Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009-2014

BACKGROUND: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. METHODS: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak (C(max)), were compared to expected ranges. RESULTS: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean C(2hr), 16.6±10.2 µg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C(2hr), 3.2±1.5 µg/mL; 1 [20%] below); capreomycin in five (mean C(2hr), 21.5±14.0 µg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C(6hr), 65.0±29.1 µg/mL; all within or above); linezolid in three (mean C(2hr), 11.4±4.1 µg/mL, 1 [33%] below); amikacin in two (mean C(2hr), 35.3±3.7 µg/mL; 1 [50%] below); ethionamide in one (C(2hr), 1.49 µg/mL, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. CONCLUSION: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.