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Shih CA, Shie CB, Hsu PI. Update on the first-line treatment of Helicobacter pylori infection in areas with high and low clarithromycin resistances. Therap Adv Gastroenterol 2022; 15:17562848221138168. [PMID: 36458050 PMCID: PMC9706057 DOI: 10.1177/17562848221138168] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 10/24/2022] [Indexed: 11/23/2022] Open
Abstract
Current international consensuses on Helicobacter pylori eradication therapy recommend that only regimens that reliably produce eradication rates of ⩾90% should be used for empirical treatment. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication Survey also showed that the accepted minimal eradication rate in H. pylori-infected patients was 91%. According to efficacy prediction model, the per-protocol eradication rates of 7-day and 14-day standard triple therapies fall below 90% when clarithromycin resistance rate ⩾5%. Several strategies including bismuth-containing, non-bismuth-containing quadruple therapies (including sequential, concomitant, hybrid and reverse hybrid therapies), high-dose dual therapy and vonoprazan-based triple therapy have been proposed to increase the eradication rate of H. pylori infection. According to efficacy prediction model, the eradication rate of 14-day concomitant therapy, 14-day hybrid therapy and 7-day vonoprazan-based triple therapy is less than 90% if the frequency of clarithromycin-resistant strains is higher than 90%, 58% and 23%, respectively. To meet the recommendation of the consensus report and patients' expectation, local surveillance networks for resistance of H. pylori to clarithromycin are required to select appropriate eradication regimens in each geographic region. In areas with low (<5%) clarithromycin resistance (e.g. Sweden, Philippine, Myanmar and Bhutan), 7-day and 14-day standard triple therapies can be adopted for the first-line treatment of H. pylori infection with eradication rates of ⩾90%. In areas with high (⩾5%) clarithromycin resistance (most other countries worldwide) or unknown clarithromycin resistance, 14-day hybrid, 14-day reverse hybrid, 14-day concomitant and 10- to 14-day bismuth quadruple therapy can be used to treat H. pylori infection.
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Affiliation(s)
- Chih-An Shih
- Division of Gastroenterology and Hepatology,
Department of Internal Medicine, Antai Medical Care Corporation, Antai
Tian-Sheng Memorial Hospital, Pingtung County
- Department of Nursing, Meiho University,
Pingtung County
| | - Chang-Bih Shie
- Division of Gastroenterology, Department of
Internal Medicine, An Nan Hospital, China Medical University, No. 66, Sec.
2, Changhe Rd., Annan Dist., Tainan City, 70965
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology,
Department of Internal Medicine, An Nan Hospital, China Medical University,
No. 66, Sec. 2, Changhe Rd., Annan Dist., Tainan City, 70965
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Gisbert JP, Alcedo J, Amador J, Bujanda L, Calvet X, Castro-Fernández M, Fernández-Salazar L, Gené E, Lanas Á, Lucendo AJ, Molina-Infante J, Nyssen OP, Pérez-Aisa A, Puig I. V Spanish Consensus Conference on Helicobacter pylori infection treatment. GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:392-417. [PMID: 34629204 DOI: 10.1016/j.gastrohep.2021.07.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 06/30/2021] [Accepted: 07/16/2021] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | - Javier Alcedo
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Zaragoza, España
| | - Javier Amador
- Medicina de Familia, Centro de Salud Los Ángeles, Dirección Asistencial Centro, SERMAS, Madrid, España
| | - Luis Bujanda
- Servicio de Aparato Digestivo, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Xavier Calvet
- Servicio de Aparato Digestivo, Hospital Parc Taulí, Universitat Autónoma de Barcelona, CIBEREHD, Sabadell, Barcelona, España
| | | | - Luis Fernández-Salazar
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Valladolid, Gerencia Regional de Salud (SACYL), Universidad de Valladolid, Valladolid, España
| | - Emili Gené
- Servicio de Urgencias, Hospital Parc Taulí Sabadell, CIBEREHD, Universitat Internacional de Catalunya, Barcelona, España
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, Instituto de Investigación Sanitaria de Aragón (IIS Aragón), CIBEREHD, Zaragoza
| | - Alfredo J Lucendo
- Servicio de Aparato Digestivo, Hospital General de Tomelloso, CIBEREHD, Ciudad Real, España
| | - Javier Molina-Infante
- Servicio de Aparato Digestivo, Hospital Universitario de Cáceres, CIBEREHD, Cáceres, España
| | - Olga P Nyssen
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
| | - A Pérez-Aisa
- Servicio de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Ignasi Puig
- Servicio de Aparato Digestivo, Althaia Xarxa Assistencial Universitària de Manresa, Universitat de Vic-Universitat Central de Catalunya (UVicUCC), Manresa, Barcelona, España
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Hernández-Ochoa B, Navarrete-Vázquez G, Aguayo-Ortiz R, Ortiz-Ramírez P, Morales-Luna L, Martínez-Rosas V, González-Valdez A, Gómez-Chávez F, Enríquez-Flores S, Wong-Baeza C, Baeza-Ramírez I, Pérez de la Cruz V, Gómez-Manzo S. Identification and In Silico Characterization of Novel Helicobacter pylori Glucose-6-Phosphate Dehydrogenase Inhibitors. Molecules 2021; 26:molecules26164955. [PMID: 34443540 PMCID: PMC8401736 DOI: 10.3390/molecules26164955] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/12/2021] [Accepted: 08/13/2021] [Indexed: 11/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a pathogen that can remain in the stomach of an infected person for their entire life. As a result, this leads to the development of severe gastric diseases such as gastric cancer. In addition, current therapies have several problems including antibiotics resistance. Therefore, new practical options to eliminate this bacterium, and its induced affections, are required to avoid morbidity and mortality worldwide. One strategy in the search for new drugs is to detect compounds that inhibit a limiting step in a central metabolic pathway of the pathogen of interest. In this work, we tested 55 compounds to gain insights into their possible use as new inhibitory drugs of H. pylori glucose-6-phosphate dehydrogenase (HpG6PD) activity. The compounds YGC-1; MGD-1, MGD-2; TDA-1; and JMM-3 with their respective scaffold 1,3-thiazolidine-2,4-dione; 1H-benzimidazole; 1,3-benzoxazole, morpholine, and biphenylcarbonitrile showed the best inhibitory activity (IC50 = 310, 465, 340, 204 and 304 μM, respectively). We then modeled the HpG6PD protein by homology modeling to conduct an in silico study of the chemical compounds and discovers its possible interactions with the HpG6PD enzyme. We found that compounds can be internalized at the NADP+ catalytic binding site. Hence, they probably exert a competitive inhibitory effect with NADP+ and a non-competitive or uncompetitive effect with G6P, that of the compounds binding far from the enzyme’s active site. Based on these findings, the tested compounds inhibiting HpG6PD represent promising novel drug candidates against H. pylori.
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Affiliation(s)
- Beatriz Hernández-Ochoa
- Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (B.H.-O.); (V.M.-R.)
- Laboratorio de Inmunoquímica, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Ciudad de México 06720, Mexico
| | - Gabriel Navarrete-Vázquez
- Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Chamilpa, Cuernavaca, Morelos 62209, Mexico;
| | - Rodrigo Aguayo-Ortiz
- Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico;
| | - Paulina Ortiz-Ramírez
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico; (P.O.-R.); (L.M.-L.)
| | - Laura Morales-Luna
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico; (P.O.-R.); (L.M.-L.)
- Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
| | - Víctor Martínez-Rosas
- Programa de Posgrado en Biomedicina y Biotecnología Molecular, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (B.H.-O.); (V.M.-R.)
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico; (P.O.-R.); (L.M.-L.)
| | - Abigail González-Valdez
- Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico;
| | - Fernando Gómez-Chávez
- Laboratorio de Inmunología Experimental, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico;
- Cátedras CONACyT-Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico
- Departamento de Formación Básica Disciplinaria, Escuela Nacional de Medicina y Homeopatía del Instituto Politécnico Nacional, Ciudad de México 07320, Mexico
| | - Sergio Enríquez-Flores
- Laboratorio de EIMyT, Grupo de Investigación en Biomoléculas y Salud Infantil, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico;
| | - Carlos Wong-Baeza
- Laboratorio de Biomembranas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (C.W.-B.); (I.B.-R.)
| | - Isabel Baeza-Ramírez
- Laboratorio de Biomembranas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (C.W.-B.); (I.B.-R.)
| | - Verónica Pérez de la Cruz
- Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”, Ciudad de México 14269, Mexico;
| | - Saúl Gómez-Manzo
- Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Ciudad de México 04530, Mexico; (P.O.-R.); (L.M.-L.)
- Correspondence: ; Tel.: +52-55-1084-0900 (ext. 1442)
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Galal AMF, Mohamed HS, Abdel-Aziz MM, Hanna AG. Development, synthesis, and biological evaluation of sulfonyl-α-l-amino acids as potential anti-Helicobacter pylori and IMPDH inhibitors. Arch Pharm (Weinheim) 2021; 354:e2000385. [PMID: 33576040 DOI: 10.1002/ardp.202000385] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/10/2021] [Accepted: 01/15/2021] [Indexed: 12/16/2022]
Abstract
Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of DNA and RNA, and it has been exploited as a promising target for antimicrobial therapy. The present study discusses the development and synthesis of a series of sulfonyl-α-l-amino acids coupled with the anisamide scaffold and evaluates their activities as anti-Helicobacter pylori and IMPDH inhibitors. Twenty derivatives were synthesized and their structures were established by high-resolution mass spectrometry and 1 H and 13 C nuclear magnetic resonance measurements. Four compounds (6, 10, 11, and 21) were found to be the most potent and selective molecules in the series with minimum inhibitory concentration (MIC) values <17 µM, which were selected to test their inhibitory activities against HpIMPDH and human (h)IMPDH2 enzymes. In all tests, amoxicillin and clarithromycin were used as reference drugs. Compounds 6 and 10 were found to have a promising activity against the HpIMPDH enzyme, with IC50 = 2.42 and 2.56 µM, respectively. Moreover, the four compounds were found to be less active and safer against hIMPDH2 than the reference drugs, with IC50 > 17.17 µM, which makes sure that their selectivity is toward HpIMPDH and reverse to that of amoxicillin and clarithromycin. Also, the synergistic antibacterial activity of compounds 6, 10, amoxicillin, and clarithromycin was investigated in vitro. The combination of amoxicillin/compound 6 (2:1 by weight) exhibited a significant antibacterial activity against H. pylori, with MIC = 0.12 µg/ml. The molecular docking study and ADMET analysis of the most active compounds were used to elucidate the mode-of-action mechanism.
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Affiliation(s)
- Alaaeldin M F Galal
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza, Egypt
| | - Hanaa S Mohamed
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Centre, Cairo, Egypt
| | - Marwa M Abdel-Aziz
- Regional Center for Mycology and Biotechnology (RCMB), Al-Azhar University, Cairo, Egypt
| | - Atef G Hanna
- Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, Giza, Egypt
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Hu CT. High-dose dual therapy versus bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection – A review of the strengths, weaknesses, and proposed solutions. Tzu Chi Med J 2021; 34:303-309. [PMID: 35912055 PMCID: PMC9333101 DOI: 10.4103/tcmj.tcmj_185_21] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/19/2021] [Accepted: 08/17/2021] [Indexed: 11/04/2022] Open
Abstract
Helicobacter pylori is the principal cause of peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. The first treatment to H. pylori infection is dual therapy (a bismuth compound plus metronidazole). On the launch of omeprazole in 1988, dual therapy became omeprazole and amoxicillin (low dose). The poor H. pylori eradication rates by either bismuth-based or low-dose dual therapy drove more combinations of antibiotics were needed. Antibiotic resistance, especially clarithromycin and metronidazole, has made bismuth-containing quadruple therapy (BCQT) a savior for first-line and second-line treatments. However, its complicated dosing regimen commonly causes more adverse events and poor drug compliance. Thus, high-dose dual therapy (HDDT) has been re-arising. This article reviews the strengths and weaknesses of HDDT versus BCQT with proposed solutions.
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Park JH, Kim D, Choe JW, Kim SY, Jung SW, Hyun JJ, Jung YK, Koo JS, Yim HJ, Lee SW. First-line Helicobacter pylori Eradication Rate of the 10-day Hybrid Therapy. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2020. [DOI: 10.7704/kjhugr.2020.0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background/Aims: To improve the eradication rate of a first-line therapy for Helicobacter pylori infection, alternate regimens such as sequential, concomitant, and hybrid therapies have been tried. The aim of this study was to evaluate the eradication rate of the 10-day hybrid therapy as a first-line therapy.Materials and Methods: This retrospective study enrolled 124 patients from the Korea University Ansan Hospital between April 2016 and December 2019. The 10-day hybrid therapy comprised 5 days of dual therapy (proton pump inhibitor [PPI] standard dose and amoxicillin 1 g, twice daily) followed by 5 days of quadruple therapy (PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily). We compared the 10-day hybrid therapy with the 10-day concomitant therapy comprising PPI, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, twice daily. Eradication was assessed by a <sup>13</sup>C-urea breath test or gastroscopic biopsy at least 4 weeks after treatment completion.Results: The eradication rates of the 10-day hybrid and concomitant therapies were 74.2% (46/62) and 67.7% (42/62), respectively, in the intention-to-treat (ITT) analysis and 88.5% (46/52) and 82.4% (42/51), respectively, in the per-protocol (PP) analysis. There was no significant difference in the eradication rates between the two groups in the ITT (P=0.429) and PP analysis (P=0.380). Adverse events developed in 75.0% and 70.6% of patients in the hybrid and concomitant groups, respectively, but there was no significant difference (P=0.615).Conclusions: The 10-day hybrid therapy can be an option for a first-line therapy of Helicobacter pylori infection.
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Jaka H, Mueller A, Kasang C, Mshana SE. Predictors of triple therapy treatment failure among H. pylori infected patients attending at a tertiary hospital in Northwest Tanzania: a prospective study. BMC Infect Dis 2019; 19:447. [PMID: 31113384 PMCID: PMC6528280 DOI: 10.1186/s12879-019-4085-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 05/14/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H.pylori) infection is a common medical problem in resource limited areas. The treatment outcome after triple therapy has not been well studied in developing countries and preliminary data suggests a high rate of treatment failure. This study investigated the triple therapy treatment failure rate and associated factors among dyspeptic patients receiving H. pylori first line therapy at a tertiary hospital, Tanzania. METHODS A prospective study in the Gastroenterology unit of the Bugando Medical Centre (BMC) was conducted between October 2015 and May 2017. All dyspeptic patients with stool antigen tests positive for H.pylori were given first line therapy, and stool antigen testing was repeated within 7 days and 5 weeks after completion of the treatment. Biopsies were taken before initiation of therapy and analysed for clarithromycin and quinolone resistance mutations using polymerise chain reaction (PCR) and sequencing. Adherence and other social-demographic characteristics were documented. RESULTS A total of 210 patients were enrolled; the median age was 35 years (interquartile range, 27-48). First line treatment failure as defined by positive stool antigen 5 weeks post treatment was observed in 65/210 (31%) of patients. Independent predictors of first line treatment failure were presence of clarithromycin resistance mutations (OR: 23.12, 95% CI (9.38-56.98), P < 0.001) and poor adherence (OR: 7.39, 95% CI (3.25-16.77), P < 0.001). The sensitivity and specificity of stool antigen testing within 7 days after completion therapy in detecting treatment failure was 100 and 93.2%, respectively. CONCLUSION Nearly one-third of patients with clarithromycin resistance mutations and poor adherence develop first line treatment failure. Routine stool antigen testing within seven days after completion of therapy can be considered in order to initiate second line treatment early to prevent associated morbidities.
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Affiliation(s)
- Hyasinta Jaka
- Department of Internal medicine-Gastroenterology and Hepatology unit, Catholic University of Health and Allied Sciences, P.O.Box 1464, Bugando, Mwanza, Tanzania.
| | - Andreas Mueller
- Tropenmedizin, Missionsärztliche Klinik, Salvatorstr. 7, 97074, Würzburg, Germany
| | - Christa Kasang
- Medical Mission Institute, Hermann Schell Str. 7, 97074, Würzburg, Germany
| | - Stephen E Mshana
- Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences, P.O.Box 1464, Bugando, Mwanza, Tanzania
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Yeo YH, Shiu SI, Ho HJ, Zou B, Lin JT, Wu MS, Liou JM, Wu CY. First-line Helicobacter pylori eradication therapies in countries with high and low clarithromycin resistance: a systematic review and network meta-analysis. Gut 2018; 67:20-27. [PMID: 27670375 DOI: 10.1136/gutjnl-2016-311868] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 09/01/2016] [Accepted: 09/02/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To determine the optimal regimen of different first-line Helicobacter pylori eradication therapies according to the clarithromycin resistance rate. DESIGN Electronic search for articles published between January 2005 and April 2016. Randomised, controlled trials that reported the effectiveness of first-line eradication therapies in treatment-naïve adults were included. Two independent reviewers performed articles screening and data extraction. Network and traditional meta-analyses were conducted using the random effect model. Subgroup analyses were performed to determine the ranking of regimens in countries with high (>15%) and low (<15%) clarithromycin resistance. Data including adverse events and therapeutic cure rate were also extracted and analysed. RESULTS 117 trials (totally 32 852 patients) for 17 H. pylori eradication regimens were eligible for inclusion. Compared with 7-day clarithromycin-based triple therapy, sequential therapy (ST) for 14 days had the highest effectiveness (OR=3.74, 95% CrI 2.37 to 5.96). ST-14 (OR=6.53, 95% CrI 3.23 to 13.63) and hybrid therapy (HY) for 10 days or more (OR=2.85, 95% CrI 1.58 to 5.37) represented the most effective regimen in areas with high and low clarithromycin resistance, respectively. The effectiveness of standard triple therapy was below therapeutic eradication rate in most of the countries. Longer duration was associated with higher eradication rate, but with a higher risk of events that lead to discontinuation. CONCLUSIONS ST and HY appeared to be the most effective therapies in countries with high and low clarithromycin resistance, respectively. The clinical decision for optimal regimen can be supported by referring to the rank ordering of relative efficacies stratified by local eradication rates, antibiotic resistance and safety profile. TRIAL REGISTRATION NUMBER CRD42015025445.
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Affiliation(s)
- Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.,Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Sz-Iuan Shiu
- Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Hsiu J Ho
- Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Biyao Zou
- Blatvatnik School of Government, University of Oxford, Oxford, UK
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.,Center for Health Policy Research and Development, Miaoli, Taiwan
| | - Ming-Shiang Wu
- National Cancer Institute, National Health Research Institutes, Miaoli, Taiwan
| | - Jyh-Ming Liou
- National Cancer Institute, National Health Research Institutes, Miaoli, Taiwan
| | - Chun-Ying Wu
- Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.,National Cancer Institute, National Health Research Institutes, Miaoli, Taiwan.,Faculty of Medicine and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Public Health and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.,Department of Life Sciences and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan
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Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis. Eur J Clin Pharmacol 2017; 74:1-13. [DOI: 10.1007/s00228-017-2347-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Accepted: 09/29/2017] [Indexed: 02/06/2023]
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10
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Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212-239. [PMID: 28071659 DOI: 10.1038/ajg.2016.563] [Citation(s) in RCA: 990] [Impact Index Per Article: 123.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 10/07/2016] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.
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Affiliation(s)
- William D Chey
- Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, USA
| | | | - Colin W Howden
- Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Steven F Moss
- Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
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Gisbert JP, Molina-Infante J, Amador J, Bermejo F, Bujanda L, Calvet X, Castro-Fernández M, Cuadrado-Lavín A, Elizalde JI, Gene E, Gomollón F, Lanas Á, Martín de Argila C, Mearin F, Montoro M, Pérez-Aisa Á, Pérez-Trallero E, McNicholl AG. IV Spanish Consensus Conference on Helicobacter pylori infection treatment. GASTROENTEROLOGIA Y HEPATOLOGIA 2016; 39:697-721. [PMID: 27342080 DOI: 10.1016/j.gastrohep.2016.05.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Revised: 05/18/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.
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Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España.
| | | | - Javier Amador
- Medicina de Familia, Centro de Salud Los Ángeles, Madrid, España
| | - Fernando Bermejo
- Servicio de Aparato Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España
| | - Luis Bujanda
- Servicio de Digestivo, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Xavier Calvet
- Servicio de Aparato Digestivo, Hospital Parc Taulí, Universitat Autónoma de Barcelona, CIBEREHD, Sabadell, Barcelona, España
| | | | | | - J Ignasi Elizalde
- Servicio de Aparato Digestivo, Hospital Clínic, CIBEREHD, Barcelona, España
| | - Emili Gene
- Servicio de Urgencias, Hospital Parc Taulí Sabadell, CIBEREHD, Universitat Internacional de Catalunya, Sabadell, Barcelona, España
| | - Fernando Gomollón
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, España
| | - Ángel Lanas
- Servicio de Aparato Digestivo, Hospital Clínico Universitario de Zaragoza, IIS Aragón, CIBEREHD, Zaragoza, España
| | - Carlos Martín de Argila
- Servicio de Aparato Digestivo, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España
| | - Fermín Mearin
- Servicio de Aparato Digestivo, Centro Médico Teknon, Barcelona, España
| | - Miguel Montoro
- Servicio de Aparato Digestivo, Hospital San Jorge, Huesca, España
| | - Ángeles Pérez-Aisa
- Servicio de Aparato Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, España
| | - Emilio Pérez-Trallero
- Servicio de Microbiología, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, CIBEREHD, San Sebastián, España
| | - Adrián G McNicholl
- Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, España
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Dolapcioglu C, Sayiner M, Akkus EE, Kural A, Dolapcioglu H, Dabak R, Ahishali E. First-line Bismuth-containing Five-day Concomitant Quintuple Therapy for Helicobacter Pylori Eradication. Helicobacter 2016; 21:100-5. [PMID: 26103789 DOI: 10.1111/hel.12241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Widespread use of antibiotics has resulted in increased rates of antibiotic resistance and decreased rates of Helicobacter pylori (H. pylori) eradication, leading to a search for newer therapeutic options. This study aimed to examine the efficacy, tolerability, and patient compliance of a first-line bismuth-containing 5-day concomitant quintuple therapy. MATERIALS AND METHODS This prospective study included 144 eradication treatment naïve H. pylori positive patients with dyspeptic complaints. Patients received the following concomitant quintuple therapy for 5 days: bismuth subcitrate 300 mg q.i.d, omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. Eradication was assessed with H. pylori stool antigen test or urea-breath test 6 weeks after the completion of therapy. RESULTS Treatment compliance rate in this study was 97.2%. Intention to treat and per-protocol eradication rates were 134/144 (93.1%, 95% CI, 88.9-97.2) and 134/140 (95.7%, 95% CI, 92.2-98.6), respectively. Side effect was reported by 8.5% of the patients that attended follow-up visits, including epigastric pain (2.8%), nausea/vomiting (2.1%), diarrhea (1.4%), taste disturbance (1.4%), and fatigue (0.7%). CONCLUSIONS Bismuth-containing, short course, quintuple concomitant therapy appears to be an effective and safe therapeutic option for the first-line H. pylori eradication, particularly in populations with high resistance.
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Affiliation(s)
- Can Dolapcioglu
- Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
| | - Mehmet Sayiner
- Department of Family Medicine, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
| | - Esra Elif Akkus
- Department of Family Medicine, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
| | - Abdulaziz Kural
- Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
| | - Hatice Dolapcioglu
- Department of Pathology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey
| | - Resat Dabak
- Department of Family Medicine, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
| | - Emel Ahishali
- Department of Gastroenterology, Dr. Lutfi Kirdar Kartal Research and Training Hospital, Istanbul, Turkey
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Comparing the Efficacy of Concomitant Therapy with Sequential Therapy as the First-Line Therapy of Helicobacter pylori Eradication. Gastroenterol Res Pract 2015; 2016:1293649. [PMID: 26823662 PMCID: PMC4707372 DOI: 10.1155/2016/1293649] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 10/01/2015] [Accepted: 10/05/2015] [Indexed: 01/13/2023] Open
Abstract
Background. The decline of Helicobacter pylori (H. pylori) eradication rates with standard triple therapy resulted in a search for novel therapies for first-line therapy of H. pylori infection. Aim. The aim of the study is to compare the efficacy of concomitant therapy with sequential therapy as the first-line therapy of H. pylori eradication. Methods. We reviewed medical records of patients who were confirmed to have H. pylori infection and received eradication treatment from September 2012 to March 2015. The concomitant group was treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. The sequential group was treated with rabeprazole and amoxicillin for 5 days and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. Six weeks after the treatment period, patients in both groups underwent 13C-Urea breath test (UBT) to confirm H. pylori eradication. Results. The eradication rate was 90.3% in the concomitant group and 85.5% in the sequential group. However, the eradication rates between the two groups showed no statistical difference (P = 0.343). Conclusion. No statistical difference was found in eradication rates between the two groups. However, in areas where antibiotic resistance is high, concomitant therapy may be more effective than sequential therapy for H. pylori eradication.
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Georgopoulos SD, Papastergiou V, Karatapanis S. Treatment of Helicobacter Pylori infection: optimization strategies in a high resistance era. Expert Opin Pharmacother 2015; 16:2307-17. [PMID: 26330278 DOI: 10.1517/14656566.2015.1084503] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders and in the prevention of gastric cancer. Due to increasing antimicrobial resistance, performance of standard triple therapies has now declined to unacceptably low levels. AREAS COVERED In this article: i) we critically revise optimization tools aiming to improve the outcome of standard treatments; ii) we provide updated evidence on the efficacy and rationale for the use of several non-bismuth quadruple regimens in clinical practice, recommended as preferred empirical therapies in areas of high clarithromycin resistance. EXPERT OPINION Prolonged (14-day) treatment duration may boost the efficacy of standard triple therapy by approximately 5%. Use of a high-dose PPI and/or new-generation PPIs, rabeprazole and esomeprazole, might improve eradication rates, particularly in regions where the CYP2C19 rapid metabolizer phenotype is prevalent. Adjunctive probiotics may be considered to improve treatment tolerability, though more data are required to better define their role in H. pylori eradication. Among non-bismuth quadruple regimens, both concomitant and sequential therapies are appropriate options for high-resistance settings; however, concomitant therapy appears to be less impaired by dual clarithromycin/metronidazole resistance. Hybrid therapy is a promising new alternative which seems not to be inferior to concomitant therapy.
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Affiliation(s)
- Sotirios D Georgopoulos
- a 1 Athens Medical P. Faliron General Hospital, Department of Gastroenterology , 17562 Athens, Greece +306 9 32 35 62 78 ; +302 1 04 11 53 75 ;
| | - Vasilios Papastergiou
- b 2 General Hospital of Rhodes, First Department of Internal Medicine , 85100 Rhodes, Greece
| | - Stylianos Karatapanis
- b 2 General Hospital of Rhodes, First Department of Internal Medicine , 85100 Rhodes, Greece
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Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection. BIOMED RESEARCH INTERNATIONAL 2015; 2015:163960. [PMID: 26090383 PMCID: PMC4450213 DOI: 10.1155/2015/163960] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Revised: 02/16/2015] [Accepted: 02/16/2015] [Indexed: 12/12/2022]
Abstract
The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid) and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid) for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%). The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P = 0.02), but only seven patients (11.5%) experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.
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Molina-Infante J, Graham DY, Gisbert JP. Editorial: quadruple therapy for H. pylori eradication is better than triple therapy - authors' reply. Aliment Pharmacol Ther 2015; 41:695-6. [PMID: 25736143 DOI: 10.1111/apt.13113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- J Molina-Infante
- Department of Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain.
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Lee JY, Ahn JY, Choi IJ. Historical Perspective ofHelicobacter pyloriTreatment in Korea. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2015. [DOI: 10.7704/kjhugr.2015.15.4.211] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Jong Yeul Lee
- Center for Gastric Cancer, National Cancer Center Hospital, Goyang, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center Hospital, Goyang, Korea
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Abstract
OBJECTIVE To compare the efficacy of sequential therapy, concomitant therapy and hybrid therapy for the treatment of Helicobacter pylori (H. pylori) infection. METHODS PubMed, Web of Science, Medline, Embase, the Cochrane Central Register of Controlled Trials and CNKI were searched up to the end of May 10, 2014 in order to identify all randomized controlled trials (RCTs) reporting the effects of sequential therapy, concomitant therapy and hybrid therapy on H. pylori eradication. The relative risk (RR) of eradicating H. pylori infection after sequential therapy compared with concomitant therapy or hybrid therapy was pooled. The eradication rates were considered both on an intention-to-treat (ITT) and per-protocol (PP) basis. RESULTS A total of 10 RCTs involving 3,501 patients were included. The pooled data suggested that the differences between the three groups were not statistically significant (ITT analysis: sequential therapy vs. concomitant therapy: RR=1.01, 95%confidence interval (CI): 0.97-1.04, sequential therapy vs. hybrid therapy: RR=1.02, 95%CI: 0.85-1.22, concomitant therapy vs. hybrid therapy: RR=1.03, 95%CI: 0.97-1.08; PP analysis: sequential therapy vs. concomitant therapy: RR=1.00, 95%CI: 0.96-1.03, sequential therapy vs. hybrid therapy: RR=0.97, 95%CI: 0.86-1.09, concomitant therapy vs. hybrid therapy: RR=1.01, 95%CI: 0.93-1.10). In the ITT and PP analyses, the overall eradication rates were 84.3% (95%CI: 79.1-89.4) and 86.4% (95%CI: 81.7-91.0) for the sequential therapy group, 86.7% (95%CI: 81.0-92.3) and 89.8% (95%CI: 85.1-94.5) for the concomitant therapy group and 86.6% (95%CI: 82.3-91.0) and 92.7% (95%CI: 90.5-94.9) for the hybrid therapy group, respectively. There were no significant differences among these therapies in terms of the rate of side effects. CONCLUSION The pooled evidence suggests that sequential therapy, concomitant therapy and hybrid therapy are similar with respect to the treatment of H. pylori infection.
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Affiliation(s)
- Lei He
- Department of Gastroenterology, Renmin Hospital of Wuhan University, China
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Heo J, Jeon SW, Jung JT, Kwon JG, Kim EY, Lee DW, Seo HE, Ha CY, Kim HJ, Kim ES, Park KS, Cho KB, Lee SH, Jang BI. A randomised clinical trial of 10-day concomitant therapy and standard triple therapy for Helicobacter pylori eradication. Dig Liver Dis 2014; 46:980-4. [PMID: 25132282 DOI: 10.1016/j.dld.2014.07.018] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 07/07/2014] [Accepted: 07/20/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND As a result of increased resistance to antibiotics, Helicobacter pylori eradication rates using standard triple therapy have been declining. AIM To validate the efficacy and tolerability of a concomitant regimen as a first-line treatment for H. pylori infection. METHODS A total of 348 naïve H. pylori-infected patients from six hospitals in Korea were randomly assigned to concomitant therapy and standard triple therapy groups. The concomitant regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, and 500 mg of clarithromycin, twice daily for 10 days. RESULTS Concomitant and standard eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat (p=0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p=0.016), respectively. The two groups were similar with regard to the incidence of adverse events. CONCLUSIONS Although 10-day concomitant therapy was validated as a suboptimal treatment option for the treatment of H. pylori infection, this regimen is expected to be a promising starting point in the development of an optimal treatment regimen for H. pylori infection.
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Affiliation(s)
- Jun Heo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Seong Woo Jeon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
| | - Jin Tae Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Joong Goo Kwon
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Eun Young Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, South Korea
| | - Dong Wook Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Hyang Eun Seo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Daegu Fatima Hospital, Daegu, South Korea
| | - Chang Yoon Ha
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Hyun Jin Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kyung Sik Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Kwang Bum Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea
| | - Si Hyung Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
| | - Byung Ik Jang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
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Kang BK, Park SM, Kim BW. [New therapeutic strategies against Helicobacter pylori]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2014; 63:146-50. [PMID: 24651587 DOI: 10.4166/kjg.2014.63.3.146] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
The standard therapy for Helicobacter pylori infection in Korea is a triple-drug regimen consisting of a proton pump inhibitor with two antibiotics such as clarithromycin, amoxicillin, and metronidazole. However, as the eradication rate of this regimen has declined over the past decade, this prompted the formulation of new therapeutic regimens. New therapeutic strategies against H. pylori infection that had been tried all over the world include sequential therapy, concomitant therapy, and tailored therapy This article will review the basic concepts and the results of previous clinical trials on the aforementioned new therapeutic regiments.
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Affiliation(s)
- Bong Ku Kang
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon 403-720, Korea
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Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol 2014; 20:5283-93. [PMID: 24833858 PMCID: PMC4017043 DOI: 10.3748/wjg.v20.i18.5283] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly associated with the occurrence of gastrointestinal diseases, including gastric inflammation, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid-tissue lymphoma. Although alternative therapies, including phytomedicines and probiotics, have been used to improve eradication, current treatment still relies on a combination of antimicrobial agents, such as amoxicillin, clarithromycin, metronidazole, and levofloxacin, and antisecretory agents, such as proton pump inhibitors (PPIs). A standard triple therapy consisting of a PPI and two antibiotics (clarithromycin and amoxicillin/metronidazole) is widely used as the first-line regimen for treatment of infection, but the increased resistance of H. pylori to clarithromycin and metronidazole has significantly reduced the eradication rate using this therapy and bismuth-containing therapy or 10-d sequential therapy has therefore been proposed to replace standard triple therapy. Alternatively, levofloxacin-based triple therapy can be used as rescue therapy for H. pylori infection after failure of first-line therapy. The increase in resistance to antibiotics, including levofloxacin, may limit the applicability of such regimens. However, since resistance of H. pylori to amoxicillin is generally low, an optimized high dose dual therapy consisting of a PPI and amoxicillin can be an effective first-line or rescue therapy. In addition, the concomitant use of alternative medicine has the potential to provide additive or synergistic effects against H. pylori infection, though its efficacy needs to be verified in clinical studies.
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De Francesco V, Hassan C, Ridola L, Giorgio F, Ierardi E, Zullo A. Sequential, concomitant and hybrid first-line therapies for Helicobacter pylori eradication: a prospective randomized study. J Med Microbiol 2014; 63:748-752. [PMID: 24586031 DOI: 10.1099/jmm.0.072322-0] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori eradication remains a challenge for physicians. Sequential, concomitant and the hybrid regimens have been proposed as novel, more effective therapies. We compare the efficacy of these therapies. Dyspeptic patients referred for upper endoscopy with H. pylori infection were enrolled. Patients were randomized to receive: (a) sequential therapy - 20 mg omeprazole and 1 g amoxicillin for 5 days, followed by 20 mg omeprazole, 500 mg clarithromycin and 500 mg tinidazole for the successive 5 days; (b) concomitant therapy - 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for either 5 days (5 day concomitant) or 14 days (14 day concomitant); or (c) hybrid therapy - 20 mg omeprazole and 1 g amoxicillin for 7 days, followed by 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for the successive 7 days. All drugs were given twice daily. Bacterial eradication was checked by using a [(13)C]urea breath test. In 'intention-to-treat' analysis, sequential therapy achieved the highest eradication rate, which was higher than that of 5 day concomitant therapy (90 vs 78.1 %; P = 0.02). The success rate did not statistically differ among the sequential and either 14 day concomitant (90 vs 86.3 %; P = not significant) or hybrid therapies (90 vs 82.7 %; P = not significant). The 10 day sequential, 14 day concomitant and 14 day hybrid therapies, but not the 5 day concomitant regimen, achieved similarly high eradication rates. The lower therapeutic cost coupled with the lower number of tablets needed would favour the sequential therapy as the first-line H. pylori treatment in clinical practice.
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Affiliation(s)
- Vincenzo De Francesco
- Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Ospedali Riuniti, Foggia, Italy
| | - Cesare Hassan
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Lorenzo Ridola
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
| | - Floriana Giorgio
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Italy
| | - Angelo Zullo
- Gastroenterology and Digestive Endoscopy, 'Nuovo Regina Margherita' Hospital, Rome, Italy
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Kim KB, Kim YS. Recent Trends ofHelicobacter pyloriEradication Therapy: Focusing on First Line Treatment. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2014. [DOI: 10.7704/kjhugr.2014.14.4.237] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Ki Bang Kim
- Department of Internal Medicine, Eulji University College of Medicine, Daejeon, Korea
| | - Yong Sik Kim
- Department of Internal Medicine, Eulji University College of Medicine, Daejeon, Korea
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Nijevitch AA, Idrisov B, Akhmadeeva EN, Graham DY. Choosing optimal first-line Helicobacter pylori therapy: a view from a region with high rates of antibiotic resistance. Curr Pharm Des 2014; 20:4510-6. [PMID: 24180406 PMCID: PMC5314729 DOI: 10.2174/13816128113196660728] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 10/10/2013] [Indexed: 02/06/2023]
Abstract
Helicobacter pylori is a gram-negative, microaerophilic spiral bacillus that is associated with life-threatening diseases such as gastric cancer, gastric MALT lymphoma, and peptic ulcer disease. The definition of an effective therapy is one that achieves at least a 90% eradication rate on a per-protocol basis with the first attempt. Eradication rates of H. pylori have declined to unacceptable levels worldwide, mostly due to antibiotic resistance and standard triple therapy gradually has lost its efficacy in most counties. However, bismuth quadruple therapy, when prescribed properly, has maintained its effectiveness. Alternative first-line regimens such as sequential and concomitant therapy were developed to substitute for standard triple therapy and were highly effective in the countries where they were developed, but proved susceptible to failure in regions with high rates of antibiotic resistance. Antibiotic resistance rates in Russia are high, however there is lack of data regarding comparative efficacy of first-line eradication options. The authors of this review extrapolate the knowledge of H. pylori first-line eradication options in Russia based on data from other countries, as well as from domestic studies. The available data support use of 14-day regimens with concomitant therapy, bismuth quadruple therapy, or furazolidone quadruple therapy for empiric use in adults. In addition, 14-day levofloxacin-containing therapies could be used if resistance is relatively low or lacking as triple therapy or possibly as a 5-day concomitant levofloxacin therapy.
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Affiliation(s)
| | | | | | - David Y Graham
- Bashkortostan State Medical University, Pediatrics Department, 3 Lenina St., Ufa, Russia, 450008.
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Zullo A, Scaccianoce G, De Francesco V, Ruggiero V, D'Ambrosio P, Castorani L, Bonfrate L, Vannella L, Hassan C, Portincasa P. Concomitant, sequential, and hybrid therapy for H. pylori eradication: a pilot study. Clin Res Hepatol Gastroenterol 2013; 37:647-50. [PMID: 23747131 DOI: 10.1016/j.clinre.2013.04.003] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Revised: 04/06/2013] [Accepted: 04/10/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVE Since the efficacy of the standard triple therapies for Helicobacter pylori eradication has decreased, novel antibiotic regimens have been introduced, including concomitant, sequential, and hybrid therapies. We aimed to compare the cure rates achieved by these new therapy regimens. METHODS This was a multicenter, open-label, pilot study enrolling consecutive non-ulcer dyspepsia patients with H. pylori infection never previously treated for the infection. Patients were randomized to receive one of the following treatments: (a) concomitant therapy: omeprazole 20mg, amoxicillin 1g, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (b) sequential therapy: omeprazole 20mg and amoxicillin 1g for 5 days followed by omeprazole 20mg, clarithromycin 500 mg, and tinidazole 500 mg for 5 days; (c) hybrid therapy: omeprazole 20mg, and amoxicillin 1g for 7 days followed by omeprazole 20mg, amoxicillin 1g, clarithromycin 500 mg, and tinidazole 500 mg, for 7 days. All drugs were administered twice daily. Bacterial eradication was checked 6 weeks after treatment by using a (13)C-urea breath test. A 10-day, second-line therapy with omeprazole 20mg, levofloxacin 250 mg, and amoxicillin 1g, all given twice daily, was offered to the eradication failure patients. RESULTS Overall, 270 patients were enrolled, but 13 patients early interrupted treatment due to side effects. At intention-to-treat (ITT) and per-protocol analysis (PP), the eradication rates were 85.5% and 91.6% with the concomitant regimen, 91.1% and 92.1% with the sequential therapy, and 80% and 85.7% with the hybrid regimen. Differences were not statistically significant. H. pylori infection was cured in 10 (55.6%) patients with the second-line regimen. CONCLUSION In our study, both concomitant and sequential therapy, but not hybrid therapy, reached high eradication rates. The success rate of second-line levofloxacin-based triple therapy is decreasing.
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Affiliation(s)
- Angelo Zullo
- Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, Rome, Italy
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Modak JK, Roujeinikova A. Cloning, purification and preliminary crystallographic analysis of the Helicobacter pylori leucyl aminopeptidase-bestatin complex. Acta Crystallogr Sect F Struct Biol Cryst Commun 2013; 69:1011-4. [PMID: 23989151 PMCID: PMC3758151 DOI: 10.1107/s174430911302054x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Accepted: 07/24/2013] [Indexed: 11/10/2022]
Abstract
Helicobacter pylori is an important human pathogenic bacterium associated with numerous severe gastroduodenal diseases, including ulcers and gastric cancer. Cytosolic leucyl aminopeptidase (LAP) is an important housekeeping protein that is involved in peptide and protein turnover, catabolism of proteins and modulation of gene expression. LAP is upregulated in metronidazole-resistant H. pylori, which suggests that, in addition to having an important housekeeping role, LAP contributes to the mechanism of drug resistance. Crystals of H. pylori LAP have been grown by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitating agent. The crystals belonged to the primitive triclinic space group P1, with unit-cell parameters a = 97.5, b = 100.2, c = 100.4 Å, α = 75.4, β = 60.9, γ = 81.8°. An X-ray diffraction data set was collected to 2.8 Å resolution from a single crystal. Molecular-replacement results using these data indicate that H. pylori LAP is a hexamer with 32 symmetry.
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Affiliation(s)
- Joyanta K. Modak
- Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
| | - Anna Roujeinikova
- Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia
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Georgopoulos SD, Papastergiou V, Karatapanis S. Current options for the treatment of Helicobacter pylori. Expert Opin Pharmacother 2013; 14:211-23. [PMID: 23331077 DOI: 10.1517/14656566.2013.763926] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Treatment of Helicobacter pylori (H. pylori) infection is crucial for prevalent disease's management, including gastritis, peptic ulcer and gastric cancer, whereas novel extradigestive causal associations are increasingly being recognized. Despite long-standing efforts, there is not as yet an optimal empirical therapy to eradicate H. pylori. AREAS COVERED In the present article the authors review current options for H. pylori eradication. Advantages and disadvantages of each of the recommended regimens, and the perspectives for their rational use in clinical practice, are critically discussed. EXPERT OPINION The continuous rising of antimicrobial resistance has accounted for the declined efficiency of standard triple therapies, yielding < 70% eradication in most countries. Alternative first-line strategies have been proposed and largely validated and are now replacing standard-of-care therapies in areas with a high incidence of clarithromycin-resistance (> 20%). Such treatments include the bismuth-containing quadruple therapy, concomitant, sequential and levofloxacin-based regimens, the later mainly designated, together with rifabutin-based therapies as second-line/rescue options. Clinicians should be aware of the local resistance pattern and maintain first-line eradication to levels > 90% (per-protocol efficacy). This will prevent both exposing the patient to repeated treatments and spreading of secondary antimicrobial resistance. In the future, perspectives of tailored therapy and a prophylactic vaccine will obviate any treatment concern.
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Affiliation(s)
- Sotirios D Georgopoulos
- Athens Medical, P. Faliron General Hospital, Department of Gastroenterology, 17562 Athens, Greece.
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Lim JH, Lee DH, Choi C, Lee ST, Kim N, Jeong SH, Kim JW, Hwang JH, Park YS, Lee SH, Shin CM, Jo HJ, Jang ES, Song IS, Jung HC. Clinical outcomes of two-week sequential and concomitant therapies for Helicobacter pylori eradication: a randomized pilot study. Helicobacter 2013; 18:180-6. [PMID: 23305083 DOI: 10.1111/hel.12034] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The eradication rate with PPI-based standard triple therapy for Helicobacter pylori infection has fallen considerably. One recent innovation is sequential therapy with PPI and three antibiotics, but the complexity of this regimen may reduce its usability. Concomitant administration of nonbismuth quadruple drugs (concomitant therapy) is also an effective treatment strategy. To investigate which regimen is a reasonable choice for Korean population, we performed two pilot studies with sequential and concomitant therapies. METHODS A total of 164 patients with proven H. pylori infection randomly received 14 days of sequential (n = 86) or concomitant (n = 78) therapies. The sequential group received 20 mg rabeprazole and 1 g amoxicillin (first week), followed by 20 mg rabeprazole, 500 mg clarithromycin, and 500 mg metronidazole (second week). The concomitant group received 20 mg rabeprazole, 1 g amoxicillin, 500 mg clarithromycin, and 500 mg metronidazole for 2 weeks. All drugs were administered BID. Helicobacter pylori status was confirmed 4 weeks later, after completion of treatment by (13) C-urea breath test. RESULTS The intention-to-treat and per-protocol eradication rates were 75.6% (95% CI, 66.3-84.9) and 76.8% (95% CI, 67.1-85.5) in the sequential group, and 80.8% (95% CI, 71.8-88.5) and 81.3% (95% CI, 71.6-90.7) in the concomitant group. There were no significant between-group differences, in regard to the eradication rates, compliance, or side effects. The most common side effects were bitter taste, epigastric soreness, and diarrhea. CONCLUSIONS Two-week concomitant and sequential therapies showed suboptimal efficacies. However, considering high antibiotics resistance, either of these two regimens may be a reasonable choice for Korean population.
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Affiliation(s)
- Ji Hyun Lim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Korea
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Clinical evaluation of twenty cases of heterotopic gastric mucosa of upper esophagus during five-year observation, using gastroscopy in combination with histopathological and microbiological analysis of biopsies. Contemp Oncol (Pozn) 2013; 17:171-5. [PMID: 23788986 PMCID: PMC3685377 DOI: 10.5114/wo.2013.34376] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 11/29/2012] [Accepted: 02/14/2013] [Indexed: 12/11/2022] Open
Abstract
Aim of the study Heterotopic gastric mucosa of the upper esophagus (HGMUE) may be connected with disorders of the upper gastrointestinal tract, exacerbated by Helicobacter pylori. Furthermore, HGMUE may be the origin of malignant progression to cervical esophageal carcinoma. Material and methods In this work, 20 patients with diagnosed heterotopic gastric mucosa of the upper esophagus (HGMUE) were subjected to 5-year follow-up to determine the extent and structure of histopathological changes within HGMUEs, as well as HGMUE dysplasia and metaplasia, and risk of their malignant transformation. As a diagnostic tool to describe localization, form, size and surface feature of HGMUEs, endoscopy was used. At the same time, the biopsies were collected for histopathological and microbiological analysis. Results In examined patients, HGMUEs were associated with inflammation, chronic gastritis, hiatus hernia, duodenal bulb erosion and ulcer and infection of H. pylori. Intestinal metaplasia and low grade dysplasia were also indicated. During 5 years of observation, both the clinical and histopathological image of diagnosed HGMUEs was stable. The patients with detected presence of H. pylori were treated with triple or quadruple therapy. These results show that HGMUEs may be associated with severe complications in the gastrointestinal tract, such as infection by H. pylori, hiatus hernia or duodenal ulcer. Although dysplasias and metaplasias found in diagnosed HGMUEs were not very numerous and relatively stable both clinically and histopathologically, at the present stage of the study we cannot exclude the possibility of HGMUE malignant transformation.
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Nonbismuth quadruple "concomitant" therapy versus standard triple therapy, both of the duration of 10 days, for first-line H. pylori eradication: a randomized trial. J Clin Gastroenterol 2013; 47:228-32. [PMID: 22858517 DOI: 10.1097/mcg.0b013e31826015b0] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS To compare the efficacy, compliance, and tolerability of a quadruple, nonbismuth-containing concomitant therapy with standard triple therapy, both of the duration of 10 days, for Helicobacter pylori eradication. BACKGROUND Eradication rates obtained with standard therapies are declining as antibiotic resistance becomes more prevalent worldwide. New first-line treatment strategies are needed. STUDY Two hundred fifty-seven patients with H. pylori infection were included in the study. Patients were randomized to receive 10-day concomitant therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after the start of treatment. RESULTS Two hundred forty-six patients completed the study. The intention-to-treat cure rates were 90.5% [95% confidence interval (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%), respectively. The eradication rate was significantly higher in the concomitant group compared with the triple therapy group in both the intention-to-treat (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally of mild/moderate intensity and did not interfere significantly with compliance, which was excellent for both treatment groups (96.6% and 98.5%, respectively, P=0.44). CONCLUSIONS Performance of a 10-day conventional triple regimen is suboptimal. A 10-day concomitant regimen achieved a significantly higher eradication rate and seems to be an effective, safe, and well-tolerated treatment option for H. pylori eradication.
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Comparative study of Helicobacter pylori eradication rates with 5-day quadruple "concomitant" therapy and 7-day standard triple therapy. J Clin Gastroenterol 2013; 47:21-4. [PMID: 22647826 DOI: 10.1097/mcg.0b013e3182548ad4] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Several studies have shown the superiority of concomitant quadruple therapy containing 3 antibiotics over triple therapy for Helicobacter pylori infection. The aim of this study was to compare concomitant quadruple therapy with standard triple therapy for first-line H. pylori eradication. METHODS A total of 270 patients with proven H. pylori infection were randomly assigned to one of 2 regimens: amoxicillin 1000 mg with clarithromycin 500 mg and lansoprazole 30 mg twice daily for 7 days (triple therapy) or amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and lansoprazole 30 mg twice daily for 5 days (concomitant therapy). The success of eradication was evaluated 4 to 5 weeks after completion of treatment. RESULTS Eradication rates were 86.1% in the triple therapy and 91.4% in the concomitant therapy (per protocol), but the difference was not statistically significant. Mild adverse events were more frequently reported in the concomitant-therapy group (35.6%) than in the triple-therapy group (25.2%) (P=0.09). CONCLUSIONS Five-day quadruple concomitant therapy eradicated H. pylori in over 90% of patients. Accordingly, concomitant therapy is thought to be a promising alternative to triple therapy as a first-line treatment regimen for H. pylori eradication.
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Kongchayanun C, Vilaichone RK, Pornthisarn B, Amornsawadwattana S, Mahachai V. Pilot studies to identify the optimum duration of concomitant Helicobacter pylori eradication therapy in Thailand. Helicobacter 2012; 17:282-5. [PMID: 22759328 DOI: 10.1111/j.1523-5378.2012.00953.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Eradication rate for Helicobacter pylori infection with standard triple therapy has globally declined including in Thailand, and new regimens are required that provide reliable high eradication rates. The study was designed to determine whether concomitant therapy administered for either 5 or 10 days would produce a ≥ 95% (grade A) treatment success in H. pylori infected Thai subjects with nonulcer dyspepsia. METHODS Two prospective, but separate, pilot single-center studies were carried out during September 2009-December 2010 at Thammasat University Hospital, Thailand. H. pylori infected subjects were randomized into the two pilot studies; either 5-day or 10-day concomitant therapy. Thai concomitant therapy consisted of rabeprazole (20 mg) twice daily, amoxicillin 1 g twice daily, metronidazole 400 mg three times a day, and clarithromycin MR 1 g once daily. H. pylori status was assessed by (13) C-urea breath test 4 weeks after completion of the treatment. Successful treatment was defined as achieving a grade A result (≥ 95%) and failure by <90% cured. RESULTS A total of 110 subjects were randomized (55 to the 5-day treatment trial and 55 to the 10-day regimen). Baseline subject demographic and clinical characteristics were similar in both studies. All subjects completed their assigned therapies. The 10-day concomitant treatment trial was successful in 53 of the 55 subjects (96.4%; 95% CI 87.4-99.5%). The 5-day concomitant pilot was judged to be a failure as only 49 of 55 subjects (89.1%; 95% CI = 77.7-95.8%) were cured. The frequency of adverse events was low and similar in the two studies. CONCLUSION The 10-day concomitant regimen provided excellent treatment success (eradication rate >95%) and was well tolerated. Ten-day concomitant therapy is likely to become useful first-line H. pylori eradication in Thailand.
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Affiliation(s)
- Chutima Kongchayanun
- GI Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
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7-Day Nonbismuth-Containing Concomitant Therapy Achieves a High Eradication Rate for Helicobacter pylori in Taiwan. Gastroenterol Res Pract 2012; 2012:463985. [PMID: 22888337 PMCID: PMC3408719 DOI: 10.1155/2012/463985] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2012] [Accepted: 06/14/2012] [Indexed: 02/06/2023] Open
Abstract
Background. Ten-day concomitant therapy achieves a high eradication rate in Taiwan. Whether shortening the duration of concomitant therapy can still keep a high eradication rate remains unclear. Aim. To assess the eradication rate of 7-day pantoprazole-containing concomitant therapy in Taiwan and to investigate factors influencing the eradication outcome. Methods. From March 2008 to March 2012, 319 H. pylori-infected patients receiving a 7-day pantoprazole-containing concomitant regimen (pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days) were included. Patients were asked to return at the second week to assess drug compliance and adverse effects. Repeated endoscopy or urea breath test was performed at 8 weeks after the end of eradication therapy. Results. The eradication rates according to intention-to-treat and per-protocol analyses were 93.7% (299/319) and 96.4% (297/308), respectively. Adverse events occurred in 13.2% (42/319) of the patients. The compliance rate was 98.4% (314/319). Multivariate analysis disclosed that poor compliance was the only independent factor influencing the efficacy of anti-H. pylori therapy with an odds ratio of 0.073 (95% confidence interval, 0.011-0.483). Conclusion. 7-day concomitant therapy achieved a very high eradication rate for H. pylori infection in Taiwan. Drug compliance was the only clinical factor influencing treatment efficacy.
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Gisbert JP, Calvet X. Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori. Clin Exp Gastroenterol 2012; 5:23-34. [PMID: 22457599 PMCID: PMC3308633 DOI: 10.2147/ceg.s25419] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Traditional standard triple therapy for Helicobacter pylori (H. pylori) infection (proton pump inhibitor-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. AIM To critically review evidence on the role of non-bismuth quadruple therapy (proton pump inhibitor-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. METHODS Bibliographical searches were performed in MEDLINE and relevant congresses up to December 2011. We performed a meta-analysis of the studies evaluating the concomitant therapy, and of the randomized controlled trials comparing the concomitant and the standard triple therapy. RESULTS A meta-analysis of 19 studies (2070 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 88% (95% confidence interval from 85% to 91%) for non-bismuth quadruple therapy. We performed a meta-analysis of the randomized controlled studies comparing the concomitant (481 patients) and the standard triple therapy (503 patients). The former was more effective than the latter: 90% versus 78% (intention-to-treat analysis). Results were homogeneous (I(2) = 0%). The odds ratio for this comparison was 2.36 (95% confidence interval from 1.67 to 3.34). A tendency toward better results with longer treatments (7-10 days versus 3-5 days) has been observed, so it seems reasonable to recommend the length of treatment achieving the highest cure rates (10 days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. CONCLUSION Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low.
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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), Madrid, Spain
| | - Xavier Calvet
- Department of Gastroenterology, Hospital de Sabadell, Departament de Medicina, Universitat Autònoma de Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
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Mégraud F. The challenge of Helicobacter pylori resistance to antibiotics: the comeback of bismuth-based quadruple therapy. Therap Adv Gastroenterol 2012; 5:103-9. [PMID: 22423259 PMCID: PMC3296089 DOI: 10.1177/1756283x11432492] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
A proton-pump inhibitor (PPI), clarithromycin-based, triple therapy has been the recommended treatment for Helicobacter pylori eradication for the past 15 years. Due to a steady increase in H. pylori resistance to clarithromycin, this triple clarithromycin-based treatment has become progressively less efficacious. Several approaches are available to address this situation: one is to test for clarithromycin resistance so that this triple clarithromycin-based regimen is given only to those who will benefit; a second is to prescribe the drugs sequentially, beginning with amoxicillin and a PPI followed by clarithromycin and metronidazole, again with a PPI or the four drugs prescribed concomitantly; a third alternative is to use bismuth-based quadruple therapy, PPI plus a standardized three-in-one capsule, bismuth subcitrate potassium, metronidazole, and tetracycline (BMT, sold under licence as Pylera®). The advantages of these different approaches are reviewed, including the relevance of BMT three-in-one capsule in clinical practice.
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Affiliation(s)
- Francis Mégraud
- INSERM U853, Université Bordeaux Segalen, Laboratoire de Bactériologie, 146 rue Leo Saignat, 33076 Bordeaux cedex, France
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Georgopoulos S, Papastergiou V, Xirouchakis E, Laudi F, Papantoniou N, Lisgos P, Spiliadi C, Fragou P, Skorda L, Karatapanis S. Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece. Helicobacter 2012; 17:49-53. [PMID: 22221616 DOI: 10.1111/j.1523-5378.2011.00911.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10-day, four-drug, three-antibiotic, nonbismuth-containing concomitant regimen. MATERIALS AND METHODS This is a prospective, open-label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and (13) C-urea breath test. For 10 days, all patients received esomeprazole 40mg, amoxycillin 1000mg, clarithromycin 500mg, and metronidazole 500mg, all b.d. eradication was assessed with (13) C urea breath test 8weeks after the start of treatment. Intention-to-treat and per-protocol eradication rates were determined. RESULTS One hundred and twenty-seven of the 131 patients completed the study. At intention-to-treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5-95.7%). For the per-protocol analysis, the eradication rate was 94.5% (95% CI, 89-97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. CONCLUSION A 10-day concomitant regimen appears to be an effective, safe, and well-tolerated treatment option for first-line H. pylori eradication in Greece.
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Gisbert JP, Calvet X. Review article: non-bismuth quadruple (concomitant) therapy for eradication of Helicobater pylori. Aliment Pharmacol Ther 2011; 34:604-17. [PMID: 21745241 DOI: 10.1111/j.1365-2036.2011.04770.x] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Traditional standard triple therapy for Helicobacter pylori infection (PPI-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily. AIM To critically review evidence on the role of non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection. METHODS Bibliographical searches were performed in MEDLINE and relevant congresses. RESULTS The first randomised comparison of the non-bismuth quadruple therapy and the sequential (PPI-amoxicillin 5days plus PPI-clarithromycin-nitroimidazole 5days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta-analysis) have demonstrated that non-bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta-analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 90% for non-bismuth quadruple therapy. A tendency towards better results with longer treatments (7-10days vs. 3-5days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited. CONCLUSIONS Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low.
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Affiliation(s)
- J 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), Madrid, Spain.
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Zhou N, Chen WX, Zhang W, Li L, Jin X, Li YM. Is short-term therapy really sufficient to eradicate Helicobacter pylori infection? J Zhejiang Univ Sci B 2011; 11:690-701. [PMID: 20803773 DOI: 10.1631/jzus.b1000008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The aim of our study was to perform a systematic review and meta-analysis of the efficacy of short-term protocols for Helicobacter pylori eradication and to review the safety and adverse profiles of these eradication protocols. METHODS Literatures were located through electronic searches by PubMed, Medline, ISI Web of Knowledge, and Cochrane Library using the relevant terms. Abstracts of important meetings were searched manually in some journal supplements. Additional bibliographies were identified from the reference lists of identified studies. Three independent reviewers systemically identified randomized controlled trials (RCTs) comparing short-duration protocols vs. 7-d proton pump inhibitor (PPI)-based triple protocols, as well as studies reporting eradication rates of short-duration protocols for H. pylori. Summary effect size was calculated as relative risk (RR) and 95% confidence intervals (CI) using Review Manager 4.2, and P<0.05 was defined as statistically significant in all analyses. RESULTS Among 90 abstracts retrieved, 15 studies were analyzed, including a total of 30 treatment regimens with 1856 subjects. Mean intention-to-treat (ITT) cure rates of 63.2% and 81.3% were achieved with short-term protocols and 7-d PPI-containing protocols, respectively. Per-protocol (PP)-based overall cure rates were 66.6% and 86.1%, respectively. Short-term therapy was inferior to 7-d triple regimen (P<0.00001). After sub-analysis, however, comparing the effects of > or = 3-d protocols and 7-d triple protocols, the cumulative ITT RR was 0.95 (P=0.26), and PP RR was 0.95 (P=0.10), without significant heterogeneity. Moreover, slightly fewer adverse-effects were found in short-term protocols. CONCLUSIONS Although more economical, short-duration protocols are inferior to 7-d PPI-based triple protocols with regarding to eradication rate of H. pylori. Protocols of more than 3 d, however, may be equivalent to 7-d protocols.
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Affiliation(s)
- Ning Zhou
- Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
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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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Abstract
BACKGROUND Alternative treatment regimens for standard triple therapy are urgently needed. AIM To critically review the evidence on the role of "sequential" regimen for the treatment of Helicobacter pylori infection. METHODS Bibliographical searches were performed in MEDLINE and international congresses. RESULTS Several pooled-data analyses and meta-analyses have demonstrated that sequential regimen is more effective than standard triple therapy. Sequential therapy is not affected by bacterial (CagA status, infection density) and host factors (underlying disease, smoking). Clarithromycin resistance seems to be the only factor reducing their efficacy. However, even in these patients, an acceptable >75% eradication rate can be achieved. Unfortunately, almost all the studies have been performed in Italy. Whether it is necessary to provide the drugs sequentially or if the 4 components of sequential therapy can be given concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective and safe alternative to triple therapy and is less complex than sequential therapy. CONCLUSIONS Sequential therapy is a novel promising treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before sequential therapy could supplant existing treatment regimens and be generally recommended in clinical practice.
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Kwon JH, Lee DH, Song BJ, Lee JW, Kim JJ, Park YS, Kim N, Jeong SH, Kim JW, Lee SH, Hwang JH, Jung HC, Song IS. Ten-day sequential therapy as first-line treatment for Helicobacter pylori infection in Korea: a retrospective study. Helicobacter 2010; 15:148-53. [PMID: 20402817 DOI: 10.1111/j.1523-5378.2010.00748.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The eradication rate of proton-pump inhibitor-based triple therapy for Helicobacter pylori infection is low due to increasing antibiotics resistance, especially clarithromycin. Recently, it was reported in Europe that a 10-day sequential strategy produced good outcomes. The aim of this study was to assess the efficacy of sequential therapy as first-line treatment for eradication of H. pylori in clinical practice in Korea. MATERIALS AND METHODS A total of 98 patients (mean age 55.2 years and male 47, female 51) with proven H. pylori infection received 10-day sequential therapy (20 mg of rabeprazole, and 1 g of amoxicillin, twice daily for the first 5 days, followed by 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for the remaining 5 days). Eradication was evaluated 4 weeks later, after completion of treatment by 13(C)-urea breath testing. Eradication rates were calculated by intention-to-treat (ITT) and by per protocol (PP). Compliance and adverse events were also assessed in study group. RESULTS The eradication rate of sequential therapy was 91.8% (90/98) by ITT and same result was reported by PP analysis (89/97). The study group consisted of 66 H. pylori associated gastritis, 7 gastric ulcer, and 25 duodenal ulcer patients (67.3%, 7.1%, 25.5%, respectively). Mild adverse events happened frequently (21.4%) but the treatment was well tolerable. The most common adverse event was a bitter taste (9.2%) followed by nausea and diarrhea (4.1%). CONCLUSIONS Ten-day sequential therapy is found to effectively eradicate H. pylori infection as first-line treatment in Korea.
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Affiliation(s)
- Jung H Kwon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Gisbert JP, Calvet X, O'Connor JPA, Mégraud F, O'Morain CA. The sequential therapy regimen forHelicobacter pylorieradication. Expert Opin Pharmacother 2010; 11:905-18. [PMID: 20205606 DOI: 10.1517/14656561003657152] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Asaka M, Kato M, Takahashi SI, Fukuda Y, Sugiyama T, Ota H, Uemura N, Murakami K, Satoh K, Sugano K. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter 2010; 15:1-20. [PMID: 20302585 DOI: 10.1111/j.1523-5378.2009.00738.x] [Citation(s) in RCA: 292] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan. MATERIALS AND METHODS Four meetings of guidelines preparation committee were held from July 2007 to December 2008. In the new guidelines, recommendations for treatment have been classified into five grades according to the Minds Recommendation Grades, while the level of evidence has been classified into six grades. The Japanese national health insurance system was not taken into consideration when preparing these guidelines. RESULTS Helicobacter pylori eradication therapy achieved a Grade A recommendation, being useful for the treatment of gastric or duodenal ulcer, for the treatment and prevention of H. pylori-associated diseases such as gastric cancer, and for inhibiting the spread of H. pylori infection. Levels of evidence were determined for each disease associated with H. pylori infection. For the diagnosis of H. pylori infection, measurement of H. pylori antigen in the feces was added to the tests not requiring biopsy. One week of proton-pump inhibitor-based triple therapy (including amoxicillin and metronidazole) was recommended as second-line therapy after failure of first-line eradication therapy. CONCLUSION The revised Japanese guidelines for H. pylori are based on scientific evidence and avoid the administrative restraints that applied to earlier versions.
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Affiliation(s)
- Masahiro Asaka
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
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Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol 2010; 8:36-41.e1. [PMID: 19804842 PMCID: PMC2838430 DOI: 10.1016/j.cgh.2009.09.030] [Citation(s) in RCA: 189] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Revised: 08/28/2009] [Accepted: 09/20/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Sequential therapy with a proton pump inhibitor (PPI) and amoxicillin followed by a PPI, clarithromycin, and an imidazole agent reportedly have a better rate of curing Helicobacter pylori infection than PPI, amoxicillin, and clarithromycin triple therapy. The concomitant administration of these 4 drugs (concomitant therapy) is also an effective treatment strategy. We compared the efficacies of sequential and concomitant therapy and analyzed the effects of antibiotic resistance in patients with H pylori infection. METHODS In a randomized trial of 232 H pylori-infected patients from 3 hospitals in Kaohsiung, Taiwan, patients were given 10 days of sequential (n = 115) or concomitant (n = 117) therapy. H pylori status was confirmed by endoscopy or urea breath test. RESULTS Intention-to-treat analysis demonstrated similar eradication rates for sequential (92.3%; 95% confidence interval [CI], 87.5%-97.1%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%)(P = .83). Per-protocol eradication results were similar for sequential (93.1%; 95% CI, 90.7%-95.5%) and concomitant therapy (93.0%; 95% CI, 88.3%-97.7%) (P = .99). Univariate analysis showed that compliance and resistance to clarithromycin were independent determinants of eradication. Dual resistance did not influence the level of eradication in the concomitant group, but significantly affected that of the sequential therapy group. Clarithromycin resistance was less frequent than expected. CONCLUSIONS Sequential or concomitant therapy with a PPI, amoxicillin, clarithromycin, and an imidazole agent are equally effective and safe for eradication of H pylori infection. Resistance to clarithromycin, compliance, and adverse events reduced the level of eradication. Concomitant therapy may be more suitable for patients with dual resistance to antibiotics.
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Affiliation(s)
- Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, National Sun Yat-Sen Univeristy-Kaoshiung Medical University Joint Center, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan
| | - Jeng-Yih Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Antone R. Opekun
- Department of Medicine, Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas, USA
| | - Chao-Hung Kuo
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Sophie S.W. Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Angela Chen
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, National Sun Yat-Sen Univeristy-Kaoshiung Medical University Joint Center, Kaohsiung, Taiwan
| | - Wen-Chun Hung
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, National Sun Yat-Sen Univeristy-Kaoshiung Medical University Joint Center, Kaohsiung, Taiwan
| | - David Y. Graham
- Department of Medicine, Veterans Affairs Medical Center, and Baylor College of Medicine, Houston, Texas, USA,Correspondence: David Y. Graham, MD, Michael E. DeBakey Veterans Affairs Medical Center, RM 3A-320 (111D), 2002 Holcombe Boulevard, Houston, Texas 77030, USA.
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Gisbert JP. Stomach: Quadruple therapy for Helicobacter pylori eradication. Nat Rev Gastroenterol Hepatol 2009; 6:385-6. [PMID: 19575021 DOI: 10.1038/nrgastro.2009.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
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Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter 2009. [PMID: 19298338 DOI: 10.1111/j.1523-5378.2009.00671x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/13/2023]
Abstract
BACKGROUND Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy). AIM To compare concomitant therapy with standard triple therapy for H. pylori infection. METHODS By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted. RESULTS We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73-4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95-6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8-92.1%) and PP was 92.9% (95% CI: 90.2-94.8%). CONCLUSION Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.
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Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter 2009; 14:109-18. [PMID: 19298338 PMCID: PMC2840655 DOI: 10.1111/j.1523-5378.2009.00671.x] [Citation(s) in RCA: 170] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy). AIM To compare concomitant therapy with standard triple therapy for H. pylori infection. METHODS By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted. RESULTS We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73-4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95-6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8-92.1%) and PP was 92.9% (95% CI: 90.2-94.8%). CONCLUSION Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.
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Ueki N, Miyake K, Kusunoki M, Shindo T, Kawagoe T, Futagami S, Tsukui T, Inagaki H, Sakamoto C. Impact of quadruple regimen of clarithromycin added to metronidazole-containing triple therapy against Helicobacter pylori infection following clarithromycin-containing triple-therapy failure. Helicobacter 2009; 14:91-9. [PMID: 19298336 DOI: 10.1111/j.1523-5378.2009.00664.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection. MATERIALS AND METHODS Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by (13)C-urea breath tests performed 2 to 3 months post-therapy. RESULTS As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group. CONCLUSIONS In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.
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Affiliation(s)
- Nobue Ueki
- Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo.
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Essa AS, Kramer JR, Graham DY, Treiber G. Meta-analysis: four-drug, three-antibiotic, non-bismuth-containing "concomitant therapy" versus triple therapy for Helicobacter pylori eradication. Helicobacter 2009. [PMID: 19298338 DOI: 10.1111/j.1523-5378.2009.00671] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy). AIM To compare concomitant therapy with standard triple therapy for H. pylori infection. METHODS By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted. RESULTS We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73-4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95-6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8-92.1%) and PP was 92.9% (95% CI: 90.2-94.8%). CONCLUSION Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.
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Graham DY, Lu H, Yamaoka Y. Therapy for Helicobacter pylori infection can be improved: sequential therapy and beyond. Drugs 2008; 68:725-36. [PMID: 18416582 DOI: 10.2165/00003495-200868060-00001] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
As with other bacterial infections, successful treatment of Helicobacter pylori infections depends on the use of antibacterial agents to which the organism is susceptible. In this article, we use the proposed report card grading scheme (i.e. grade A, B, C, D, F) for the outcome of clinical trials, where intention-to-treat cure rates >95% = A, 90-95% = B, 85-89% = C, 81-84% = D and <81% = F. The goal of therapy is to consistently cure >95% of patients (e.g. provide grade A results). Like tuberculosis, H. pylori infections are difficult to cure and successful treatment generally requires the administration of several antibacterial agents simultaneously. Duration of therapy is also important and depends upon whether resistance is present; 14 days is often best. With few exceptions, worldwide increasing macrolide resistance now undermines the effectiveness of the legacy triple therapy (e.g. a proton pump inhibitor [PPI], clarithromycin and amoxicillin) and, in most areas, cure rates have declined to unacceptable levels (e.g. grade F). The development of sequential therapy was one response to this problem. Sequential therapy has repeatedly been shown in head-to-head studies to be superior to legacy triple therapy. Sequential therapy, as originally described, is the sequential administration of a dual therapy (a PPI plus amoxicillin) followed by a Bazzoli-type triple therapy (a PPI plus clarithromycin and tinidazole) and has been shown to be especially useful where there is clarithromycin resistance. However, the cure rates of the original sequential treatment are grade B and can probably be further improved by changes in dose, duration or administration, such as by continuing the amoxicillin into the triple therapy arm. The sequential approach may also be more complicated than necessary, based on the fact that the same four drugs have also been given concomitantly (at least nine publications with >700 patients) as a quadruple therapy with excellent success. This article discusses the approach to therapy in the modern era where antimicrobial resistance is an increasing problem and legacy triple therapy is no longer an acceptable initial choice. Methods to achieve acceptable eradication rates (e.g. grade A or B results) are discussed and, specifically, sequential therapy is considered both conceptually and practically. Suggestions are provided regarding how sequential therapy might be improved to become a grade A therapy as well as how to identify situations where it can be expected to yield unacceptable results. New uses for current drugs are discussed and suggestions for subsequent randomized comparisons to overcome phenotypic and genotypic resistance are given. We propose a change in focus from comparative studies (designed to prove that a new therapy is superior to a known inferior therapy) to demanding that efficacious therapies meet or exceed a pre-specified level of success (i.e. grade A or B result). To do so, coupled with less concern about the effect of recommendations on the pharmaceutical industry, should provide clinicians with much higher quality information, and improve the quality of medical care and recommendations regarding treatment. Ultimately, there is little or no justification for comparative testing that includes an arm with known unacceptably low results. H. pylori gastritis is an infectious disease and should be approached and treated as such.
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Affiliation(s)
- David Y Graham
- Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA.
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