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Liu YX, Liu HN, Liu HQ, Yang YY, Cui HL, Fan LL, Sun WJ, Mei H, Wang XW, Yan G, Lan CH. Vonoprazan-Amoxicillin Dual Therapy Versus Drug Sensitivity-Based Individualized Therapy as a Rescue Regimen for Helicobacter pylori Infection: A Multicenter, Randomized Controlled Trial. Helicobacter 2025; 30:e70009. [PMID: 39996433 DOI: 10.1111/hel.70009] [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: 05/31/2024] [Revised: 01/02/2025] [Accepted: 01/06/2025] [Indexed: 02/26/2025]
Abstract
OBJECTIVE Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that offers several advantages, such as fast onset time and strong acid inhibition, in the treatment of Helicobacter pylori infection. This study aims to evaluate the efficacy, adverse reactions, and compliance of the 14-day vonoprazan-amoxicillin dual therapy versus drug sensitivity-based individualized therapy in the retreatment of H. pylori infection. METHODS This multicenter, open-label, randomized, controlled non-inferiority study enrolled 240 adult patients who previously failed anti-H. pylori treatment. These patients were randomly assigned to receive the 14-day vonoprazan-amoxicillin dual therapy or drug sensitivity-based individualized therapy. The primary outcome was the eradication rate, and the secondary outcomes mainly included adverse events, patient compliance, antibiotic resistance rates, and risk factors that affected the eradication rate. RESULTS The intention-to-treat (ITT) and per-protocol (PP) analyses revealed that the eradication rates for the vonoprazan-amoxicillin dual therapy and drug sensitivity-based individualized therapy were comparably high, with rates of 87.50% and 83.33%, respectively. Furthermore, the vonoprazan-amoxicillin dual therapy fulfilled the criteria for the non-inferiority test, when compared to individualized therapy. The incidence of adverse reactions was significantly lower in the vonoprazan-amoxicillin dual therapy group. Both groups showed similarly good compliance and comparable rates of antibiotic resistance. The previous treatment with a clarithromycin-containing regimen was identified as an independent risk factor for clarithromycin resistance. CONCLUSION The 14-day vonoprazan-amoxicillin dual therapy exhibits high eradication rates and low incidence of adverse reactions in retreated patients, indicating its effectiveness and safety as a rescue regimen for patients with H. pylori infection.
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Affiliation(s)
- Yu-Xiang Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Han-Ning Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Heng-Qi Liu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Ying-Ying Yang
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Hong-Li Cui
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Li-Lin Fan
- Department of Gastroenterology, West District Hospital of Chongqing, Chongqing, P. R. China
| | - Wen-Jing Sun
- Department of Gastroenterology, The 13th People's Hospital of Chongqing, Chongqing, P. R. China
| | - Hao Mei
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Xing-Wei Wang
- Department of Emergency Medicine, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Guo Yan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
| | - Chun-Hui Lan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, P. R. China
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Kuhn EMA, Sominsky LA, Chittò M, Schwarz EM, Moriarty TF. Antibacterial Mechanisms and Clinical Impact of Sitafloxacin. Pharmaceuticals (Basel) 2024; 17:1537. [PMID: 39598446 PMCID: PMC11597390 DOI: 10.3390/ph17111537] [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: 10/14/2024] [Revised: 11/09/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Sitafloxacin is a 4th generation fluoroquinolone antibiotic with broad activity against a wide range of Gram-negative and Gram-positive bacteria. It is approved in Japan and used to treat pneumonia and urinary tract infections (UTIs) as well as other upper and lower respiratory infections, genitourinary infections, oral infections and otitis media. Compared to other fluoroquinolones, sitafloxacin displays a low minimal inhibitory concentration (MIC) for many bacterial species but also activity against anaerobes, intracellular bacteria, and persisters. Furthermore, it has also shown strong activity against biofilms of P. aeruginosa and S. aureus in vitro, which was recently validated in vivo with murine models of S. aureus implant-associated bone infection. Although limited in scale at present, the published literature supports the further evaluation of sitafloxacin in implant-related infections and other biofilm-related infections. The aim of this review is to summarize the chemical-positioning-based mechanisms, activity, resistance profile, and future clinical potential of sitafloxacin.
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Affiliation(s)
- Elian M. A. Kuhn
- AO Research Institute Davos, 7270 Davos, Switzerland; (E.M.A.K.); (M.C.)
- Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland
| | - Levy A. Sominsky
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA (E.M.S.)
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
- Medical Scientist Training Program, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
| | - Marco Chittò
- AO Research Institute Davos, 7270 Davos, Switzerland; (E.M.A.K.); (M.C.)
| | - Edward M. Schwarz
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA (E.M.S.)
| | - T. Fintan Moriarty
- AO Research Institute Davos, 7270 Davos, Switzerland; (E.M.A.K.); (M.C.)
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Benito BM, Nyssen OP, Gisbert JP. Efficacy and Safety of Vonoprazan in Dual/Triple/Quadruple Regimens Both in First-Line and Rescue Therapy for Helicobacter pylori Eradication: A Systematic Review With Meta-Analysis. Helicobacter 2024; 29:e13148. [PMID: 39533409 DOI: 10.1111/hel.13148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 10/04/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The efficacy of Helicobacter pylori (H. pylori) eradication therapies encompassing one or more antibiotics and a proton pump inhibitor (PPI) has lately decreased. Vonoprazan (VPZ), a potassium-competitive acid blocker, provides higher gastric acid suppression than PPIs. We performed a meta-analysis evaluating the efficacy and safety of VPZ in H. pylori eradication therapies. METHODS Studies were searched in PubMed, Embase, and the Cochrane Library up to June 2023. Efficacy was evaluated by intention-to-treat analysis. Data were combined by meta-analyzing risk differences (RD). Heterogeneity was evaluated by subgrouping. RESULTS Seventy-seven studies (24 randomized clinical trials) evaluated 44,162 patients (22,297 receiving VPZ and 21,865 PPIs). Overall VPZ efficacy was 88% (95% CI = 87%-90%): 86%, 88%, and 94% for dual/triple/quadruple-VPZ-containing therapies. VPZ efficacy was 87% (86%-89%) in first-line and 90% (87%-93%) in rescue therapy. VPZ performed better than PPIs in treatment-naïve patients (87% vs. 70%; RD = 0.13, 95% CI = 0.11-0.15) and when using triple regimens. No significant differences were observed in rescue and quadruple therapies. In patients with clarithromycin-resistant infection, VPZ-based therapies demonstrated an 81% efficacy (76%-85%), surpassing PPIs (76% vs. 40%; RD = 0.33, 95% CI = 0.24-0.43). For clarithromycin-susceptible strains, VPZ efficacy was 92% (89%-95%), similar to PPIs. VPZ adverse events rate was 19% (16%-21%), comparable to PPI-based regimens (18% vs. 13%, respectively; RD = 0.00, 95% CI = -0.01 to 0.02, p = 0.57). CONCLUSIONS The efficacy of VPZ-based regimens was over 85% in all treatment combinations. In treatment-naïve and clarithromycin-resistant patients, VPZ performed better than PPIs. In rescue therapy, in clarithromycin-susceptible patients or when quadruple regimens were prescribed, this advantage was not confirmed. Tolerability was similar in both regimens.
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Affiliation(s)
- Belén Martínez Benito
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Olga P Nyssen
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
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Huang TT, Cao YX, Cao L. Novel therapeutic regimens against Helicobacter pylori: an updated systematic review. Front Microbiol 2024; 15:1418129. [PMID: 38912349 PMCID: PMC11190606 DOI: 10.3389/fmicb.2024.1418129] [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: 04/16/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a strict microaerophilic bacterial species that exists in the stomach, and H. pylori infection is one of the most common chronic bacterial infections affecting humans. Eradicating H. pylori is the preferred method for the long-term prevention of complications such as chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. However, first-line treatment with triple therapy and quadruple therapy has been unable to cope with increasing antibacterial resistance. To provide an updated review of H. pylori infections and antibacterial resistance, as well as related treatment options, we searched PubMed for articles published until March 2024. The key search terms were "H. pylori", "H. pylori infection", "H. pylori diseases", "H. pylori eradication", and "H. pylori antibacterial resistance." Despite the use of antimicrobial agents, the annual decline in the eradication rate of H. pylori continues. Emerging eradication therapies, such as the development of the new strong acid blocker vonoprazan, probiotic adjuvant therapy, and H. pylori vaccine therapy, are exciting. However, the effectiveness of these treatments needs to be further evaluated. It is worth mentioning that the idea of altering the oxygen environment in gastric juice for H. pylori to not be able to survive is a hot topic that should be considered in new eradication plans. Various strategies for eradicating H. pylori, including antibacterials, vaccines, probiotics, and biomaterials, are continuously evolving. A novel approach involving the alteration of the oxygen concentration within the growth environment of H. pylori has emerged as a promising eradication strategy.
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Affiliation(s)
- Ting-Ting Huang
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Yong-Xiao Cao
- Department of Pharmacology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, China
| | - Lei Cao
- Precision Medical Institute, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Dirjayanto VJ, Audrey J, Simadibrata DM. Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications. World J Gastroenterol 2024; 30:1280-1286. [PMID: 38596495 PMCID: PMC11000074 DOI: 10.3748/wjg.v30.i10.1280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 01/22/2024] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.
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Affiliation(s)
| | - Jessica Audrey
- Faculty of Medicine, Universitas Indonesia, Jakarta Pusat 10430, DKI Jakarta, Indonesia
| | - Daniel Martin Simadibrata
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, United States
- Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, United Kingdom
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Graham DY. Crises in Antimicrobial Stewardship: Misuse of Clarithromycin for Helicobacter pylori Therapy. PHARMACOEPIDEMIOLOGY 2024; 3:82-93. [PMID: 39777230 PMCID: PMC11706568 DOI: 10.3390/pharma3010006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Helicobacter pylori is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for H. pylori has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship. A combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin (triple therapy) remains popular despite increasing clarithromycin resistance and poor cure rates. Concomitant therapy (a PPI, amoxicillin, clarithromycin, and metronidazole) is recommended and widely used despite all patients receiving at least one unneeded antibiotic. In 2020, the Food and Drug Administration approved vonoprazan, amoxicillin, and clarithromycin triple therapy, which administers unneeded clarithromycin to >90% of patients (i.e., ~6 tons of unneeded clarithromycin/million treatments). In the late 1980s, the infectious disease community functionally transferred responsibility for the management of H. pylori to gastroenterology, which has managed the infection as another common gastrointestinal disease such as constipation. In 2022, both traditional and noninvasive molecular-based susceptibility testing for H. pylori became available in the United States. In order to reduce and prevent antibiotic misuse, the infectious disease community should reclaim responsibility for the management of this important infectious disease.
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Affiliation(s)
- David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine Houston, 2002 Holcombe Blvd (111D), Houston, TX 77030, USA
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Liu L, Nahata MC. Vonoprazan With Amoxicillin or Amoxicillin and Clarithromycin for the Treatment of Helicobacter pylori Infection. Ann Pharmacother 2023; 57:1185-1197. [PMID: 36688309 DOI: 10.1177/10600280221149708] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
OBJECTIVES To describe the pharmacology, efficacy, safety, and potential role of vonoprazan with amoxicillin or amoxicillin and clarithromycin for the treatment of Helicobacter pylori infection in adults. DATA SOURCES PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched using the terms: (vonoprazan OR voquezna) AND ("H. pylori" OR "Helicobacter pylori") AND amoxicillin with no date limitations up to November 3, 2022. STUDY SELECTION AND DATA EXTRACTION Studies assessing the efficacy and safety of vonoprazan with amoxicillin and/or clarithromycin were included and divided into 3 groups based on different comparisons between treatment regimens used in each group. DATA SYNTHESIS Ten clinical trials and 17 observational studies were included. Vonoprazan-based therapy demonstrated greater acid inhibition and similar or higher efficacy than proton-pump inhibitor (PPI)-based therapy in treatment-naïve patients and with clarithromycin-resistant infections. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Proton-pump inhibitor-based therapies have not reached the desired successful eradication rate of 90% for H. pylori infection. Vonoprazan-based therapies being at least as effective as PPI-based therapies offer an alternative for patients with H. pylori infection. CONCLUSION Vonoprazan-based therapies were effective and well tolerated for the treatment of H. pylori infection in adults. These regimens provide an important alternative with prolonged acid inhibition, lower potential for CYP2C19 polymorphism, and at least comparable efficacy and safety versus PPI-based therapies in patients with H. pylori infections. Thus, vonoprazan-based therapy should be considered for certain patients, for example, those with failure to PPI-based treatments.
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Affiliation(s)
- Ligang Liu
- Institute of Therapeutic Innovations and Outcomes, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Milap C Nahata
- Institute of Therapeutic Innovations and Outcomes, College of Pharmacy, The Ohio State University, Columbus, OH, USA
- College of Medicine, The Ohio State University, Columbus, OH, USA
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Noiri Y, Nagata R. Current status of gastric and oral infection/diseases caused by Helicobacter pylori. ORAL SCIENCE INTERNATIONAL 2023; 20:182-189. [DOI: 10.1002/osi2.1172] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Accepted: 01/17/2023] [Indexed: 01/06/2025]
Abstract
AbstractHelicobacter pylori is found in the stomach, which is its optimal habitat, and is considered an important factor in various serious diseases, including stomach cancer. The World Health Organization has identified H. pylori as a causative agent of gastric cancer, as confirmed by animal experiments in rodents. The fact that H. pylori can live in the harsh environment of stomach acid was the greatest hindrance to the discovery of H. pylori. It was not so long ago, in 1983, that it was successfully isolated and cultured. Subsequently, H. pylori eradication therapy was established, and it became possible to control gastric cancer to some extent. However, the mechanism, route, and mode of H. pylori infection still remain unclear. Furthermore, currently, the prevention of first‐episode gastric cancer and control of recurrent gastric cancer are not perfect. One of the reasons for this may be that the status of H. pylori in the oral cavity, which is the entry point for the organism (the beginning of the digestive system: the first route of infection), is still unknown. Therefore, we reviewed the current status of H. pylori infection in the stomach and oral cavity, focusing on (1) the mechanism of infection, (2) pathogenic factors, (3) the actual status of eradication therapy, and (4) control strategies.
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Affiliation(s)
- Yuichiro Noiri
- Division of Cariology, Operative Dentistry and Endodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences Niigata University Niigata Japan
| | - Ryoko Nagata
- Division of Cariology, Operative Dentistry and Endodontics, Faculty of Dentistry and Graduate School of Medical and Dental Sciences Niigata University Niigata Japan
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Yu J, Lv YM, Yang P, Jiang YZ, Qin XR, Wang XY. Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection. World J Gastroenterol 2023; 29:3133-3144. [PMID: 37346155 PMCID: PMC10280792 DOI: 10.3748/wjg.v29.i20.3133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/25/2023] [Accepted: 04/23/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Vonoprazan (VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori (H. pylori) infection. However, their value as a rescue therapy needs to be explored. AIM To assess a VPZ-based regimen as H. pylori rescue therapy. METHODS This prospective, single-center, clinical trial was conducted between January and August 2022. Patients with a history of H. pylori treatment failure were administered 20 mg VPZ twice daily, 750 mg amoxicillin 3 times daily, and 250 mg Saccharomyces boulardii (S. boulardii) twice daily for 14 d (14-d VAS regimen). VPZ and S. boulardii were taken before meals, while amoxicillin was taken after meals. Within 3 d after the end of eradication therapy, all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced. At least 4-6 wk after the end of eradication therapy, eradication success was assessed using a 13C-urea breath test, and factors associated with eradication success were explored. RESULTS Herein, 103 patients were assessed, and 68 patients were finally included. All included patients had 1-3 previous eradication failures. The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6% (63/68) and 92.3% (60/65), respectively. The eradication rate did not differ with the number of treatment failures (P = 0.433). The rates of clarithromycin, metronidazole, and levofloxacin resistance were 91.3% (21/23), 100.0% (23/23), and 60.9% (14/23), respectively. There were no cases of resistance to tetracycline, amoxicillin, or furazolidone. In 60.9% (14/23) patients, the H. pylori isolate was resistant to all 3 antibiotics (clarithromycin, metronidazole, and levofloxacin); however, eradication was achieved in 92.9% (13/14) patients. All patients showed metronidazole resistance, and had an eradication rate of 91.3% (21/23). The eradication rate was higher among patients without anxiety (96.8%) than among patients with anxiety (60.0%, P = 0.025). No severe adverse events occurred; most adverse events were mild and disappeared without intervention. Good compliance was seen in 95.6% (65/68) patients. Serological examination showed no significant changes in liver and kidney function. CONCLUSION VAS is a safe and effective rescue therapy, with an acceptable eradication rate (> 90%), regardless of the number of prior treatment failures. Anxiety may be associated with eradication failure.
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Affiliation(s)
- Jing Yu
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Yi-Ming Lv
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Peng Yang
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Yi-Zhou Jiang
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xiang-Rong Qin
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xiao-Yong Wang
- Department of Gastroenterology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
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Wang SW, Yu FJ, Kuo FC, Wang JW, Wang YK, Chen YH, Hsu WH, Liu CJ, Wu DC, Kuo CH. Rescue therapy for refractory Helicobacter pylori infection: current status and future concepts. Therap Adv Gastroenterol 2023; 16:17562848231170941. [PMID: 37168402 PMCID: PMC10164852 DOI: 10.1177/17562848231170941] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 04/04/2023] [Indexed: 05/13/2023] Open
Abstract
Helicobacter pylori infection is an important issue worldwide, and several guidelines have been published for clinicians to achieve successful eradication. However, there are still some patients who remain infected with H. pylori after treatment. Clinicians should identify the reasons that caused treatment failure and find strategies to manage them. We have searched and organized the literature and developed methods to overcome factors that contribute to prior treatment failure, such as poor compliance, inadequate intragastric acid suppression, and antibiotic resistance. To improve compliance, telemedicine or smartphone applications might play a role in the modern world by increasing doctor-patient relationships, while concomitant probiotics could be administered to reduce adverse effects and enhance adherence. For better acid suppression, high-potency and high-dose proton-pump inhibitors or potassium-competitive acid blockers have preferable efficacy. To overcome antibiotic resistance, susceptibility tests either by culture or by genotyping are the most commonly used methods and have been suggested for antibiotic selection before rescue therapy, but empirical therapy according to detailed medical history could be an alternative. Eradication with a longer treatment period (14 days) has a better outcome than shorter period (7 or 10 days). Ultimately, clinicians should select antibiotics based on the patient's history of drug allergy, previous antibiotic exposure, local antibiotic resistance, available medications, and cost. In addition, identifying patients with a high risk of cancer and shared decision-making are also essential for those who have experienced eradication failure.
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Affiliation(s)
- Song-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Fang-Jung Yu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Fu-Chen Kuo
- School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung
| | - Jiunn-Wei Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Yi-Hsun Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung
| | - Chung-Jung Liu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Regenerative Medicine and Cell therapy Research Center, Kaohsiung Medical University, Kaohsiung
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung 80756
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung
- Regenerative Medicine and Cell therapy Research Center, Kaohsiung Medical University, Kaohsiung
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11
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Deng D, Zhang Y, Zhang R, Yi J, Dong J, Sha L, Yan M. Circulating Proteins and Metabolite Biomarkers in Gastric Cancer: A Systematic Review and Meta-analysis. Arch Med Res 2023; 54:124-134. [PMID: 36759293 DOI: 10.1016/j.arcmed.2022.12.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 12/08/2022] [Accepted: 12/20/2022] [Indexed: 02/10/2023]
Abstract
BACKGROUND Gastric cancer (GC) is often diagnosed at an advanced stage and thus patients have a poor prognosis. This implies that early detection of this cancer will improve patient prognosis and survival. This systematic review explored the association of circulating protein and metabolite biomarkers with GC development. METHODS A literature search was conducted until November 2021 on Medline, Embase, Cochrane library, and Web of Science databases. Studies were included if they assessed circulating proteins and metabolites in blood, urine, or saliva and determined their association with GC risk. Quality of identified studies was determined using the Newcastle-Ottawa scale for cohort studies. Random and fixed effects meta-analyses were performed to calculate pooled odds ratio. RESULTS A total of 53 studies were included. High levels of anti-Helicobacter pylORi IgG levels, pepsinogen I (PGI) <30 µg/L and serum pepsinogen I/ pepsinogen II (PGI/II) ratio<3 were positively associated with risk of developing GC (pooled odds ratio (OR): 2.70; 95% CI: 1.44-5.04, 5.96, 95% CI: 2.65-13.42 and 4.43; 95% CI: 3.04-6.47). In addition, an inverse relationship was found between ferritin, iron and transferrin levels and risk of developing GC (OR: 0.62; 95% CI: 0.38-1,0.97; 95% CI: 0.94-1 and 0.85; 95% CI: 0.76-0.94). However, there was no association between levels of glucose, cholesterol, vitamin C, vitamin B12, vitamin A, α-Carotene, β-Carotene, α-Tocopherol, γ-Tocopherol, and GC risk. CONCLUSION The pooled analysis demonstrated that high levels of anti-Helicobacter pylORi IgG, PGI<30µg/L and serum PGI/II ratio <3 and low levels of ferritin, iron and transferrin were associated with risk of GC.
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Affiliation(s)
- Dawei Deng
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yuhan Zhang
- Department of Nursing, School of Nursing, Shanxi Medical University, Taiyuan, Shanxi, China.
| | - Rongzhi Zhang
- Department of Nursing, The Second Hospital of Dalian Medical University, Dalian, China
| | - Jing Yi
- Department of Nursing, The Second Hospital of Dalian Medical University, Dalian, China
| | - Jianli Dong
- Department of Nursing, The Second Hospital of Dalian Medical University, Dalian, China
| | - Liyan Sha
- Department of Nursing, The Second Hospital of Dalian Medical University, Dalian, China
| | - Meiqin Yan
- Department of Science and Education, Children's Hospital of Shanxi and Women Health Center of Shanxi, China
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12
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de Moraes Andrade PV, Monteiro YM, Chehter EZ. Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review. World J Gastroenterol 2023; 29:390-409. [PMID: 36687120 PMCID: PMC9846933 DOI: 10.3748/wjg.v29.i2.390] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/12/2022] [Accepted: 12/01/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Due to increasing resistance rates of Helicobacter pylori (H. pylori) to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H. pylori infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory H. pylori infection.
AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H. pylori infection.
METHODS A systematic search of available rescue treatments for refractory H. pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H. pylori infection rescue therapies were included.
RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera® (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.
CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.
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Affiliation(s)
| | - Yan Mosca Monteiro
- Department of Gastroenterology, Faculdade de Medicina do ABC, Santo André 09060-650, SP, Brazil
| | - Ethel Zimberg Chehter
- Department of Gastroenterology, Faculdade de Medicina do ABC, Santo André 09060-650, SP, Brazil
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13
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Zou SP, Cheng Q, Feng CY, Xu C, Sun MH. Comparative effectiveness of first-line therapies for eradication of antibiotic-resistant Helicobacter pylori strains: A network meta-analysis. World J Clin Cases 2022; 10:12959-12970. [PMID: 36569016 PMCID: PMC9782940 DOI: 10.12998/wjcc.v10.i35.12959] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 10/08/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND As a first-line treatment regimen for Helicobacter pylori (H. pylori) infection, antibiotic therapy is widely used worldwide. However, the question of increasing antibiotic resistance must be considered. Given this issue, we need to find ways to reduce drug resistance. This study examined all currently available first-line regimens and compared them with standard triple treatment through a network meta-analysis of randomized controlled trials (RCTs). AIM To compare first-line treatment regimens for eradication of antibiotic-resistant H. pylori strains. METHODS To compare the effectiveness of the first-line regimens for treating H. pylori infection, a Bayesian network meta-analysis was applied to process data extracted from RCTs. The plausible ranking for each regimen was assessed by the surface under the cumulative ranking curve (SUCRA). In addition, we conducted a relevant search by reference citation analysis. RESULTS Twenty-five RCTs involving 12029 participants [including 1602 infected with clarithromycin (CAM)-resistant strains and 1716 infected with metronidazole (MNZ)-resistant strains] were included, in which a total of seven regimens were used for H. pylori eradication. The results showed that dual therapy containing a high-dose proton pump inhibitor (HDDT) [odds ratio (OR): 4.20, 95% confidence interval (CI): 2.29-8.13] was superior to other therapies for all patients, including those with CAM/MNZ-resistant H. pylori infection. In the comparative effectiveness ranking, for CAM-resistant H. pylori, HDDT (OR: 96.80, 95%CI: 22.46-521.9) had the best results, whereas standard triple therapy ranked last (SUCRA: 98.7% vs 0.3%). In the subgroup of high cure rates (≥ 90%), HDDT was also generally better than other therapies. CONCLUSION For the eradication of CAM- and MNZ-resistant H. pylori strains, HDDT exhibited considerable advantages. The studies of CAM-resistant H. pylori were based on small samples due to a lack of antibiotic sensitivity tests in many RCTs, but the results showed that all patients, including those with CAM-resistant H. pylori infection, had a concordant trend. Overall, HDDT may be a reference for RCTs and other studies of H. pylori eradication.
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Affiliation(s)
- Shu-Peng Zou
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Qian Cheng
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Cheng-Yang Feng
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Chan Xu
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Ming-Hui Sun
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
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14
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Nishizawa T, Munkjargal M, Ebinuma H, Toyoshima O, Suzuki H. Sitafloxacin for Third-Line Helicobacter pylori Eradication: A Systematic Review. J Clin Med 2021; 10:2722. [PMID: 34202993 PMCID: PMC8234224 DOI: 10.3390/jcm10122722] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/04/2021] [Accepted: 06/18/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND AND AIM Sitafloxacin-based therapy is a potent candidate for third-line Helicobacter pylori eradication treatment. In this systematic review, we summarise current reports with sitafloxacin-based therapy as a third-line treatment. METHODS Clinical studies were systematically searched using PubMed, Cochrane library, Web of Science, and the Igaku-Chuo-Zasshi database. We combined data from clinical studies using a random-effects model and calculated pooled event rates, 95% confidence intervals (CIs), and the pooled odds ratio (OR). RESULTS We included twelve clinical studies in the present systematic review. The mean eradication rate for 7-day regimens of either PPI (proton pump inhibitor) or vonoprazan-sitafloxacin-amoxicillin was 80.6% (95% CI, 75.2-85.0). The vonoprazan-sitafloxacin-amoxicillin regimen was significantly superior to the PPI-sitafloxacin-amoxicillin regimen (pooled OR of successful eradication: 6.00; 95% CI: 2.25-15.98, p < 0.001). The PPI-sitafloxacin-amoxicillin regimen was comparable with PPI-sitafloxacin-metronidazole regimens (pooled OR: 1.06; 95% CI: 0.55-2.07, p = 0.86). CONCLUSIONS Although the 7-day regimen composed of vonoprazan, sitafloxacin, and amoxicillin is a good option as the third-line Helicobacter pylori eradication treatment in Japan, the extension of treatment duration should be considered to further improve the eradication rate. Considering the safety concern of fluoroquinolones, sitafloxcin should be used after confirming drug susceptibility.
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Affiliation(s)
- Toshihiro Nishizawa
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hospital, Narita 286-8520, Japan; (T.N.); (M.M.); (H.E.)
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 157-0066, Japan;
| | - Munkhbayar Munkjargal
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hospital, Narita 286-8520, Japan; (T.N.); (M.M.); (H.E.)
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hospital, Narita 286-8520, Japan; (T.N.); (M.M.); (H.E.)
| | - Osamu Toyoshima
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 157-0066, Japan;
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan
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15
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Sue S, Maeda S. Is a Potassium-Competitive Acid Blocker Truly Superior to Proton Pump Inhibitors in Terms of Helicobacter pylori Eradication? Gut Liver 2021; 15:799-810. [PMID: 33850058 PMCID: PMC8593510 DOI: 10.5009/gnl20242] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/17/2020] [Accepted: 12/01/2020] [Indexed: 11/20/2022] Open
Abstract
Vonoprazan (VPZ), a new potassium-competitive acid blocker, has been approved and used for Helicobacterpylori eradication in Japan. To date, many studies, as well as several systematic reviews and meta-analyses (MAs), have compared VPZ-based 7-day triple therapy with proton pump inhibitor (PPI)-based therapy. An MA of randomized controlled trials (RCTs) comparing first-line VPZ- with PPI-based triple therapy, the latter featuring amoxicillin (AMPC) and clarithromycin (CAM), found that approximately 30% of patients hosted CAM-resistant H. pylori; however, the reliability was poor because of high heterogeneity and a risk of selection bias. VPZ-based triple therapy is superior to PPI-based triple therapy for patients with CAM-resistant H. pylori, but not for those with CAM-susceptible H. pylori. An MA of non-RCTs found that second-line VPZ-based triple therapies were slightly (~2.6%) better than PPI-based triple therapies (with AMPC and metronidazole). However, the reliability of that MA was also low because of selection bias, confounding variables and a risk of publication bias; in addition, it is difficult to generalize the results because of a lack of data on antibiotic resistance. VPZ-based triple therapy (involving AMPC and sitafloxacin) was more effective than PPI-based triple therapy in a third-line setting, but a confirmatory RCT is needed. Non-RCT studies indicated that VPZ-based triple therapy involving CAM and metronidazole may be promising. Any further RCTs must explore the antibiotic-resistance status when evaluating the possible superiority of a potassium-competitive acid blocker.
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Affiliation(s)
- Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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16
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Liou JM, Lee YC, Wu MS. Treatment of Refractory Helicobacter pylori Infection-Tailored or Empirical Therapy. Gut Liver 2021; 16:8-18. [PMID: 33782215 PMCID: PMC8761919 DOI: 10.5009/gnl20330] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 12/14/2020] [Indexed: 01/08/2023] Open
Abstract
The treatment of refractory Helicobacter pylori remains challenging in clinical practice. Factors that should be considered in the treatment of refractory H. pylori infection include treatment length, dosage of antibiotics and proton pump inhibitors (PPIs), number of drugs, and the selection of appropriate antibiotics. Extending the treatment length of triple therapy and non-bismuth quadruple therapy to 14 days may increase the eradication rate compared with a shorter period (7 or 10 days). The use of a higher dose of PPIs or vonoprazan may also increase the efficacy of triple therapy. Four-drug therapy, including bismuth or non-bismuth quadruple therapies, usually achieve higher eradication rates than triple therapy. The addition of bismuth or metronidazole to levofloxacin-amoxicillin-PPI therapy may also increase the eradication rate. Therefore, four-drug therapies containing a higher dose of PPIs for 14 days are recommended in the third-line treatment setting for refractory H. pylori infection. The selection of appropriate antibiotics may be guided by susceptibility testing or empirically by medication history. Tailored therapy guided by susceptibility testing or genotypic resistance is recommended whenever possible. However, properly designed empirical therapy based on prior medication history (i.e., avoid the reuse of clarithromycin or levofloxacin empirically) is an acceptable alternative to tailored therapy after considering accessibility, cost, and the preference of the patient.
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Affiliation(s)
- Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Yi-Chia Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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17
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Liang CM, Tai WC, Hsu PI, Wu DC, Kuo CH, Tsay FW, Lee CL, Chen KY, Chuah SK. Trend of changes in antibiotic resistance in Helicobacter pylori from 2013 to 2019: a multicentre report from Taiwan. Therap Adv Gastroenterol 2020; 13:1756284820976990. [PMID: 33354229 PMCID: PMC7734532 DOI: 10.1177/1756284820976990] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 11/03/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Antibiotic resistance plays a crucial role in the treatment failure of Helicobacter pylori (H. pylori) infection. This study aimed to determine the trend of changes in the primary, secondary and tertiary antibiotic resistance of H. pylori in Taiwan over the last 7 years. METHODS We retrospectively analysed H. pylori-infected isolates from patients with primary resistance (n = 1369), secondary resistance (n = 196) and tertiary resistance (n = 184) from January 2013 to December 2019. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the Epsilometer test method. RESULTS A progressively higher primary resistance rate was observed for clarithromycin (11.8-20.4%, p = 0.039 in χ2 test for linear trend), levofloxacin (17.3-38.8%, p < 0.001) and metronidazole (25.6-42.3%, p < 0.001) among naïve patients who received first-line eradication therapy. The dual primary resistance to clarithromycin and metronidazole also progressively increased in a linear trend (2.4-10.4%, p = 0.009). For secondary resistance, an increase was observed for levofloxacin (30.5-64.7%, p = 0.006) and metronidazole (40.5-77.4%, p < 0.001). For tertiary resistance, the observed increase was even more significant for levofloxacin (65.9-100.0%, p = 0.106) and metronidazole (44.4-88.2%, p < 0.001). The resistance to amoxicillin and tetracycline remained very low in Taiwan regardless of primary, secondary and tertiary resistance. CONCLUSION Primary, secondary and tertiary antibiotic resistance to clarithromycin, levofloxacin and metronidazole for H. pylori has been increasing in Taiwan since 2013. Treatment should be targeted for eradication success rates of more than 90%. Third-line treatment should be based on antibiotic susceptibility.
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Affiliation(s)
- Chih-Ming Liang
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung
| | - Wei-Chen Tai
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung
- Chang Gung University College of Medicine, Taoyuan City
| | - Pin-I Hsu
- Department of Medicine, An Nan Hospital, China Medical University
| | - Deng-Chyang Wu
- Department of Internal Medicine, Division of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung
| | - Chao-Hung Kuo
- Department of Internal Medicine, Division of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung
| | - Feng-Woey Tsay
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kaohsiung Veterans General Hospital, Kaohsiung
| | - Chia-Long Lee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Cathay General Hospital, Taipei
| | - Kuan-Yang Chen
- Department of Gastroenterology, Taipei City Hospital, 10, Section 4, Ren’ai Road, Da’an District 106, Taipei
| | - Seng-Kee Chuah
- Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, 833 Chang Gung University College of Medicine, Taoyuan City
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18
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The Potential Benefits of Vonoprazan as Helicobacter pylori Infection Therapy. Pharmaceuticals (Basel) 2020; 13:ph13100276. [PMID: 32998241 PMCID: PMC7600708 DOI: 10.3390/ph13100276] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/24/2020] [Accepted: 09/24/2020] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori infection is a severe global health problem that is closely associated with acid-related diseases and gastric malignancies. Eradicating H. pylori is strongly recommended for lowering peptic ulcer recurrence and preventing gastric cancer. The current approved H. pylori eradication regimen combines a proton pump inhibitor (PPI) with two antibiotics. Unfortunately, this regimen failed to meet expectations mostly due to antibiotic resistance and insufficient gastric acid suppression. Vonoprazan, a novel potassium-competitive acid blocker, showed promising results as a PPI replacement. Vonoprazan inhibits gastric acid secretion by acting as a reversible competitive inhibitor against potassium ions and forming disulfide bonds with the cysteine molecule of H+/K+-ATPase. Vonoprazan has superior pharmacological characteristics over PPI, such as no requirement for acid activation, stability in acidic conditions, shorter optimum acid suppression period, and resistance to cytochrome P (CYP)2C19 polymorphism. Several comparative randomized controlled trials and meta-analyses revealed the superiority of vonoprazan in eradicating H. pylori, notably the resistant strains. The adverse effect caused by vonoprazan is long-term acid suppression that may induce elevated gastrin serum, hypochlorhydria, and malabsorption. All vonoprazan studies have only been conducted in Japan. Further studies outside Japan are necessary for universally conclusive results.
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19
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O'Connor A, Furuta T, Gisbert JP, O'Morain C. Review - Treatment of Helicobacter pylori infection 2020. Helicobacter 2020; 25 Suppl 1:e12743. [PMID: 32918350 DOI: 10.1111/hel.12743] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance, and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth-based regimens as a first-line regimen. Antibiotic resistance is rising wherever it is being assessed, and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth-based quadruple therapy as a first-line therapy is now very clearly established, and there is substantial evidence that it is the best performing first-line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.
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Affiliation(s)
- Anthony O'Connor
- Department of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
| | - Takahisa Furuta
- The Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Javier P Gisbert
- Gastroenterology Unit, 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, Spain
| | - Colm O'Morain
- Department of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
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20
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Abstract
The main challenge in the field of Helicobacter pylori (H. pylori) infection is antibiotic resistance, which influences the efficacy of eradication regimens. Bismuth-containing quadruple therapy has been confirmed as an effective regimen for eradicating H. pylori, especially in strains with antibiotic resistance. High-dose proton-pump inhibitor-amoxicillin dual therapy could decrease the use of unnecessary antibiotics, which is a promising alternative approach. Adjuvant therapy (specific probiotic or vitamin) also showed good results, although more evidence is needed. Novel anti-H. pylori drugs are needed, and the establishment of the H. pylori database is an effective way to acknowledge the real-time information of H. pylori management. This review provides the recent progress of H. pylori treatment, and further studies are needed to address the role of different regimens in improving H. pylori eradication rate, especially in strains with antibiotics resistance.
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Affiliation(s)
- Yi Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
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21
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Abstract
PURPOSE OF REVIEW Helicobacter pylori eradication has become more challenging over the past decade due to increasing antimicrobial resistance, especially to clarithromycin and levofloxacin. We identified 508 recent publications on H. pylori treatment (published between January 2018 and June 2019), focusing on the most highly clinically relevant for this review. RECENT FINDINGS Declining H. pylori eradication rates with clarithromycin triple therapy have led to most guidelines recommending 14 days bismuth-based quadruple therapy or concomitant therapy as the best initial empiric regimen. Substituting amoxicillin for tetracycline or metronidazole in quadruple therapy, and a three-in-one pill version of the regimen, also appear effective. Vonoprazan, a potent acid inhibitor, can overcome much clarithromycin resistance in triple therapy. High-dose dual therapy (proton pump inhibitor with amoxicillin) is a promising alternative approach. Reviewing resistance patterns to select suitable first-line empiric therapies is important in high resistance regions. Molecular methods to evaluate H. pylori antimicrobial susceptibility promise to be simpler than standard microbiological culture. The cost-effectiveness of antimicrobial susceptibility testing in refractory cases remains unproven. SUMMARY Updating clinicians treating H. pylori is important to combat the emerging problems of multidrug antimicrobial resistance in H. pylori strains. Truly novel approaches to H. pylori eradication are needed.
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22
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O'Connor A, Liou JM, Gisbert JP, O'Morain C. Review: Treatment of Helicobacter pylori Infection 2019. Helicobacter 2019; 24 Suppl 1:e12640. [PMID: 31486235 DOI: 10.1111/hel.12640] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/08/2019] [Indexed: 02/06/2023]
Abstract
This review summarizes important studies regarding Helicobacter pylori therapy published from May 2018 to May 2019. The main themes that emerge involve studies assessing the efficacy of bismuth-based regimens. While in recent years the efficacy of bismuth-based quadruple therapy as a second-line therapy has been clearly established, there is now substantial evidence that it is the best performing first-line therapy. Antibiotic resistance was again intensely studied this year, and a clear and dramatic increase in resistance is noted for clarithromycin and levofloxacin; most notably, it may not be possible to support these therapies in most regions of the world much longer without testing. The utility of vonoprazan as an alternative to proton-pump inhibitor therapy, especially in resistant and difficult to treat groups, has also been considered in greater detail this year, as well as means of supporting and enhancing adherence to therapy. Several studies showed that the diversity of gut microbiota was significantly altered shortly after H pylori eradication. However, the diversity was restored to pre-treatment state after 2 months in patients treated with triple therapy. More studies are warranted to assess the long-term changes of gut microbiota after H pylori eradication.
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Affiliation(s)
- Anthony O'Connor
- Department Of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
| | - Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Javier P Gisbert
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Universitario de La Princesa, Madrid, Spain
| | - Colm O'Morain
- Department Of Gastroenterology, Tallaght University Hospital/Trinity College, Dublin, Ireland
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Fallone CA, Moss SF, Malfertheiner P. Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics. Gastroenterology 2019; 157:44-53. [PMID: 30998990 DOI: 10.1053/j.gastro.2019.04.011] [Citation(s) in RCA: 198] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/25/2019] [Accepted: 04/03/2019] [Indexed: 12/13/2022]
Abstract
Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth quadruple therapy for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts. The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.
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Affiliation(s)
- Carlo A Fallone
- Department of Medicine, Division of Gastroenterology, McGill University Health Center, Montreal, Québec, Canada.
| | - Steven F Moss
- Department of Medicine, Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany; Ludwig Maximilian University Clinic, Medical Clinic II, München, Germany
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Abadi ATB, Ierardi E. Vonoprazan and Helicobacter pylori Treatment: A Lesson From Japan or a Limited Geographic Phenomenon? Front Pharmacol 2019; 10:316. [PMID: 31024299 PMCID: PMC6459936 DOI: 10.3389/fphar.2019.00316] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 03/15/2019] [Indexed: 12/12/2022] Open
Abstract
Within a short time after the discovery of Helicobacter pylori, its critical role in many gastroduodenal disorders became evident. Many in vitro and in vivo data have proven that infection should be treated in order to avoid lasting colonization which may lead to problematic gastroduodenal diseases. Probiotics, preventive and therapeutic vaccines and antibiotic therapy are the main options proposed to cure these disorders. 25 years ago, triple therapy including a traditional proton pump inhibitor (PPI) and two antibiotics (amoxicillin and clarithromycin or metronidazole) was defined as the best therapy formulation for the H. pylori infection. With the strongly decreased effectiveness of this scheme, many empirical therapeutic regimens have been developed. However, the prevalence of resistance is increasing worldwide and reveals important geographic differences and even the most recent and effective regimens show some critical points. Therefore, efficacy of vonoprazan-based therapy in regions with low rate of clarithromycin resistance may be limited. In this review, we attempt to open a new window to overcome the problem of antibiotic resistance to H. pylori. In fact, we focused our attention on the possibility that conventional PPI may be replaced by vonoprazan, thus giving rise to the beginning of a new era characterized by an improved therapeutic option for H. pylori infection. Therefore, we hypothesize that switching to vonoprazan as a novel acid blocker for H. pylori treatment might allow an unexpected reassessment of the triple therapy, at least in regions with low rate of clarithromycin resistance. Nevertheless, this optimistic view of the problem could be disproved by the possible failure of vonoprazan based therapeutic regimens outside of Japan in geographic areas characterized by different rates of antibiotic resistances.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy
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