title: Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis.
abstract: The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.
authors.affiliation: Central Clinical School, University of Sydney, Camperdown, Australia.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Fox
authors.affiliation: Dept of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Benedetti
authors.affiliation: Dept of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: Cox
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
authors.affiliation: National Institute for Health Development, Tallinn, Estonia.
authors.forename: Piret
authors.initials: P
authors.lastname: Viiklepp
authors.affiliation: Bureau of Tuberculosis Control, New York City Department of Health and Mental Hygiene, Long Island City, NY, USA.
authors.forename: Shama
authors.initials: S
authors.lastname: Ahuja
authors.affiliation: Dept of Life Sciences, Imperial College London, London, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pasvol
authors.affiliation: Central Clinical School, University of Sydney, Camperdown, Australia Dick.Menzies@McGill.ca.|Respiratory Epidemiology and Clinical Research Unit, McGill University, Montreal, QC, Canada.
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002991:Clofazimine / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use; D000069349:Linezolid / Q000627:therapeutic use; D016015:Logistic Models; D018942:Macrolides / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D023303:Oxazolidinones / Q000627:therapeutic use; D013828:Thioacetazone / Q000627:therapeutic use; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007555:Isoxazoles; D018942:Macrolides; D023303:Oxazolidinones; C100142:terizidone; D000658:Amoxicillin; D002991:Clofazimine; D000069349:Linezolid; D013828:Thioacetazone