title: Bedaquiline versus placebo for management of multiple drug-resistant tuberculosis: A systematic review.
abstract: BACKGROUND
  Multidrug-resistant tuberculosis (MDR-TB) is associated with significant morbidity and mortality. Bedaquiline is the first drug approved for treating MDR-TB.
  
  
  OBJECTIVE
  We performed a systematic review and meta-analysis to summarize the totality of all available evidence on the efficacy of bedaquiline for the management of MDR-TB.
  
  
  METHODS
  We searched the following PubMed and Cochrane Registry of Clinical Trials. Randomized controlled trials (RCTs) with a parallel design comparing bedaquiline versus any treatment for the management of MDR-TB in adults were eligible for inclusion. Data were pooled under a random effects model.
  
  
  RESULTS
  Two trials published as three manuscripts with a total of 207 patients were included. As per the Cochrane risk of bias tool, majority of parameter were labeled as high or unclear risk of bias. Bedaquiline compared with placebo was associated with a statistically significant decrease in time to conversion of positive sputum culture to negative at 8 and 24 weeks with a significant increase in mortality on long-term follow-up. There was no difference in completion rates between bedaquiline and placebo.
  
  
  CONCLUSIONS
  Bedaquiline is an effective treatment modality for MDR-TB but needs to be balanced against significant mortality. Future Phase 3 RCTs are needed to make a conclusive recommendation.
authors.affiliation: Department of Pharmacology, GMERS Medical College, Patan, Gujarat, India.
authors.forename: Jaykaran
authors.initials: J
authors.lastname: Charan
authors.affiliation: Department of Internal Medicine, USF Health Program for Comparative Effectiveness Research, Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Tea
authors.initials: T
authors.lastname: Reljic
authors.affiliation: Department of Internal Medicine, USF Health Program for Comparative Effectiveness Research, Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D064687:Diarylquinolines / Q000627:therapeutic use*; D006801:Humans; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D010919:Placebos; C493870:bedaquiline
keywords: Bedaquiline; multidrug resistance; sputum conversion; tuberculosis