Therapeutic drug monitoring in the treatment of tuberculosis: a retrospective analysis

SETTING: Tuberculosis (TB) in-patient treatment unit in Vancouver, Canada. OBJECTIVE: To examine the results of therapeutic drug monitoring (TDM) in anti-tuberculosis treatment. DESIGN: We performed a retrospective analysis of TDM data from 2000 to 2010. All in-patients treated for TB with TDM performed during their treatment course were included. RESULTS: TDM was performed on 52 patients in 76 treatment episodes from 2000 to 2010. Overall, 103/213 (48.4%) drug levels measured were low, and 5/213 (2.3%) were high. At least one drug level was low in 47/52 (90.3%) patients. Initial serum levels were low in respectively 76.6% and 68.4% of isoniazid (INH) and rifampicin (RMP) levels. In contrast, only 2.9% of initial pyrazinamide levels were low. Five patients with a susceptible strain on initial presentation later developed drug-resistant disease, with all five patients demonstrating at least one low drug level and two demonstrating multiple low levels. Dose adjustments were made in response to 26 INH and RMP levels, with variable serum responses. CONCLUSION: In this population with high rates of treatment failure and acquired resistance, we demonstrate that most patients had low drug levels. Prospective studies are required to examine the relationship between drug levels and clinical outcomes.