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Mori H, Nishizawa T, Morioka K, Kato M, Kanai T. Should Metronidazole Be Included in Second-Line Treatment After Standard Triple Therapy for Helicobacter pylori?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Helicobacter 2025; 30:e70010. [PMID: 39868753 PMCID: PMC11771550 DOI: 10.1111/hel.70010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/06/2025] [Accepted: 01/11/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND AND AIM Although standard triple therapy remains the first-line eradication treatment for H. pylori worldwide, it is unclear whether metronidazole should be included empirically in second-line eradication treatments. The aim of this study was to compare the efficacy of metronidazole-containing regimens with that of metronidazole-free regimens after failure of first-line eradication using standard triple therapy. METHODS PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify RCTs eligible for inclusion in this systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Thirteen eligible RCTs were included, with a total of 2039 patients assigned to metronidazole-containing (975 patients) or metronidazole-free (1064 patients) regimens. Metronidazole-containing regimens had significantly lower eradication failure rates than regimens without metronidazole (OR 0.55; 95% CI, 0.39-0.78). Subgroup analysis based on the regional risk of metronidazole resistance demonstrated that metronidazole-containing regimens had lower eradication failure rates not only in low-risk regions but also in high-risk regions (OR, 0.29; 95% CI, 0.11-0.74 and OR, 0.66; 95% CI, 0.49-0.91, respectively). CONCLUSION After failure of standard triple therapy, secondary eradication treatment regimens containing metronidazole demonstrate higher eradication rates than those without metronidazole.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Toshihiro Nishizawa
- Department of Gastroenterology and HepatologyInternational University of Health and Welfare, Narita HospitalNaritaJapan
| | - Kohei Morioka
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Center for Diagnostic and Therapeutic EndoscopyKeio University School of MedicineTokyoJapan
| | - Motohiko Kato
- Center for Diagnostic and Therapeutic EndoscopyKeio University School of MedicineTokyoJapan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
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Nepalia A, Fernandes SE, Singh H, Rana S, Saini DK. Anti-microbial resistance and aging-A design for evolution. WIREs Mech Dis 2023; 15:e1626. [PMID: 37553220 DOI: 10.1002/wsbm.1626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 07/18/2023] [Accepted: 07/18/2023] [Indexed: 08/10/2023]
Abstract
The emergence of resistance to anti-infective agents poses a significant threat to successfully treating infections caused by bacteria. Bacteria acquire random mutations due to exposure to environmental stresses, which may increase their fitness to other selection pressures. Interestingly, for bacteria, the frequency of anti-microbial resistance (AMR) seems to be increasing in tandem with the human lifespan. Based on evidence from previous literature, we speculate that increased levels of free radicals (Reactive Oxygen Species-ROS and Reactive Nitrosative Species-RNS), elevated inflammation, and the altered tissue microenvironment in aged individuals may drive pathogen mutagenesis. If these mutations result in the hyperactivation of efflux pumps or alteration in drug target binding sites, it could confer AMR, thus rendering antibiotic therapy ineffective while leading to the selection of novel drug-resistant variants. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Environmental Factors Metabolic Diseases > Environmental Factors.
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Affiliation(s)
- Amrita Nepalia
- Department of Developmental Biology and Genetics, Division of Biological Sciences, Indian Institute of Science, Bangalore, India
| | - Sheryl Erica Fernandes
- Department of Developmental Biology and Genetics, Division of Biological Sciences, Indian Institute of Science, Bangalore, India
| | - Harpreet Singh
- Division of Biomedical Informatics, ICMR-AIIMS Computational Genomics Centre, Indian Council of Medical Research, New Delhi, India
| | - Shweta Rana
- Division of Biomedical Informatics, ICMR-AIIMS Computational Genomics Centre, Indian Council of Medical Research, New Delhi, India
| | - Deepak Kumar Saini
- Department of Developmental Biology and Genetics, and Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India
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Inokuchi K, Mori H, Matsuzaki J, Hirata K, Harada Y, Saito Y, Suzuki H, Kanai T, Masaoka T. Efficacy and safety of low-dose rifabutin-based 7-day triple therapy as a third- or later-line Helicobacter pylori eradication regimen. Helicobacter 2022; 27:e12900. [PMID: 35644041 PMCID: PMC9539484 DOI: 10.1111/hel.12900] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 04/30/2022] [Accepted: 05/02/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection. MATERIALS AND METHODS Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using a 13 C urea breath test or the H. pylori stool antigen test. The results obtained from our previous study that reported a 10-day or 14-day esomeprazole based rifabutin-containing triple therapy as a third- or fourth-line rescue therapy treated patients were used as historical control. We determined the minimum inhibitory concentrations of amoxicillin and rifabutin. We also evaluated whether the patients were positive for the mutation of the rpoB gene. RESULTS Intention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%-99% and 92.7%, 95% CI: 86%-100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy. CONCLUSIONS This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.
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Affiliation(s)
- Kazumi Inokuchi
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Translational Research Center for Gastrointestinal Disorders (TARGID)University of LeuvenLeuvenBelgium
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of PharmacotherapeuticsKeio University Faculty of PharmacyTokyoJapan
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Yosuke Harada
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Yoshimasa Saito
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of PharmacotherapeuticsKeio University Faculty of PharmacyTokyoJapan
- Department of Gastroenterology and HepatologyKitasato University Kitasato Institute HospitalTokyoJapan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTokai University School of MedicineIseharaJapan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal MedicineKeio University School of MedicineTokyoJapan
- Department of Gastroenterology and HepatologyInternational University of Health and Welfare, Mita HospitalTokyoJapan
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Nyssen OP, Vaira D, Saracino IM, Fiorini G, Caldas M, Bujanda L, Pellicano R, Keco-Huerga A, Pabón-Carrasco M, Oblitas Susanibar E, Di Leo A, Losurdo G, Pérez-Aísa Á, Gasbarrini A, Boltin D, Smith S, Phull P, Rokkas T, Lamarque D, Cano-Català A, Puig I, Mégraud F, O’Morain C, Gisbert JP. Experience with Rifabutin-Containing Therapy in 500 Patients from the European Registry on Helicobacter pylori Management (Hp-EuReg). J Clin Med 2022; 11:1658. [PMID: 35329984 PMCID: PMC8949410 DOI: 10.3390/jcm11061658] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND First-line Helicobacter pylori (H. pylori) treatments have been relatively well evaluated; however, it remains necessary to identify the most effective rescue treatments. Our aim was to assess the effectiveness and safety of H. pylori regimens containing rifabutin. METHODS International multicentre prospective non-interventional European Registry on H. pylori Management (Hp-EuReg). Patients treated with rifabutin were registered in AEG-REDCap e-CRF from 2013 to 2021. Modified intention-to-treat and per-protocol analyses were performed. Data were subject to quality control. RESULTS Overall, 500 patients included in the Hp-EuReg were treated with rifabutin (mean age 52 years, 72% female, 63% with dyspepsia, 4% with peptic ulcer). Culture was performed in 63% of cases: dual resistance (to both clarithromycin and metronidazole) was reported in 46% of the cases, and triple resistance (to clarithromycin, metronidazole, and levofloxacin) in 39%. In 87% of cases rifabutin was utilised as part of a triple therapy together with amoxicillin and a proton-pump-inhibitor, and in an additional 6% of the patients, bismuth was added to this triple regimen. Rifabutin was mainly used in second-line (32%), third-line (25%), and fourth-line (27%) regimens, achieving overall 78%, 80% and 66% effectiveness by modified intention-to-treat, respectively. Compliance with treatment was 89%. At least one adverse event was registered in 26% of the patients (most frequently nausea), and one serious adverse event (0.2%) was reported in one patient with leukopenia and thrombocytopenia with fever requiring hospitalisation. CONCLUSION Rifabutin-containing therapy represents an effective and safe strategy after one or even several failures of H. pylori eradication treatment.
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Affiliation(s)
- Olga P. Nyssen
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain; (O.P.N.); (M.C.)
| | - Dino Vaira
- Department of Surgical and Medical Sciences, IRCCS S. Orsola, University of Bologna, 40138 Bologna, Italy; (D.V.); (I.M.S.); (G.F.)
| | - Ilaria Maria Saracino
- Department of Surgical and Medical Sciences, IRCCS S. Orsola, University of Bologna, 40138 Bologna, Italy; (D.V.); (I.M.S.); (G.F.)
| | - Giulia Fiorini
- Department of Surgical and Medical Sciences, IRCCS S. Orsola, University of Bologna, 40138 Bologna, Italy; (D.V.); (I.M.S.); (G.F.)
| | - María Caldas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain; (O.P.N.); (M.C.)
| | - Luis Bujanda
- Hospital Donostia, Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), 20014 San Sebastián, Spain;
| | | | - Alma Keco-Huerga
- Servicio de Gastroenterolgía, Hospital de Valme, 41014 Sevilla, Spain; (A.K.-H.); (M.P.-C.)
| | - Manuel Pabón-Carrasco
- Servicio de Gastroenterolgía, Hospital de Valme, 41014 Sevilla, Spain; (A.K.-H.); (M.P.-C.)
| | | | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University Hospital Policlinico Consorziale, 70124 Bari, Italy; (A.D.L.); (G.L.)
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University Hospital Policlinico Consorziale, 70124 Bari, Italy; (A.D.L.); (G.L.)
| | - Ángeles Pérez-Aísa
- Agencia Sanitaria Costa del Sol, Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), 29651 Marbella, Spain;
| | - Antonio Gasbarrini
- Medicina Interna, Fondazione Policlinico Universitario A, Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy;
| | - Doron Boltin
- Division of Gastroenterology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv 49100, Israel;
| | - Sinead Smith
- Faculty of Health Sciences, Trinity College Dublin, D02PN40 Dublin, Ireland; (S.S.); (C.O.)
| | - Perminder Phull
- Department of Digestive Disorders, Aberdeen Royal Infirmary, Foresterhill Health Campus, Aberdeen AB25 2ZN, UK;
| | - Theodore Rokkas
- Gastroenterology Clinic, Henry Dunant Hospital, 11526 Athens, Greece;
| | - Dominique Lamarque
- Hôpital Ambroise Paré, Université de Versailles St-Quentin en Yvelines, Boulogne Billancourt, 92100 Paris, France;
| | - Anna Cano-Català
- Gastroenterology Service, Althaia Xarxa Assistencial Universitària de Manresa, 08243 Manresa, Spain; (A.C.-C.); (I.P.)
- Medicine Department, Universitat de Vic-Universitat Central de Catalunya (UVicUCC), 08500 Manresa, Spain
| | - Ignasi Puig
- Gastroenterology Service, Althaia Xarxa Assistencial Universitària de Manresa, 08243 Manresa, Spain; (A.C.-C.); (I.P.)
- Medicine Department, Universitat de Vic-Universitat Central de Catalunya (UVicUCC), 08500 Manresa, Spain
| | - Francis Mégraud
- INSERM U1312, Université de Bordeaux, 33076 Bordeaux, France;
| | - Colm O’Morain
- Faculty of Health Sciences, Trinity College Dublin, D02PN40 Dublin, Ireland; (S.S.); (C.O.)
| | - Javier P. Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), 28006 Madrid, Spain; (O.P.N.); (M.C.)
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Xirouchakis E, Georgopoulos SD. Evaluating treatments with rifabutin and amoxicillin for eradication of Helicobacter pylori infection in adults: a systematic review. Expert Opin Pharmacother 2021; 23:201-210. [PMID: 34595999 DOI: 10.1080/14656566.2021.1982894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Helicobacter pylori causes dyspepsia, peptic ulcer, and gastric malignancies. Treatments for Helicobacter pylori are mostly empirical depending on regional antibiotic resistances and the patient's history and less frequently susceptibility guided. Helicobacter pylori has a low resistance to rifabutin and has been proposed as an alternative for third-line treatment and beyond but recently has also gained attention for use as first- and second-line treatment. AREAS COVERED In this review, the authors systematically searched medical databases in order to present the current eradication rates for any treatment based on the two antibiotics, rifabutin and amoxicillin with a potent acid inhibitor. They also assessed the safety and tolerance of all the relative regimens. EXPERT OPINION Treatment with a rifabutin- and amoxicillin-containing regimen is a valuable option when treating difficult to eradicate Helicobacter pylori infections. Its efficacy is overall 71.4%, and it is not influenced by previous antibiotics, gender, smoking habits, and age. Its results were better when used as a first- or second-line treatment. In third-line therapy and beyond, eradication rates are lower. Adverse effects of all rifabutin regimens occurred in 23% of patients and were mostly mild with bone marrow suppression being very low and reversible.
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Affiliation(s)
- Elias Xirouchakis
- Department of Gastroenterology and Hepatology, Athens Medical, Paleo Faliron Hospital, Athens, Greece
| | - Sotirios D Georgopoulos
- Department of Gastroenterology and Hepatology, Athens Medical, Paleo Faliron Hospital, Athens, Greece
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence based guidelines for the treatment of Helicobacter pylori infection in Korea 2020. Korean J Intern Med 2021; 36:807-838. [PMID: 34092054 PMCID: PMC8273819 DOI: 10.3904/kjim.2020.701] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 05/06/2021] [Indexed: 01/10/2023] Open
Abstract
Helicobacter pylori infection is one of the most common infectious diseases worldwide. H. pylori is responsible for substantial gastrointestinal morbidity with a high disease burden. Since the revision of the H. pylori Clinical Practice Guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin based triple therapy. According to a nationwide randomized controlled study by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance to clarithromycin. The clinical practice guidelines for treatment of H. pylori were updated based on evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after expert consensus on three recommendations regarding the indication for treatment and eight recommendations on the treatment itself. These guidelines were designed to provide clinical evidence for the treatment of H. pylori to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards, and will be revised if more evidence emerges in the future.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul,
Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul,
Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju,
Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan,
Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin,
Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul,
Korea
| | - Su Youn Nam
- Center for Gastric Cancer, Kyungpook National University Chilgok Hospital, Daegu,
Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon,
Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang,
Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul,
Korea
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Cortés P, Nelson AD, Bi Y, Stancampiano FF, Murray LP, Pujalte GGA, Gomez V, Harris DM. Treatment Approach of Refractory Helicobacter pylori Infection: A Comprehensive Review. J Prim Care Community Health 2021; 12:21501327211014087. [PMID: 33949229 PMCID: PMC8114244 DOI: 10.1177/21501327211014087] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.
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Affiliation(s)
| | | | - Yan Bi
- Mayo Clinic, Jacksonville, FL, USA
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Gingold-Belfer R, Niv Y, Levi Z, Boltin D. Rifabutin triple therapy for first-line and rescue treatment of Helicobacter pylori infection: A systematic review and meta-analysis. J Gastroenterol Hepatol 2021; 36:1392-1402. [PMID: 33037845 DOI: 10.1111/jgh.15294] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 08/18/2020] [Accepted: 10/06/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIM Due to the increasing resistance of Helicobacter pylori, there is a need for novel antibiotic treatment protocols. We aimed to perform a systematic review and meta-analysis in order to determine the effectiveness and safety of rifabutin triple therapy for H. pylori infection. METHODS We performed a systematic review of prospective clinical trials with a treatment arm consisting of proton pump inhibitor, amoxicillin, and rifabutin and a meta-analysis of randomized controlled trials (RCTs). RESULTS Thirty-three prospective studies including 44 datasets were identified. Meta-analysis of four RCTs for rescue treatment found no difference between treatment groups (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.437-1.791, I2 = 68.1%, P = 0.733). Only one RCT compared rifabutin therapy with control for first-line treatment of H. pylori infection (OR 3.78, 95% CI 2.44-5.87, P < 0.0001). Treatment was more likely to be successful in Asian versus non-Asian populations (81.0% vs 72.4%, P = 0.001) and when daily amoxicillin dose was ≥ 3000 mg or proton pump inhibitor dose was ≥ 80 mg or treatment duration was 14 days (80.6% vs 66.0%, P = 0.0001). The overall event rate for adverse effects was 24.8% (729/2937) (95% CI 0.23-0.26), and the pooled OR for adverse effects in the treatment versus control group was 0.93 (95% CI 0.50-1.75) (I2 = 79.76, P = 0.82). CONCLUSION Evidence for the effectiveness of rifabutin for the first-line treatment of H. pylori infection in adults is limited, and studies comparing rifabutin with conventional first-line treatments are lacking.
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Affiliation(s)
- Rachel Gingold-Belfer
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yaron Niv
- Division of Patient Safety and Quality Improvement, Ministry of Health, Jerusalem, Israel
| | - Zohar Levi
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Doron Boltin
- Division of Gastroenterology, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Helicobacter Pylori: a comprehensive review for primary care providers. ACTA ACUST UNITED AC 2021; 59:112-118. [PMID: 33565305 DOI: 10.2478/rjim-2020-0043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Indexed: 12/15/2022]
Abstract
Helicobacter pylori is the most prevalent bacteria infecting humans resulting in a variety of gastrointestinal and extra gastrointestinal complications. Although most of the infected adults are asymptomatic, the prevalence varies in different parts of the world it is higher in Eastern and Southern Europe. Eradication of Helicobacter pylori is necessary to prevent precancerous conditions like gastric atrophy, gastric intestinal metaplasia and gastric dysplasia. This comprehensive review addresses briefly on: whom and how to test and treat including recommended first line therapies, salvage therapies, testing for eradication and strategy to be used in primary care clinics.
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10
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Jung HK, Kang SJ, Lee YC, Yang HJ, Park SY, Shin CM, Kim SE, Lim HC, Kim JH, Nam SY, Shin WG, Park JM, Choi IJ, Kim JG, Choi M. Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020. Gut Liver 2021; 15:168-195. [PMID: 33468712 PMCID: PMC7960974 DOI: 10.5009/gnl20288] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/14/2020] [Accepted: 10/20/2020] [Indexed: 01/10/2023] Open
Abstract
Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world's population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Su Youn Nam
- Center for Gastric Cancer, Kyungpook National University Hospital Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Woon Geon Shin
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea
| | - Jae Myung Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Goyang, Korea
| | - Jae Gyu Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Miyoung Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
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Gisbert JP. Rifabutin for the Treatment of Helicobacter Pylori Infection: A Review. Pathogens 2020; 10:pathogens10010015. [PMID: 33379336 PMCID: PMC7823349 DOI: 10.3390/pathogens10010015] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/17/2020] [Accepted: 12/24/2020] [Indexed: 12/12/2022] Open
Abstract
Nowadays, apart from having to know first-line Helicobacter pylori eradication regimens well, we must also be prepared to face treatment failures. The aim of this review is to summarize the role of rifabutin in the management of H. pylori infection. Bibliographical searches were performed in PubMed. Data on resistance and efficacy of rifabutin-containing regimens on H. pylori eradication were meta-analyzed. Mean H. pylori rifabutin resistance rate (39 studies, including 9721 patients) was 0.13%; when studies only including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.07%). Mean H. pylori eradication rate (by intention-to-treat) with rifabutin-containing regimens (3052 patients) was 73%. Respective cure rates for second-, third-, fourth- and fifth-line therapies, were 79%, 69%, 69% and 72%. Most studies administered rifabutin 300 mg/day, which seemed to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10–12-day regimens are generally recommended. Adverse events to rifabutin treatment in H. pylori studies were relatively infrequent (15%), and severe adverse events were exceptional (myelotoxicity was the most significant, although always reversible). In summary, rifabutin-containing therapy represents an encouraging strategy generally restricted, at present, to patients where previous (usually multiple) eradication regimens have failed.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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12
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Affiliation(s)
- Sheila E Crowe
- From the Department of Medicine, Division of Gastroenterology, University of California at San Diego, La Jolla
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13
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Siavoshi F, Saniee P, Malekzadeh R. Effective antimicrobial activity of rifabutin against multidrug-resistant Helicobacter pylori. Helicobacter 2018; 23:e12531. [PMID: 30230637 DOI: 10.1111/hel.12531] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 07/21/2018] [Accepted: 07/21/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Helicobacter pylori resistance to more than one antibiotic is the main reason for failure in bacterial eradication in a considerable number of patients. Rifabutin (RFB) with a broad-spectrum of antimicrobial therapy has been suggested for treatment of refractory multidrug-resistant infections. METHODS Helicobacter pylori isolates from 104 patients were examined for resistance to 5 currently used antibiotics and RFB, using agar dilution method. Twofold serial dilutions of antibiotics were used and MICs (μg/mL) determined as metronidazole (MTZ 8), clarithromycin (CLR 2), amoxicillin (AMX 1), tetracycline (TET 0.5), furazolidone (FRZ 0.5), and RFB (0.06). RESULTS Of 104 H. pylori isolates, only 7 (6.7%) were sensitive to all the 6 antibiotics. However, 30 (28.8%) were resistant to one antibiotic, 28 (26.9%) to two, 19 (18.2%) to three, 14 (13.4%) to four, and 6 (5.7%) to five currently used antibiotics. Overall, 67(64.4%) of isolates were resistant to 2-5 currently used antibiotics and considered as multidrug-resistant (MDR), with 59 (88.1%) showing sensitivity to RFB and 8 (11.9%) resistance (P < 0.05). Of 33 isolates resistant to both MTZ and CLR, 25 (75.7%) were sensitive to RFB and 8 (24.3%) resistant (P < 0.05). DISCUSSION In vitro antimicrobial effectiveness of RFB on MDR H. pylori including those with resistance to both MTZ and CLR was demonstrated. However, RFB efficacy decreased as the number of antibiotics responsible for MDR increased. Considering that RFB inhibits both extra- and intracellular H. pylori, it can be suggested as an effective antibiotic against of MDR H. pylori.
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Affiliation(s)
- Farideh Siavoshi
- Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran
| | - Parastoo Saniee
- Faculty of Life Sciences and Biotechnology, Department of Microbiology, Shahid Beheshti University G.C, Tehran, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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14
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Huang HT, Wang HM, Yang SC, Tai WC, Liang CM, Wu KL, Lee CH, Chuah SK. Efficacy of a 14-day quadruple-therapy regimen for third-line Helicobacter pylori eradication. Infect Drug Resist 2018; 11:2073-2080. [PMID: 30464550 PMCID: PMC6214414 DOI: 10.2147/idr.s185511] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
PURPOSE To assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication. METHODS We enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylori culture. Seven patients were lost to follow-up. Patients were treated according to the results of antibiotic-susceptibility testing reports (cultured group, n=39). Those who failed the H. pylori culture were prescribed 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily (empirical group, n=24). A follow-up urea breath test was performed 8 weeks later. RESULTS Antibiotic-resistance rates were 79.5% (clarithromycin), 94.9% (levofloxacin), 66.7% (metronidazole), 2.6% (amoxicillin), and 0 (tetracycline). Eradication rates attained by the cultured and empirical group were 89.7% (95% CI 72.7%-97.1%) and 58.3% (95% CI 36.6%-77.9%) in per-protocol analysis (P=0.004) and 81.4% (95% CI 66.6%-91.6%) and 51.8% (95% CI 31.9%-71.3%) in intention-to-treat analysis (P=0.014), respectively. Culture-guided therapy was the only clinical factor influencing the efficacy of H. pylori eradication (OR 0.16, 95% CI 0.04-0.60; P=0.006). Despite the high metronidazole-resistance rate (66.7%) after two treatment failures, the eradication rate in patients with this condition was 84%. CONCLUSION Empirical 14-day modified quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment. The success rate of third-line susceptibility-guided treatment was near 90%. This report is valuable as a reminder to medical practitioners that rather than a try-and-see approach, susceptibility-guided therapy should always be considered whenever possible for patients who have undergone several treatment failures.
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Affiliation(s)
- Hsiang Tso Huang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Hsin-Ming Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Shih-Cheng Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Wei-Chen Tai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Chih-Ming Liang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Keng-Liang Wu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
| | - Chen-Hsiang Lee
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan
| | - Seng-Kee Chuah
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Song District, Kaohsiung 833, Taiwan,
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15
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Suzuki H, Mori H. World trends for H. pylori eradication therapy and gastric cancer prevention strategy by H. pylori test-and-treat. J Gastroenterol 2018; 53:354-361. [PMID: 29138921 PMCID: PMC5847180 DOI: 10.1007/s00535-017-1407-1] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 10/25/2017] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori-associated gastritis leads to the development of gastric cancer. Kyoto global consensus report on H. pylori gastritis recommended H. pylori eradication therapy to prevent gastric cancer. To manage H. pylori infection, it is important to choose the appropriate regimen considering regional differences in resistance to clarithromycin and metronidazole. Quinolones and rifabutin-containing regimens are useful as third- and fourth-line rescue therapies.
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Affiliation(s)
- Hidekazu Suzuki
- Fellowship Training Center, Medical Education Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Hideki Mori
- Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan
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16
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Mori H, Suzuki H. Reply to letter to the editor: "The dosage of rifabutin in H. pylori eradication regimen should be appropriately determined in each area of the world". United European Gastroenterol J 2016; 4:476-477. [PMID: 27403316 PMCID: PMC4924443 DOI: 10.1177/2050640616631477] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hidekazu Suzuki
- Medical Education Center, Keio University School of Medicine, Tokyo, Japan
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17
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Mori H, Suzuki H, Matsuzaki J, Tsugawa H, Fukuhara S, Miyoshi S, Hirata K, Seino T, Matsushita M, Nishizawa T, Masaoka T, Kanai T. Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study. United European Gastroenterol J 2016; 4:380-387. [PMID: 27403304 PMCID: PMC4924440 DOI: 10.1177/2050640615618043] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 10/28/2015] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND AND AIM This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. METHODS Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. RESULTS Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. CONCLUSION Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy.
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Affiliation(s)
- Hideki Mori
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- Medical Education Center, Keio University School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Hitoshi Tsugawa
- Department of Biochemistry and Integrative Medical Biology, Keio University School of Medicine, Tokyo, Japan
| | - Seiichiro Fukuhara
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Sawako Miyoshi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Kenro Hirata
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takashi Seino
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Misako Matsushita
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Toshihiro Nishizawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Tatsuhiro Masaoka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
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18
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Liu X, Wang H, Lv Z, Wang Y, Wang B, Xie Y, Zhou X, Lv N. Rescue Therapy with a Proton Pump Inhibitor Plus Amoxicillin and Rifabutin for Helicobacter pylori Infection: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2015; 2015:415648. [PMID: 26106411 PMCID: PMC4461753 DOI: 10.1155/2015/415648] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 04/16/2015] [Accepted: 04/16/2015] [Indexed: 12/12/2022] Open
Abstract
Background. To conduct a systematic review and meta-analysis of clinical trials for eradication of Helicobacter pylori (H. pylori) that included a treatment arm with a proton pump inhibitor, rifabutin, and amoxicillin. Materials and Methods. We selected clinical trials that examined the efficacy of H. pylori eradication therapies and included a study arm using the test regimen from major medical literature databases and abstracts from major gastroenterology meetings. We also did subgroup and sensitivity analyses. Results. Twenty-one studies were included in systematic review. The total eradication rates of the test regimen were 70.4% by intent-to-treat (ITT) and 72.0% by per-protocol (PP) analyses. The pooled odds ratio (OR) was 0.55 using fixed effects model (P = 0.283) for the test regimen versus other triple regimens. The total eradication rates were 68.4% for the test regimen and 81.9% in the control group by ITT, while the OR was 1.08 using random effects model (P = 0.019). The pooled eradication rate was 66.4% for the test regimen and 67.4% for the control group by ITT. The total adverse effects incidence were 25.1% for the test regimen. Conclusions. The test regimen for H. pylori rescue therapy may be not superior to control regimens in efficacy.
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Affiliation(s)
- Xiaoqun Liu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Hui Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Zhifa Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Youhua Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Ben Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Yong Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Xiaojiang Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Nonghua Lv
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
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19
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Bang CS, Baik GH. Attempts to enhance the eradication rate of Helicobacter pylori infection. World J Gastroenterol 2014; 20:5252-5262. [PMID: 24833855 PMCID: PMC4017040 DOI: 10.3748/wjg.v20.i18.5252] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/17/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Increasing rates of antimicrobial resistance to clarithromycin and metronidazole present challenges in maintaining optimal eradication rates. Knowledge of local antibiotic resistance and consumption pattern is important in selecting a reliable regimen. In addition, adverse effect profiles of therapeutic regimens are important and must be addressed to enhance compliance rates. Various methods of enhancing the eradication rates of Helicobacter pylori (H. pylori) have been investigated, including changing combinations or durations of established drugs, adding adjuvant drugs, or development of new molecules or agents. Bismuth-containing quadruple, sequential, concomitant, and levofloxacin-based triple therapies are replacing the long-standing standard of the triple regimen. Despite the encouraging results of these regimens, individualized approaches like treatment after antibiotics resistance test or CYP2C19 genotyping would be the mainstream of future therapy. Because scientific, economic, and technical problems make these advance therapies unfit for widespread use, future development for H. pylori therapy should be directed to overcome individualized antibiotic resistance. Although various novel regimens and additive agents have indicated favorable outcomes, more studies or validations are needed to become a mainstream H. pylori therapy.
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20
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Buzás GM, Györffy H, Széles I, Szentmihályi A. Second-line and third-line trial for helicobacter pylori infection in patients with duodenal ulcers: A prospective, crossover, controlled study. Curr Ther Res Clin Exp 2014; 65:13-25. [PMID: 24764586 DOI: 10.1016/s0011-393x(04)90001-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2004] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Following standard first-line triple therapies for Helicobacter pylori infection, up to 20% of patients require further eradication. OBJECTIVE The aim of this study was to assess the effects of second-line triple therapies and third-line quadruple therapies for the eradication of H pylori. METHODS This 7-week, prospective, crossover, controlled, second- and third-line trial was conducted at the Department of Gastroenterology, Ferencváros Health Center (Budapest, Hungary). Patients aged 18 to 80 years with duodenal ulcers and an H pylori infection resistant to first-line triple therapy (pantoprazole 40 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID [PAC] given as tablets) received a different triple therapy regimen (ranitidine bismuth citrate 400 mg BID + metronidazole 500 mg BID + clarithromycin 500 mg BID [RBC-MC]) for 7 days (group 1A), and nonresponders after RBC + 2 antimicrobials received the pantoprazole-based regimen (group 1B). After secondary failure, patients were randomized to receive quadruple therapies: pantoprazole, amoxicillin, tetracycline, and either nitrofurantoin or bismuth subsalicylate (groups 2A and 2B). RESULTS One hundred thirty-four patients were enrolled in the second-line study (56 men, 78 women; mean [SD] age, 51.1 [12.4] years; group 1A, 68 patients; group 1B, 66 patients). Subsequently, 41 (30.6%) of these patients were randomized to receive quadruple therapies. Using intent-to-treat (ITT) analysis, the eradication rates did not differ significantly (60.3% and 65.2% in groups 1A and 1B, respectively; 61.9% and 55.0% in groups 2A and 2B, respectively). Perprotocol eradication rates did not differ significantly (66.1% and 68.3% in groups 1A and 1B, respectively); however, the rates were significantly different in group 2A (66.7%) versus group 2B (55.5%) (P = 0.03).
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Affiliation(s)
- György M Buzás
- Department of Gastroenterology, Ferencváros Health Center, Budapest, Hungary
| | - Hajnalka Györffy
- 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary
| | - Ilona Széles
- Central Laboratory, 2nd District Health Center, Budapest, Hungary
| | - Anna Szentmihályi
- Department of Bacteriology, Johan Béla National Institute of Epidemiology, Budapest, Hungary
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21
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Gisbert JP. Rescue Therapy for Helicobacter pylori Infection 2012. Gastroenterol Res Pract 2012; 2012:974594. [PMID: 22536225 PMCID: PMC3299261 DOI: 10.1155/2012/974594] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 12/10/2011] [Indexed: 12/18/2022] Open
Abstract
Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final-overall-eradication rate. The choice of a "rescue" treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line "rescue" option. Alternatively, it has recently been suggested that levofloxacin-based "rescue" therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line "rescue" option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several "rescue" therapies are consecutively given.
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Affiliation(s)
- Javier P. Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain
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22
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Park HK, Lee DH, Suh S, Seo PJ, Kim N, Jeong SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM. Dual therapy trial using esomeprazole and amoxicillin as third-line rescue therapy for Helicobacter pylori infection. Clin Endosc 2011; 44:33-7. [PMID: 22741110 PMCID: PMC3363043 DOI: 10.5946/ce.2011.44.1.33] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Revised: 08/16/2011] [Accepted: 08/31/2011] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIMS The purpose of this study was to evaluate the efficacy and tolerability of dual therapy consisting of esomeprazole and amoxicillin as a rescue therapy for Helicobacter pylori infection. METHODS From December 2009 to August 2010, 21 patients who experienced two consecutive eradication failures were included. They received esomeprazole (40 mg, b.i.d.) and amoxicillin (1,000 mg, b.i.d.) for 14 days as a third eradication regimen. Compliance and side effects were determined from an interview. H. pylori status was evaluated using the (13)C urea breath test at least 6 weeks after treatment. RESULTS The mean age of the patients was 59 years and included 52% males. Indications for treatment were functional dyspepsia (61.9%), peptic ulcer disease (28.6%), and gastric adenoma (9.5%). H. pylori was eradicated in 14 of 21 (66.7%) patients. Minor side effects were reported in three of the 21 patients (14.3%). These side effects consisted mainly of nausea and epigastric discomfort. CONCLUSIONS A 2-week course of dual therapy failed to show satisfactory results in third-line H. pylori eradication, but it was very safe and tolerable. Therefore, dual therapy constitutes an encouraging empirical strategy for the elderly and infirm patients with multiple previous eradication failures.
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Affiliation(s)
- Hyun Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Bohr URM, Malfertheiner P. Eradication of H. pylori Infection: the Challenge is on if Standard Therapy Fails. Therap Adv Gastroenterol 2011; 2:59-66. [PMID: 21180534 DOI: 10.1177/1756283x08100352] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The recommended standard triple therapy for Helicobacter pylori infection, consisting of a proton pump inhibitor, clarithromycin and amoxicillin or metronidazole, can reach eradication rates in over 90%. However, in recent years resistance to antibiotics has increased and eradication rates have declined. Approximately one in five patients need a second-line therapy because eradication therapy fails. Second-line treatment with a bismuth-based quadruple therapy leads to satisfactory eradication rates, but bismuth is not available in many countries. Modern second- and third-line treatments can only be successful if they are adapted to the current resistance situation and they need to evolve continuously. Moreover, pharmacodynamic effects due to polymorphisms of the cytochrome P450 system are important. Because therapy adherence is significantly associated with therapy success, modern regimens if possible should be easy to take and well tolerated. In recent years, various novel salvage-therapy regimens have been investigated that significantly improve treatment options.
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Affiliation(s)
- Ulrich R M Bohr
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
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Chiba N. Ulcer Disease and Helicobacter pyloriInfection: Etiology and Treatment. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:102-138. [DOI: 10.1002/9781444314403.ch6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Rescue therapy using a rifabutin-based regimen is effective for cure of Helicobacter pylori infection. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2010; 24:303-6. [PMID: 20485704 DOI: 10.1155/2010/637908] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To evaluate the efficacy of rescue therapy using rifabutin, amoxicillin and a proton pump inhibitor (PPI) in the eradication of Helicobacter pylori in patients who have failed at least one course of PPI-based triple therapy. METHODS The present study was a single-centre case series of 16 consecutive patients who had received at least one course of standard eradication therapy. Pretreatment evaluation included endoscopy with biopsies for histology and culture for H pylori infection. Treatment consisted of a one-week regimen containing a PPI twice daily, amoxicillin (A) 1 g twice daily and rifabutin (R) 300 mg once daily (PPI-AR). Post-treatment evaluation consisted of a repeat endoscopy with biopsy for histology and culture, or a validated urea breath test at least four weeks after treatment was completed. Pretreatment antibiotic susceptibility to metronidazole, clarithromycin and A was evaluated using a validated epsilometer test. RESULTS Of the 16 patients, four had previously received one course of triple therapy, 10 had received two courses and two had received more than two courses. The overall success rate of PPI-AR was 63% (10 of 16). Resistance to A was 0% (0 of 13), metronidazole 77% (10 of 13), clarithromycin 70% (seven of 10), and both metronidazole and clarithromycin 60% (six of 10). There was no correlation between resistance patterns and cure rate. CONCLUSIONS An R-containing regimen such as PPI-AR is a viable option as rescue therapy for H pylori infection.
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Abstract
Helicobacter pylori infection is the main known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. After more than 20 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a 'rescue' treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third-line 'rescue' option. Alternatively, it has recently been suggested that levofloxacin-based 'rescue' therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a third-line 'rescue' option. Finally, rifabutin-based 'rescue' therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several 'rescue' therapies are consecutively given. Therefore, the attitude in H. pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Abstract
Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a clarithromycin-based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin-based combination would be a third “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth-line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, even after two or more unsuccessful attempts, should be to fight and not to surrender.
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Elliott PR, Mohammad S, Melrose HJ, Moody PCE. Expression, purification, crystallization and preliminary X-ray analysis of an NAD-dependent glyceraldehyde-3-phosphate dehydrogenase from Helicobacter pylori. Acta Crystallogr Sect F Struct Biol Cryst Commun 2008; 64:727-9. [PMID: 18678942 PMCID: PMC2494976 DOI: 10.1107/s1744309108020368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2008] [Accepted: 07/02/2008] [Indexed: 12/27/2022]
Abstract
Helicobacter pylori is a dangerous human pathogen that resides in the upper gastrointestinal tract. Little is known about its metabolism and with the onset of antibiotic resistance new treatments are required. In this study, the expression, purification, crystallization and preliminary X-ray diffraction of an NAD-dependent glyceraldehyde-3-phosphate dehydrogenase from H. pylori are reported.
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Affiliation(s)
- Paul R. Elliott
- Henry Wellcome Laboratories for Structural Biology, University of Leicester, Leicester LE1 9HN, England
| | - Shabaz Mohammad
- Henry Wellcome Laboratories for Structural Biology, University of Leicester, Leicester LE1 9HN, England
| | - Helen J. Melrose
- Henry Wellcome Laboratories for Structural Biology, University of Leicester, Leicester LE1 9HN, England
| | - Peter C. E. Moody
- Henry Wellcome Laboratories for Structural Biology, University of Leicester, Leicester LE1 9HN, England
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Rodgers C, van Zanten SV. A meta-analysis of the success rate of Helicobacter pylori therapy in Canada. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 21:295-300. [PMID: 17505565 PMCID: PMC2657711 DOI: 10.1155/2007/419784] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Helicobacter pylori treatment success rates have varied. A systematic review of the success rate of anti- H pylori therapy in Canada was performed. METHODS All clinical trials containing Canadian data on the success rate of H pylori treatment were identified using MEDLINE searches, through review of references of retrieved studies and by contacting key investigators. Both randomized and open-label trials were included. Treatment effect size was calculated using a variation of Cochran's Q method. RESULTS Seventeen papers met the inclusion criteria. Both triple therapies consisting of a proton pump inhibitor (PPI), clarithromycin and either amoxicillin or metronidazole performed well, achieving a success rate of 84% and 82%, respectively. The cure rate of PPI-amoxicillin + metronidazole was 76%. Quadruple therapy consisting of a PPI, bismuth, metronidazole and tetracycline, given for seven to 10 days, achieved a success rate of 87%. CONCLUSION Both PPI-based triple therapy and quadruple therapy perform well in Canada for the treatment of H pylori infection.
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Affiliation(s)
| | - Sander Veldhuyzen van Zanten
- Correspondence: Dr Sander Veldhuyzen van Zanten, Division of Gastroenterology, University of Alberta, Zeidler Ledcor Centre, 130 University Campus, Edmonton, Alberta T6G 2X8. Telephone 902-473-1499, fax 902-473-6891, e-mail
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Navarro-Jarabo JM, Fernández N, Sousa FL, Cabrera E, Castro M, Ramírez LM, Rivera R, Ubiña E, Vera F, Méndez I, Rivas-Ruiz F, Moreno JL, Perea-Milla E. Efficacy of rifabutin-based triple therapy as second-line treatment to eradicate helicobacter pylori infection. BMC Gastroenterol 2007; 7:31. [PMID: 17651479 PMCID: PMC1941741 DOI: 10.1186/1471-230x-7-31] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2006] [Accepted: 07/25/2007] [Indexed: 12/23/2022] Open
Abstract
Background Rifabutin has been found to be effective in multi-resistant patients after various treatment cycles for Helicobacter pylori (HP) infection, but it has not been analysed as a second-line treatment. Therefore, we seek to compare the effectiveness of a treatment regimen including rifabutin versus conventional quadruple therapy (QT). Methods Open clinical trial, randomised and multi-centre, of two treatment protocols: A) Conventional regime -QT- (omeprazole 20 mg bid, bismuth citrate 120 mg qid, tetracycline 500 mg qid and metronidazole 500 mg tid); B) Experimental one -OAR- (omeprazole 20 mg bid, amoxicillin 1 gr bid, and rifabutin 150 mg bid), both taken orally for 7 days, in patients with HP infection for whom first-line treatment had failed. Eradication was determined by Urea Breath Test (UBT). Safety was determined by the adverse events. Results 99 patients were randomised, QT, n = 54; OAR, n = 45. The two groups were homogeneous. In 8 cases, treatment was suspended (6 in QT and 2 in OAR). The eradication achieved, analysed by ITT, was for QT, 38 cases (70.4%), and for OAR, 20 cases (44.4%); p = 0.009, OR = 1.58. Of the cases analysed PP, QT were 77.1%; OAR, 46.5%; p = 0.002. Adverse effects were described in 64% of the QT patients and in 44% of the OAR patients (p = 0.04). Conclusion A 7-day rifabutin-based triple therapy associated to amoxicillin and omeprazole at standard dose was not found to be effective as a second-line rescue therapy. The problem with quadruple therapy lies in the adverse side effects it provokes. We believe the search should continue for alternatives that are more comfortably administered and that are at least as effective, but with fewer adverse side effects. Trial Registration Current Controlled Trials ISRCTN81058036
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Affiliation(s)
- José M Navarro-Jarabo
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Nuria Fernández
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Francisca L Sousa
- Sección de Aparato Digestivo, Hospital de Motril, Av. Enrique Martín Cuevas, S/N 18600 Motril, Spain
| | - Encarnación Cabrera
- Servicio de Aparato Digestivo, Hospital General de Especialidades de Jaén, Avda. del Ejército Español, 10. 23007 Jaén, Spain
| | - Manuel Castro
- Servicio de Aparato Digestivo, Hospital Universitario Ntra. Sra. de Valme, Ctra. de Cádiz km. 548,9, 41014 Sevilla, Spain
| | - Luz M Ramírez
- Sección de Aparato Digestivo, Hospital Comarcal Valle de los Pedroches, Juan del Rey Calero s/n, 14400 Pozoblanco, Córdoba, Spain
| | - Robin Rivera
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Esther Ubiña
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Francisco Vera
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Isabel Méndez
- Unidad de Aparato Digestivo, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Francisco Rivas-Ruiz
- Unidad de Apoyo a la Investigación, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - José L Moreno
- Unidad de Farmacia, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
| | - Emilio Perea-Milla
- Unidad de Apoyo a la Investigación, Hospital Costa del Sol, Ctra Nacional 340, km 187, 29600 Marbella, Spain
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Lee YC, Wu HM, Chen THH, Liu TY, Chiu HM, Chang CC, Wang HP, Wu MS, Chiang H, Wu MC, Lin JT. A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. Helicobacter 2006; 11:418-24. [PMID: 16961802 DOI: 10.1111/j.1523-5378.2006.00432.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention-to-treat and per protocol) of a community-based H. pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. MATERIALS AND METHODS In 2004, a total of 2658 residents were recruited for 13C-urea breath testing. Participants with positive results for infection received a standard 7-day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow-up tests remained positive. Both H. pylori status and side-effects were assessed 6 weeks after treatment. RESULTS Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat and per protocol analysis, respectively. Re-treatment eradicated infection in 91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re-treated subjects. Mild side-effects occurred in 24% of subjects. Overall intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7-98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re-treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country- or region-wide eradication programs.
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Affiliation(s)
- Yi-Chia Lee
- Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
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Marzio L, Coraggio D, Capodicasa S, Grossi L, Cappello G. Role of the preliminary susceptibility testing for initial and after failed therapy of Helicobacter pylori infection with levofloxacin, amoxicillin, and esomeprazole. Helicobacter 2006; 11:237-42. [PMID: 16882326 DOI: 10.1111/j.1523-5378.2006.00407.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori. AIM To evaluate primary and secondary resistance of H. pylori to levofloxacin, and to test the role of susceptibility test on the efficacy of levofloxacin-based triple therapy. METHODS Eighty consecutive dyspeptic patients with positive (13)C-urea breath test never treated were randomly allocated into group A(1) (40 patients) and group B(1) (39 patients). Eighty-three patients already treated unsuccessfully with positive (13)C-urea breath test were divided into group A(2) (51 patients) and group B(2) (32 patients). Patients in group A(1) and group A(2) underwent upper gastrointestinal endoscopy for H. pylori susceptibility test to amoxicillin, clarithromycin, tinidazole, rifabutin, and levofloxacin. These patients were treated with levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and esomeprazole (20 mg b.i.d.) for 10 days if sensitive to these two antibiotics. If H. pylori was found resistant to amoxicillin and/or levofloxacin the treatment was based on the indications of the susceptibility test. Patients in group B(1) and group B(2) were treated empirically with levofloxacin, amoxicillin, and esomeprazole at the same dose and duration as group A. All patients underwent (13)C-urea breath test 2 months after the end of therapy. RESULTS The antibiotic resistance of H. pylori strains in group A(1) and group A(2) was (%): amoxicillin: 2.4, 10; clarithromycin: 21.9, 43.1; tinidazole: 31.7, 70; rifabutin: 2.4, 4; and levofloxacin: 9.7, 12.2, respectively. In group A(1) with susceptibility test-driven therapy, eradication was 97.2%, and in group B(1) with empirical treatment, 94.1% (n.s.). In group A(2) with susceptibility test, eradication was 97.5%, whereas in group B(2) with empirical treatment 81.2% (p < .01). CONCLUSION Primary and secondary resistance of H. pylori to levofloxacin is approximately 10% of the tested strains. The susceptibility test does not influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin in patients never treated, while it is determinant for patients who were previously treated without success.
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Affiliation(s)
- Leonardo Marzio
- Section of Digestive Sciences, Department of Medicine and Aging, G.d'Annunzio University, Chieti-Pescara, Italy.
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Sharara AI, Chaar HF, Aoun E, Abdul-Baki H, Araj GF, Kanj SS. Efficacy and safety of rabeprazole, amoxicillin, and gatifloxacin after treatment failure of initial Helicobacter pylori eradication. Helicobacter 2006; 11:231-236. [PMID: 16882325 DOI: 10.1111/j.1523-5378.2006.00416.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To evaluate the efficacy of a 7-day regimen of gatifloxacin (400 mg daily), amoxicillin (1 g twice a day), and rabeprazole (20 mg twice a day) in the secondary eradication of Helicobacter pylori infection. METHODS Eligible patients with persistent infection following one or more conventional clarithromycin-containing triple therapies were enrolled in this open-label trial. Eradication of infection was documented by (14)C-urea breath test a minimum of 4 weeks after therapy and 2 weeks off any acid suppressive therapy. Culture of H. pylori and in vitro susceptibility testing to amoxicillin, clarithromycin, and gatifloxacin was done in cases of failed eradication. RESULTS A total of 45 patients (22 females:23 males; mean age 44.5 +/- 13 years) were enrolled. Eradication occurred in 38 patients [both per-protocol (PP) and intention-to-treat analysis: 84.4%; 95% CI: 74-95%]. No significant adverse effects were reported. In vitro susceptibility testing showed no secondary resistance to gatifloxacin or amoxicillin in any of the seven nonresponders. Smoking, age, and sex were not predictors of potential eradication failure. CONCLUSIONS A 7-day regimen of gatifloxacin, rabeprazole, and amoxicillin is effective after failed eradication therapy for H. pylori and does not appear to result in secondary resistance. This combination is simple, well tolerated, and may lead to higher compliance and lower costs.
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Affiliation(s)
- Ala I Sharara
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Miehlke S, Hansky K, Schneider-Brachert W, Kirsch C, Morgner A, Madisch A, Kuhlisch E, Bästlein E, Jacobs E, Bayerdörffer E, Lehn N, Stolte M. Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther 2006; 24:395-403. [PMID: 16842467 DOI: 10.1111/j.1365-2036.2006.02993.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.
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Affiliation(s)
- S Miehlke
- Medical Department I, Technical University Hospital, Dresden, Germany.
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Cianci R, Montalto M, Pandolfi F, Gasbarrini GB, Cammarota G. Third-line rescue therapy for Helicobacter pylori infection. World J Gastroenterol 2006; 12:2313-9. [PMID: 16688818 PMCID: PMC4088063 DOI: 10.3748/wjg.v12.i15.2313] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.
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Borody TJ, Pang G, Wettstein AR, Clancy R, Herdman K, Surace R, Llorente R, Ng C. Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection. Aliment Pharmacol Ther 2006; 23:481-8. [PMID: 16441468 DOI: 10.1111/j.1365-2036.2006.02793.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Current 'rescue' therapies provide inadequate Helicobacter pylori eradication rates because of antibiotic resistance. AIM To test the efficacy of a modified triple regimen combining rifabutin, pantoprazole and amoxicillin as rescue therapy for patients in whom eradication of H. pylori had failed standard clarithromycin-based triple therapy. METHODS One hundred and thirty patients (mean age 51.7 +/- 14.8 years) who had failed one or more eradication attempts with omeprazole, clarithromycin and amoxicillin were treated for 12 days with rifabutin 150 mg daily, amoxicillin 1 g or 1.5 g t.d.s, and pantoprazole 80 mg t.d.s. RESULTS The intention-to-treat and per-protocol eradication rates were 90.8/90.8%. Metronidazole or/and clarithromycin resistance had no significant impact on H. pylori eradication rates. A higher overall eradication rate of 96.6% (95% CI: 92.1-101%) was obtained in patients treated with a regimen containing 1.5 g amoxicillin t.d.s compared with 90.7% (95% CI: 82-98.6%) using a regimen with 1 g amoxicillin t.d.s but the difference was not significant. Side-effects reported in 40% of patients were mild. CONCLUSION A 12-day course of low dose of rifabutin with an increased dose of amoxicillin and pantoprazole is well-tolerated and highly effective against dual-resistant H. pylori infection after failure of triple therapy.
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Affiliation(s)
- T J Borody
- Centre for Digestive Disease, NSW, Australia.
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Wong WM, Gu Q, Chu KM, Yee YK, Fung FMY, Tong TSM, Chan AOO, Lai KC, Chan CK, Wong BCY. Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection. Aliment Pharmacol Ther 2006; 23:421-7. [PMID: 16423001 DOI: 10.1111/j.1365-2036.2006.02764.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. METHODS One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. RESULTS Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). CONCLUSION Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.
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Affiliation(s)
- W M Wong
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
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Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006; 23:35-44. [PMID: 16393278 DOI: 10.1111/j.1365-2036.2006.02737.x] [Citation(s) in RCA: 193] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND A quadruple therapy has been generally recommended as rescue regimen for Helicobacter pylori eradication failures. AIMS To systematically review the efficacy and tolerance of levofloxacin-based rescue regimens, and to conduct a meta-analysis of studies comparing these regimens with quadruple therapy for H. pylori eradication failures. METHODS Selection of studies -- levofloxacin-based rescue regimens. For the meta-analysis, randomized-controlled trials comparing levofloxacin-based and quadruple regimens. Search strategy -- electronic and manual. Assessment of study quality -- independently by two reviewers. Data synthesis --'intention-to-treat' eradication rate. RESULTS Mean eradication rate with levofloxacin-based regimens was 80%. Ten-day regimens were more effective than 7-day combinations (81% vs. 73%; P < 0.01). The meta-analysis showed better results with levofloxacin than with the quadruple combination (81% vs. 70%; OR = 1.80; 95% CI = 0.94-3.46). This difference reached statistical significance and heterogeneity markedly decreased when a single outlier study was excluded or when only high-quality studies were considered. Meta-analysis showed less adverse effects with levofloxacin than with quadruple regimen, both overall (19% vs. 44%; OR = 0.27; 95% CI = 0.16-0.46) and regarding severe adverse effects (0.8% vs. 8.4%; OR = 0.20; 95% CI =0.06-0.67). CONCLUSIONS After H. pylori eradication failure, levofloxacin-based rescue regimen is more effective and better tolerated than the generally recommended quadruple therapy. A 10-day combination of levofloxacin-amoxicillin-proton pump inhibitor constitutes an encouraging second-line alternative.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital of 'La Princesa', Madrid, Spain.
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McLoughlin RM, O'Morain CA, O'Connor HJ. Eradication of Helicobacter pylori: recent advances in treatment. Fundam Clin Pharmacol 2005; 19:421-427. [PMID: 16011728 DOI: 10.1111/j.1472-8206.2005.00340.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Helicobacter pylori plays a key role in dyspepsia, peptic ulcer disease, and gastric neoplasia and eradication of the infection has become an important treatment goal in clinical practice. Seven-day proton-pump inhibitor-amoxicillin-clarithromycin triple therapy is the current first-line therapy for H. pylori but eradication rates are compromised by poor compliance and antibiotic resistance. Ten-day sequential treatment may emerge as an alternative first-line therapy. Bismuth-based quadruple therapy is the second-line regimen of choice. Antimicrobial sensitivity testing is not recommended in the routine management of H. pylori infection. Novel triple-therapy regimens containing rifabutin, levofloxacin, or furazolidone may be useful alternatives as second- or third-line therapy.
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Affiliation(s)
- Ramona M McLoughlin
- Department of Gastroenterology, Adelaide and Meath Hospital, Tallaght, Dublin 24 and Faculty of Health Sciences, Trinity College, Dublin, Ireland
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Gatta L, Zullo A, Perna F, Ricci C, De Francesco V, Tampieri A, Bernabucci V, Cavina M, Hassan C, Ierardi E, Morini S, Vaira D. A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses. Aliment Pharmacol Ther 2005; 22:45-49. [PMID: 15963079 DOI: 10.1111/j.1365-2036.2005.02522.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND A standard third-line treatment is lacking, and European guidelines recommend performing culture in these patients. However, the use of this procedure as 'routine practice' is definitively not feasible. AIM To evaluate the eradication rate of a 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses for Helicobacter pylori. METHODS A total of 151 patients with persistent Helicobacter pylori infection after two treatments were studied. Patients were considered positive if two of three endoscopic tests were positive. Susceptibility testing was also performed. Patients received a standard dose of proton-pump inhibitors twice daily, levofloxacin 250 mg twice daily and amoxicillin 1 g twice daily, for 10 days. Endoscopic follow-up was carried out 4-6 weeks after the end of eradication therapy. RESULTS About 76% (95% CI: 68.8-82.3), and 85% (95% CI: 77.5-89.7) of patients were eradicated according to intention-to-treat and per-protocol analysis, respectively. Eradication rates of the strains showed as 92% (95% CI: 83.2-96.7) of those resistant to both metronidazole and clarithromycin but susceptible to levofloxacin. CONCLUSIONS In patients who failed previous regimens, the 10-day levofloxacin-based triple therapy is safe and effective, allowing eradication in almost 80% of the patients.
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Affiliation(s)
- L Gatta
- Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy
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Gisbert JP, Fuentes J, Carpio D, Tito L, Guardiola J, Tomas A, Olivares D, Calvet X. 7-day rescue therapy with ranitidine bismuth citrate after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2005; 21:1249-53. [PMID: 15882246 DOI: 10.1111/j.1365-2036.2005.02465.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Quadruple rescue therapy requires a complex scheme with four drugs. AIM To evaluate the efficacy of ranitidine bismuth citrate-tetracycline-metronidazole rescue regimen, and to compare two different metronidazole dose schemes. METHODS Prospective multicentre study including proton-pump inhibitor + clarithromycin + amoxicillin failures. Rescue regimen included two 7-day treatment: (i) ranitidine bismuth citrate (400 mg b.d.)-tetracycline (500 mg q.d.s.)-metronidazole (500 mg t.d.s.; RTM1); or (ii) the same regimen but with metronidazole 250 mg q.d.s. (RTM2). Eradication was confirmed with (13)C-urea breath test. RESULTS A total of 150 patients were included (58 RTM1, 92 RTM2). All patients but two (one in each group) returned after treatment. About 86% in group RTM1 and 95% in RTM2 correctly took all the medications (P = 0.076). Per-protocol eradication rates with RTM1 and RTM2 were 74 (95% CI: 60-84) and 69% (59-78). The intention-to-treat eradication rates were 64 (51-75) and 70% (59-78; P > 0.05). The type of regimen was not associated with eradication in the multivariate analysis. Adverse effects were more frequent with RTM1 (41%) than with RTM2 (30%; P > 0.05). CONCLUSION Seven-day triple rescue therapy with ranitidine bismuth citrate-tetracycline-metronidazole is effective for Helicobacter pylori eradication, and represents an encouraging alternative to quadruple therapy, with the advantage of simplicity. The administration of metronidazole every 6 h (together with tetracycline), and at a low dose (250 mg), achieves similar efficacy and is probably associated with a better compliance and a lower incidence of adverse effects.
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Affiliation(s)
- J P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, Spain.
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Köksal AS, Parlak E, Filik L, Yolcu OF, Odemiş B, Ulker A, Saşmaz N, Ozden A, Sahin B. Ranitidine bismuth citrate-based triple therapies as a second-line therapy for Helicobacter pylori in Turkish patients. J Gastroenterol Hepatol 2005; 20:637-42. [PMID: 15836716 DOI: 10.1111/j.1440-1746.2005.03801.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline is recommended as the optimal second-line therapy of Helicobacter pylori infection in the Maastricht Consensus Report. The aim of the present paper was to evaluate the efficacy of ranitidine bismuth citrate (RBC)-based regimens as second-line therapies after failure of the standard Maastricht triple therapy. MATERIALS AND METHODS One hundred and sixteen H. pylori-positive patients were given omeprazole 20 mg b.d., clarithromycin 500 mg b.d., and amoxicillin 1 g b.d for 10 days. Patients remaining H. pylori-positive (n = 29) were combined with 27 patients enrolled after an initial eradication failure from proton-pump inhibitor (PPI), amoxicillin and clarithromycin therapy for at least 7 days and were randomly given one of the following second-line 10-day treatments: RBC 400 mg b.d., amoxicillin 1 g b.d and clarithromycin 500 mg b.d. (RAC group, n = 28) and RBC 400 mg b.d., metronidazole 500 mg b.d and tetracycline 500 mg b.d. (RMT group, n = 28). Eradication was assessed by either histology and rapid urease test or (13)C urea breath test 8 weeks after therapy. RESULTS The eradication rate of first-line Maastricht therapy was 67% for intention-to-treat analysis (95% confidence interval [CI]: 58-75). Per-protocol and intention-to-treat eradication was achieved in 60.7% of patients (95%CI: 42-79) in the RAC group and in 85.7% of patients (95%CI: 73-98) in the RMT group (P = 0.03). Fifty-three percent of patients in the RAC and 50% of patients in the RMT group experienced at least one slight side-effect (P = 0.6). CONCLUSIONS RMT is an effective and well-tolerated second-line therapy after H. pylori eradication failure from PPI, amoxicillin, and clarithromycin.
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Affiliation(s)
- Aydin S Köksal
- Department of Gastroenterology, Türkiye Yüksek Ihtisas Hospital, Ankara, Turkey.
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Mirbagheri SA, Sohrabpour AA, Hasibi M, Moghimi B, Mohamadnejad M. 14C-urea breath test in patients undergoing anti-tuberculosis therapy. World J Gastroenterol 2005; 11:1712-4. [PMID: 15786557 PMCID: PMC4305961 DOI: 10.3748/wjg.v11.i11.1712] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Urea breath test (UBT) is a non-invasive diagnostic test for detecting the presence of Helicobacter pylori (H pylori). In this study we evaluated the effect of anti-tuberculosis therapy on the results of 14C-UBT.
METHODS: Patients, with the diagnosis of tuberculosis (TB) who had a positive UBT at the point of starting anti-TB therapy, were included. None had a history of peptic ulcer disease or had taken antibiotics, bismuth compounds and/or PPI in the previous month. 14C-UBT was repeated at the end of the second month and the end of treatment period and one month after completion of treatment course.
RESULTS: Thirty-five patients (23 males) were enrolled. 14C-UBT was negative in all 35 patients (100%) at the end of the second month and remained negative in 30 cases (85.7%) at the end of the treatment course. One month after completion of treatment course, UBT remained negative in 13 patients (37.1%).
CONCLUSION: Our report underscores the need for caution while interpreting urea breath test results in patients undergoing anti-TB therapy. Furthermore, the combination of drugs used in this study resulted in H pylori eradication in a minority of patients.
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Affiliation(s)
- Sayed Amir Mirbagheri
- Department of Gastroenterology, Amir-Alam General Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Qasim A, Sebastian S, Thornton O, Dobson M, McLoughlin R, Buckley M, O'Connor H, O'Morain C. Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients. Aliment Pharmacol Ther 2005; 21:91-96. [PMID: 15644050 DOI: 10.1111/j.1365-2036.2004.02210.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Optimal management approach is not well defined for subjects who fail initial first- and second-line Helicobacter pylori eradication attempts and are dealt on a case-by-case basis by the specialists. AIM To evaluate the efficacy and safety of standard and 'rescue' eradication therapies at primary and secondary care levels. METHODS H. pylori infected dyspepsia patients referred to our C13 urea breath testing laboratory between January 1999 to February 2002 were included. Eradication failure at secondary care level was treated using strategies including antibiotic sensitivity testing and the use of rifabutin- and furazolidone-based therapies. RESULTS 3280 patients received standard first-line eradication therapy, which was successful in 2530 (77%) patients. Second-line therapy (bismuth-based 'quadruple') or triple therapy (altering constituent antibiotics) was successful in 56% of 270 treated patients. Subsequent eradication attempts using rifabutin-based (n = 34) and furazolidone-based (n = 10) regimens were successful in 38% and 60% patients respectively. H. pylori eradication rates were significantly different for guidelines compliant (94.8%) and non-compliant (82%) groups (P = 0.0001). H. pylori eradication rates for non-ulcer dyspepsia (40%) and peptic ulcer disease (36%) were not significantly different. CONCLUSIONS Available H. pylori eradication therapies remain very effective and compliance to guidelines achieves high success rates. Furazolidone-based 'rescue' regimen achieved high eradication rates after failure of the standard first-line, second-line and rifabutin-based therapies.
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Affiliation(s)
- Asghar Qasim
- Gastroenterology Department, Adelaide and Meath Hospital, Tallaght, Dublin, Ireland
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Abstract
The discovery that most stomach diseases are a consequence of an Helicobacter pylori infection has completely changed the management of stomach diseases. Antibacterials are the treatment of choice in addition to proton pump inhibitors (PPIs) or ranitidine bismuth. We are now faced with the problem of antimicrobial resistance, which is the main cause of treatment failure. H. pylori acquires resistance essentially via point mutations, and today this phenomenon is found with most antibacterials. The most important resistance to consider is that to clarithromycin, since it is the first-choice antibacterial and clarithromycin resistance is highly clinically significant. Quadruple therapy or triple therapies with amoxicillin-metronidazole or tetracycline-metronidazole and a PPI or ranitidine bismuth can then be used despite a possible resistance to metronidazole if the strain is resistant to clarithromycin. Resistance to both clarithromycin and metronidazole may lead to the use of other combinations, i.e. amoxicillin-rifabutin, amoxicillin-levofloxacin or amoxicillin-furazolidone. Resistance to any of these drugs means their use must be avoided. In some instances, it may also be advisable to prescribe amoxicillin as the sole antibacterial, or to use a quadruple therapy with furazolidone instead of metronidazole. Although it is theoretically possible to cure a drug-resistant H. pylori infection, a practical limitation is the availability of the drugs in certain countries. Furthermore, the progressive increase in drug resistance warrants the need for new antibacterials in the near future.
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Affiliation(s)
- Francis Mégraud
- Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, Bordeaux, France.
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Bochenek WJ, Peters S, Fraga PD, Wang W, Mack ME, Osato MS, El-Zimaity HMT, Davis KD, Graham DY. Eradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies. Helicobacter 2003; 8:626-42. [PMID: 14632678 DOI: 10.1111/j.1523-5378.2003.00179.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
AIM To compare the short-term (7-day) safety and efficacy of two triple-therapy regimens using pantoprazole with those of two dual-therapy regimens (one with pantoprazole and one without), for Helicobacter pylori eradication in patients with peptic ulcer disease. METHODS H. pylori infection was identified by rapid urease (CLOtest), and confirmed by histology and culture. Patients were enrolled into one of two randomized, double-blind, multicenter, parallel-group studies. In study A, patients received oral pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg (PCM); pantoprazole, clarithromycin and amoxicillin 1000 mg (PCA); or pantoprazole and clarithromycin (PC). In study B, patients received PCM, PCA, PC, or clarithromycin and metronidazole without pantoprazole (CM). Treatments were given twice daily for 7 days. H. pylori status after therapy was assessed by histology and culture at 4 weeks after completing the course of study treatment. Modified intent-to-treat (MITT; each study: n = 424, n = 512) and per-protocol (PP; each study: n = 371, n = 454) populations were analyzed. The MITT population comprised all patients whose positive H. pylori status was confirmed by culture and histology; the PP population comprised patients who also complied with > or = 85% of study medication doses. RESULTS A total of 1016 patients were enrolled. Cure rates among patients with clarithromycin-susceptible H. pylori strains were 82 and 86% for PCM, and 72 and 71% for PCA, in studies A and B, respectively. Cure rates among patients with metronidazole-susceptible H. pylori strains were 82 and 87% for PCM, and 71 and 69% for PCA, in studies A and B, respectively. The combined eradication rates observed with the PCM regimen were superior to those of all other regimens tested. Side-effects were infrequent and mild. CONCLUSIONS PCM had the highest overall eradication rate in these two studies examining 7-day treatment regimens. All regimens were safe and well tolerated.
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Gisbert JP, Calvet X, Bujanda L, Marcos S, Gisbert JL, Pajares JM. 'Rescue' therapy with rifabutin after multiple Helicobacter pylori treatment failures. Helicobacter 2003; 8:90-94. [PMID: 12662375 DOI: 10.1046/j.1523-5378.2003.00128.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
AIM Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A 'rescue' therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin-based regimen in patients with two consecutive H. pylori eradication failures. DESIGN Prospective multicenter study. PATIENTS Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. INTERVENTION A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. OUTCOME H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy. RESULTS Fourteen patients have been included. Mean age +/- SD was 42 +/- 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per-protocol and intention-to-treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49-95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. CONCLUSION Rifabutin-based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline.
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Affiliation(s)
- Javier P Gisbert
- Department of Gastroenterology, La Princesa University Hospital, Madrid, Spain
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Abstract
Review of the recently published data on Helicobacter pylori management highlights various interesting aspects. Current H. pylori eradication guidelines generally suggest a noninvasive 'test and treat' strategy for all dyspeptic patients with certain age limits depending on the local gastric neoplasia risk. According to the 'Maastricht 2-2000 Consensus Report' treatment should be thought of as a 'package' considering first- and second-line eradication therapies together. Various centres have published their results using novel antimicrobial formulations and 'rescue' and 'sequential' therapies. Review suggests that care at the specialist level remains a challenge and guidelines are deficient particularly as regards the selection and duration of eradication therapies. Results indicate that differences for CYP2C19 genotype and the selection of proton pump inhibitors have no significant role in determining eradication rates whereas antibiotic resistance and socio-economic factors play a variable role according to different geographical areas. Compliance remains an important factor in determining clinical outcome at the primary and secondary levels worldwide.
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Affiliation(s)
- Francesco Perri
- Department of Internal Medicine, 'Casa Sollievo della Sofferenza' IRCCS, San Giovanni Rotondo, Italy.
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Abstract
For the therapeutic management of Helicobacter pylori infection, the Maastricht 2-2000 Consensus Report have introduced the concept of the 'treatment package' that considers first- and second-line eradication therapies together. According to this consensus statement, the first-line therapy for H. pylori eradication is a combination of the proton pump inhibitors (PPI) or ranitidine bismuth citrate (RBC) and claritromycin plus either amoxicillin or metronidazole. The second-line treatment is suggested to be PPI-quadruple therapy for a minimum of 7 days. If bismuth compounds are not available, PPI-based triple therapy will have to be used as a second-line treatment only after susceptibility testing. Since no considerable progress has been made during the past year in treatment regimens, there is still a need for new compounds that are specific for H. pylori, which could constitute future therapies.
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Affiliation(s)
- Franco Bazzoli
- 2nd Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.
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Affiliation(s)
- Sebastian Suerbaum
- Institute of Hygiene and Microbiology, University of Würzburg, Würzburg, Germany
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