title: Therapeutic drug monitoring in anti-tuberculosis treatment: a systematic review and meta-analysis.
abstract: Therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes, but there is little evidence to guide TDM in clinical practice.
  
  
  
  We performed a systematic review and meta-analysis to summarise existing literature on TDM in first-line drugs.
  
  
  
  We identified 41 studies that reported 2 h post-dose drug concentrations (C2h) for first-line drugs and 12 studies that reported clinical outcomes. We pooled data by study quality, design, region, dosing modality and patient characteristics. The pooled proportion of subjects with low isoniazid C2h was 0.43 (95%CI 0.32-0.55), 0.67 (95%CI 0.60-0.74) had low rifampicin C2h, 0.27 (95%CI 0.17-0.38) had low ethambutol C2h, and 0.12 (95%CI 0.07-0.19) had low pyrazinamide C2h. Patients with diabetes had a non-significant increase in the proportion of subjects with low C2h levels across all four drugs. Only three of 12 studies that examined clinical outcomes demonstrated an association between low C2h and unsuccessful treatment outcomes.
  
  
  
  Across a wide variety of studies, a high proportion of patients undergoing first-line anti-tuberculosis treatment had 2 h drug concentrations below the accepted normal threshold. These findings point to a discrepancy between accepted 2 h TDM thresholds and TB drug dosing recommendations.
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Mota
authors.affiliation: University of British Columbia, Faculty of Medicine, Division of Respirology, Vancouver, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Al-Efraij
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Campbell
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, University of British Columbia, Faculty of Medicine, Division of Respirology, Vancouver, Canada.
authors.forename: V J
authors.initials: VJ
authors.lastname: Cook
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Marra
authors.affiliation: British Columbia Centre for Disease Control, Vancouver, University of British Columbia, Faculty of Medicine, Division of Respirology, Vancouver, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Johnston
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004977:Ethambutol / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D011718:Pyrazinamide / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012293:Rifampin / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin