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

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

• Heysell SK
• Moore JL
• Peloquin C
• Ashkin D
• Houpt ER

• KMID: 2320598
• DOI: http://doi.org/10.4046/trd.2015.78.2.78

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 microg/mL; 4 [57%] below expected range); moxifloxacin in five (mean C2hr, 3.2+/-1.5 microg/mL; 1 [20%] below); capreomycin in five (mean C2hr, 21.5+/-14.0 microg/mL; 3 [60%] below); para-aminosalicylic acid in five (mean C6hr, 65.0+/-29.1 microg/mL; all within or above); linezolid in three (mean C2hr, 11.4+/-4.1 microg/mL, 1 [33%] below); amikacin in two (mean C2hr, 35.3+/-3.7 microg/mL; 1 [50%] below); ethionamide in one (C2hr, 1.49 microg/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.

Keyword

Pharmacokinetics; Cycloserine; Capreomycin; Moxifloxacin; Linezolid

MeSH Terms

Adult
Aged
Amikacin
Aminosalicylic Acid
Capreomycin
Cohort Studies
Cycloserine
Drug Monitoring*
Ethionamide
Female
Humans
Pharmacokinetics
Retrospective Studies
Tuberculosis
Tuberculosis, Meningeal
Tuberculosis, Multidrug-Resistant*
Virginia*
Linezolid
Amikacin
Aminosalicylic Acid
Capreomycin
Cycloserine
Ethionamide

Figure

• 

  Figure 1 Mean change in 2-hour concentration in repeated samples with or without dose adjustment in second-line medications. CYC: cycloserine; AMK: amikacin; CAP: capreomycin; MXF: moxifloxacin; LNZ: linezolid. ↑: C2hr concentration after dose increase; ↓: dose decrease; or ↔: no change in dose. No repeat samples from patients with initial therapeutic drug monitoring for para-aminosalicylic acid or ethionamide.

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