Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis

Eur Respir J. 2017 Jan 3;49(1):1600993. doi: 10.1183/13993003.00993-2016. Print 2017 Jan.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amoxicillin / therapeutic use
  • Antitubercular Agents / therapeutic use*
  • Clofazimine / therapeutic use
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Isoxazoles / therapeutic use
  • Linezolid / therapeutic use
  • Logistic Models
  • Macrolides / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Multivariate Analysis
  • Oxazolidinones / therapeutic use
  • Thioacetazone / therapeutic use
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Young Adult

Substances

  • Antitubercular Agents
  • Isoxazoles
  • Macrolides
  • Oxazolidinones
  • terizidone
  • Amoxicillin
  • Clofazimine
  • Linezolid
  • Thioacetazone