Serum drug concentrations of INH and RMP predict 2-month sputum culture results in tuberculosis patients.

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. DESIGN: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.