title: Therapeutic drug monitoring in the treatment of active tuberculosis.
abstract: BACKGROUND
  Therapeutic drug monitoring (TDM) is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In the treatment of active tuberculosis (TB), TDM is not routine, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes.
  
  
  METHODS
  In a retrospective case control study, patients with active TB in whom TDM was performed were considered cases and compared with controls who did not undergo TDM, and matched according to year of diagnosis and the results of direct smear microscopy. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion.
  
  
  RESULTS
  In total, 20 patients were identified in whom TDM was performed, of whom 17 (87%) had at least one low drug concentration. Overall, 27 of 45 (60%) initial drug concentrations were low and resulted in an increased drug dosage. Low drug levels were found in 13 of 15 (87%) isoniazid, four of five (80%) rifabutin and eight of 12 (67%) rifampin measurements, but in only two of 13 (15%) pyrazinamide measurements. Within cases only, the 17 patients with low serum drug levels were significantly more likely to have comorbid illnesses, be smear positive, have lower serum albumin levels and had nonsignificantly longer time to culture conversion, compared with the three cases in whom all drug levels were within therapeutic ranges.
  
  
  CONCLUSIONS
  TB drug levels were frequently below clinically acceptable levels in patients with active TB, particularly in those with HIV infection or other comorbidities. TDM is potentially useful for the treatment of active TB, but is currently underused.
authors: Montreal Chest Institute, McGill University, Canada.
authors: Aylin
authors: A
authors: Babalik
authors: Aylin
authors: A
authors: Babalik
authors: Sharyn
authors: S
authors: Mannix
authors: Denis
authors: D
authors: Francis
authors: Dick
authors: D
authors: Menzies
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D005260:Female; D015658:HIV Infections / Q000453:epidemiology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008828:Microbiological Techniques; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012107:Research Design; D012189:Retrospective Studies; D017828:Rifabutin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology
chemical_list: D000995:Antitubercular Agents; D017828:Rifabutin; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin