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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.

Author information

1
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
2
Tuberculosis Control and Newcomer Health, Virginia Department of Health, Richmond, VA, USA.
3
College of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
4
Southeastern National Tuberculosis Center and the University of Miami, Miami, FL, USA.

Abstract

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 (Cmax), 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 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.

CONCLUSION:

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

KEYWORDS:

Capreomycin; Cycloserine; Linezolid; Moxifloxacin; Pharmacokinetics

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