was to evaluate the antibiotic resistance in H. pylori strains isolated from children and adolescents in Southwest China. Gastric biopsies from 157 pediatric patients with or without previous H. pylori eradication treatment were collected for H. pylori culture. Susceptibility to amoxicillin (AML), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET), furazolidone (FZD), and rifampicin (RIF) was determined by E-test or a disk diffusion assay. A total of 87 patients from three ethnic groups (Han/Tibetan/Yi) were H. pylori culture positive (55.4%). The overall resistance rates were 55.2% for CLR, 71.3% for MTZ, 60.9% for RIF, and 18.4% for LEV. No isolate was found to be resistant to AML, TET, and FZD. Among the 53 treatment-naïve pediatric patients, primary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 45.3, 73.6, 15.1, and 60.4%, respectively. Among the 34 treatment-experienced patients, secondary resistance rates to clarithromycin, metronidazole, levofloxacin, and rifampicin were 70.6, 67.6, 23.5, and 61.8%, respectively. Isolates exhibiting simultaneous resistance to clarithromycin and metronidazole were 28.3 and 52.9% among the treatment-naïve and treatment-experienced patients, respectively. In conclusion, among pediatric patients in Southwest China, resistance rates were high for clarithromycin, metronidazole, levofloxacin, and rifampicin, whereas nil resistance was found to amoxicillin, tetracycline, and furazolidone. Our data suggest that the standard clarithromycin-based triple therapy should be abandoned as empiric therapy, whereas the bismuth quadruple therapy (bismuth/PPI/amoxicillin/tetracycline) would be suitable as first-line empiric treatment regimen for this pediatric population. Tetracycline and furazolidone may be considered for treating refractory H. pylori infections in adolescent patients.
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Affiliation(s)
- Juan Li
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Department of Infection Control, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Jianjun Deng
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
- Department of Infection Control, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Zhiling Wang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Chaomin Wan
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
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Ji CR, Liu J, Li YY, Guo CG, Qu JY, Zhang Y, Zuo X. Safety of furazolidone-containing regimen in Helicobacter pylori infection: a systematic review and meta-analysis. BMJ Open 2020; 10:e037375. [PMID: 33077561 PMCID: PMC7574948 DOI: 10.1136/bmjopen-2020-037375] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 08/07/2020] [Accepted: 08/22/2020] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVES Furazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection. DESIGN A systematic review and meta-analysis. DATA SOURCES PubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials. ELIGIBILITY CRITERIA Studies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included. DATA EXTRACTION AND SYNTHESIS Two reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance. RESULTS Twenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments. CONCLUSION Furazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered. PROSPERO REGISTRATION NUMBER CRD42019137247.
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Affiliation(s)
- Chao-Ran Ji
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Jing Liu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yue-Yue Li
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Chuan-Guo Guo
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Jun-Yan Qu
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yan Zhang
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Xiuli Zuo
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shangdong, China
- Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
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Chen Y, Liu Q, Hu F, Ma J. Identifying the best regimen for primary eradication of Helicobacter pylori: analysis of 240 cases. Microbiologyopen 2020; 9:e1120. [PMID: 33026166 PMCID: PMC7658452 DOI: 10.1002/mbo3.1120] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/25/2020] [Accepted: 08/30/2020] [Indexed: 12/13/2022] Open
Abstract
The treatment regimen for the eradication of Helicobacter pylori may be best when therapy is susceptibility guided. However, it is unrealistic to use a strategy based on susceptibility testing to prioritize therapy for every patient in China. Empirical therapy of H. pylori is still widely used. The study was designed to discuss the best first‐line treatment regimen depending on empirical therapy. The focal point of the study was the optimal length of the therapy. Also, the selection of antibiotics was discussed in the article. This was a prospective, randomized, non‐inferiority trial. H. pylori‐infected patients who have no previous eradication therapy were randomly assigned to the following: 20 mg of rabeprazole, 1000 mg of amoxicillin, 500 mg of clarithromycin, and 220 mg of bismuth potassium citrate (BACPPI), administered twice a day for 10 or 14 days. The efficacy, side effects, and remission rate of clinical symptoms were determined. A total of 240 subjects were included in the study. The eradication rate with 14 and 10 days was essentially identical in both intention‐to‐treat (90.83% [95% CI, 86%–96%] vs. 87.50% [95% CI, 82%–93%]) and per‐protocol (94.78% [95% CI, 91%–99%] vs. 92.11% [95% CI, 87%–97%]) analyses. Loss of appetite and belching symptoms were significantly better in the BACPPI‐10 group than those in the control group after treatment. Side effects were generally mild and similar between groups. Our results showed that a 10‐day amoxicillin–clarithromycin‐containing bismuth quadruple therapy may be recommended for the primary empirical treatment of H. pylori infection in Beijing, China.
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Affiliation(s)
- Yao Chen
- Department of Traditional Chinese Medicine, Peking University International Hospital, Beijing, China
| | - Qingyi Liu
- Department of Domestic Department One, The Second Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Fulian Hu
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Jizheng Ma
- Department of Gastroenterology, Xiyuan Hospital, Beijing, China
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Zhou Y, Ye Z, Lu J, Miao S, Lu X, Sun H, Wu J, Wang Y, Huang Y. Long-term changes in the gut microbiota after 14-day bismuth quadruple therapy in penicillin-allergic children. Helicobacter 2020; 25:e12721. [PMID: 32656891 DOI: 10.1111/hel.12721] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/09/2020] [Accepted: 06/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Penicillin-allergic children who are infected with Helicobacter pylori constitute a relatively common subgroup. We aimed to study the short-term and long-term effects of bismuth quadruple therapy on gut microbiota in penicillin-allergic children. METHODS We prospectively recruited treatment-naive children with H pylori infection and H pylori-negative asymptomatic children as healthy controls. Patients received 14-day bismuth quadruple therapy consisting of omeprazole, clarithromycin, metronidazole, and bismuth. Fecal samples were collected at weeks 0, 2, 6, and 52. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS Twenty-two subjects (14 gastritis patients, 8 duodenal ulcer patients) and 23 controls participated in this study. At week 2, alpha diversity was reduced in both gastritis (P < .05) and ulcer (except P = .16 with Chao 1 index) patients compared with baseline. Some changes persisted at week 6, and all were restored at week 52. Beta diversity was significantly altered 2 weeks after treatment in the gastritis and duodenal ulcer groups (P = .001, P = .002, respectively) and restored at weeks 6 and 52. The mean relative abundance of Bacteroidetes (P < .001, P = .005, respectively) decreased and that of Proteobacteria increased (P < .001, P = .03, respectively). All alterations recovered at week 6 and 52. In both the gastritis and ulcer groups at week 2, some beneficial bacteria were decreased including Bacteroides (P < .001 and P = .003), Faecalibacterium (P < .001 and P = .02), Phascolarctobacterium (P = .002 and P = .004), Roseburia ( P < .001 and P = .13), Bifidobacterium (P = .08 and P = .04), and Blautia (P < .001 and P = .002). Some detrimental bacteria were increased including Escherichia-Shigella (P < .001 and P = .19), Klebsiella (P < .001, and P = .09), Enterococcus (P < .001 and P = .007), and Streptococcus (P = .002 and P = .004). The changes returned to almost the pre-eradication level 1 year after therapy. CONCLUSION Bismuth quadruple therapy causes short-term dysbiosis of the gut microbiota. Most changes recovered 1-year post-eradication, indicating the long-term safety of H pylori therapy.
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Affiliation(s)
- Ying Zhou
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ziqing Ye
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Junping Lu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Shijian Miao
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaolan Lu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Hua Sun
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Jie Wu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
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Tang X, Chen X, Shen Y, Yang T, Hu R, Debowski AW, Stubbs KA, Benghezal M, Marshall BJ, Li H, Tang H. Primary antibiotic resistance of Helicobacter pylori among a Chinese Tibetan population. Future Microbiol 2020; 15:1353-1361. [PMID: 32900223 DOI: 10.2217/fmb-2020-0206] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Aim: To evaluate the primary antibiotic resistance in Helicobacter pylori strains isolated from a Chinese Tibetan population. Methods & materials: Gastric biopsies from 400 H. pylori treatment-naive Tibetan patients were collected for H. pylori isolation. Susceptibility to amoxicillin (AML)/clarithromycin (CLR)/levofloxacin (LEV)/metronidazole (MTZ)/tetracycline (TET)/rifampicin (RIF)/furazolidone (FZD) was determined by E-test or a disk diffusion assay. Results: Biopsies from 117 patients were H. pylori culture positive (29.3%). The primary resistance rates to MTZ, CLR, LEV, RIF, AML, TET and FZD were 90.6, 44.4, 28.2, 69.2, 7.7, 0.8 and 0.8%, respectively. Interestingly, 42.7% of the strains had simultaneous resistance to CLR and MTZ. Conclusion: Among Tibetan strains, primary resistance rates were high for CLR/MTZ/LEV, whereas primary resistance rates to AML/TET/FZD were low. The high resistance to RIF is a concerning finding.
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Affiliation(s)
- Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiaohong Chen
- Department of Digestive Medicine, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, 610041, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tiankuo Yang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Aleksandra W Debowski
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research & Training, University of Western Australia, Nedlands, Perth, 6009, Australia.,School of Molecular Sciences, University of Western Australia, Crawley, Perth, 6009, Australia
| | - Keith A Stubbs
- School of Molecular Sciences, University of Western Australia, Crawley, Perth, 6009, Australia
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Barry J Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research & Training, University of Western Australia, Nedlands, Perth, 6009, Australia
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, 610041, 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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Luo L, Huang Y, Liang X, Ji Y, Yu L, Lu H. Susceptibility-guided therapy for Helicobacter pylori-infected penicillin-allergic patients: A prospective clinical trial of first-line and rescue therapies. Helicobacter 2020; 25:e12699. [PMID: 32428369 DOI: 10.1111/hel.12699] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/03/2020] [Accepted: 04/09/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori (H pylori) treatment remains a challenge for penicillin-allergic patients. AIM To evaluate the efficacy and tolerability of susceptibility-guided first-line and rescue treatment in H pylori-infected penicillin-allergic patients. METHODS Consecutive H pylori-infected patients with penicillin allergy received a 14-day triple or quadruple therapy based on susceptibility to clarithromycin, levofloxacin, and metronidazole. All received esomeprazole 20 mg twice a day. Metronidazole-susceptible infections received metronidazole plus clarithromycin or levofloxacin triple therapy if susceptible. Clarithromycin- and levofloxacin-resistant infections received metronidazole plus tetracycline triple therapy. Metronidazole-resistant infections received a bismuth-high-dose metronidazole plus clarithromycin or levofloxacin quadruple therapy. Triple-resistant infections received classical bismuth quadruple therapy with high-dose metronidazole. Antimicrobial susceptibility was assessed using the E test method. RESULTS 112 patients were entered (34.8% men, average 47.1 years). Infections in 83.8% (31/37) of treatment-naive subjects and 12.0% (9/75) (P < .001) receiving rescue treatment were susceptible to at least one of the three tested antibiotics. Overall, susceptibility-guided therapy achieved eradication rates of 92.9% (104/112, 95% CI 88.1%-97.7%) by intent-to-treat analysis and 99% (100/101, 95% CI 97.1%-100%) by per-protocol analysis. All regimens achieved eradication rates greater than 90% (P = .327) in the PP populations. Adverse events were relatively frequent; however, compliance remained high. CONCLUSION Susceptibility-guided therapy proved highly effective for penicillin-allergic patients. When available and proven locally effective, the alternative was empiric classical bismuth quadruple therapy. This trial is registered with ClinicalTrials.gov as NCT03708848.
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Affiliation(s)
- Laisheng Luo
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Huang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and 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 and 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 and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lou Yu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Lu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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48
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Hsieh MT, Chang WL, Wu CT, Yang HB, Kuo HY, Lin MY, Cheng HC, Tsai YC, Sheu BS. Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen. Eur J Clin Pharmacol 2020; 76:1581-1589. [PMID: 32591943 DOI: 10.1007/s00228-020-02938-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 06/16/2020] [Indexed: 01/10/2023]
Abstract
PURPOSE H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection. METHODS We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7-14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy. RESULTS The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025). CONCLUSION Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.
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Affiliation(s)
- Ming-Tsung Hsieh
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wei-Lun Chang
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chung-Tai Wu
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsiao-Bai Yang
- Department of Pathology, Ton Yen General Hospital, Hsin-Chu, Taiwan
| | - Hsin-Yu Kuo
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Meng-Ying Lin
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsiu-Chi Cheng
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Chin Tsai
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, and Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. .,Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Yang T, Hu R, Tang X, Shen Y, Tay A, Pi X, Wang G, Debowski AW, Stubbs KA, Benghezal M, Marshall BJ, Li H, Tang H. Susceptibility-guided bismuth quadruple therapies for resistant Helicobacter pylori infections. PRECISION CLINICAL MEDICINE 2020; 3:127-135. [PMID: 35692608 PMCID: PMC8985787 DOI: 10.1093/pcmedi/pbaa010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/11/2020] [Accepted: 03/15/2020] [Indexed: 02/05/2023] Open
Abstract
Increasing Helicobacter pylori resistance to antibiotics has ledthat molecular testing is appropriate as a sub to adoption of seven different bismuth quadruple therapies (BQT) in China without differentiation of first-line or second-line regimens. The objective of this study was to evaluate the efficacy of susceptibility-guided BQT for patients who had experienced previous treatment failures. A total of 133 patients was included and H. pylori was successfully cultured from 101 patients (75.9%) for subsequent antimicrobial susceptibility testing (AST). Based on the AST results, 88 patients completed one of five AST-guided 14-day BQT regimens: esomeprazole and bismuth colloidal pectin, along with either, amoxicillin and clarithromycin (EBAC), amoxicillin and levofloxacin (EBAL), amoxicillin and furazolidone (EBAF), amoxicillin and tetracycline (EBAT), or tetracycline and furazolidone (EBTF). H. pylori eradication rates were 100% for EBAC (5/5), EBAL (13/13), EBAF (14/14), and EBTF (43/43), but 76.9% for EBAT (10/13). The three patients that failed the EBAT regimen were all cured after subsequent treatment with the EBTF regimen. Our study demonstrates the excellent efficacy of the AST-guided BQT for referred H. pylori patients, and that the current EBAT regimen, used in clinics, needs to be optimized. In addition, 57 of the isolates were subjected to whole-genome sequencing. Analysis of the sequences revealed that point mutations in 23S rRNA correlated well with the phenotypic clarithromycin resistance with a concordance of 91.2%, while the concordance between phenotypic levofloxacin resistance and gyrA point mutations was 82.3%. This suggests that molecular testing is appropriate as a substitute for AST as a more rapid and cost-effective method for determining clarithromycin and levofloxacin resistance in Chinese patients.
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Affiliation(s)
- Tiankuo Yang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Renwei Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiaoqiong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yalin Shen
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Alfred Tay
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands 6009, Australia
| | - Xuenan Pi
- Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Chengdu 610041, China
| | - Gang Wang
- Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Chengdu 610041, China
| | - Aleksandra W Debowski
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands 6009, Australia
- School of Molecular Sciences, University of Western Australia, Nedlands 6009, Australia
| | - Keith A Stubbs
- School of Molecular Sciences, University of Western Australia, Nedlands 6009, Australia
| | - Mohammed Benghezal
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Barry J Marshall
- Helicobacter pylori Research Laboratory, School of Biomedical Sciences, Marshall Centre for Infectious Disease Research and Training, University of Western Australia, Nedlands 6009, Australia
| | - Hong Li
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hong Tang
- West China Marshall Research Center for Infectious Diseases, Center of Infectious Diseases, Division of Infectious Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
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50
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Burke KJ, Stephens LJ, Werrett MV, Andrews PC. Bismuth(III) Flavonolates: The Impact of Structural Diversity on Antibacterial Activity, Mammalian Cell Viability and Cellular Uptake. Chemistry 2020; 26:7657-7671. [PMID: 32297355 DOI: 10.1002/chem.202000562] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 04/01/2020] [Indexed: 12/16/2022]
Abstract
A series of homoleptic and heteroleptic bismuth(III) flavonolate complexes derived from six flavonols of varying substitution have been synthesised and structurally characterised. The complexes were evaluated for antibacterial activity towards several problematic Gram-positive (Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE)) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria. The cell viability of COS-7 (monkey kidney) cells treated with the bismuth flavonolates was also studied to determine the effect of the complexes on mammalian cells. The heteroleptic complexes [BiPh(L)2 ] (in which L=flavonolate) showed good antibacterial activity towards all of the bacteria but reduced COS-7 cell viability in a concentration-dependent manner. The homoleptic complexes [Bi(L)3 ] exhibited activity towards the Gram-positive bacteria and showed low toxicity towards the mammalian cell line. Bismuth uptake studies in VRE and COS-7 cells treated with the bismuth flavonolate complexes indicated that Bi accumulation is influenced by both the substitution of the flavonolate ligands and the degree of substitution at the bismuth centre.
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Affiliation(s)
- Kirralee J Burke
- School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800, Australia
| | - Liam J Stephens
- School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800, Australia
| | - Melissa V Werrett
- School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800, Australia
| | - Philip C Andrews
- School of Chemistry, Monash University, Clayton, Melbourne, VIC 3800, Australia
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