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 $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, 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.