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Tuberc Respir Dis (Seoul). 2015 Apr;78(2):78-84. doi: 10.4046/trd.2015.78.2.78. Epub 2015 Apr 2.

Outcomes and use of therapeutic drug monitoring in multidrug-resistant tuberculosis patients treated in virginia, 2009-2014.

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Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
Tuberculosis Control and Newcomer Health, Virginia Department of Health, Richmond, VA, USA.
College of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Southeastern National Tuberculosis Center and the University of Miami, Miami, FL, USA.



Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited.


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 (Cmax), were compared to expected ranges.


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 C2hr, 16.6±10.2 µg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2±1.5 µg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5±14.0 µg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0±29.1 µg/mL; all within or above); linezolid in three (mean C2hr, 11.4±4.1 µg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3±3.7 µg/mL; 1 [50%] below); ethionamide in one (C2hr, 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.


Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.


Capreomycin; Cycloserine; Linezolid; Moxifloxacin; Pharmacokinetics

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