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Georgopoulos SD, Xirouchakis E, Liatsos C, Apostolopoulos P, Kasapidis P, Martinez-Gonzalez B, Laoudi F, Stoupaki M, Axiaris G, Sgouras D, Mentis A, Michopoulos S. Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas. Antibiotics (Basel) 2024; 13:280. [PMID: 38534715 DOI: 10.3390/antibiotics13030280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 03/12/2024] [Accepted: 03/15/2024] [Indexed: 03/28/2024] Open
Abstract
Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.
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Affiliation(s)
| | - Elias Xirouchakis
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 17562 Athens, Greece
| | - Christos Liatsos
- Gastroenterology Department, 401 General Military Hospital of Athens, 17562 Athens, Greece
| | | | | | | | - Fotini Laoudi
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 17562 Athens, Greece
| | - Maria Stoupaki
- Gastroenterology Department, Alexandra General Hospital, 11528 Athens, Greece
| | - Georgios Axiaris
- Gastroenterology Department, Alexandra General Hospital, 11528 Athens, Greece
| | - Dionysios Sgouras
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece
| | - Andreas Mentis
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece
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Kiani F, Khademolhosseini S, Mohammadi J, Tavasol A, Hajibeygi R, Fathi M, Dousti M. Novel Information Regarding the Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Curr Rev Clin Exp Pharmacol 2024; 19:184-203. [PMID: 36683319 DOI: 10.2174/2772432818666230120111237] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 10/08/2022] [Accepted: 11/15/2022] [Indexed: 01/24/2023]
Abstract
OBJECTIVE Helicobacter pylori infects at least 50% of the world's human population. The current study aimed to assess and compare the efficacy of triple versus quadruple therapy. METHODS Randomized clinical trials (RCTs) consisting of triple and quadruple therapy were identified through electronic and manual searches in the national and international online databases (IsI, Magiran, Embase, PubMed, and Scopus). The random-effects model was applied to pool analysis. Funnel plots and the Egger test were used to examine publication bias. RESULTS After a detailed review of the selected articles, 80 RCTs were included in the meta-analysis; it was based on using triple and quadruple therapy as the first and second-line treatment. The results showed that quadruple therapy in the first-line treatment had a higher eradication rate than triple therapy. Overall, the eradication rate with triple therapy was 74% (95% CI, 71%-77%) for intention-totreat (ITT) analysis and 80% (95% CI, 77%-82%) for per-protocol (PP) analysis. Generally, the eradication rate with quadruple therapy was 82% (95% CI, 78.0%-86.0%) for ITT analysis and 85% (95% CI, 82.0%-89.0%) for PP analysis. The analysis also revealed that quadruple therapy was more effective for 7 or 10 days. CONCLUSION The current study results demonstrated that quadruple therapy has better effectiveness than triple therapy as the first-line treatment; however, in the second-line treatment, the effectiveness of quadruple and triple regimens is almost similar. The effectiveness of quadruple therapy in the Asian population was found to be slightly higher than that of triple therapy, while this difference was considerably higher in the European population.
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Affiliation(s)
- Faezeh Kiani
- Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Jasem Mohammadi
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Arian Tavasol
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ramtin Hajibeygi
- Department of Cardiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mobina Fathi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Dousti
- Department of Parasitology, Faculty of Medicine, Shiraz University of Medical Sciences, Fars, Iran
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Gisbert JP, Alcedo J, Amador J, Bujanda L, Calvet X, Castro-Fernández M, Fernández-Salazar L, Gené E, Lanas Á, Lucendo AJ, Molina-Infante J, Nyssen OP, Pérez-Aisa A, Puig I. V Spanish Consensus Conference on Helicobacter pylori infection treatment. GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:392-417. [PMID: 34629204 DOI: 10.1016/j.gastrohep.2021.07.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/30/2021] [Accepted: 07/16/2021] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Javier Alcedo
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, España
| | - Javier Amador
- Medicina de Familia, Centro de Salud Los Ángeles, Dirección Asistencial Centro, SERMAS, Madrid, España
| | - Luis Bujanda
- Servicio de Aparato Digestivo, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Xavier Calvet
- Servicio de Aparato Digestivo, Hospital Parc Taulí, Universitat Autónoma de Barcelona, CIBEREHD, Sabadell, Barcelona, España
| | | | - Luis Fernández-Salazar
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud (SACYL), Universidad de Valladolid, Valladolid, España
| | - Emili Gené
- Servicio de Urgencias, Hospital Parc Taulí Sabadell, CIBEREHD, Universitat Internacional de Catalunya, Barcelona, España
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), CIBEREHD, Zaragoza
| | - Alfredo J Lucendo
- Servicio de Aparato Digestivo, Hospital General de Tomelloso, CIBEREHD, Ciudad Real, España
| | - Javier Molina-Infante
- Servicio de Aparato Digestivo, Hospital Universitario de Cáceres, CIBEREHD, Cáceres, España
| | - Olga P Nyssen
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - A Pérez-Aisa
- Servicio de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Ignasi Puig
- Servicio de Aparato Digestivo, Althaia Xarxa Assistencial Universitària de Manresa, Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Barcelona, España
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Viazis N, Argyriou K, Kotzampassi K, Christodoulou DK, Apostolopoulos P, Georgopoulos SD, Liatsos C, Giouleme O, Koustenis K, Veretanos C, Stogiannou D, Moutzoukis M, Poutakidis C, Mylonas II, Tseti I, Mantzaris GJ. A Four-Probiotics Regimen Combined with A Standard Helicobacter pylori-Eradication Treatment Reduces Side Effects and Increases Eradication Rates. Nutrients 2022; 14:nu14030632. [PMID: 35276991 PMCID: PMC8838490 DOI: 10.3390/nu14030632] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/28/2022] [Accepted: 01/29/2022] [Indexed: 12/18/2022] Open
Abstract
Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.
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Affiliation(s)
- Nikos Viazis
- Gastroenterology Department, Evangelismos Hospital, 10676 Athens, Greece; (K.K.); (C.V.); (G.J.M.)
- Correspondence: ; Tel.: +30-2132041609; Fax: +30-2132041634
| | - Konstantinos Argyriou
- Department of Gastroenterology, University Hospital of Larisa, 41334 Larissa, Greece;
| | - Katerina Kotzampassi
- Endoscopy Unit, Department of Surgery, Aristotle University of Thessaloniki, 15341 Athens, Greece; (K.K.); (D.S.)
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology, University Hospital of Ioannina, 45500 Ioannina, Greece; (D.K.C.); (M.M.)
| | - Periklis Apostolopoulos
- Gastroenterology Department, Army Share Fund Hospital (NIMTS), 11521 Athens, Greece; (P.A.); (C.P.)
| | | | - Christos Liatsos
- Gastroenterology Department, 401 General Military Hospital of Athens, 11525 Athens, Greece; (C.L.); (I.I.M.)
| | - Olga Giouleme
- Second Propedeutic Department of Internal Medicine, Medical School, Hippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Kanellos Koustenis
- Gastroenterology Department, Evangelismos Hospital, 10676 Athens, Greece; (K.K.); (C.V.); (G.J.M.)
| | - Christos Veretanos
- Gastroenterology Department, Evangelismos Hospital, 10676 Athens, Greece; (K.K.); (C.V.); (G.J.M.)
| | - Dimitris Stogiannou
- Endoscopy Unit, Department of Surgery, Aristotle University of Thessaloniki, 15341 Athens, Greece; (K.K.); (D.S.)
| | - Miltiadis Moutzoukis
- Department of Gastroenterology, University Hospital of Ioannina, 45500 Ioannina, Greece; (D.K.C.); (M.M.)
| | - Charalambos Poutakidis
- Gastroenterology Department, Army Share Fund Hospital (NIMTS), 11521 Athens, Greece; (P.A.); (C.P.)
| | - Ioannis Ioardanis Mylonas
- Gastroenterology Department, 401 General Military Hospital of Athens, 11525 Athens, Greece; (C.L.); (I.I.M.)
| | - Ioulia Tseti
- Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A., 14564 Athens, Greece;
| | - Gerassimos J. Mantzaris
- Gastroenterology Department, Evangelismos Hospital, 10676 Athens, Greece; (K.K.); (C.V.); (G.J.M.)
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Kim YJ, Chung WC. Bismuth-containing Standard Triple Therapy the First-line Eradication Therapy for Helicobacter pylori. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Hwang JY, Kim C, Kwon YH, Lee JE, Jeon SW, Nam SY, Seo AN, Han MH, Park JH. Dual Clarithromycin and Metronidazole Resistance Is the Main Cause of Failure in Ultimate Helicobacter pylori Eradication. Dig Dis 2021; 39:451-461. [PMID: 33429397 DOI: 10.1159/000514278] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 01/10/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND/AIM Antimicrobial resistance significantly affects the cure rate of Helicobacter pylori (H. pylori) eradication. We evaluated the risk factor of failure in ultimate H. pylori eradication and assessed the efficacy of current regimens to overcome antibiotic resistance. METHODS Patients with H. pylori infection were prospectively enrolled in a single center. They were classified into 3 groups according to the previous history of H. pylori eradication, and antibiotic susceptibility was evaluated by culture and minimum inhibitory concentrations (MICs). RESULTS Ninety-seven patients were successfully cultured for H. pylori and 81 (83.5%), 7 (7.2%), and 9 (9.3%) were classified into primary resistance, 1st eradication failure, and 2nd or more eradication failure groups; the resistance to clarithromycin (CLA), metronidazole (MET), and levofloxacin increased in the 1st eradication failure (85.7, 57.1, and 42.9%) and 2nd or more eradication failure (88.9, 88.9, and 55.6%) groups. The prevalence of MDR was 21.0% (17/81), 57.1% (4/7), and 88.9% (8/9) in the primary, 1st eradication failure, and 2nd or more eradication failure groups, respectively. In multivariate analysis, dual CLA/MET resistance (CLA/MET-R) (OR = 31.432, 95% CI: 3.094-319.266, p = 0.004) was an independent risk factor for ultimate H. pylori eradication failure. In patients with dual CLA/MET-R, the eradication ratio of concomitant therapy was 57.1% (4/7), whereas that of bismuth-containing quadruple therapy was 27.3% (3/11) (p = 0.350). CONCLUSIONS Dual CLA/MET-R was the main cause of failure in ultimate H. pylori eradication, and 7-day bismuth quadruple or concomitant regimen would not be suitable for H. pylori eradication in the dual CLA/MET-R group.
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Affiliation(s)
- Ji Yong Hwang
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Changho Kim
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Yong Hwan Kwon
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.,School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Ji Eun Lee
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Seong Woo Jeon
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.,School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Su Youn Nam
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - An Na Seo
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea.,Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Man-Hoon Han
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea.,Department of Pathology, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Ji Hye Park
- Department of Internal medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
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Georgopoulos S, Papastergiou V. An update on current and advancing pharmacotherapy options for the treatment of H. pylori infection. Expert Opin Pharmacother 2020; 22:729-741. [PMID: 33131337 DOI: 10.1080/14656566.2020.1845649] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Eradication of Helicobacter pylori (H. pylori) becomes more challenging due to increasing antimicrobial resistance. Consequently, the performance of clarithromycin-containing triple therapies is now declining to unacceptable levels and should be abandoned unless a prior susceptibility test precludes clarithromycin resistance.Areas covered: This review summarizes updated evidence concerning new and advancing pharmacotherapy options for H. pylori eradication.Expert opinion: Due to the declining efficacy of legacy triple therapies, most guidelines recommend bismuth quadruple therapy as the best initial empiric treatment. Concomitant, sequential and hybrid therapies are remarkable bismuth-free quadruple options, provided that dual clarithromycin-metronidazole resistance is low. Levofloxacin-, rifabutin-, furazolidone- and sitafloxacin-containing regimens remain useful, particularly as salvage options. To eradicate H. pylori in line with the rules of antibiotic stewardship, susceptibility-guided treatment appears as the ideal approach. However, the feasibility and cost-effectiveness of universal pre-treatment susceptibility testing warrants further evaluation. Molecular testing methods promise convenient characterization of H. pylori antibiotic susceptibility. High-dose dual therapy (proton-pump-inhibitor plus amoxicillin) and vonoprazan, a more potent acid inhibitor that likely enhances the activity of amoxicillin, are promising alternatives that could decrease misuse of antibiotics. Addition of certain probiotics could somewhat increase the performance of H. pylori eradication regimens, while improving tolerability.
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Affiliation(s)
- Sotirios Georgopoulos
- Department of Gastroenterology, Athens Medical P. Faliron General Hospital, Athens, Greece
| | - Vasilios Papastergiou
- Department of Gastroenterology, "Konstantopoulion-Patision" General Hospital, Athens, Greece
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10-Day Versus 14-Day Quadruple Concomitant Nonbismuth Therapy for the Treatment of Helicobacter pylori Infection: Results From a Randomized Prospective Study in a High Clarithromycin Resistance Country. J Clin Gastroenterol 2020; 54:522-527. [PMID: 32028286 DOI: 10.1097/mcg.0000000000001328] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
GOALS The aim of this study was to investigate the implementation of a 14-day quadruple nonbismuth concomitant regimen, as proposed by recent Guidelines and Consensus Statements. BACKGROUND In Greece, a region with >20% clarithromycin resistance where bismuth is unavailable, the 10-day quadruple concomitant scheme has already been adopted as the accepted first-line Helicobacter pylori eradication treatment. STUDY Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day or a 14-day nonbismuth quadruple concomitant scheme. Treatment outcome was assessed by C-urea breath test and/or histology at least 4 weeks after therapy. Intention to treat and per protocol analyses of the eradication rates were performed. Secondary endpoints included patient adherence, safety, and the impact of prior antibiotic exposure in treatment efficacy. RESULTS The overall eradication rates of the 2 treatments were 87.9% versus 87.4% in the intention to treat analysis, P=1.000, and 93% versus 94.1%, P=0.859, in the per protocol analysis for the 10-day and the 14-day treatment group, respectively. Both groups displayed excellent compliance rates (99.5% for the 10-day vs. 96.2% for the 14-day treatment duration, P=0.067). As regards treatment safety, serious adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the 2 groups (0.5% in the 10-day group and 2.2% in the 14-day group, P>0.05). Previous antibiotic exposure was not significant with regard to treatment efficacy. CONCLUSION In Greece, the 10-day concomitant nonbismuth quadruple regimen for first-line treatment remains the most efficient strategy for H. pylori eradication.
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Georgopoulos SD, Michopoulos S, Rokkas T, Apostolopoulos P, Giamarellos E, Kamberoglou D, Mentis A, Triantafyllou K. Hellenic consensus on Helicobacter pylori infection. Ann Gastroenterol 2020; 33:105-124. [PMID: 32127732 PMCID: PMC7049243 DOI: 10.20524/aog.2020.0446] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 10/30/2019] [Indexed: 02/06/2023] Open
Abstract
The Hellenic Society of Gastroenterology recently organized the “Hellenic consensus on Helicobacter pylori (H. pylori) infection”. The aim of this publication is to report the guidelines in order to aid the national gastroenterology community in the management of H. pylori infection. Forty-one delegates from all Greek regions, including gastroenterologists, pathologists, clinical microbiologists, epidemiologists and basic scientists, were invited to this meeting. The participants were allocated to 1 of the 4 main topics of the meeting: i.e., H. pylori diagnosis and association with diseases; H. pylori and gastric cancer; H. pylori and extragastric associated disorders; and H. pylori treatment. The results of each subgroup were submitted to a final consensus vote that included all participants. Relevant data based on international and Greek publications were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. The cutoff level of 70% was considered as acceptance for the final statement. It is hoped that the recommendations and conclusions of this report will guide Greek doctors in their daily practice concerning the management of H. pylori infection.
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Affiliation(s)
| | | | - Theodoros Rokkas
- Gastroenterology Department, Henry Dynan Hospital (Theodoros Rokkas)
| | | | - Evangelos Giamarellos
- 4 Department of Internal Medicine, Attikon University Hospital (Evangelos Giamarellos)
| | | | - Andreas Mentis
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, (Andreas Mentis)
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10
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Optimal duration of concomitant nonbismuth quadruple therapy as first-line therapy for Helicobacter pylori: a prospective, open-label, comparative study. Eur J Gastroenterol Hepatol 2019; 31:1206-1210. [PMID: 31441794 DOI: 10.1097/meg.0000000000001517] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Concomitant nonbismuth quadruple therapy is recommended as first-line treatment for Helicobacter pylori infection in high clarithromycin resistance areas, but the ideal duration of the regimen remains elusive. Aim of this study was to assess the efficacy and tolerability of 10- versus 14-day concomitant therapy for H. pylori eradication in an area of high clarithromycin and low dual clarithromycin/metronidazole resistance. METHODS This was a prospective, open-label study including adult patients with H. pylori infection without previous treatment, from September 2014 to June 2017. Concomitant therapy consisting of pantoprazole 40 mg, amoxicillin 1g, clarithromycin 500 mg, and a nitroimidazole 500 mg was administered twice daily for 10 days in the first phase and for 14 days in the second phase of the study. Efficacy and side effects were compared between groups using chi-square and Fisher's exact tests. RESULTS In per protocol analysis, rates of eradication for the 10- and 14-day regimen were 91.9% (114/124) and 90.9% (110/121), respectively (P = 0.77). In intention to treat analysis, rates of eradication were lower than 90%. Specifically, rates were 86.3% (114/132) for the 10-day regimen and 85.2% (110/129) for the 14-day regimen (P = 0.8). Side effects, present in 31.3% of treated patients, were significantly more common in the 14-day group (P = 0.015). Four patients discontinued treatment, all in the 14-day group. CONCLUSIONS Ten day concomitant nonbismuth quadruple therapy for H. pylori is highly efficacious and better tolerated than the 14-day regimen. Thus, 10-day therapy may be preferred as first-line treatment in clinical practice.
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Lu HH, Lai FP, Lo HY, Sheu BS, Yang YJ. Increasing antimicrobial resistance to clarithromycin and metronidazole in pediatric Helicobacter pylori infection in southern Taiwan: A comparison between two decades. Helicobacter 2019; 24:e12633. [PMID: 31295754 DOI: 10.1111/hel.12633] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 05/01/2019] [Accepted: 06/15/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Antimicrobial resistance of Helicobacter pylori reduces the eradication rate. This study aimed to investigate changes in antimicrobial susceptibility of H pylori isolated from children in Taiwan in the past two decades. METHODS This study enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a national tertiary referring hospital from 1998 to 2018. H pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E test. The antibiotic resistance rates and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018. RESULTS A total of 70 Helicobacter pylori isolates (29 from 1998 to 2008 and 41 from 2009 to 2018) were identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n = 31), gastric ulcers (n = 9), and gastritis (n = 30). The overall antimicrobial resistance rates of clarithromycin and metronidazole were 22.9% and 21.4%, respectively. The dual resistance rate of clarithromycin and metronidazole was 10%. Resistance rates of levofloxacin and amoxicillin were 8.3% and 2.9%, respectively. None of the isolates were resistant to tetracycline. Compared with the isolates from 1998 to 2008, those from 2009 to 2018 had higher MICs and resistance rates of clarithromycin (26.8% vs 17.2%, P = 0.35) and metronidazole (26.8% vs 13.8%, P = 0.19), but not levofloxacin (9.8% vs 5.3%, P = 1.0) or coresistance to clarithromycin and metronidazole (12.2% vs 6.9%, P = 0.69). CONCLUSIONS The antimicrobial resistance rates of pediatric H pylori isolates to clarithromycin and metronidazole increased during the past decade. The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H pylori eradication rates.
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Affiliation(s)
- Hsiao-Han Lu
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Fu-Ping Lai
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Hsiao-Yu Lo
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Bor-Shyang Sheu
- Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Departments of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
| | - Yao-Jong Yang
- Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.,Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan
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12
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Güven B, Gülerman F, Kaçmaz B. Helicobacter pylori resistance to clarithromycin and fluoroquinolones in a pediatric population in Turkey: A cross-sectional study. Helicobacter 2019; 24:e12581. [PMID: 30950125 DOI: 10.1111/hel.12581] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 02/23/2019] [Accepted: 02/27/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori antimicrobial resistance is gradually increasing around the world. However, there are a limited number of studies reporting on this issue in the pediatric population. In this study, we aimed to determine H pylori resistance to clarithromycin and fluoroquinolones in the pediatric patients living in Kırıkkale province that were detected with H pylori in gastric biopsies. Moreover, we also aimed to investigate the concordance between the histopathologic and molecular methods used in the diagnosis of H pylori infection. MATERIALS AND METHODS Patients aged 2-18 years who had a history of epigastric pain and/or nausea persisting for longer than 1 month underwent upper gastrointestinal endoscopy. Biopsies were taken from the gastric antral mucosa. In the samples detected with H pylori in the histopathologic examination, the presence of H pylori and H pylori resistance to clarithromycin and fluoroquinolones was investigated using the GenoType HelicoDR test which allows the detection of wild-type and mutant genes. The strains detected with more than one mutant gene are defined as hetero-resistant strains. RESULTS The 93 patients that underwent DNA extraction and amplification included 68 (73.1%) girls and 25 (26.9%) boys with a median age of 15 ± 2.62 (range 6-17) years. The overall concordance for the diagnosis of H pylori infection between histopathology and PCR was 94%, and H pylori resistance to clarithromycin and fluoroquinolones was 27% and 15%, respectively. CONCLUSIONS The high H pylori resistance to clarithromycin and fluoroquinolones among the pediatric patients in our region implicates that the antibiotic sensitivity of strains should be studied prior to administration in accordance with the recommendations provided in the guidelines. Moreover, the presence of hetero-resistant strains in our patients may be a reason for treatment failure.
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Affiliation(s)
- Burcu Güven
- Pediatric Gastroenterology Department, Yüzüncü Yıl University Medical School, Van, Turkey
| | - Fulya Gülerman
- Pediatric Gastroenterology Department, Kırıkkale University Medical School, Kırıkkale, Turkey
| | - Birgül Kaçmaz
- Infectious Diseases & Clinical Microbiology Department, Kırıkkale University Medical School, Kırıkkale, Turkey
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13
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Kocazeybek B, Sakli MK, Yuksel P, Demirci M, Caliskan R, Sarp TZ, Saribas S, Demiryas S, Kalayci F, Cakan H, Uysal HK, Gareayaghi N, Ergin S, Erzin YZ, Bal K, Tascı İ, Tokman HB. Comparison of new and classical point mutations associated with clarithromycin resistance in Helicobacter pylori strains isolated from dyspeptic patients and their effects on phenotypic clarithromycin resistance. J Med Microbiol 2019; 68:566-573. [PMID: 30724729 DOI: 10.1099/jmm.0.000944] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE We aimed to investigate the presence of three recently identified point mutations (A2115G, G2141A and A2144T) of the 23 S rRNA gene and compare them with the three most frequently encountered point mutations (A2142G, A2142C and A2143G) in Helicobacter pylori strains in Turkey. METHODOLOGY A total of 63 patients (mean 47.08±12.27) were included. The E-test method (for clarithromycin) was used for the clarithromycin antimicrobial susceptibility test of isolated H. pylori strains. Real-time PCR was used to detect the point mutations. RESULTS A total of 24 out of 63 H. pylori strains (38.1%) were detected as clarithromycin resistant (>0.5 mg l-1 ). The new A2115G (n:6, 25%), A2144T (n:7, 29.1%) and G2141A, 8 (n:8, 33.3%) mutations and the classical A2142G (n:8, 33.3%) and A2143G (n:11, 45.8%) point mutations were detected in the 24 clarithromycin-resistant strains. The A2144T point mutation had the highest median MIC value (3 mg l-1 ) amongst the new mutations, but the classical mutations (A2142G and A2143G) had the highest median MIC values (256 mg l-1 ) overall. The presence of the A2115G (OR:31.66), A2144T (OR:36.92) or G2141A (OR:28.16) mutations increased the likelihood of clarithromycin resistance in H. pylori strains by 31.66-, 36.92- and 28.16-fold (ORs), respectively, according to the binary logistic regression analysis. CONCLUSION We concluded that classical mutations of the 23 S rRNA gene resulted in higher clarithromycin MIC values than new mutations. These new point mutations caused moderate elevations in the MIC values of clarithromycin-resistant H. pylori strains.
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Affiliation(s)
- Bekir Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Merve Kutlu Sakli
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Pelin Yuksel
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Mehmet Demirci
- Beykent University Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Reyhan Caliskan
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Tevhide Ziver Sarp
- Eastern Mediterranean University, Faculty of Health Sciences, Nutrition and Dietetic Department, Famagusta, North Cyprus
| | - Suat Saribas
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Suleyman Demiryas
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Fatma Kalayci
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Huseyin Cakan
- Department of Microbiology, Istanbul University-Cerrahpasa, Institute of Forensic Sciences, Istanbul, Turkey
| | - Hayriye Kirkoyun Uysal
- Istanbul University, Istanbul Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey
| | - Nesrin Gareayaghi
- Istanbul Sisli Hamidiye Etfal Training and Research Hospita, Blood Center, Istanbul, Turkey
| | - Sevgi Ergin
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Yusuf Ziya Erzin
- Department of Gastroenterology, Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Kadir Bal
- Department of Gastroenterology, Cerrahpasa Medical Faculty, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - İhsan Tascı
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
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14
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Macías-García F, Bastón-Rey I, de la Iglesia-García D, Calviño-Suárez C, Nieto-García L, Domínguez-Muñoz JE. Bismuth-containing quadruple therapy versus concomitant quadruple therapy as first-line treatment for Helicobacter Pylori infection in an area of high resistance to clarithromycin: A prospective, cross-sectional, comparative, open trial. Helicobacter 2019; 24:e12546. [PMID: 30346636 DOI: 10.1111/hel.12546] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/14/2018] [Accepted: 09/18/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Concomitant quadruple (CQT) or bismuth-containing quadruple therapy (BQT) is recommended as first-line treatment for Helicobacter pylori infection depending on antibiotic resistance. AIM To compare the efficacy, safety, and compliance of CQT and BQT as first-line therapy for H. pylori eradication in real clinical practice in an area of high resistance to clarithromycin. METHODS A prospective, open, comparative cross-sectional study including dyspeptic patients >18 years with H. pylori infection and with no previous eradication treatment was performed. CQT (omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + metronidazole 500 mg, all given twice daily, for 14 days) or BQT (omeprazole 20 mg twice daily + 3 capsules of Pylera® 4 times a day, for 10 days) was prescribed at the discretion of the prescribing physician. Eradication was tested by 13 C-urea breath test. Efficacy was assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS One hundred and four consecutive patients were included (64.4% female, age 52.9 years). Fifty patients received CQT and 54 BQT. Eradication rate was similar with both therapies at the PP (CQT 97.9%, 95% CI: 93.9-100 vs BQT 96.2%, 95% CI: 90.9-100, P = 0.605) and ITT analyses (CQT 98.0%, 95% CI: 94-100 vs BQT 94.4%, 95% CI: 88.1-100, P = 0.346). The rate of adverse events was also similar with CQT (56%) and BQT (46.3%). One patient in each group discontinued the treatment due to significant adverse events. CONCLUSION The use of CQT and BQT as first-line treatment against H. pylori is similarly effective and safe strategy in an area of high clarithromycin resistance.
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Affiliation(s)
- Fernando Macías-García
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Iria Bastón-Rey
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Daniel de la Iglesia-García
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Cristina Calviño-Suárez
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Laura Nieto-García
- Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Juan Enrique Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.,Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
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15
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Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology 2018; 155:1372-1382.e17. [PMID: 29990487 PMCID: PMC6905086 DOI: 10.1053/j.gastro.2018.07.007] [Citation(s) in RCA: 778] [Impact Index Per Article: 111.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Revised: 06/27/2018] [Accepted: 07/05/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. METHODS We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. RESULTS We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). CONCLUSIONS Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
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Affiliation(s)
- Alessia Savoldi
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany
| | - Elena Carrara
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
| | - Michela Conti
- Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy
| | - Evelina Tacconelli
- Division of Infectious Diseases, Department of Internal Medicine I, German Center for Infection Research, University of Tübingen, Tübingen, Germany; Division of Infectious Diseases, Department of Diagnostic and Public Health, G.B. Rossi University Hospital, University of Verona, Verona, Italy.
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16
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Systematic Review with Meta-Analysis: Concomitant Therapy vs. Triple Therapy for the First-Line Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2018; 113:1444-1457. [PMID: 30171216 DOI: 10.1038/s41395-018-0217-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 06/29/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Whether concomitant therapy is superior to triple therapy of various treatment lengths for the first-line treatment of H. pylori remains controversial. The objective of this study is to compare the efficacy of concomitant therapy and triple therapy given for 5-14 days. METHODS Randomized control trials (RCTs) comparing the efficacy of concomitant therapy for 5-14 days and proton pump inhibitor-amoxicillin-clarithromycin (PAC)-based triple therapy for 5-14 days in the first-line treatment of adult patients with H. pylori infection published from 1990 to January 2018 were searched from the PubMed, Cochrane Library, and Embase. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and the adverse effects, respectively. Subgroup analyses were also performed according to treatment length. This study is registered with PROSPERO, number CRD42017081328. RESULTS Of the 639 articles identified, 23 RCTs including 3305 patients in the concomitant therapy group and 3327 patients in the triple therapy group were eligible. Overall, concomitant therapy was superior to triple therapy [risk ratio (RR): 1.15; 95% confidence interval (CI): 1.09-1.21; p < 0.001]. However, there were significant heterogeneity (I2 = 74.0%, p < 0.001). In the subgroup analysis, 5-day concomitant therapy was superior to 5-day triple therapy (RR: 1.30; 95% CI: 1.04-1.62; p = 0.02), 5- or 7-day concomitant therapy was superior to 7-day triple therapy (RR: 1.16; 95% CI: 1.12-1.21; p < 0.001), and 5- or 7-, or 10- or 14-day concomitant therapy was superior to 10-day triple therapy (RR: 1.15; 95% CI: 1.08-1.23; p < 0.001). However, 5- or 10-day concomitant therapy was not superior to 14-day triple therapy (RR: 1.02; 95% CI: 0.89-1.16; p = 0.796). The frequency of adverse effects was significantly higher in concomitant therapy than triple therapy (RR: 1.19; 95% CI: 1.06-1.34; P = 0.004). CONCLUSIONS Concomitant therapy given for 5 or 10 days was superior to 5- or 7-, or 10-day PAC-based triple therapy, but was not superior to 14-day triple therapy.
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Kim J, Kim K, Lee JS, Kim SY, Kim KO, Kim YJ, Kwon KA, Park DK, Chung JW. [The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 71:204-212. [PMID: 29684969 DOI: 10.4166/kjg.2018.71.4.204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Background/Aims Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. Methods We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). Results The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00-12.32; p=0.05). Conclusions Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.
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Affiliation(s)
- Joonhwan Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kyungwon Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Jun Soo Lee
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Su Young Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kyung Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Yoon Jae Kim
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Kwang An Kwon
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Dong Kyun Park
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Jun Won Chung
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
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18
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Choe JW, Jung SW, Kim SY, Hyun JJ, Jung YK, Koo JS, Yim HJ, Lee SW. Comparative study of Helicobacter pylori eradication rates of concomitant therapy vs modified quadruple therapy comprising proton-pump inhibitor, bismuth, amoxicillin, and metronidazole in Korea. Helicobacter 2018; 23:e12466. [PMID: 29369454 DOI: 10.1111/hel.12466] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The standard triple Helicobacter pylori regimen now shows unacceptably low treatment success in Korea. Administration of the concomitant therapy for 10 days, which has a high cure rate, is recommended as an alternative first-line treatment in areas of high clarithromycin resistance including Korea. Recently, modified bismuth-containing quadruple therapy with amoxicillin (PAM-B therapy) showed excellent results, regardless of dual clarithromycin and metronidazole resistance. This study compared the concomitant therapy with PAM-B therapy as a first-line treatment for H. pylori infection. METHOD Subjects infected with H. pylori and naïve to treatment were performed a head-to-head comparison between 10-day concomitant therapy [rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily] and 14-day PAM-B therapy [rabeprazole 20 mg, amoxicillin 1 g, metronidazole 750 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily]. Six weeks after treatment, H. pylori eradication was assessed. RESULTS Two hundred and seventy subjects were randomized. Both regimens achieved high cure rates: 83.0% (112/135) and 88.1% (119/135) by the intention-to-treat analysis and 95.5% (106/111) and 96.6% (114/118) by the per-protocol analysis, respectively. The intention-to-treat and per-protocol analyses revealed no statistically significant difference in the eradication rate (P = .299 and P = .743, respectively). Rates of adverse events were similar between groups (25.2% vs 23.0%, P -value: .776) Adverse events, which resulted in poor compliance, occurred in six patients of each group, but there were no serious complications. CONCLUSIONS PAM-B therapy is as effective as concomitant therapy for eradicating H. pylori with comparative safety. PAM-B therapy is regarded as a promising alternative to standard triple therapy for a first-line eradication in Korea.
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Affiliation(s)
- Jung Wan Choe
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sung Woo Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seung Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jong Jin Hyun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ja Seol Koo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Woo Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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19
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Georgopoulos SD, Papastergiou V, Martinez-Gonzalez B, Xirouchakis E, Familias I, Sgouras D, Mentis A, Karatapanis S. Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial. Ann Gastroenterol 2018; 31:205-210. [PMID: 29507467 PMCID: PMC5825950 DOI: 10.20524/aog.2017.0221] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 10/26/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hybrid therapy is a promising first-line regimen for Helicobacter pylori (H. pylori) eradication. We evaluated a hybrid therapy, assessing the impact of antibiotic resistance on eradication outcome. METHODS This was a prospective study that included 155 treatment-naïve patients diagnosed with H. pylori infection by positive CLO-test, confirmed with histology and/or culture. The hybrid therapy consisted of 40 mg esomeprazole and 1 g amoxicillin for 14 days, with the addition of 500 mg clarithromycin and 500 mg metronidazole for the final 7 days (all b.i.d.). Eradication was defined by negative 13C-urea breath test or histology. RESULTS The eradication rates were 85.8% (133/155; 95% confidence interval [CI] 79.4-90.5%) by intention-to-treat and 90.2% (129/143; 95%CI 84.1-94.2%) by per-protocol analysis in a setting of high antibiotic resistance (clarithromycin 25.9%, metronidazole 31.1%, dual resistance 8.9%). Adverse events occurred in 29.7% and 1.3% discontinued treatment because of adverse events. Adherence >90% was achieved in 96.6%. The eradication rate in patients with dual clarithromycin/metronidazole resistance (50%) was markedly lower compared to those with single clarithromycin resistance (91.4%), single metronidazole resistance (90.5%) or dual susceptibility (97.8%). Dual resistance was the only factor to correlate with the failure of hybrid therapy (odds ratio 14.4, 95%CI 3.8-54.9, P=0.0003). CONCLUSIONS Hybrid therapy is an effective and safe first-line regimen in populations with relatively high rates of antibiotic resistance. However, dual clarithromycin/metronidazole resistance may significantly compromise its efficacy.
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Affiliation(s)
- Sotirios D. Georgopoulos
- Gastroenterology Department, Athens Medical, Paleo Faliron Hospital, Athens (Sotirios D. Georgopoulos, Elias Xirouchakis), Greece
| | - Vasilios Papastergiou
- First Department of Internal Medicine, General Hospital of Rhodes, Rhodes (Vasilios Papastergiou, Ioannis Familias, Stylianos Karatapanis), Greece
| | - Beatriz Martinez-Gonzalez
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens (Beatriz Martinez-Gonzalez, Dionysis Sgouras, Andreas Mentis), Greece
| | - Elias Xirouchakis
- Gastroenterology Department, Athens Medical, Paleo Faliron Hospital, Athens (Sotirios D. Georgopoulos, Elias Xirouchakis), Greece
| | - Ioannis Familias
- First Department of Internal Medicine, General Hospital of Rhodes, Rhodes (Vasilios Papastergiou, Ioannis Familias, Stylianos Karatapanis), Greece
| | - Dionysis Sgouras
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens (Beatriz Martinez-Gonzalez, Dionysis Sgouras, Andreas Mentis), Greece
| | - Andreas Mentis
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens (Beatriz Martinez-Gonzalez, Dionysis Sgouras, Andreas Mentis), Greece
| | - Stylianos Karatapanis
- First Department of Internal Medicine, General Hospital of Rhodes, Rhodes (Vasilios Papastergiou, Ioannis Familias, Stylianos Karatapanis), Greece
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Ye JF, Hong JB, Zhu Y, Xie Y, Shu X, Luo LY, Xie C, Zhu ZH, Lu NH. Evaluation of first-line bismuth-containing 7-day concomitant quintuple therapy for Helicobacter pylori eradication. J Dig Dis 2017; 18:704-708. [PMID: 29119724 DOI: 10.1111/1751-2980.12559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 10/14/2017] [Accepted: 11/05/2017] [Indexed: 01/06/2023]
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) infection is difficult to cure, mainly due to antibiotic resistance. This study aimed to determine the efficacy and safety of 7-day bismuth-containing concomitant quintuple regimen for H. pylori eradication. METHODS Conducted from August 2015 to February 2016 at the First Affiliated Hospital of Nanchang University, this prospective trial enrolled 70 untreated patients who were positive for H. pylori. The patients received 7-day quintuple therapy consisting of bismuth subcitrate 220 mg, esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1 g and metronidazole 400 mg, each was given twice daily. All patients underwent a 13 C-urea breath test at 4 weeks after treatment. RESULTS A total of 70 patients at a mean age of 43.5 years, including 36 men, were included in this trial. One person who violated the protocol was further excluded. The treatment compliance rate was 99.6%. The overall eradication rates of the 7-day bismuth-containing concomitant quintuple therapy were 75.4% (intention-to-treat analysis) and 86.7% (per-protocol analysis). The prevalence of side effects was 31.9%, including a bitter taste (23.2%), nausea (4.3%), dizziness (2.9%), diarrhea (2.9%), limb asthenia (2.9%), skin rash (1.4%), numbness of the tip of the tongue (1.4%) and insomnia (1.4%). CONCLUSIONS The 7-day bismuth-containing concomitant quintuple therapy may not be superior to traditionally widely accepted therapy due to its lack of acceptable efficacy and high rate of side effects.
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Affiliation(s)
- Jian Fang Ye
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Jun Bo Hong
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yin Zhu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Institute of Digestion, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Xu Shu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Ling Yu Luo
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Chuan Xie
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Zhen Hua Zhu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Nong Hua Lu
- Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
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21
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Which Regimens Should Be Used and Which Rejected for the Treatment of Helicobacter pylori? Am J Gastroenterol 2017; 112:1168-1169. [PMID: 28725073 DOI: 10.1038/ajg.2017.90] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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22
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Wang ZJ, Chen XF, Zhang ZX, Li YC, Deng J, Tu J, Song ZQ, Zou QH. Effects of anti-Helicobacter pylori concomitant therapy and probiotic supplementation on the throat and gut microbiota in humans. Microb Pathog 2017; 109:156-161. [PMID: 28552806 DOI: 10.1016/j.micpath.2017.05.035] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 05/22/2017] [Accepted: 05/23/2017] [Indexed: 02/07/2023]
Abstract
The microbiota within humans maintains homeostasis and plays important roles in human health. However, some situations such as the use of antibiotics may disrupt the microbiota balance and result in a series of adverse effects. This study aimed to investigate the effects of a commonly used anti-Helicobacter pylori concomitant therapy on the composition of the gut and throat microbiota and any antibiotic resistance that may develop. In addition to the standard regimen, two different supplementary probiotic regimens that both used Saccharomyces boulardii were included. Microbiological culture-based techniques were used to analyse the microbiota composition and antibiotic resistance. Our results showed marked quantitative and qualitative alterations in both the gut and throat microbiota after treatment with not only the standard concomitant therapy but also with either supplementary probiotic regimen. Nevertheless, most of the changes in the gut microbiota (except for yeast and Bacteroides spp. counts) reverted by Day 71, whereas the alterations in the throat microbiota appeared to persist. Patients treated with the eradication therapy in the absence of probiotic supplementation experienced the most pronounced disturbances in the throat microbiota, whereas changes in the throat microbiota appeared to stabilize in the groups that received probiotic supplementation. We also detected higher antibiotic resistance rates for Enterobacteriaceae, Enterococcus spp. and Bacteroides spp. after treatment with the eradication therapy. Co-administration of probiotics is likely to be more effective than post-antibiotic supplementation, and although some beneficial effects were observed, the probiotic combination did not exert significant effects on the unbalanced commensal gut and throat microbiota composition.
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Affiliation(s)
- Zi-Juan Wang
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | - Xiao-Feng Chen
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | - Zi-Xiao Zhang
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | - Yu-Chen Li
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | - Juan Deng
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | - Jing Tu
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China
| | | | - Qing-Hua Zou
- Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China.
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23
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Marin AC, Nyssen OP, McNicholl AG, Gisbert JP. Efficacy and Safety of Quinolone-Containing Rescue Therapies After the Failure of Non-Bismuth Quadruple Treatments for Helicobacter pylori Eradication: Systematic Review and Meta-Analysis. Drugs 2017; 77:765-776. [DOI: 10.1007/s40265-017-0730-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Branquinho D, Almeida N, Gregório C, Cabral JEP, Casela A, Donato MM, Tomé L. Levofloxacin or Clarithromycin-based quadruple regimens: what is the best alternative as first-line treatment for Helicobacter pylori eradication in a country with high resistance rates for both antibiotics? BMC Gastroenterol 2017; 17:31. [PMID: 28202013 PMCID: PMC5312567 DOI: 10.1186/s12876-017-0589-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 02/11/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Helicobacter pylori eradication rates in Portugal are declining, due to increased resistance of this bacterium to antimicrobial agents, especially Clarithromycin. Quadruple Levofloxacin-containing regimens could be an option for first-line treatment, but its efficacy should be evaluated as fluoroquinolone resistance is rapidly increasing. Our aim was to compare the efficacy of Clarithromycin and Levofloxacin-based sequential quadruple therapies as first-line treatment options and determine factors associated with treatment failure. METHODS A total of 200 Helicobacter pylori infected patients were retrospectively included (female 57.5%; average age: 53.2 ± 15.7) and received either 10-day sequential therapy (Proton-Pump Inhibitor + Amoxicillin 1 g bid for 5 days and Proton-Pump Inhibitor + Clarithromycin 500 mg + Metronidazole/Tinidazole 500 mg bid/tid in the following 5 days; group A) or a 10-day modified sequential therapy with Levofloxacin 500 mg id instead of Clarithromycin (group B). Eradication was confirmed with urea breath test. Variables that could influence success rate were analyzed. RESULTS There were no differences between groups in terms of gender, age, smoking habits and indications for treatment. The eradication rate obtained with Clarithromycin-based sequential treatment was significantly higher than with Levofloxacin-based therapy (90%, CI95%: 84-96% vs. 79%, CI95%: 71-87%, p = 0.001). Using full-dose proton-pump inhibitor and high-dose Metronidazole in group A, and full-dose proton-pump inhibitor and prescription from a Gastroenterologist in group B were associated with eradication success. CONCLUSIONS Ten-day Levofloxacin-based sequential treatment achieved inadequate efficacy rate (<80%) and should not be adopted as first-line therapy. Standard sequential therapy showed significantly better results in this naïve population. Using full-dose proton-pump inhibitor and higher doses of Metronidazole is essential to achieve such results.
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Affiliation(s)
- Diogo Branquinho
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. .,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal.
| | - Nuno Almeida
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
| | - Carlos Gregório
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - José Eduardo Pina Cabral
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - Adriano Casela
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal
| | - Maria Manuel Donato
- Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
| | - Luís Tomé
- Gastroenterology Department, Coimbra University Hospital, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.,Gastroenterology Centre, Faculty of Medicine, Coimbra University, R. Larga, 3004-504, Coimbra, Portugal
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25
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Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017; 66:6-30. [PMID: 27707777 DOI: 10.1136/gutjnl-2016-312288] [Citation(s) in RCA: 1943] [Impact Index Per Article: 242.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 08/09/2016] [Indexed: 02/06/2023]
Abstract
Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
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Affiliation(s)
- P Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - F Megraud
- Laboratoire de Bactériologie, Inserm U853, Université de Bordeaux, Bordeaux, France
| | - C A O'Morain
- Faculty of Health Sciences, Trinity College, Dublin, Ireland
| | - J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - E J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - F Bazzoli
- Internal Medicine and Gastroenterology, University of Bologna Italy, Bologna, Italy
| | - A Gasbarrini
- Gastroenterology, and Liver Unit, Internal Medicine, Roma, Italy
| | | | - D Y Graham
- Department of Medicine (111D), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - R Hunt
- Department of Medicine, McMaster University, Hamilton, Canada.,Hillcroft, Beaconsfield, Buckinghamshire, UK
| | - P Moayyedi
- Department of Gastroenterology, McMaster University, Hamilton, Canada
| | - T Rokkas
- Department of Gastroenterology, Henry Dunant Hospital, Athens, Greece
| | - M Rugge
- Department of Diagnostic Sciences, University of Padova, Padova, Italy
| | | | - S Suerbaum
- Medizinische Hochschule Hannover, Institut für Medizinische Mikrobiologie, Hannover, Germany
| | - K Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - E M El-Omar
- St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
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26
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Liou JM, Fang YJ, Chen CC, Bair MJ, Chang CY, Lee YC, Chen MJ, Chen CC, Tseng CH, Hsu YC, Lee JY, Yang TH, Luo JC, Chang CC, Chen CY, Chen PY, Shun CT, Hsu WF, Hu WH, Chen YN, Sheu BS, Lin JT, Wu JY, El-Omar EM, Wu MS. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet 2016; 388:2355-2365. [PMID: 27769562 DOI: 10.1016/s0140-6736(16)31409-x] [Citation(s) in RCA: 129] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 08/04/2016] [Accepted: 08/09/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.
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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
| | - Yu-Jen Fang
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, National Taiwan University College of Medicine, Yun-Lin, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan; Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Chi-Yang Chang
- Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Mei-Jyh Chen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Cheng-Hao Tseng
- Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - Yao-Chun Hsu
- Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung County, Taiwan
| | - Ji-Yuh Lee
- 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
| | - Jiing-Chyuan Luo
- Department of Medicine, National Yang-Ming University, School of Medicine, and Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Po-Yueh Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Chia-Tung Shun
- Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Feng Hsu
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Wen-Hao Hu
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Yen-Nien Chen
- Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Bor-Shyang Sheu
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; National Cheng Kung University Medical Center, Tainan, Taiwan
| | - Jaw-Town Lin
- 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
| | - Jeng-Yih Wu
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Emad M El-Omar
- Department of Medicine, St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
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27
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Apostolopoulos P, Koumoutsos I, Ekmektzoglou K, Dogantzis P, Vlachou E, Kalantzis C, Tsibouris P, Alexandrakis G. Concomitant versus sequential therapy for the treatment of Helicobacter pylori infection: a Greek randomized prospective study. Scand J Gastroenterol 2016; 51:145-51. [PMID: 26435055 DOI: 10.3109/00365521.2015.1079646] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The objective of this study is to compare, in Greece, a region with >20% local resistance to clarithromycin, the efficacy rates of the concomitant versus the sequential H. pylori eradication therapy. MATERIALS AND METHODS Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day concomitant or 10-day sequential therapy. Treatment outcome was assessed by C(13)-urea breath test at least 4 weeks after therapy. Intention to treat (ITT) and per protocol (PP) analysis of the eradication rates were performed. Secondary end points included patient compliance and safety. RESULTS The concomitant therapy group achieved statistically significant higher eradication rates when compared with the sequential treatment group, both in the ITT and in the PP analysis (84.6% versus 70.9%, p = 0.002, and 90.6% versus 78.1%, p = 0.001, respectively), after adjusting for age, gender, smoking status, and the presence or not of ulcer and/or non-ulcer dyspepsia. Both groups displayed excellent compliance rates (99.5% for the concomitant therapy group and 96.2% for the sequential therapy group, p = 0.067). Regarding treatment safety, major adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the two groups (7.0% for the concomitant therapy group and 2.9% for the sequential therapy group). CONCLUSIONS Concomitant therapy led to statistically significant higher eradication rates over sequential therapy. Both therapies showed excellent compliance and an acceptable safety profile. The 10-day quadruple concomitant scheme should be the adopted for first-line H. pylori eradication in Greece.
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Affiliation(s)
| | - Ioannis Koumoutsos
- a Department of Gastroenterology , Army Share Fund Hospital (NIMTS) , Athens , Greece
| | | | - Panagiotis Dogantzis
- a Department of Gastroenterology , Army Share Fund Hospital (NIMTS) , Athens , Greece
| | - Erasmia Vlachou
- a Department of Gastroenterology , Army Share Fund Hospital (NIMTS) , Athens , Greece
| | | | - Panagiotis Tsibouris
- a Department of Gastroenterology , Army Share Fund Hospital (NIMTS) , Athens , Greece
| | - Georgios Alexandrakis
- a Department of Gastroenterology , Army Share Fund Hospital (NIMTS) , Athens , Greece
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28
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Kocazeybek B, Tokman HB. Prevalence of Primary Antimicrobial Resistance of H. pylori in Turkey: A Systematic Review. Helicobacter 2016; 21:251-260. [PMID: 26395982 DOI: 10.1111/hel.12272] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The prevalence of clarithromycin resistance has increased to the 20% or more in different regions of the world. Clarithromycin resistance is known to be responsible for most of the treatment failures in Helicobacter pylori (H. pylori) infection. The aim of this systematic review was to summarize the prevalence of primary antibiotic resistance (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline) of H. pylori strains in different geographical regions of Turkey. MATERIAL AND METHODS An Internet search was performed using PubMed and the ULAKBIM Turkish Medical Database. The terms "primary antibiotic resistance (separately; amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline) of H. pylori" with and without "Turkey" or "different geographical regions of Turkey" were searched among articles published in both English and Turkish language within the time span from 1999 to 2015. Data analysis was performed using MedCalc 12.7.0. Each article was weighted according to the number of isolated H. pylori strains. Pooled proportion analysis was performed. RESULTS Twenty-one Turkish studies including 1059 H. pylori strains were included in this review. The overall primary antibiotic resistance rates of H. pylori strains isolated in Turkey were as follows: amoxicillin 3 (0.971%), clarithromycin 425 (24.864%), metronidazole 75 (33.747%), tetracycline 2 (3.511%), and levofloxacin 31 (23.769%). CONCLUSIONS Primary antibiotic resistance against H. pylori in Turkey shows differences between geographical regions and population densities. There is an increase in primary resistance rates to clarithromycin and metronidazole in different years. The data are not sufficient for tetracycline, amoxicillin, and levofloxacin. High clarithromycin resistance rates were mostly detected in overpopulated cities like Ankara (north), Izmir (west), Istanbul (west), and Bursa (west).
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Affiliation(s)
- Bekir Kocazeybek
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Georgopoulos SD, Xirouchakis E, Martinez-Gonzales B, Zampeli E, Grivas E, Spiliadi C, Sotiropoulou M, Petraki K, Zografos K, Laoudi F, Sgouras D, Mentis A, Kasapidis P, Michopoulos S. Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area. Eur J Intern Med 2016; 32:84-90. [PMID: 27134145 DOI: 10.1016/j.ejim.2016.04.011] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 04/09/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations. MATERIALS AND METHODS This multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by (13)C-urea breath test or histology 4-6weeks after treatment. Adverse events and adherence were evaluated. RESULTS Allocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7-18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6-17.6). Overall, adherence was (98.9%, 95% CI=97-100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5-33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment. CONCLUSIONS Concomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.
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Affiliation(s)
- Sotirios D Georgopoulos
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece.
| | - Elias Xirouchakis
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece
| | | | - Evanthia Zampeli
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece
| | - Elias Grivas
- Gastrenterology Department, Central Clinic of Athens, Athens, Greece
| | - Charikleia Spiliadi
- Department of Histopathology, Athens Medical, Amaroussion Hospital, Athens, Greece
| | - Maria Sotiropoulou
- Department of Histopathology, Alexandra General Hospital, Athens, Greece
| | - Kalliopi Petraki
- Department of Histopathology, Metropolitan Hospital, Athens, Greece
| | - Kostantinos Zografos
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece
| | - Fotini Laoudi
- GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece
| | - Dionysios Sgouras
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece
| | - Andreas Mentis
- Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece
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Lin LC, Hsu TH, Huang KW, Tam KW. Nonbismuth concomitant quadruple therapy for Helicobacter pylori eradication in Chinese regions: A meta-analysis of randomized controlled trials. World J Gastroenterol 2016; 22:5445-5453. [PMID: 27340362 PMCID: PMC4910666 DOI: 10.3748/wjg.v22.i23.5445] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 04/08/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the applicability of nonbismuth concomitant quadruple therapy for Helicobacter pylori (H. pylori) eradication in Chinese regions.
METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the efficacy of nonbismuth concomitant quadruple therapy between sequential therapy or triple therapy for H. pylori eradication in Chinese regions. The defined Chinese regions include China, Hong Kong, Taiwan, and Singapore. The primary outcome was the H. pylori eradication rate; the secondary outcome was the compliance with therapy. The PubMed, Embase, Scopus, and Cochrane databases were searched for studies published in the period up to March 2016 with no language restriction.
RESULTS: We reviewed six randomized controlled trials and 1616 patients. In 3 trials comparing concomitant quadruple therapy with triple therapy, the H. pylori eradication rate was significantly higher for 7-d nonbismuth concomitant quadruple therapy than for 7-d triple therapy (91.2% vs 77.9%, risk ratio = 1.17, 95%CI: 1.09-1.25). In 3 trials comparing quadruple therapy with sequential therapy, the eradication rate was not significant between groups (86.9% vs 86.0%). However, higher compliance was achieved with concomitant therapy than with sequential therapy.
CONCLUSION: The H. pylori eradication rate was higher for nonbismuth concomitant quadruple therapy than for triple therapy. Moreover, higher compliance was achieved with nonbismuth concomitant quadruple therapy than with sequential therapy. Thus, nonbismuth concomitant quadruple therapy should be the first-line treatment in Chinese regions.
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Gisbert JP, Molina-Infante J, Amador J, Bermejo F, Bujanda L, Calvet X, Castro-Fernández M, Cuadrado-Lavín A, Elizalde JI, Gene E, Gomollón F, Lanas Á, Martín de Argila C, Mearin F, Montoro M, Pérez-Aisa Á, Pérez-Trallero E, McNicholl AG. IV Spanish Consensus Conference on Helicobacter pylori infection treatment. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:697-721. [PMID: 27342080 DOI: 10.1016/j.gastrohep.2016.05.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 05/18/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | | | - Javier Amador
- Medicina de Familia, Centro de Salud Los Ángeles, Madrid, España
| | - Fernando Bermejo
- Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Luis Bujanda
- Servicio de Digestivo, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Xavier Calvet
- Servicio de Aparato Digestivo, Hospital Parc Taulí, Universitat Autónoma de Barcelona, CIBEREHD, Sabadell, Barcelona, España
| | | | | | - J Ignasi Elizalde
- Servicio de Aparato Digestivo, Hospital Clínic, CIBEREHD, Barcelona, España
| | - Emili Gene
- Servicio de Urgencias, Hospital Parc Taulí Sabadell, CIBEREHD, Universitat Internacional de Catalunya, Sabadell, Barcelona, España
| | - Fernando Gomollón
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, España
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, España
| | - Carlos Martín de Argila
- Servicio de Aparato Digestivo, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Fermín Mearin
- Servicio de Aparato Digestivo, Centro Médico Teknon, Barcelona, España
| | - Miguel Montoro
- Servicio de Aparato Digestivo, Hospital San Jorge, Huesca, España
| | - Ángeles Pérez-Aisa
- Servicio de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Emilio Pérez-Trallero
- Servicio de Microbiología, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Adrián G McNicholl
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
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Hong J, Shu X, Liu D, Zhu Y, Xie C, Xie Y, Zhang K, Wang A, Xiong H, Zeng H, Yu H, Ma J, Chen Y, Zhu X, Lu N. Antibiotic resistance and CYP2C19 polymorphisms affect the efficacy of concomitant therapies for Helicobacter pylori infection: an open-label, randomized, single-centre clinical trial. J Antimicrob Chemother 2016; 71:2280-5. [PMID: 27107097 DOI: 10.1093/jac/dkw118] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 03/09/2016] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated. METHODS In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined. RESULTS A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, P = 0.003 (PP) and 89.8% versus 82.4%, P = 0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (P = 0.039), as were CYP2C19 extensive metabolizer (P = 0.005), clarithromycin (P = 0.000) and metronidazole resistance (P = 0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious. CONCLUSIONS The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy.
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Affiliation(s)
- Junbo Hong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Dongsheng Liu
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Chuan Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Yong Xie
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Kunhe Zhang
- Institute of Digestion, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Anjiang Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huifang Xiong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Huilie Zeng
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Huiqiang Yu
- Department of Statistics of Medical College of Nanchang University, 681 Bayi Road, Nanchang, Jiangxi, P.R. China
| | - Jiuhong Ma
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Youxiang Chen
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Xuan Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Zheng Street, Nanchang, Jiangxi, P.R. China
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Talebi Bezmin Abadi A. Vaccine against Helicobacter pylori: Inevitable approach. World J Gastroenterol 2016; 22:3150-3157. [PMID: 27003991 PMCID: PMC4789989 DOI: 10.3748/wjg.v22.i11.3150] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 01/05/2016] [Accepted: 01/30/2016] [Indexed: 02/06/2023] Open
Abstract
Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.
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Caliskan R, Tokman HB, Erzin Y, Saribas S, Yuksel P, Bolek BK, Sevuk EO, Demirci M, Yılmazli O, Akgul O, Kalayci F, Cakan H, Salih B, Bal K, Kocazeybek B. Antimicrobial resistance of Helicobacter pylori strains to five antibiotics, including levofloxacin, in Northwestern Turkey. Rev Soc Bras Med Trop 2016; 48:278-84. [PMID: 26108005 DOI: 10.1590/0037-8682-0027-2015] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 04/24/2015] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Antibiotic resistance is the main factor that affects the efficacy of current therapeutic regimens against Helicobacter pylori. This study aimed to determine the rates of resistance to efficacy clarithromycin, amoxicillin, tetracycline, levofloxacin and metronidazole among H. pylori strains isolated from Turkish patients with dyspepsia. METHODS H. pylori was cultured from corpus and antrum biopsies that were collected from patients with dyspeptic symptoms, and the antimicrobial susceptibility of H. pylori was determined using the E-test (clarithromycin, amoxicillin, tetracycline, metronidazole and levofloxacin) according to the EUCAST breakpoints. Point mutations in the 23S rRNA gene of clarithromycin-resistant strains were investigated using real-time PCR. RESULTS A total of 98 H. pylori strains were isolated, all of which were susceptible to amoxicillin and tetracycline. Of these strains, 36.7% (36/98) were resistant to clarithromycin, 35.5% (34/98) were resistant to metronidazole, and 29.5% (29/98) were resistant to levofloxacin. Multiple resistance was detected in 19.3% of the isolates. The A2143G and A2144G point mutations in the 23S rRNA-encoding gene were found in all 36 (100%) of the clarithromycin-resistant strains. Additionally, the levofloxacin MIC values increased to 32 mg/L in our H. pylori strains. Finally, among the clarithromycin-resistant strains, 27.2% were resistant to levofloxacin, and 45.4% were resistant to metronidazole. CONCLUSIONS We conclude that treatment failure after clarithromycin- or levofloxacin-based triple therapy is not surprising and that metronidazole is not a reliable agent for the eradication of H. pylori infection in Turkey.
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Affiliation(s)
- Reyhan Caliskan
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Hrisi Bahar Tokman
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Yusuf Erzin
- Cerrahpasa Faculty of Medicine, Department of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Suat Saribas
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Pelin Yuksel
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Bora Kazim Bolek
- Medical Laboratory Techniques Program, Vocational School of Health Services, Istanbul Esenyurt University, Istanbul, Turkey
| | - Ecehan Ozge Sevuk
- Faculty of Arts and Sciences, Department of Biology, Fatih University, Istanbul, Turkey
| | - Mehmet Demirci
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Ozge Yılmazli
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Ozer Akgul
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Fatma Kalayci
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
| | - Huseyin Cakan
- Institute of Forensic Sciences,, Department of Microbiology, Istanbul University, Istanbul, Turkey
| | - Barik Salih
- Faculty of Arts and Sciencs, Department of Biology, Fatih University, Istanbul, Turkey
| | - Kadir Bal
- Cerrahpasa Faculty of Medicine, Department of Gastroenterology, Istanbul University, Istanbul, Turkey
| | - Bekir Kocazeybek
- Cerrahpasa Faculty of Medicine, Department of Medical Microbiology, Istanbul University, Istanbul, Turkey
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Chang SS, Hu HY. Helicobacter pylori: Effect of coexisting diseases and update on treatment regimens. World J Gastrointest Pharmacol Ther 2015; 6:127-136. [PMID: 26558147 PMCID: PMC4635153 DOI: 10.4292/wjgpt.v6.i4.127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 06/10/2015] [Accepted: 09/15/2015] [Indexed: 02/06/2023] Open
Abstract
The presence of concomitant diseases is an independent predictive factor for non-Helicobacter pylori (H. pylori) peptic ulcers. Patients contracting concomitant diseases have an increased risk of developing ulcer disease through pathogenic mechanisms distinct from those of H. pylori infections. Factors other than H. pylori seem critical in peptic ulcer recurrence in end stage renal disease (ESRD) and cirrhotic patients. However, early H. pylori eradication is associated with a reduced risk of recurrent complicated peptic ulcers in patients with ESRD and liver cirrhosis. Resistances to triple therapy are currently detected using culture-based and molecular methods. Culture susceptibility testing before first- or second-line therapy is unadvisable. Using highly effective empiric first-line and rescue regimens can yield acceptable results. Sequential therapy has been included in a recent consensus report as a valid first-line option for eradicating H. pylori in geographic regions with high clarithromycin resistance. Two novel eradication regimens, namely concomitant and hybrid therapy, have proven more effective in patients with dual- (clarithromycin- and metronidazole-) resistant H. pylori strains. We aim to review the prevalence of and eradication therapy for H. pylori infection in patients with ESRD and cirrhosis. Moreover, we summarized the updated H. pylori eradication regimens.
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Georgopoulos SD, Papastergiou V, Karatapanis S. Treatment of Helicobacter Pylori infection: optimization strategies in a high resistance era. Expert Opin Pharmacother 2015; 16:2307-17. [PMID: 26330278 DOI: 10.1517/14656566.2015.1084503] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders and in the prevention of gastric cancer. Due to increasing antimicrobial resistance, performance of standard triple therapies has now declined to unacceptably low levels. AREAS COVERED In this article: i) we critically revise optimization tools aiming to improve the outcome of standard treatments; ii) we provide updated evidence on the efficacy and rationale for the use of several non-bismuth quadruple regimens in clinical practice, recommended as preferred empirical therapies in areas of high clarithromycin resistance. EXPERT OPINION Prolonged (14-day) treatment duration may boost the efficacy of standard triple therapy by approximately 5%. Use of a high-dose PPI and/or new-generation PPIs, rabeprazole and esomeprazole, might improve eradication rates, particularly in regions where the CYP2C19 rapid metabolizer phenotype is prevalent. Adjunctive probiotics may be considered to improve treatment tolerability, though more data are required to better define their role in H. pylori eradication. Among non-bismuth quadruple regimens, both concomitant and sequential therapies are appropriate options for high-resistance settings; however, concomitant therapy appears to be less impaired by dual clarithromycin/metronidazole resistance. Hybrid therapy is a promising new alternative which seems not to be inferior to concomitant therapy.
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Affiliation(s)
- Sotirios D Georgopoulos
- a 1 Athens Medical P. Faliron General Hospital, Department of Gastroenterology , 17562 Athens, Greece +306 9 32 35 62 78 ; +302 1 04 11 53 75 ;
| | - Vasilios Papastergiou
- b 2 General Hospital of Rhodes, First Department of Internal Medicine , 85100 Rhodes, Greece
| | - Stylianos Karatapanis
- b 2 General Hospital of Rhodes, First Department of Internal Medicine , 85100 Rhodes, Greece
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Molina-Infante J, Shiotani A. Practical Aspects in Choosing a Helicobacter pylori Therapy. Gastroenterol Clin North Am 2015; 44:519-35. [PMID: 26314666 DOI: 10.1016/j.gtc.2015.05.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Cure rates greater than 90%-95% should be expected with an antimicrobial therapy for Helicobacter pylori infection. Standard triple therapy does not guarantee these efficacy rates in most settings worldwide anymore. The choice of eradication regimen should be dictated by factors that can predict the outcome: (1) H. pylori susceptibility; (2) patients' history of prior antibiotic therapy; and (3) local data, either resistance patterns or clinical success. Currently, the preferred first-line choices are 14-day bismuth quadruple and 14-day non-bismuth quadruple concomitant therapy. Bismuth quadruple (if not used previously), fluoroquinolone-, furazolidone- and rifabutin-containing regimens might be effective rescue treatments.
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Affiliation(s)
- Javier Molina-Infante
- Department of Gastroenterology, Hospital San Pedro de Alcantara, C/Pablo Naranjo s/n, Caceres 10003, Spain.
| | - Akiko Shiotani
- Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama Prefecture 701-0114, Japan
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Seven-Day Nonbismuth Containing Quadruple Therapy Could Achieve a Grade "A" Success Rate for First-Line Helicobacter pylori Eradication. BIOMED RESEARCH INTERNATIONAL 2015; 2015:623732. [PMID: 26090428 PMCID: PMC4452293 DOI: 10.1155/2015/623732] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 01/10/2015] [Indexed: 01/10/2023]
Abstract
This prospective study was to assess the efficacy of nonbismuth containing quadruple therapy as first-line H. pylori treatment and to determine the clinical factors influencing patient outcome. We enrolled 200 H. pylori-infected naïve patients. They were prescribed either a 7-day nonbismuth containing quadruple therapy group (EACM, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily) or a 7-day standard triple therapy group (EAC, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily). Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by EACM and EAC groups were 95.6% (95% confidence interval [CI] = 89.4%–98.3%) and 79.3% (95% CI = 70%–86.4%) in the per-protocol analysis (P < 0.001) and 88% (95% CI = 80.2%–93.0%) and 73% (95% I = 63.6%–80.3%) in the intention-to-treat analysis (P = 0.007). Clarithromycin resistance, metronidazole resistance, and dual clarithromycin and metronidazole resistances were the clinical factors influencing H. pylori eradication in EACM group. Clarithromycin resistance and dual clarithromycin and metronidazole resistances were the influential factor for EAC treatment. In conclusion, the results suggest that 7-day nonbismuth containing quadruple therapy could achieve a grade “A” report card for first-line H. pylori treatment.
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Molina-Infante J, Lucendo AJ, Angueira T, Rodriguez-Tellez M, Perez-Aisa A, Balboa A, Barrio J, Martin-Noguerol E, Gomez-Rodriguez BJ, Botargues-Bote JM, Gomez-Camarero J, Huerta A, Modolell I, Ariño I, Herranz-Bachiller MT, Bermejo F, McNicholl AG, O'Morain C, Gisbert JP. Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study. Aliment Pharmacol Ther 2015; 41:581-9. [PMID: 25776067 DOI: 10.1111/apt.13069] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 12/09/2014] [Accepted: 12/14/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. AIM To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. RESULTS Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97% mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of participating centres achieving cure rates ≥ 90% favoured OPT-CON therapy (OPT-TRI 25% vs. OPT-CON 62%). CONCLUSIONS Empiric OPT-CON therapy achieved significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.
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Affiliation(s)
- J Molina-Infante
- Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: Past, present and future. World J Gastrointest Pathophysiol 2014; 5:392-399. [PMID: 25400982 PMCID: PMC4231503 DOI: 10.4291/wjgp.v5.i4.392] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 04/15/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.
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Abstract
This review summarizes important studies regarding H.pylori therapy published from April 2013 to April 2014. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, predominantly optimized triple therapies and non-bismuth quadruple schemes. Regarding newer non-bismuth quadruple regimens, the compliance and tolerance seem to be similar for sequential and concomitant regimens. Notably, no study yet has demonstrated a clear statistical superiority for either, and a systematic review and meta-analysis may be warranted. Other studies examined the role of levofloxacin and bismuth based therapies in H. pylori eradication. The efficacy of bismuth as a second-line after sequential therapy was particularly noteworthy. Levofloxacin-based therapies also appear to be useful and versatile as part of different antibiotic combinations and in first-, second-, and third-line therapies. The emerging problem of quinolone resistance remains a worry. Individualized therapy, based on factors such as antimicrobial information, resistance data, and CYP2C19 metabolism, may well be the most notable future trend to emerge this year.
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Affiliation(s)
- Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
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Molina-Infante J, Gisbert JP. Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance. World J Gastroenterol 2014; 20:10338-10347. [PMID: 25132750 PMCID: PMC4130841 DOI: 10.3748/wjg.v20.i30.10338] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high-dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates.
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Papastergiou V, Georgopoulos SD, Karatapanis S. Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance. World J Gastroenterol 2014; 20:9898-911. [PMID: 25110420 PMCID: PMC4123371 DOI: 10.3748/wjg.v20.i29.9898] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 01/27/2014] [Accepted: 03/12/2014] [Indexed: 02/06/2023] Open
Abstract
Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.
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Wu JY, Hsu PI, Wu DC, Graham DY, Wang WM. Feasibility of shortening 14-day hybrid therapy while maintaining an excellent Helicobacter pylori eradication rate. Helicobacter 2014; 19:207-13. [PMID: 24612093 DOI: 10.1111/hel.12113] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The need for new effective Helicobacter pylori eradication therapy has focused efforts on the development and optimization of regimens with excellent eradication rates such as 14-day hybrid therapy. This study evaluated whether the duration of hybrid therapy could be reduced while maintaining a high eradication rate and to examine the effect of antibiotic resistance on outcome. MATERIALS AND METHODS Three separate multicenter pilot studies were carried out concurrently. To reduce selection bias, eligible subjects were randomized to 10-day, 12-day, or 14-day hybrid therapy consisting of esomeprazole 40 mg and amoxicillin 1 gm twice daily for 10, 12, or 14 days plus clarithromycin 500 mg, and metronidazole 500 mg twice daily for the final 7 days. The primary outcome was H. pylori eradication per-protocol assessed at least 8 weeks after therapy. RESULTS A total of 220 subjects were entered. The per-protocol analyses contained 60, 61, 61 subjects in the 10-, 12- and 14-day therapy studies, respectively. The eradication rates, per-protocol, were similar: 95% (95% confidence interval (CI); 89.5-100%) for 10-day, 95.1% (95% CI; 89.7-100%) for 12-day, and 93.4% (95% CI; 87.2-99.7%) for 14-day hybrid therapies. Antibiotic resistance was infrequent; however, all metronidazole or clarithromycin resistances were cured with 12- and 14-day therapies. CONCLUSION These results suggest that in regions of moderate to low clarithromycin and/or metronidazole resistance it may be feasible to shorten hybrid therapy to 10 or 12 days. Further study is needed to compare hybrid and concomitant therapy in regions with moderate-to-high clarithromycin and/or metronidazole resistance.
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Affiliation(s)
- Jeng-Yih Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
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Kanizaj TF, Kunac N. Helicobacter pylori: Future perspectives in therapy reflecting three decades of experience. World J Gastroenterol 2014; 20:699-705. [PMID: 24574743 PMCID: PMC3921479 DOI: 10.3748/wjg.v20.i3.699] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/05/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori (H. pylori) eradication protocols, and to develop new ones. Various bacterial and host factors are evaluated, and their contribution to eradication failure is estimated. For a long time being considered the cornerstone eradication scheme, the standard triple therapy has been replaced with novel, more efficient regimens, namely sequential and concomitant, along with the emergence of a new design of bismuth quadruple therapy. A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant (clarithromycin and metronidazole) H. pylori. Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy, making eradication success close to originally desirable rates. Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes, so various probiotic compound supplements are taken into consideration. Finally, we summarize the emerging efforts and obstacles in creating efficient H. pylori vaccine.
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Ierardi E, Giorgio F, Losurdo G, Di Leo A, Principi M. How antibiotic resistances could change Helicobacter pylori treatment: A matter of geography? World J Gastroenterol 2013; 19:8168-8180. [PMID: 24363506 PMCID: PMC3857438 DOI: 10.3748/wjg.v19.i45.8168] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 10/18/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
Therapeutic management of Helicobacter pylori (H. pylori) remains an unsolved issue. Indeed, no therapeutic regimen is able to cure the infection in all treated patients, and in many the infection persists despite the administration of several consecutive standard therapies. Although antibiotic resistance reports describe alarming results, the outcome of therapeutic regimens does not seem to parallel this scenario in most cases, since a successful performance is often reached in more than 80% of cases. However, the phenomenon of increasing antibiotic resistance is being closely studied, and the results show controversial aspects even in the same geographic area. For the continents of Europe, America, Asia, Africa, and Oceania, minimal and maximal values of resistance to the main antibiotics (clarithromycin, amoxicillin, metronidazole, and levofloxacin) feature wide ranges in different countries. The real enigma is therefore linked to the several different therapeutic regimens, which show results that often do not parallel the in vitro findings even in the same areas. A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts. Moreover, not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome. The additional use of probiotics may help to reduce adverse events, but their therapeutic impact is doubtful. In conclusion, the “ideal therapy”, paradoxically, appears to be a “utopia”, despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H. pylori. The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide. On these bases, one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances. In this context, geography must be considered a relevant matter.
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Georgopoulos SD, Xirouchakis E, Mentis A. Is there a nonbismuth quadruple therapy that can reliably overcome bacterial resistance? Gastroenterology 2013; 145:1496-7. [PMID: 24409502 DOI: 10.1053/j.gastro.2013.07.054] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Molina-Infante J, Romano M, Gisbert JP. Reply: To PMID 23562754. Gastroenterology 2013; 145:1497-8. [PMID: 24409504 DOI: 10.1053/j.gastro.2013.10.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
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