title: Effect of Intermittency on Treatment Outcomes in Pulmonary Tuberculosis: An Updated Systematic Review and Metaanalysis.
abstract: Intermittent regimens offer operational advantages in tuberculosis treatment, but their efficacy has been questioned. We updated a systematic review and metaanalysis to examine the efficacy of different intermittent dosing schedules in first-line pulmonary tuberculosis therapy.
  
  
  
  An updated search included randomized control trials (RCTs) that reported on first-line pulmonary tuberculosis therapy between June 2008 and March 2016. We pooled proportions of failure, relapse, and acquired drug resistance (ADR) for 4 dosing schedules: daily throughout, thrice weekly throughout, daily (intensive phase) then thrice weekly (continuation phase), and daily (intensive phase) then twice weekly (continuation phase). Metaregression was performed using a negative binomial regression model.
  
  
  
  After screening 5874 citations, 7 RCTs with 10 arms were added for a total of 56 RCTs with 110 arms. The pooled proportion of relapse was significantly higher in arms with thrice weekly therapy throughout (6.8; 95% confidence interval [CI], 3.8-9.9) and twice weekly therapy in the continuation phase (7.3; 95% CI, 3.5-11.1) when compared with daily therapy (2.5; 95% CI, 1.8-3.2; P < .01). Metaregression revealed higher rates of relapse (2.2; 95% CI, 1.2-4.0), failure (3.7; 95% CI, 1.1-12.6), and ADR (10.0; 95% CI, 2.1-46.7) in arms with thrice weekly throughout and higher rates of failure (3.0; 95% CI, 1.0-8.8) with twice weekly in the continuation phase when compared with daily therapy.
  
  
  
  Thrice weekly dosing throughout therapy, and twice weekly dosing in the continuation phase appear to have worse microbiological treatment outcomes when compared with daily therapy.
authors.affiliation: Division of Respiratory Medicine, University of British Columbia, Vancouver, Canada.|BC Centre for Disease Control, Vancouver, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Johnston
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Jonathon R
authors.initials: JR
authors.lastname: Campbell
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, McGill University; McGill International TB Centre, Montreal, Quebec, Canada.
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D024881:Drug Resistance, Bacterial; D004358:Drug Therapy / Q000379:methods*; D006801:Humans; D012008:Recurrence; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: intermittent therapy; systematic review; treatment outcomes; tuberculosis; metaanalysis