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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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Feng S, Lin J, Zhang X, Hong X, Xu W, Wen Y, She F. Role of AlgC and GalU in the Intrinsic Antibiotic Resistance of Helicobacter pylori. Infect Drug Resist 2023; 16:1839-1847. [PMID: 37016632 PMCID: PMC10066898 DOI: 10.2147/idr.s403046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023] Open
Abstract
Purpose Helicobacter pylori is associated with the development of gastrointestinal diseases. However, its eradication is challenged by an increased rate of drug resistance. AlgC and GalU are important for the synthesis of UDP-glucose, which is a substrate for the synthesis of lipopolysaccharide (LPS) in H. pylori. In this study, we investigated the role of UDP-glucose in the intrinsic drug resistance in H. pylori. Methods Gene knockout strains or complementation strains, including ΔalgC, ΔgalU, ΔgalE, Δhp0045, ΔalgC/algC* and ΔgalU/galU* were constructed in Hp26695; and ΔalgC and ΔgalU were also constructed in two clinical drug-resistant strains, Hp008 and Hp135. The minimum inhibitory concentrations (MIC) of H. pylori to amoxicillin (AMO), tetracycline (TET), clarithromycin (CLA), metronidazole (MNZ), levofloxacin (LEV), and rifampicin (RIF) were measured using MIC Test Strips. Silver staining was performed to examine the role of AlgC and GalU in LPS synthesis. Ethidium bromide (EB) accumulation assay was performed to assess the outer membrane permeability of H. pylori strains. Results Knockout of algC and galU in H. pylori resulted in increased drug sensitivity to AMO, MNZ, CLA, LEV, and RIF; whereas knockout of hp0045 and galE, which are involved in GDP-fucose and UDP-galactose synthesis, respectively, did not significantly alter the drug sensitivity of H. pylori. Knockout of algC and galU in clinically drug-resistant strains resulted in significantly increased drug sensitivity to all the antibiotics, except MNZ. The lipid A-core structure was altered in ΔalgC and ΔgalU when their EB accumulation was higher than that in the wild type and complementation strains. Conclusion UDP-glucose may play an important role in increasing drug resistance to AMO, MNZ, CLA, LEV, TET, and RIF by maintaining the lipid A-core structure and decreasing membrane permeability. AlgC and GalU may serve as potential drug targets for decreasing antibiotic resistance in clinical isolates.
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Affiliation(s)
- Shunhang Feng
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Jiansheng Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Xiaoyan Zhang
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Xin Hong
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Wanyin Xu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Yancheng Wen
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Feifei She
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, People’s Republic of China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, School for Basic Medical Sciences, Fujian Medical University, Fuzhou, People’s Republic of China
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Kwon YH. Tailored Therapy Based on Antibiotic Resistance. HELICOBACTER PYLORI 2023:575-586. [DOI: 10.1007/978-981-97-0013-4_48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Romano M, Gravina AG, Eusebi LH, Pellegrino R, Palladino G, Frazzoni L, Dajti E, Gasbarrini A, Di Mario F, Zagari RM. Management of Helicobacter pylori infection: Guidelines of the Italian Society of Gastroenterology (SIGE) and the Italian Society of Digestive Endoscopy (SIED). Dig Liver Dis 2022; 54:1153-1161. [PMID: 35831212 DOI: 10.1016/j.dld.2022.06.019] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 06/25/2022] [Accepted: 06/25/2022] [Indexed: 12/18/2022]
Abstract
Helicobacter pylori infection is very common and affects more than one-third of adults in Italy. Helicobacter pylori causes several gastro-duodenal diseases, such as gastritis, peptic ulcer and gastric malignancy, and extra-gastric diseases. The eradication of the bacteria is becoming complex to achieve due to increasing antimicrobial resistance. To address clinical questions related to the diagnosis and treatment of Helicobacter pylori infection, three working groups examined the following topics: (1) non-invasive and invasive diagnostic tests, (2) first-line treatment, and (3) rescue therapies for Helicobacter pylori infection. Recommendations are based on the best available evidence to help physicians manage Helicobacter pylori infection in Italy, and have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.
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Affiliation(s)
- Marco Romano
- Department of Precision Medicine and Complex Operative Unit of Hepatogastroenterology and Digestive Endoscopy, University Hospital, University of Campania "Luigi Vanvitelli", Via Luigi de Crecchio, 80138, Napoli, Italy.
| | - Antonietta Gerarda Gravina
- Department of Precision Medicine and Complex Operative Unit of Hepatogastroenterology and Digestive Endoscopy, University Hospital, University of Campania "Luigi Vanvitelli", Via Luigi de Crecchio, 80138, Napoli, Italy
| | - Leonardo Henry Eusebi
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Raffaele Pellegrino
- Department of Precision Medicine and Complex Operative Unit of Hepatogastroenterology and Digestive Endoscopy, University Hospital, University of Campania "Luigi Vanvitelli", Via Luigi de Crecchio, 80138, Napoli, Italy
| | - Giovanna Palladino
- Department of Precision Medicine and Complex Operative Unit of Hepatogastroenterology and Digestive Endoscopy, University Hospital, University of Campania "Luigi Vanvitelli", Via Luigi de Crecchio, 80138, Napoli, Italy
| | - Leonardo Frazzoni
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Elton Dajti
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Antonio Gasbarrini
- Complex Operating Unit of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Via della Pineta Sacchetti, 217, 00168, Rome, Italy
| | - Francesco Di Mario
- Geriatric-Rehabilitation Department, University of Parma, Department of Medicine and Surgery, University of Parma, Via Gramsci, 14, 43126, Parma, Italy
| | - Rocco Maurizio Zagari
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
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Nyssen OP, Espada M, Gisbert JP. Empirical vs. Susceptibility-Guided Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Front Microbiol 2022; 13:913436. [PMID: 35774456 PMCID: PMC9237546 DOI: 10.3389/fmicb.2022.913436] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 05/17/2022] [Indexed: 01/30/2023] Open
Abstract
Background Treating Helicobacter pylori infection according to antibiotic resistance has been frequently recommended. However, information on its real effectiveness is scarce. Aim The aim of this study is to perform a meta-analysis comparing empirical vs. susceptibility-guided treatment of H. pylori. Methods Selection of studies: Studies comparing empirical versus susceptibility-guided treatment were selected. Search strategy: electronic and manual up to August 2021. Data synthesis: by intention-to-treat (random-effects model). Results Overall, 54 studies were included (6,705 patients in the susceptibility-guided group and 7,895 in the empirical group). H. pylori eradication rate was 86 vs. 76%, respectively (RR: 1.12; 95% CI: 1.08-1.17; I 2: 83%). Similar results were found when only RCTs were evaluated (24 studies; RR: 1.16; 95% CI: 1.11-1.22; I 2: 71%) and when susceptibility testing was assessed by culture (RR: 1.12; 95% CI: 1.06-1.18) or PCR (RR: 1.14; 95% CI: 1.05-1.23). For first-line treatments (naïve patients; 30 studies), better efficacy results were obtained with the susceptibility-guided strategy (RR: 1.15; 95% CI: 1.11-1.20; I 2: 79%). However, for empirical first-line quadruple regimens, in particular (both with and without bismuth, excluding the suboptimal triple therapies), not based on CYP2C19 gene polymorphism, no differences in efficacy were found compared with the susceptibility-guided group (RR: 1.04; 95% CI: 0.99-1.09); this lack of difference was confirmed in RCTs (RR: 1.05; 95% CI: 0.99-1.12). For rescue therapies (13 studies, most 2nd-line), similar results were demonstrated for both strategies, including all studies (RR: 1.09; 95% CI: 0.97-1.22; I 2: 82%) and when only RCTs were considered (RR: 1.15; 95% CI: 0.97-1.36). Conclusion The benefit of susceptibility-guided treatment over empirical treatment of H. pylori infection could not be demonstrated, either in first-line (if the most updated quadruple regimens are prescribed) or in rescue therapies.
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Affiliation(s)
- Olga P. Nyssen
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Marta Espada
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Javier P. Gisbert
- Gastroenterology Unit, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Hospital Universitario de La Princesa, Madrid, Spain
- Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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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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Cortés P, Nelson AD, Bi Y, Stancampiano FF, Murray LP, Pujalte GGA, Gomez V, Harris DM. Treatment Approach of Refractory Helicobacter pylori Infection: A Comprehensive Review. J Prim Care Community Health 2021; 12:21501327211014087. [PMID: 33949229 PMCID: PMC8114244 DOI: 10.1177/21501327211014087] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.
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Affiliation(s)
| | | | - Yan Bi
- Mayo Clinic, Jacksonville, FL, USA
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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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Iqbal U, Khara HS, Akhtar D, Hu Y, Anwar H, Haq KF, Siddiqui HU, Bergenstock MK, Shellenberger MJ. Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Gastroenterology Res 2020; 13:260-268. [PMID: 33447305 PMCID: PMC7781276 DOI: 10.14740/gr1342] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 12/16/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Helicobacter pylori (HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP. METHODS We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP. RESULTS Thirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%). CONCLUSION Nitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.
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Affiliation(s)
- Umair Iqbal
- Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA 17822, USA
| | - Harshit S. Khara
- Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA 17822, USA
| | - Daud Akhtar
- Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Yirui Hu
- Department of Population Health Sciences, Geisinger Medical Center, Danville, PA 17822, USA
| | - Hafsa Anwar
- Department of Internal Medicine, Capital Health Regional Medical Center, Trenton, NJ 08638, USA
| | - Khwaja F. Haq
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202, USA
| | - Hafiz U. Siddiqui
- Department of Surgery, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA
| | - Marika K. Bergenstock
- Division of Gastroenterology and Hepatology, Geisinger Medical Center, Danville, PA 17822, USA
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10
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Gisbert JP. Empirical or susceptibility-guided treatment for Helicobacter pylori infection? A comprehensive review. Therap Adv Gastroenterol 2020; 13:1756284820968736. [PMID: 33240392 PMCID: PMC7675893 DOI: 10.1177/1756284820968736] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/01/2020] [Indexed: 02/06/2023] Open
Abstract
Although susceptibility-guided therapy is frequently recommended for Helicobacter pylori infection, the evidence available to date supporting this strategy is limited. The aim of the present article is to review the advantages and limitations of the susceptibility-guided and the empirical strategies to treat this infection. We performed a bibliographic search to identify studies investigating H. pylori susceptibility-guided therapy. Culture is not the only way to assess antibiotic resistance, as different polymerase chain reaction-based approaches have been developed as alternative methods. For detecting H. pylori antimicrobial resistance, a molecular approach based on a stool sample might enable more convenient, time-saving methods. Unfortunately, the antimicrobial susceptibility cannot be obtained in all cases. Furthermore, antibiotic susceptibility testing in clinical practice yields useful information only for a few antibiotics: clarithromycin, metronidazole, and quinolones. In addition, susceptibility towards clarithromycin and metronidazole in vitro does not necessarily lead to eradication in vivo. In the case of H. pylori therapy failure, we should not re-administer any of the antibiotics against which H. pylori has probably become resistant. Our updated meta-analysis showed that susceptibility-guided treatment is not better than empirical treatment of H. pylori infection in first-line therapy if the most updated quadruple regimens are empirically prescribed, and similar efficacy results were also demonstrated with the two strategies for second-line therapy. Cumulative H. pylori eradication rate with several successive rescue therapies empirically prescribed reaches almost 100%. Finally, the studies that have evaluated the cost-effectiveness of the susceptibility-guided treatment have achieved contradictory results. In summary, we can conclude that the evidence is too limited to support the generalized use of susceptibility-guided therapy for H. pylori treatment in routine clinical practice, either as first-line or as rescue treatment. Nevertheless, it would be recommended that susceptibility tests are performed routinely, even before prescribing first-line treatment, in specialized centers with an interest in H. pylori management.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La
Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad
Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades
Hepáticas y Digestivas (CIBEREHD), Diego de León, 62, Madrid, 28006, Spain
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11
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Nyssen OP, Perez-Aisa A, Rodrigo L, Castro M, Mata Romero P, Ortuño J, Barrio J, Huguet JM, Modollel I, Alcaide N, Lucendo A, Calvet X, Perona M, Gomez B, Gomez Rodriguez BJ, Varela P, Jimenez-Moreno M, Dominguez-Cajal M, Pozzati L, Burgos D, Bujanda L, Hinojosa J, Molina-Infante J, Di Maira T, Ferrer L, Fernández-Salazar L, Figuerola A, Tito L, de la Coba C, Gomez-Camarero J, Fernandez N, Caldas M, Garre A, Resina E, Puig I, O'Morain C, Megraud F, Gisbert JP. Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg). Helicobacter 2020; 25:e12722. [PMID: 32656898 DOI: 10.1111/hel.12722] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.
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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, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - Luis Rodrigo
- Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Manuel Castro
- Gastroenterology Unit, Hospital de Valme and CIBEREHD, Sevilla, Spain
| | - Pilar Mata Romero
- Gastroenterology Unit, Hospital San Pedro de Alcántara and CIBEREHD, Cáceres, Spain
| | - Juan Ortuño
- Gastroenterology Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Jesus Barrio
- Gastroenterology Unit, Hospital Rio Hortega, Valladolid, Spain
| | - Jose Maria Huguet
- Gastroenterology Unit, Consorci Hospital General Universitari Valencia, Valencia, Spain
| | - Ines Modollel
- Gastroenterology Unit, Consorci Sanitari Terrassa, Terrassa, Spain
| | - Noelia Alcaide
- Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Alfredo Lucendo
- Gastroenterology Unit, Hospital de Tomelloso, Ciudad Real, Spain
| | - Xavier Calvet
- Gastroenterology Unit, Hospital de Sabadell and CIBEREHD, Barcelona, Spain
| | - Monica Perona
- Gastroenterology Unit, Hospital Quiron, Marbella, Spain
| | - Barbara Gomez
- Gastroenterology Unit, Hospital de Mataró, Barcelona, Spain
| | | | - Pilar Varela
- Gastroenterology Unit, Hospital de Cabueñes Gijon, Spain
| | | | | | | | - Diego Burgos
- Gastroenterology Unit, Hospital Ramon y Cajal, Madrid, Spain
| | - Luis Bujanda
- Gastroenterology Unit, Hospital Donostia/Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Jenifer Hinojosa
- Gastroenterology Unit, Agencia Sanitaria Costa del Sol, Málaga, Spain
| | | | - Tommaso Di Maira
- Gastroenterology Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Luis Ferrer
- Gastroenterology Unit, Consorci Hospital General Universitari Valencia, Valencia, Spain
| | | | - Ariadna Figuerola
- Gastroenterology Unit, Hospital de Sabadell and CIBEREHD, Barcelona, Spain
| | - Llucia Tito
- Gastroenterology Unit, Hospital de Mataró, Barcelona, Spain
| | | | | | - Nuria Fernandez
- Gastroenterology Unit, Agencia Sanitaria Costa del Sol, Málaga, Spain
| | - Maria Caldas
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ana Garre
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Elena Resina
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Ignasi Puig
- Gastroenterology Unit, Althaia Xarxa Assistencial Universitària de Manresa and Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Spain
| | - Colm O'Morain
- Gastroenterology Unit, Trinity College, Dublin, Ireland
| | - Francis Megraud
- Gastroenterology Unit, Centre National de Référence des Campylobacters et Hélicobacters, Université de Bordeaux, Bordeaux, France
| | - Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Belay AS, Abateneh DD, Yehualashet SS. <p>Seroprevalence of <em>Helicobacter pylori</em> Infection and Associated Factors Among Adult Dyspeptic Patients in Public Health Facilities, Mizan Aman Town, Southwest, Ethiopia: Institutional-Based Cross-Sectional Study</p>. Int J Gen Med 2020; 13:577-585. [PMID: 32982374 PMCID: PMC7490056 DOI: 10.2147/ijgm.s273523] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 08/22/2020] [Indexed: 12/30/2022] Open
Abstract
Background Helicobacter pylori infection is a public health problem associated with chronic gastritis, peptic ulcer, and gastric cancer. It is endemic in developing countries like Ethiopia. This study was aimed to assess seroprevalence of H. pylori infection and associated factors among adults’ dyspeptic patients in public health facilities of Mizan Aman Town, Southwest Ethiopia. Methods Cross-sectional study was conducted in public health facilities of Mizan Aman Town, from April 1, 2018, to June 30, 2018. A total of 208 adult dyspeptic patients were included in the study. A structured questionnaire was used to collect data. Serum was tested for anti-H. pylori antibody using a commercial test strip. Data were entered using Epi info 6.04 and exported to SPSS 21 for analysis. Bivariate and multivariate logistic regression was employed and OR with 95% CI was retrieved. P-value of less than 0.05 was considered as statistically significant. Results A total of 208 participants were interviewed. The mean age of respondents was 31.70 (SD ±9.123) years. Seroprevalence of H. pylori infection was 89 (42.8%). Presence of domestic animals (AOR = 13.33, 95% CI = (2.203–80.692)), sources of drinking water (AOR = 0.011, 95% CI = (0.001–0.110)), toilet type (AOR = 11.236, 95% CI = (1.921–65.73)), shared beds with siblings (AOR = 7.775, 95% CI = (1.676–36.082)), family size (AOR = 0.015, 95% CI = (0.003, 0.089)), storing and reusing water (AOR =0.014, 95% CI = (0.002–0.103)) and occupational status (AOR = 23.33, 95% CI = (2.034–67.661)) were variables significantly associated with seroprevalence of H. pylori. Conclusion Seroprevalence of H. pylori infection is relatively high in Ethiopia. Family size, shared bed, presences of domestic animals, storage and reuse of water, toilet type, sources of drinking water, and occupation were significant factors associated with H. pylori infection. The possible identified modifiable risk factors should be addressed through effective health education.
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Affiliation(s)
- Alemayehu Sayih Belay
- Mizan Tepi University, College of Health Sciences, Department of Nursing, Mizan Aman, Ethiopia
- Correspondence: Alemayehu Sayih Belay Mizan Tepi University, College of Health Sciences, Department of Nursing, P.O. Box: 260, Mizan Teferi, EthiopiaTel +251-911669861 Email
| | - Dejene Derseh Abateneh
- Mizan Tepi University, College of Health Sciences, Department of Nursing, Mizan Aman, Ethiopia
- Kotebe Metropolitan University, Menelik II College of Medicine and Health Sciences, Department of Medical Laboratory Sciences, Addis Ababa, Ethiopia
| | - Sisay Shewasinad Yehualashet
- Mizan Tepi University, College of Health Sciences, Department of Nursing, Mizan Aman, Ethiopia
- Debre Berhan University, Institute of Health Sciences, Debre Berhan, Ethiopia
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Abstract
GOALS The goal of this study was to examine the impact of prior treatment with a nitroimidazole antibiotic on the success of Helicobacter pylori treatment. BACKGROUND Prior nitroimidazole exposure may increase the likelihood of nitroimidazole-resistant H. pylori. Current H. pylori treatment guidelines recommend that, in the absence of susceptibility testing, patients with prior nitroimidazole exposure should not be treated with a nitroimidazole antibiotic. Data to support this recommendation are lacking. STUDY We searched the Clalit Health Services database to identify subjects 25 to 60 years old who underwent a first-ever C-urea breath test between 2010 and 2015. Patients who underwent a previous H. pylori stool antigen test or gastroscopy were excluded. Pharmacy dispensation data were retrieved. RESULTS A total of 1386 subjects (34.8% male individuals, age 40.7±10.7 y) received a nitroimidazole-containing regimen including 282 (20.4%) with prior nitroimidazole exposure. Successful eradication was achieved in 58.9% and 73.8% of subjects with and without prior nitroimidazole exposure, respectively (odds ratio, 0.51; 95% confidence interval, 0.39-0.67; P<0.0001). Nitroimidazole exposure adversely impacted the success of triple therapy with nitroimidazole, proton pump inhibitor, and amoxicillin or clarithromycin (39.4% vs. 63.4% and 54.4% vs. 73.6%, P<0.01, respectively), but not quadruple therapy. Following multivariate analysis, nitroimidazole exposure was significantly associated with eradication failure (odds ratio, 1.89; 95% confidence interval, 1.43-2.50; P<0.0001). A greater time elapsed from nitroimidazole exposure, and a lower cumulative nitroimidazole dose were observed in subjects with successful eradication (P<0.0001 for both). CONCLUSION Nitroimidazole exposure may adversely impact the success of nitroimidazole-based triple therapy, but not quadruple therapy. Clinicians should conduct a thorough patient drug history before administering empiric treatment for H. pylori infection.
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Burgos‐Santamaría D, McNicholl AG, Gisbert JP. Empirical
Helicobacter pylori
rescue therapy: an 18‐year single‐centre study of 1200 patients. ACTA ACUST UNITED AC 2019. [DOI: 10.1002/ygh2.372] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Diego Burgos‐Santamaría
- Department of Gastroenterology and Hepatology Hospital Universitario Ramón y Cajal Instituto Ramón y Cajal De Investigación Sanitaria (IRYCIS) Universidad de Alcalá Madrid Spain
| | - Adrian G. McNicholl
- Gastroenterology Unit Hospital Universitario de La Princesa Instituto de Investigación Sanitaria Princesa (IIS‐IP) Universidad Autónoma de Madrid Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Madrid Spain
| | - Javier P. Gisbert
- Gastroenterology Unit Hospital Universitario de La Princesa Instituto de Investigación Sanitaria Princesa (IIS‐IP) Universidad Autónoma de Madrid Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Madrid Spain
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Gu L, Li S, He Y, Chen Y, Jiang Y, Peng Y, Liu X, Yang H. Bismuth, rabeprazole, amoxicillin, and doxycycline as first-line Helicobacter pylori therapy in clinical practice: A pilot study. Helicobacter 2019; 24:e12594. [PMID: 31119830 DOI: 10.1111/hel.12594] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Revised: 04/18/2019] [Accepted: 04/22/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Bismuth-containing quadruple therapy (BQT) is a recommended alternative first-line therapy for Helicobacter pylori (H. pylori) infection. We aim to evaluate the efficacy and safety of a new BQT with amoxicillin and doxycycline as a first-line treatment for H. pylori infection in clinical practice. METHODS An open, prospective pilot clinical study including H. pylori-positive outpatients who had never received eradication treatment was carried out. An RADB regimen (10 mg rabeprazole, 1000 mg amoxicillin, 100 mg doxycycline, and 220 mg colloidal bismuth tartrate, all given bid for 14 days) was prescribed by gastroenterologists. H. pylori eradication was confirmed by a 13 C-urea breath test performed at least 6 weeks after the end of treatment. Regimen efficacy was evaluated by per-protocol (PP) and intention-to-treat (ITT) analyses. RESULTS One hundred eighteen patients were included in the study. The eradication rate of RADB was 93.8% (105/112; 95% CI 89.2%-98.3%) in PP analysis and 89.8% (106/118; 95% CI 84.3%-95.4%) in ITT analysis. The patient compliance rate was 97.5% (115/118). The adverse event rate was 6.8% (8/118). Adverse events included asthenia, loss of appetite, dry mouth, heartburn, diarrhea, and abdominal pain. All adverse events disappeared after completion of therapy. CONCLUSION Our results suggest that 14-day BQT with amoxicillin and doxycycline can be an effective and safe eradication regimen for first-line therapy against H. pylori infection in clinical practice.
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Affiliation(s)
- Lei Gu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Shenglan Li
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Ying He
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Chen
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Yanzhi Jiang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Yu Peng
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Huixiang Yang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
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Liou JM, Chen PY, Luo JC, Lee JY, Chen CC, Fang YJ, Yang TH, Chang CY, Bair MJ, Chen MJ, Hsu YC, Hsu WF, Chang CC, Lin JT, Shun CT, El-Omar EM, Wu MS. Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection. Gastroenterology 2018; 155:1109-1119. [PMID: 29964036 DOI: 10.1053/j.gastro.2018.06.047] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Revised: 05/24/2018] [Accepted: 06/24/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. METHODS We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. RESULTS H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance-guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. CONCLUSIONS Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.
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Affiliation(s)
- Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Po-Yueh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Jiing-Chyuan Luo
- Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ji-Yuh Lee
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Tsung-Hua Yang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Chi-Yang Chang
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan and Mackay Medical College, New Taipei City, Taiwan
| | - Mei-Jyh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yao-Chun Hsu
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Wen-Feng Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jaw-Town Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Emad M El-Omar
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
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Nitazoxanide and Doxycycline Sensitivity Among Metronidazole Resistant Helicobacter pylori Isolates from Patients with Gastritis. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2018. [DOI: 10.5812/archcid.66693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Mahachai V, Vilaichone RK, Pittayanon R, Rojborwonwitaya J, Leelakusolvong S, Maneerattanaporn M, Chotivitayatarakorn P, Treeprasertsuk S, Kositchaiwat C, Pisespongsa P, Mairiang P, Rani A, Leow A, Mya SM, Lee YC, Vannarath S, Rasachak B, Chakravuth O, Aung MM, Ang TL, Sollano JD, Trong Quach D, Sansak I, Wiwattanachang O, Harnsomburana P, Syam AF, Yamaoka Y, Fock KM, Goh KL, Sugano K, Graham D. Helicobacter pylori management in ASEAN: The Bangkok consensus report. J Gastroenterol Hepatol 2018; 33:37-56. [PMID: 28762251 DOI: 10.1111/jgh.13911] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Revised: 07/11/2017] [Accepted: 07/21/2017] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.
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Affiliation(s)
- Varocha Mahachai
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- National Gastric Cancer and Gastrointestinal Diseases Research Center, Bangkok, Pathumthani, Thailand
| | - Ratha-Korn Vilaichone
- Department of Medicine, Thammasat University Hospital, Khlong Luang, Pathumthani, Thailand
- National Gastric Cancer and Gastrointestinal Diseases Research Center, Bangkok, Pathumthani, Thailand
| | - Rapat Pittayanon
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- National Gastric Cancer and Gastrointestinal Diseases Research Center, Bangkok, Pathumthani, Thailand
| | | | | | - Monthira Maneerattanaporn
- Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
- National Gastric Cancer and Gastrointestinal Diseases Research Center, Bangkok, Pathumthani, Thailand
| | - Peranart Chotivitayatarakorn
- Department of Medicine, Thammasat University Hospital, Khlong Luang, Pathumthani, Thailand
- National Gastric Cancer and Gastrointestinal Diseases Research Center, Bangkok, Pathumthani, Thailand
| | - Sombat Treeprasertsuk
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Chomsri Kositchaiwat
- Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | | | - Pisaln Mairiang
- Department of Medicine, Faculty of Medicine, KhonKaen University, Khon Kaen, Thailand
| | - Aziz Rani
- Department of Gastroenterology and Hepatology, University of Jakarta, Jakarta, Indonesia
| | - Alex Leow
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Swe Mon Mya
- Department of Gastroenterology, Yangon General Hospital, Yangon, Myanmar
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | | | | | - Oung Chakravuth
- Calmette Hospital, University of Health Science, Phnom Penh, Cambodia
| | - Moe Myint Aung
- Department of Gastroenterology, Yangon General Hospital, Yangon, Myanmar
| | - Tiing-Leong Ang
- Department of Gastroentrology and Hepatology, Changi General Hospital, Singapore
| | - Jose D Sollano
- Section of Gastroenterology, University of Santo Tomas Hospital, Manila, Philippines
| | - Duc Trong Quach
- Department of Internal Medicine, University of Medicine and Pharmacy, Hochiminh City, Vietnam
| | | | | | | | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Depok, Indonesia
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kwong-Ming Fock
- Faculty of Medicine, National University of Singapore, Singapore
| | - Khean-Lee Goh
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - David Graham
- Department of Medicine, Gastroenterology Section, Baylor College of Medicine and Michael E. DeBakey VA Medicine Center, Houston, Texas, USA
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Abstract
OBJECTIVE The aim of this study was to evaluate the efficacy/tolerability of a culture-guided approach in the eradication of Helicobacter pylori and identify factors associated with antibiotic resistance/treatment failure. PATIENTS AND METHODS This retrospective single-center study included patients who underwent culture-guided treatment for H. pylori infection, after two ineffective eradication attempts, between October 2012 and December 2016. We assessed the following demographic and clinical data of the patients: sex, age, BMI, alcohol and tobacco consumption, history of dyspepsia, peptic ulceration and first-degree relatives with gastric cancer, antibiotic susceptibility results, treatment composition, tolerability, and success. The treatment success was confirmed by a monoclonal stool antigen test. RESULTS Culture-guided treatment was performed in 42 patients (57% women, mean age±SD: 48.9±11.4 years). The rates of antibiotic resistance were as follows: clarithromycin 86%, metronidazole 67%; levofloxacin 52%, tetracycline 2%, and amoxicillin and rifampicin 0%. Double resistance to clarithromycin and metronidazole was found in 59.5% of the patients. Most patients showed resistance to less than three antibiotics, but 31% were resistant to three or more. Intention-to-treat and per-protocol eradication rates were 59.5 and 61.5%. Adverse events occurred in 15 (35.7%) patients, but only two (4.8%) patients did not complete treatment because of adverse events. Only age more than 50 years was associated with resistance to three or more antibiotics. Having a first-degree relative with gastric cancer was associated with treatment failure and having a BMI of at least 25 kg/m protected from failure. CONCLUSION Third-line culture-guided treatment often fails to eradicate H. pylori infection. We need to find factors other than in-vitro antibiotic resistance to explain these suboptimal results.
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Redondo JJ, Keller PM, Zbinden R, Wagner K. A novel RT-PCR for the detection of Helicobacter pylori and identification of clarithromycin resistance mediated by mutations in the 23S rRNA gene. Diagn Microbiol Infect Dis 2017; 90:1-6. [PMID: 29111147 DOI: 10.1016/j.diagmicrobio.2017.09.014] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 09/21/2017] [Accepted: 09/22/2017] [Indexed: 12/16/2022]
Abstract
In this study we evaluated the commercially available LightMix® RT-PCR assay for Helicobacter pylori detection and identification of clarithromycin (CLR) resistance in culture and clinical specimens (gastric biopsies and stool). The H. pylori LightMix® RT-PCR detects a 97bp long fragment of the 23S rRNA gene and allows the identification of 3 distinct point mutations conferring CLR resistance via melting curve analysis. The performance of the H. pylori LightMix® RT-PCR was evaluated using a set of 60 H. pylori strains showing phenotypical CLR susceptibility or CLR resistance (Minimum inhibitory concentrations from 0.016 to 256mg/L). We found high concordance (95%) between phenotypical CLR resistance screening by E-Test® and the Lightmix® RT-PCR. Discrepant results were verified by sequencing of the 23S rRNA gene that always confirmed the results obtained by Lightmix® RT-PCR. Furthermore, H. pylori was detected in clinical biopsy and stool specimens by Lightmix® RT-PCR that identified the correct H. pylori genotype. The LightMix® RT-PCR is an accurate, sensitive and easy to use test for H. pylori and CLR resistance detection and can therefore be readily implemented in any diagnostic laboratory.
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Affiliation(s)
| | - Peter M Keller
- Institute of Medical Microbiology, University of Zurich, Switzerland
| | - Reinhard Zbinden
- Institute of Medical Microbiology, University of Zurich, Switzerland
| | - Karoline Wagner
- Institute of Medical Microbiology, University of Zurich, Switzerland.
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Sheu B, Wu M, Chiu C, Lo J, Wu D, Liou J, Wu C, Cheng H, Lee Y, Hsu P, Chang C, Chang W, Lin J. Consensus on the clinical management, screening-to-treat, and surveillance of Helicobacter pylori infection to improve gastric cancer control on a nationwide scale. Helicobacter 2017; 22:e12368. [PMID: 28066960 PMCID: PMC5434958 DOI: 10.1111/hel.12368] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2016] [Revised: 11/12/2016] [Accepted: 11/16/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer. MATERIALS AND METHODS This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening-to-treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty-five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting. RESULTS There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first-line, second-line, and third-line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost-benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer. CONCLUSIONS This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer.
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Affiliation(s)
- Bor‐Shyang Sheu
- Departments of Institute of Clinical Medicine and Internal MedicineNational Cheng Kung University HospitalCollege of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of Internal MedicineTainan HospitalMinistry of Health and WelfareTainanTaiwan
| | - Ming‐Shiang Wu
- Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Cheng‐Tang Chiu
- Gastroenterology Endoscopy CenterChang Gung Memorial HospitalLinkoTaiwan
| | - Jing‐Chuan Lo
- Department of Internal MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Deng‐Chyang Wu
- Department of Internal MedicinePrivate Kaohsiung Medical University HospitalKaohsiungTaiwan
| | - Jyh‐Ming Liou
- Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Chun‐Ying Wu
- Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan
| | - Hsiu‐Chi Cheng
- Departments of Institute of Clinical Medicine and Internal MedicineNational Cheng Kung University HospitalCollege of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of Internal MedicineTainan HospitalMinistry of Health and WelfareTainanTaiwan
| | - Yi‐Chia Lee
- Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Ping‐I Hsu
- Department of Internal MedicineKaohsiung Veterans General HospitalKaohsiungTaiwan
| | - Chun‐Chao Chang
- Department of Internal MedicinePrivate Taipei Medical University HospitalTaipeiTaiwan
| | - Wei‐Lun Chang
- Departments of Institute of Clinical Medicine and Internal MedicineNational Cheng Kung University HospitalCollege of MedicineNational Cheng Kung UniversityTainanTaiwan
- Department of Internal MedicineTainan HospitalMinistry of Health and WelfareTainanTaiwan
| | - Jaw‐Town Lin
- School of MedicineFu Jen Catholic UniversityNew Taipei CityTaiwan
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Boltin D, Ben-Zvi H, Perets TT, Gingold-Belfer R, Dickman R, Niv Y. Appropriateness of Repeating Helicobacter pylori Culture and Susceptibility Testing Following Failure of Individualized Antibiotic Therapy. Digestion 2017; 92:66-72. [PMID: 27355208 DOI: 10.1159/000435950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 06/14/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Current guidelines recommend direct Helicobacter pylori culture and antibiotic susceptibility testing following 2 failed eradication attempts. If this process is followed and yet subsequent treatment is unsuccessful, it is unclear whether susceptibility testing should be repeated. This is the first study to examine the appropriateness of repeated H. pylori culture and susceptibility testing following failure of individualized treatment. METHODS Between 2007 and 2014, consecutive patients who underwent at least 2 upper gastrointestinal endoscopies with H. pylori culture and susceptibility testing at our institution following several treatment failures were retrospectively identified. Antibiotic susceptibility was recorded and linked to demographic data. RESULTS A total of 68 cultures from 34 patients were included (12 (35.3%) men, 41.4 ± 16.6 years), and 20 (58.8%) cultures had a different antibiotic susceptibility profile on repeat testing (8 (23.5%) with new susceptibility and 13 (38.2%) with new resistance). Acquired resistance to clarithromycin, levofloxacin and metronidazole was observed in 9 (26.5%), 2 (5.9%) and 10 (29.4%) cultures, respectively. Subjects with resistance to ≤1 antibiotic at baseline were more likely to develop resistance to at least 1 antibiotic on subsequent culture, compared to subjects with resistance to ≥2 antibiotics at baseline (13 (100%) vs. 5 (23.8%), p < 0.01). CONCLUSION Repeating H. pylori culture and susceptibility testing usually yields new antimicrobial susceptibility data. However, the clinical usefulness of this approach remains unclear.
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Affiliation(s)
- Doron Boltin
- Department of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Talebi Bezmin Abadi A. Helicobacter pylori treatment: New perspectives using current experience. J Glob Antimicrob Resist 2017; 8:123-130. [PMID: 28131855 DOI: 10.1016/j.jgar.2016.11.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/10/2016] [Accepted: 11/20/2016] [Indexed: 02/08/2023] Open
Abstract
Infection with Helicobacter pylori plays an essential role in the development of duodenal and gastric ulcers as well as in the pathobiology of gastric adenocarcinoma. Thus, successful elimination of the bacterium can reduce the risk of development of these diseases. Currently, most guidelines recommend standard triple therapy (amoxicillin+clarithromycin+proton pump inhibitor), although its efficacy is rapidly falling. Notably, traditional first-line therapy fails in almost 32% of H. pylori-carrying cases, suggesting the importance of choosing the best formulation for first-line therapy. Hence, due to the decreasing effectiveness of first-line treatment, we should be prepared to confront increasing H. pylori therapeutic defeat. Owing to increasing reports of antibiotic resistance worldwide, newer approaches and directions are necessary for managing this problematic infection. Developing and providing better anti-H. pylori strategies (probiotics, antibiotic therapy and non-traditional medicine) without using current clinical experience in treating the infection is impossible. Furthermore, development and examination of new preventive vaccines may also be a new therapeutic direction. Taken together, with regard to current experience, clinicians are highly recommended to consider all alternatives to eradicate H. pylori until a universal vaccine becomes practically available. This article aims to give an overview regarding the current status of H. pylori treatment, accordingly designing an actual overview to gain optimal strategies against this infection.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran.
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Puig I, López-Góngora S, Calvet X, Villoria A, Baylina M, Sanchez-Delgado J, Suarez D, García-Hernando V, Gisbert JP. Systematic review: third-line susceptibility-guided treatment for Helicobacter pylori infection. Therap Adv Gastroenterol 2016; 9:437-48. [PMID: 27366212 PMCID: PMC4913327 DOI: 10.1177/1756283x15621229] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Susceptibility-guided therapies (SGTs) have been proposed as preferable to empirical rescue treatments after two treatment failures. The aim of this study was to perform a systematic review and meta-analysis evaluating the effectiveness and efficacy of SGT as third-line therapy. METHODS A systematic search was performed in multiple databases. Studies reporting cure rates of Helicobacter pylori with SGT in third-line therapy were selected. A qualitative analysis describing the current evidence and a pooled mean analysis summarizing the cure rates of SGT in third-line therapy was performed. RESULTS No randomized controlled trials or comparative studies were found. Four observational studies reported cure rates with SGT in third-line treatment, and three studies which mixed patients with second- and third-line treatment also reported cure rates with SGT. The majority of the studies included the patients when culture had been already obtained, and so the effectiveness of SGT and empirical therapy has never been compared. A pooled mean analysis including four observational studies (283 patients) showed intention-to-treat and per-protocol eradication rates with SGT of 72% (95% confidence interval 56-87%; I(2) : 92%) and 80% (95% confidence interval 71-90%; I(2) : 80%), respectively. CONCLUSIONS SGT may be an acceptable option as rescue treatment. However, cure rates are, at best, moderate and this approach has never been compared with a well-devised empirical therapy. The evidence in favor of SGT as rescue therapy is currently insufficient to recommend its use.
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Affiliation(s)
| | | | | | - Albert Villoria
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain,Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain,Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Mireia Baylina
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Jordi Sanchez-Delgado
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain,Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain,Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - David Suarez
- Unitat d’Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain
| | | | - Javier P. Gisbert
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain,Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
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Chuah SK, Liang CM, Lee CH, Chiou SS, Chiu YC, Hu ML, Wu KL, Lu LS, Chou YP, Chang KC, Kuo CH, Kuo CM, Hu TH, Tai WC. A Randomized Control Trial Comparing 2 Levofloxacin-Containing Second-Line Therapies for Helicobacter pylori Eradication. Medicine (Baltimore) 2016; 95:e3586. [PMID: 27175657 PMCID: PMC4902499 DOI: 10.1097/md.0000000000003586] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Summary of Trial Design.Lengthy exposure to quinolone-containing triple therapy in Helicobacter pylori eradication leads to the development of drug resistance. Sequential therapy with a quinolone and metronidazole -containing regimen appears to be an effective treatment option. This randomized controlled trial aimed to compare the efficacy of 5-plus 5 days' levofloxacin and metronidazole-containing sequential therapy (EALM) with that of 10-day levofloxacin-containing triple therapy (EAL) in second-line H pylori eradication treatment.One hundred and sixty-four patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an EALM therapy group (n = 82; esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days) or a 10-day EAL therapy group (n = 82; levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid). One patient was lost to follow-up in each group. Follow-up for H pylori status was performed 4 to 8 weeks later.Eradication rates for the EALM and EAL groups were 90.2% (74/82, 95% confidence interval [CI] = 83.7%-96.8%) and 80.5% (66/82, 95% CI = 71.7%-89.2%, P = 0.077) in the intention-to-treat analysis; and 91.4% (74/81, 95% CI = 85.1%-97.6%) and 81.5% (66/81, 95% CI = 72.8%-90.1%, P = 0.067) in the per-protocol analysis. The adverse events for the EALM and EAL groups were 23.5% versus 11.1%, P = 0.038 but were all very mild and were well tolerated except for 1 patient with poor compliance. The compliances were 98.8% and 100%, respectively, between the 2 groups. An antibiotic resistance to levofloxacin was the clinical factor influencing the efficacy of H. pylori eradication therapy in the EAL group, and dual resistance to levofloxacin and metronidazole in the EALM group.Levofloxacin and metronidazole-containing sequential therapy achieved a >90% eradication rate as a second-line H pylori therapy. Dual antibiotic resistance to levofloxacin and metronidazole was the clinical factor influencing the efficacy of H pylori eradication therapy in the sequential therapy (ClinicalTrials.gov number: NCT02596620).
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Affiliation(s)
- Seng-Kee Chuah
- From the Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital (S-KC, C-ML, S-SC, Y-CC, M- LH, K-LW, L-SL, Y-PC, K-CC, C-HK, C-MK, T-HH, W-CT); Chang Gung University, College of Medicine, Kaohsiung, Taiwan. (S-KC, C-HL, Y-CC, K-LW, K-CC, T-HH, W- CT); Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital (C-HL)
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Quek C, Pham ST, Tran KT, Pham BT, Huynh LV, Luu NBL, Le TKT, Quek K, Pham VH. Antimicrobial susceptibility and clarithromycin resistance patterns of Helicobacter pylori clinical isolates in Vietnam. F1000Res 2016; 5:671. [PMID: 27583131 PMCID: PMC4972085 DOI: 10.12688/f1000research.8239.1] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/06/2016] [Indexed: 12/27/2022] Open
Abstract
Helicobacter pylori is a gastric pathogen that causes several gastroduodenal disorders such as peptic ulcer disease and gastric cancer. Eradication efforts of
H. pylori are often hampered by antimicrobial resistance in many countries, including Vietnam. Here, the study aimed to investigate the occurrence of antimicrobial resistance among
H. pylori clinical isolates across 13 hospitals in Vietnam. The study further evaluated the clarithromycin resistance patterns of
H. pylori strains. In order to address the study interests, antimicrobial susceptibility testing, epsilometer test and PCR-based sequencing were performed on a total of 193 strains isolated from patients, including 136 children (3–15 years of age) and 57 adults (19–69 years of age). Antimicrobial susceptibility testing showed that the overall resistance to amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline was 10.4%, 85.5%, 24.4%, 37.8%, and 23.8% respectively. The distribution of minimum inhibitory concentrations (MICs) of clarithromycin-resistant strains was 85.5% with MIC >0.5 μg/mL. The majority of the clarithromycin resistant isolates (135 of 165 subjects) have MICs ranging from 2 μg/mL to 16 μg/mL. Furthermore, sequencing detection of mutations in 23S rRNA gene revealed that strains resistant and susceptible to clarithromycin contained both A2143G and T2182C mutations. Of all isolates, eight clarithromycin-resistant isolates (MIC >0.5 μg/mL) had no mutations in the 23S rRNA gene. Collectively, these results demonstrated that a proportion of clarithromycin-resistant
H. pylori strains, which are not related to the 23S rRNA gene mutations, could be potentially related to other mechanisms such as the presence of an efflux pump or polymorphisms in the CYP2C19 gene. Therefore, the present study suggests that providing susceptibility testing prior to treatment or alternative screening strategies for antimicrobial resistance is important for future clinical practice. Further studies on clinical guidelines and treatment efficacy are pivotal for successful eradication of
H. pylori infection.
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Affiliation(s)
- Camelia Quek
- Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia
| | - Son T Pham
- Sydney Medical School, University of Sydney, Sydney, Australia
| | - Kieu T Tran
- Department of Research and Development, NK-Biotek, Ho Chi Minh, Vietnam
| | - Binh T Pham
- School of Medicine, University of Medicine and Pharmacy, Ho Chi Minh, Vietnam
| | - Loc V Huynh
- Department of Research and Development, NK-Biotek, Ho Chi Minh, Vietnam
| | - Ngan B L Luu
- Department of Research and Development, NK-Biotek, Ho Chi Minh, Vietnam
| | - Thao K T Le
- Department of Research and Development, NK-Biotek, Ho Chi Minh, Vietnam
| | - Kelly Quek
- Department of Thoracic Head/Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA
| | - Van H Pham
- Department of Research and Development, NK-Biotek, Ho Chi Minh, Vietnam; School of Medicine, University of Medicine and Pharmacy, Ho Chi Minh, Vietnam; School of Medicine, Tan Tao University, Duc Hoa, Vietnam
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Kwon YH, Kim N, Lee JY, Choi YJ, Yoon K, Nam RH, Suh JH, Lee JW, Lee DH. Comparison of the efficacy of culture-based tailored therapy for Helicobacter pylori eradication with that of the traditional second-line rescue therapy in Korean patients: a prospective single tertiary center study. Scand J Gastroenterol 2016; 51:270-6. [PMID: 26452405 DOI: 10.3109/00365521.2015.1095352] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The effectiveness of Helicobacter pylori therapies has declined with an increase in antibiotic resistance. To overcome this problem, the efficacy of tailored H. pylori eradication therapy based on antimicrobial susceptibility testing was compared with that of empirical second-line rescue regimens. MATERIAL AND METHODS Patients who had persistent H. pylori infection after the first eradication were recommended to undergo culture for determining the minimal inhibitory concentration (MIC) via gastroscopy, which increased the cost by 300%. Fourteen-day esomeprazole, tripotassium dicitrate bismuthate, metronidazole and tetracycline (EBMT) therapy or esomeprazole, moxifloxacin and amoxicillin (MEA) therapy was performed according to the results of antibiotic susceptibility testing. In case of refusal to undergo culture, the participants were treated with either 14-day empirical EBMT or MEA regimen for second eradication after explaining the complexity, side effects and costs associated with each regimen. This trial was registered at ClinicalTrials.Gov (NCT 02349685). RESULTS In the 219 patients included, the intention to treat (ITT) and per protocol (PP) eradication rates was 75.3% and 79.8% in the 14-day EBMT group (n = 89), 70.8% and 72.4% in the 14-day MEA group (n = 89) and 87.8% and 100.0% in the 14-day tailored therapy group (n = 41), respectively. Based on the PP analysis, the 14-day tailored therapy group showed a significantly higher eradication rate than the 14-day EBMT or MEA group (both p ≤ 0.001). CONCLUSIONS Tailored therapy based on H. pylori culture and MIC test could be an option as a second-line eradication regimen in the presence of high level of antimicrobial resistance.
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Affiliation(s)
- Yong Hwan Kwon
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea ;,b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , South Korea
| | - Nayoung Kim
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea ;,c Department of Internal Medicine and Liver Research Institute , Seoul National University College of Medicine , Seoul , South Korea
| | - Ju Yup Lee
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea
| | - Yoon Jin Choi
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea
| | - Kichul Yoon
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea
| | - Ryung Hee Nam
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea
| | - Ji Hyung Suh
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea
| | - Jung Won Lee
- c Department of Internal Medicine and Liver Research Institute , Seoul National University College of Medicine , Seoul , South Korea
| | - Dong Ho Lee
- a Department of Internal Medicine , Seoul National University Bundang Hospital , Seongnam , South Korea ;,c Department of Internal Medicine and Liver Research Institute , Seoul National University College of Medicine , Seoul , South Korea
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Ciccaglione AF, Cellini L, Grossi L, Manzoli L, Marzio L. A Triple and Quadruple Therapy with Doxycycline and Bismuth for First-Line Treatment of Helicobacter pylori Infection: A Pilot Study. Helicobacter 2015; 20:390-6. [PMID: 25801708 DOI: 10.1111/hel.12209] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Tetracycline-containing triple therapy has been suggested as an alternative first-line therapy for H. pylori infection. AIM To evaluate the effect of two dosages of doxycycline (DOX) associated with amoxicillin and esomeprazole with and without bismuth subcitrate as first-line treatment of H. pylori infection. METHODS Helicobacter pylori-positive patients underwent a 10-day therapy randomized into four groups: Group A received esomeprazole, amoxicillin, and DOX-100 mg b.i.d. (EAD-100), Group B a quadruple therapy with esomeprazole, amoxicillin, DOX-100 mg b.i.d. and bismuth subcitrate (EADB-100), Group C a triple therapy with esomeprazole, amoxicillin, and DOX-200 mg b.i.d. (EAD-200) and Group D a quadruple therapy with esomeprazole, amoxicillin, DOX-200 mg b.i.d., and bismuth subcitrate (EADB-200). Success was accessed by (13)C urea breath test 2 months after the end of treatment. The number of patients to be recruited for each group had to be at least 50 subjects. Treatment success of 80% or less was considered unacceptable. Stopping rules therefore were anytime six failures had occurred. RESULTS In the EAD-100 group and in EAD-200 group, the recruitment was stopped at the 14th and 15th patient, respectively. Fifty-two patients entered in the EADB-100 group and 51 in the EADB-200 group. Intention to treat eradication was in EADB-100 group 46/52 (88.5%, 95% CI 76.6-95.6); in the EADB-200 group 47/51 (92.1%, 95% CI: 81.1-97.8) (n.s.). Side effects were absent. CONCLUSION The adjunction of bismuth subcitrate to a triple therapy that includes esomeprazole, amoxicillin, and DOX in patients who are treated for the first time for the H. pylori infection potentiates the therapeutic effect. This regimen, however, deserves to be optimized in terms of duration and dose of DOX.
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Affiliation(s)
- Antonio Francesco Ciccaglione
- Digestive Physiopathology Unit, Pescara Civic Hospital, G. d'Annunzio University, Via Fonte Romana 8, 65124, Pescara, Italy
| | - Luigina Cellini
- Department of Drug Sciences, G. d'Annunzio University, Via dei Vestini, 66013, Chieti, Italy
| | - Laurino Grossi
- Digestive Physiopathology Unit, Pescara Civic Hospital, G. d'Annunzio University, Via Fonte Romana 8, 65124, Pescara, Italy
| | - Lamberto Manzoli
- Department of Medicine and Aging Sciences, G. d'Annunzio University, Via dei Vestini, 66013, Chieti, Italy
| | - Leonardo Marzio
- Digestive Physiopathology Unit, Pescara Civic Hospital, G. d'Annunzio University, Via Fonte Romana 8, 65124, Pescara, Italy
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Graham DY, Lee SY. How to Effectively Use Bismuth Quadruple Therapy: The Good, the Bad, and the Ugly. Gastroenterol Clin North Am 2015; 44:537-63. [PMID: 26314667 PMCID: PMC4555994 DOI: 10.1016/j.gtc.2015.05.003] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Bismuth triple therapy was the first effective Helicobacter pylori eradication therapy. The addition of a proton pump inhibitor helped overcome metronidazole resistance. Its primary indication is penicillin allergy or when clarithromycin and metronidazole resistance are both common. Resistance to the primary first-line therapy have centered on complexity and difficulties with compliance. Understanding regional differences in effectiveness remains unexplained because of the lack of studies including susceptibility testing and adherence data. We discuss regimen variations including substitutions of doxycycline, amoxicillin, and twice a day therapy and provide suggestions regarding what is needed to rationally and effectively use bismuth quadruple therapy.
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Affiliation(s)
- David Y. Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA
| | - Sun-Young Lee
- Department of Internal Medicine, Konkuk University School of Medicine, 120-1 Neungdong-ro, Seoul 143-729, Korea
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Ermis F, Tasci ES. Current Helicobacter pylori treatment in 2014. World J Methodol 2015; 5:101-107. [PMID: 26140276 PMCID: PMC4482816 DOI: 10.5662/wjm.v5.i2.101] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2015] [Revised: 04/28/2015] [Accepted: 05/18/2015] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori is one of the most commonly seen bacterium worldwide. It’s in the etiology of multiple gastrointestinal diseases, ranging from gastritis to gastric carcinoma. The antimicrobial therapies, which are frequently prescribed empirically, are losing their effectivity as a result of the increasing antimicrobial resistance. As the standard triple therapy is now left especially in areas with high-clarithromycin resistance due to decreased eradication rates, quadruple therapies are recommended in most regions of the world. Alternatively, concomitant, sequential and hybrid therapies are used. There is still a debate going on about the use of levofloxacin-based therapy in order to prevent the increase in quinolone resistance. If no regimen can achieve the desired eradication rate, culture-guided individualized therapies are highly recommended. Probiotics, statins and n-acetylcysteine are helpful as adjuvant therapies in order to increase the effectiveness of the eradication therapy. Herein, we focused on different eradication regimens in order to highlight the current Helicobacter pylori treatment.
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López-Góngora S, Puig I, Calvet X, Villoria A, Baylina M, Muñoz N, Sanchez-Delgado J, Suarez D, García-Hernando V, Gisbert JP. Systematic review and meta-analysis: susceptibility-guided versus empirical antibiotic treatment for Helicobacter pylori infection. J Antimicrob Chemother 2015; 70:2447-55. [PMID: 26078393 DOI: 10.1093/jac/dkv155] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2015] [Accepted: 05/16/2015] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND The cure rate of standard triple therapy for Helicobacter pylori infection is unacceptably low. Susceptibility-guided therapies (SGTs) have been proposed as an alternative to standard empirical treatments. The aim of this study was to perform a systematic review and meta-analysis evaluating the efficacy of SGTs. METHODS A systematic search was performed in multiple databases. Randomized controlled trials comparing cure rates of SGTs versus those of empirical therapy were selected and analysed separately for first- and second-line treatments. A meta-analysis was performed using risk ratio (RR) and number needed to treat (NNT) to measure the effect. RESULTS Twelve studies were included in the meta-analysis. In first-line treatment, SGT was more efficacious than empirical 7-10 day triple therapy (RR 1.16, 95% CI 1.10-1.23, I (2) = 33%; NNT = 8). Most studies used a 7-10 day triple therapy and randomized the patients after endoscopy and/or culture, thus precluding the comparison of SGT versus non-invasive testing and empirical treatment in clinical practice. For second-line therapy, only four studies were found. Results were highly heterogeneous and no significant differences were found (RR 1.11, 95% CI 0.82-1.51, I (2) = 87%). CONCLUSIONS Once endoscopy and culture have been performed, SGT is superior to empirical 7 or 10 day triple therapy for first-line treatment. Further studies are needed to evaluate the effectiveness of SGT in clinical practice, especially when compared with currently recommended first-line quadruple therapies.
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Affiliation(s)
- Sheila López-Góngora
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Ignasi Puig
- Digestive Diseases Unit, Althaia Xarxa Assistencial, Universitaria de Manresa, Barcelona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Departament de Medicina, Universitat Internacional de Catalunya, Barcelona, Spain
| | - Xavier Calvet
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Albert Villoria
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - Mireia Baylina
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Neus Muñoz
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Jordi Sanchez-Delgado
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitaria Universitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain
| | - David Suarez
- Unitat d'Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain
| | - Victor García-Hernando
- Internal Medicine Department, Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Madrid, Spain Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
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Paoluzi OA, Del Vecchio Blanco G, Visconti E, Coppola M, Fontana C, Favaro M, Pallone F. Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy. World J Gastroenterol 2015; 21:6698-6705. [PMID: 26074708 PMCID: PMC4458780 DOI: 10.3748/wjg.v21.i21.6698] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 01/23/2015] [Accepted: 02/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication.
METHODS: A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed.
RESULTS: H. pylori eradication was achieved in < 50% of patients [per prototol (PP) = 49%; intention to treat (ITT) = 46%]. Eradication rate was higher in patients administered probiotics than in those without (PP = 55% vs 43%; ITT = 54% vs 40%). Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects.
CONCLUSION: Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.
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Lv ZF, Wang FC, Zheng HL, Wang B, Xie Y, Zhou XJ, Lv NH. Meta-analysis: Is combination of tetracycline and amoxicillin suitable for Helicobacter pylori infection? World J Gastroenterol 2015; 21:2522-2533. [PMID: 25741163 PMCID: PMC4342932 DOI: 10.3748/wjg.v21.i8.2522] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2014] [Revised: 07/20/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To access the efficacy of combination with amoxicillin and tetracycline for eradication of Helicobacter pylori (H. pylori), thus providing clinical practice guidelines.
METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature databases and abstract books of major European, American, and Asian gastroenterological meetings were searched. All clinical trials that examined the efficacy of H. pylori eradication therapies and included both tetracycline and amoxicillin in one study arm were selected for this systematic review and meta-analysis. Statistical analysis was performed with Comprehensive Meta-Analysis Software (Version 2). Subgroup, meta-regression, and sensitivity analyses were also carried out.
RESULTS: Thirty-three studies met the inclusion criteria. The pooled odds ratio (OR) was 0.90 (95%CI: 0.42-1.78) for quadruple therapy with amoxicillin and tetracycline vs other quadruple regimens, and total eradication rates were 78.1% by intention-to-treat (ITT) and 84.5% by per-protocol (PP) analyses in the experimental groups. The pooled eradication rates of 14-d quadruple regimens with a combination of amoxicillin and tetracycline were 82.3% by ITT and 89.0% by PP, and those of 10-d regimens were 84.6% by ITT and 93.7% by PP. The OR by ITT were 1.21 (95%CI: 0.64-2.28) for triple regimens with amoxicillin and tetracycline vs other regimens and 1.81 (95%CI: 1.37-2.41) for sequential treatment with amoxicillin and tetracycline vs other regimens, respectively.
CONCLUSION: The effectiveness of regimens employing amoxicillin and tetracycline for H. pylori eradication may be not inferior to other regimens, but further study should be necessary.
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Quinolone-containing therapies in the eradication of Helicobacter pylori. BIOMED RESEARCH INTERNATIONAL 2014; 2014:151543. [PMID: 25243116 PMCID: PMC4163380 DOI: 10.1155/2014/151543] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Accepted: 08/08/2014] [Indexed: 02/06/2023]
Abstract
Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.
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Rollan A, Arab JP, Camargo MC, Candia R, Harris P, Ferreccio C, Rabkin CS, Gana JC, Cortés P, Herrero R, Durán L, García A, Toledo C, Espino A, Lustig N, Sarfatis A, Figueroa C, Torres J, Riquelme A. Management of Helicobacter pylori infection in Latin America: a Delphi technique-based consensus. World J Gastroenterol 2014; 20:10969-83. [PMID: 25152601 PMCID: PMC4138478 DOI: 10.3748/wjg.v20.i31.10969] [Citation(s) in RCA: 17] [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: 01/14/2014] [Revised: 03/21/2014] [Accepted: 05/23/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature. METHODS Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria. RESULTS A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing. CONCLUSION These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.
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Bang CS, Baik GH. Attempts to enhance the eradication rate of Helicobacter pylori infection. World J Gastroenterol 2014; 20:5252-5262. [PMID: 24833855 PMCID: PMC4017040 DOI: 10.3748/wjg.v20.i18.5252] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/17/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates. Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen. In addition, adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates. Various methods of enhancing the eradication rates of Helicobacter pylori (H. pylori) have been investigated, including changing combinations or durations of established drugs, adding adjuvant drugs, or development of new molecules or agents. Bismuth-containing quadruple, sequential, concomitant, and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen. Despite the encouraging results of these regimens, individualized approaches like treatment after antibiotics resistance test or CYP2C19 genotyping would be the mainstream of future therapy. Because scientific, economic, and technical problems make these advance therapies unfit for widespread use, future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Although various novel regimens and additive agents have indicated favorable outcomes, more studies or validations are needed to become a mainstream H. pylori therapy.
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Cammarota G, Ianiro G, Bibbò S, Di Rienzo TA, Masucci L, Sanguinetti M, Gasbarrini A. Culture-guided treatment approach for Helicobacter pylori infection: Review of the literature. World J Gastroenterol 2014; 20:5205-5211. [PMID: 24833850 PMCID: PMC4017035 DOI: 10.3748/wjg.v20.i18.5205] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 12/09/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
The progressive loss of efficacy of standard eradication therapies has made the treatment of Helicobacter pylori (H. pylori) more challenging than ever. Endoscopic-guided antibiotic susceptibility testing had previously been suggested to guide treatment after failure of second-line therapies. However, its role has expanded over the years, in accordance with the current Maastricht Guidelines. Several authors have dealt with this topic, developing both efficacy trials and cost-effectiveness trials against resistant H. pylori infections as well as infections in naïve patients. However, results are not homogeneous enough to provide definite advice, because antibiotic resistance is not the only reason for treatment failure. Moreover, the culture-guided approach is surrounded by many practical issues, such as the availability of both endoscopy units and microbiology laboratories, and the need for a standard of quality that cannot be satisfied everywhere. Finally, pre-treatment susceptibility testing should be part - and not the only weapon - of a targeted, personalized strategy to overcome H. pylori infection.
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Talebi Bezmin Abadi A. Therapy of Helicobacter pylori: present medley and future prospective. BIOMED RESEARCH INTERNATIONAL 2014; 2014:124607. [PMID: 24800203 PMCID: PMC3988734 DOI: 10.1155/2014/124607] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Accepted: 03/16/2014] [Indexed: 12/19/2022]
Abstract
The increasing prevalence of antimicrobial resistance has warned clinicians to adopt new strategies for dealing with the H. pylori infection. The success of various therapeutic regimens has recently declined to unacceptable levels. To date, first line therapies (including concomitant therapy and hybrid therapy), second line therapies (including bismuth-containing quadruple therapy and levofloxacin-containing therapy), and third line therapy (culture-guided therapy) had been introduced. In the near future, treatment of H. pylori is entering into a completely new resistance era. In this setting, despite the recent progress, we may only be targeting the patients with problematic H. pylori. Local preference for antibiotic selection should be an inevitable article in each therapeutic regimen worldwide. Meanwhile, improving the patients' compliance protocols and observed side effects in suggested therapeutic regimens should be considered cautiously. The new strategies in treatment should be adopted based upon local resistance patterns, which requires physician's resistance about the recommended guidelines. Designing new therapeutic regimen, which contains most effective available antibiotics with less possible side effects and high patient compliance, represents a challenging task in treatment of H. pylori infections.
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Affiliation(s)
- Amin Talebi Bezmin Abadi
- Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
- Department of Medical Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Almeida N, Romãozinho JM, Donato MM, Luxo C, Cardoso O, Cipriano MA, Marinho C, Sofia C. Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study. Helicobacter 2014; 19:90-7. [PMID: 24506175 DOI: 10.1111/hel.12106] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable. AIM To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori. PATIENTS AND METHODS This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires. RESULTS Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%. CONCLUSIONS Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication.
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Affiliation(s)
- Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital, Coimbra, Portugal
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Gisbert JP, Perez-Aisa A, Rodrigo L, Molina-Infante J, Modolell I, Bermejo F, Castro-Fernández M, Antón R, Sacristán B, Cosme A, Barrio J, Harb Y, Gonzalez-Barcenas M, Fernandez-Bermejo M, Algaba A, Marín AC, McNicholl AG. Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection. Dig Dis Sci 2014; 59:383-9. [PMID: 24126798 DOI: 10.1007/s10620-013-2900-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2013] [Accepted: 09/25/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IP), Playa de Mojácar 29. Urb. Bonanza., 28669, Boadilla del Monte, Madrid, Spain,
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Wu TS, Hu HM, Kuo FC, Kuo CH. Eradication of Helicobacter pylori infection. Kaohsiung J Med Sci 2013; 30:167-72. [PMID: 24656156 DOI: 10.1016/j.kjms.2013.11.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 06/28/2013] [Indexed: 01/10/2023] Open
Abstract
Eradication of Helicobacter pylori infection has become an important issue recently, because this bacterial species cluster can cause many gastrointestinal diseases. Elevated antibiotic resistance is related to an increasing failure rate of H. pylori eradication. Standard triple therapy is still the first-line therapy; however, according to the Maastricht IV Consensus Report, it should be abandoned in areas of high clarithromycin resistance. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential, concomitant, and hybrid therapies. Quinolone-based triple therapy may be considered as first-line therapy in areas of clarithromycin resistance >15-20% and quinolone resistance <10%. Unique second-line therapy is still unclear, and bismuth-containing quadruple therapy or levofloxacin-based triple therapy can be used as rescue treatment. Third-line therapy should be under culture guidance to select the most effective regimens (such as levofloxacin-based, rifabutin-based, or furazolidone-based therapies). Antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports.
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Affiliation(s)
- Tzung-Shiun Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Huang-Ming Hu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Fu-Chen Kuo
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Olokoba AB, Obateru OA, Bojuwoye MO. Helicobacter pylori eradication therapy: A review of current trends. Niger Med J 2013; 54:1-4. [PMID: 23661891 PMCID: PMC3644737 DOI: 10.4103/0300-1652.108884] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.
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Affiliation(s)
- A B Olokoba
- Department of Medicine, Gastroenterology Unit, University of Ilorin Teaching Hospital, Ilorin, Nigeria
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Gisbert JP, Calvet X, Bermejo F, Boixeda D, Bory F, Bujanda L, Castro-Fernández M, Dominguez-Muñoz E, Elizalde JI, Forné M, Gené E, Gomollón F, Lanas Á, Martín de Argila C, McNicholl AG, Mearin F, Molina-Infante J, Montoro M, Pajares JM, Pérez-Aisa A, Pérez-Trallero E, Sánchez-Delgado J. [III Spanish Consensus Conference on Helicobacter pylori infection]. GASTROENTEROLOGIA Y HEPATOLOGIA 2013; 36:340-374. [PMID: 23601856 DOI: 10.1016/j.gastrohep.2013.01.011] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Accepted: 01/31/2013] [Indexed: 01/06/2023]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
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44
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Liou JM, Chen CC, Chang CY, Chen MJ, Fang YJ, Lee JY, Chen CC, Hsu SJ, Hsu YC, Tseng CH, Tseng PH, Chang L, Chang WH, Wang HP, Shun CT, Wu JY, Lee YC, Lin JT, Wu MS. Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial. J Antimicrob Chemother 2013; 68:450-456. [PMID: 23099849 DOI: 10.1093/jac/dks407] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.
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Affiliation(s)
- Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Chuah SK, Tai WC, Hsu PI, Wu DC, Wu KL, Kuo CM, Chiu YC, Hu ML, Chou YP, Kuo YH, Liang CM, Chiu KW, Hu TH. The efficacy of second-line anti-Helicobacter pylori therapy using an extended 14-day levofloxacin/amoxicillin/proton-pump inhibitor treatment--a pilot study. Helicobacter 2012; 17:374-381. [PMID: 22967121 DOI: 10.1111/j.1523-5378.2012.00960.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Large meta-analyses of second-line Helicobacter pylori eradication with fluoroquinolone triple therapy have shown that neither 7-day nor 10-day therapy provides 90% or better treatment success. Reports describing second-line H. pylori eradication using 14-day fluoroquinolone-containing triple therapy are few. Current study aimed to determine the efficacy of a 14-day levofloxacin/amoxicillin/proton-pump inhibitor regimen as second-line therapy and the clinical factors influencing the outcome. MATERIALS AND METHODS One-hundred and one patients who failed H. pylori eradication using the standard triple therapy for 7 days were randomly assigned to either a levofloxacin/amoxicillin/esomeprazole group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 14 days) or a esomeprazole/metronidazole/bismuth salt/tetracycline group (esomeprazole 40 mg twice daily, metronidazole 250 mg four times daily, tripotassium dicitrate bismuthate 300 mg four times daily, and tetracycline 500 mg four times daily for 14 days). Follow-up to assess treatment response consisted of either endoscopy or a urea breath test, which were carried out 8 weeks later. RESULTS Eradication rates attained by levofloxacin/amoxicillin/esomeprazole and esomeprazole/metronidazole/bismuth salt/tetracycline treatments in the per-protocol analysis were 44/47 (93.6%; 95% CI = 86-99.8) and 43/47 (91.8%; 95% CI = 83.2-98.5). In the intention-to-treat analysis, these were 43/47 (86.3%; 95% CI = 76.5-96.1) in the LAE group (four lost to follow-up) and 43/50 (86%; 95% CI = 76-96) in the EMBT groups. The observed adverse events were 25.5% and 38.5% among the two groups. There was 100% drug compliance among the levofloxacin/amoxicillin/esomeprazole group. Levofloxacin-resistant strains occurred at a frequency of 32.3%. H. pylori eradication rates for the levofloxacin-susceptible strains and levofloxacin-resistant strains were 92% (11/12) and 33% (1/3) in the per-protocol analysis. CONCLUSIONS A 14-day levofloxacin/amoxicillin/esomeprazole triple therapy approach provides a >90% per-protocol report card with the caveat that this approach is markedly less effective in the presence of fluoroquinolone resistance. Levofloxacin-resistant strains are increasing in Taiwan.
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Affiliation(s)
- Seng-Kee Chuah
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Urgesi R, Cianci R, Riccioni ME. Update on triple therapy for eradication of Helicobacter pylori: current status of the art. Clin Exp Gastroenterol 2012; 5:151-157. [PMID: 23028235 PMCID: PMC3449761 DOI: 10.2147/ceg.s25416] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2012] [Indexed: 12/19/2022] Open
Abstract
With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has recently declined to unacceptable levels (ie, 80% or less). Following the failure of conventional triple therapy, novel eradication regimens have been developed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, bismuth-containing quadruple therapy, and a therapy with administration of N-acetylcysteine before a culture-guided antibiotic regimen. This article reviews the literature published on Helicobacter pylori eradication in the last year, focusing on the development of alternative strategies for first-, second-, and third-line rescue therapy for the eradication of H. pylori.
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Segarra-Newnham M, Coakley C. Salvage Options for Eradication of Helicobacter pylori During Tetracycline Backorder. J Pharm Technol 2012. [DOI: 10.1177/875512251202800502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Objective: To review salvage options for Helicobacter pylori eradication regimens during a tetracycline backorder for patients with triple-therapy failure. Data Sources: A search of PubMed (1980-June 2012) was conducted using a combination of the terms H. pylori or Helicobacter pylori, salvage therapy, and eradication or treatment as text word searches. Study Selection and Data Extraction: Clinical trials and meta-analyses published in English were included. A manual review of the bibliographies of available literature was conducted and relevant articles were reviewed for inclusion. Data Synthesis: Treatment of H. pylori consists of a triple-drug regimen that includes a proton pump inhibitor (PPI), amoxicillin or metronidazole, and clarithromycin. Failure with this therapy is becoming increasingly common due to macrolide resistance. Upon failure with this regimen, it is recommended that a quadruple regimen with bismuth subsalicylate, metronidazole, tetracycline, and a histamine2 receptor antagonist or a PPI be used. Recent backorders by the 2 manufacturers for tetracycline restrict the use of this regimen. Options that can be considered include minocycline or doxycycline in place of tetracycline, levofloxacin- or moxifloxacin-based regimens, a tinidazole-based regimen, or a rifabutin-based regimen. This article includes a review of 1 study each of minocycline and doxycycline, 5 levofloxacin studies (including meta-analyses), 2 moxifloxacin studies, 1 rifabutin study, and 1 tinidazole study. There are limited data with other tetracyclines; however, given the resistance to quinolones in some areas and possible drug interactions and adverse effects from rifabutin, minocycline or doxycycline regimens may be a better second-line regimen option. Conclusions: Given the current tetracycline shortage, minocycline and doxycycline are options to be considered in patients with a macrolide-based treatment failure. Fluoroquinolones may be an option for patients who have not received these drugs for other indications in the recent past or in areas where resistance is low.
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Affiliation(s)
- Marisel Segarra-Newnham
- MARISEL SEGARRA-NEWNHAM PharmD MPH FCCP BCPS, Clinical Pharmacy Specialist in Infectious Diseases, Veterans Affairs Medical Center, West Palm Beach, FL
| | - Christina Coakley
- CHRISTINA COAKLEY PharmD, at time of writing, PGY1 Pharmacy Resident; now, PGY2 Cardiology Pharmacy Resident, Veterans Affairs Medical Center, West Palm Beach
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Kuo CH, Kuo FC, Hu HM, Liu CJ, Wang SSW, Chen YH, Hsieh MC, Hou MF, Wu DC. The Optimal First-Line Therapy of Helicobacter pylori Infection in Year 2012. Gastroenterol Res Pract 2012; 2012:168361. [PMID: 22792095 PMCID: PMC3390052 DOI: 10.1155/2012/168361] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 04/17/2012] [Indexed: 02/08/2023] Open
Abstract
This paper reviews the literature about first-line therapies for H. pylori infection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.
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Affiliation(s)
- Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Fu-Chen Kuo
- Department of Health Management, I-Shou University, E-Da Hospital, Kaohsiung County 824, Taiwan
- Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
| | - Huang-Ming Hu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Chung-Jung Liu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Sophie S. W. Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Yen-Hsu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Ming-Chia Hsieh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
| | - Ming-Feng Hou
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan
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Basu PP, Rayapudi K, Pacana T, Shah NJ, Krishnaswamy N, Flynn M. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol 2011; 106:1970-5. [PMID: 21989146 PMCID: PMC3209586 DOI: 10.1038/ajg.2011.306] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients. METHODS Patients with a diagnosis of HP gastritis or peptic ulcer disease confirmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD-10), including levofloxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confirmed by stool antigen testing at least 4 weeks after cessation of therapy. RESULTS Intention-to-treat analysis revealed significant differences (P<0.05) in the respective eradication rates of the LOAD therapies (88.9% (80/90) LOAD-10, 90% (81/90) LOAD-7, 89.4% (161/180) for combined LOAD) compared with those receiving LAC, 73.3% (66/90). There were no differences in adverse effects between the groups. CONCLUSIONS This open-label, prospective trial demonstrates that LOAD is a highly active regimen for the treatment of HP in treatment-naive patients. A large randomized controlled trial is warranted to further evaluate the efficacy of this regimen.
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Affiliation(s)
- P Patrick Basu
- Department of Gastroenterology, Hepatology and Liver Transplant, Columbia University, College of Physicians and Surgeons, New York, New York, USA,Department of Internal Medicine, Forest Hills Hospital, Forest Hills, New York, USA,North Shore University Hospital, 5 Station Square, Forest Hills, New York 11375, USA. E-mail:
| | - Krishna Rayapudi
- Department of Internal Medicine, Forest Hills Hospital, Forest Hills, New York, USA
| | - Tommy Pacana
- Department of Internal Medicine, Forest Hills Hospital, Forest Hills, New York, USA
| | - Niraj James Shah
- Department of Internal Medicine, Forest Hills Hospital, Forest Hills, New York, USA
| | - Nithya Krishnaswamy
- Department of Internal Medicine, Forest Hills Hospital, Forest Hills, New York, USA
| | - Molly Flynn
- University of Florida College of Pharmacy, Gainesville, Florida, USA
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Park HK, Lee DH, Suh S, Seo PJ, Kim N, Jeong SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM. Dual therapy trial using esomeprazole and amoxicillin as third-line rescue therapy for Helicobacter pylori infection. Clin Endosc 2011; 44:33-7. [PMID: 22741110 PMCID: PMC3363043 DOI: 10.5946/ce.2011.44.1.33] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 08/16/2011] [Accepted: 08/31/2011] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. METHODS From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the (13)C urea breath test at least 6 weeks after treatment. RESULTS The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. CONCLUSIONS A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.
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Affiliation(s)
- Hyun Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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