title: Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients.
abstract: BACKGROUND
  In Alberta provincial tuberculosis (TB) clinics, serum drug concentrations (SDCs) are measured in patients with human immunodeficiency virus, diabetes mellitus or at extremes of weight, or showing slow clinical response to treatment, to guide treatment.
  
  
  METHODS
  A retrospective review was performed of TB cases in Northern Alberta with SDCs measured from 1998 to 2013. Adequacy of SDC was based on the maximum concentration (Cmax) achieved in serum, with rifampicin (RMP) values <8 μg/ml and isoniazid (INH) values <3 μg/ml for daily dosing and <9 μg/ml for intermittent dosing considered inadequate. Clinical variables and microbiological outcomes were then compared between the adequate and inadequate groups.
  
  
  RESULTS
  Of 134 pulmonary TB cases with SDCs for INH and/or RMP, we found a significant increase in 2-month sputum culture positivity in the cohort with inadequate concentrations of INH compared to those with adequate INH concentrations (42.5% vs. 18.3%, P = 0.0084). A similar trend was seen in the cohort with inadequate concentrations of RMP (39% vs. 21%, P = 0.0725).
  
  
  CONCLUSIONS
  Among our study population, low SDCs of INH and, to a lesser extent, RMP, appear to be associated with reduced sputum culture conversion after 2 months of treatment.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Mah
authors.affiliation: Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Kharrat
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Alberta Health Services TB Program, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Central TB Services, Alberta Health Services, Calgary, Alberta, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Der
authors.affiliation: Alberta Health Services TB Program, Alberta Health Services, Edmonton, Alberta, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Hansen
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Long
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kunimoto
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D000416:Alberta; D000995:Antitubercular Agents / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012293:Rifampin / Q000097:blood / Q000627:therapeutic use*; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin