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KMID : 0383820150780020078
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Tuberculosis and Respiratory Diseases
2015 Volume.78 No. 2 p.78 ~ p.84
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Outcomes and Use of Therapeutic Drug Monitoring in Multidrug-Resistant Tuberculosis Patients Treated in Virginia, 2009?2014
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Heysell Scott K.
Moore Jane L.
Peloquin Charles A.
Ashkin David
Houpt Eric R.
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Abstract
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Background : Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited.
Materials and 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.
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KEYWORD
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Pharmacokinetics, Cycloserine, Capreomycin, Moxifloxacin, Linezolid
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