title: Systematic review and meta-analysis: triple therapy combining a proton-pump inhibitor, amoxicillin and metronidazole for Helicobacter pylori first-line treatment.
abstract: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies.
  
  
  
  The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis.
  
  
  
  Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates.
  
  
  
  Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies.
  
  
  
  PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate.
authors.affiliation: Digestive Diseases Unit, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Spain Universitat Internacional de Catalunya, Barcelona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Puig
authors.affiliation: Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Baylina
authors.affiliation: Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sánchez-Delgado
authors.affiliation: Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: López-Gongora
authors.affiliation: Unitat d'Epidemiologia i Avaluació, Hospital de Sabadell, Sabadell, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Suarez
authors.affiliation: Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Iglesias
authors.affiliation: Internal Medicine Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Muñoz
authors.affiliation: Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Cristina
authors.initials: C
authors.lastname: Dacoll
authors.affiliation: Clínica de Gastroenterología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Henry
authors.initials: H
authors.lastname: Cohen
authors.affiliation: Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain Centro de Investigación Biomédica en Red de enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain xcalvet@tauli.cat.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008795:Metronidazole / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D000658:Amoxicillin