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

Heysell SK, Moore JL, Peloquin CA, Ashkin D, Houpt ER - Tuberc Respir Dis (Seoul) (2015)

Bottom Line: Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, 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.

No MeSH data available.


Related in: MedlinePlus

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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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.

Mentions: Eight patients (80%) had TDM for at least one drug performed (maximum 6 drugs). Patients without TDM either died early (patient 2) or were transferred out of care (patient 6). Initial TDM was performed at a median of 6.5 weeks (minimum 2, maximum 14 weeks) after MDR-TB treatment initiation. Of the eight subjects with initial TDM, six (75%) had at least one follow-up concentration performed, though for some medications repeat testing was performed without dose adjustment (Figure 1). All dose increase or decrease led to C2hr increase or decrease respectively in subjects with follow-up samples, while follow-up C2hr concentrations were not significantly different if the dose was unchanged (Figure 1). Limited 6-hour concentrations for delayed absorption generally supported the 2-hour result (Table 2). For the medications most frequently checked (cycloserine, capreomycin, and moxifloxacin), no demographic characteristic was associated with a C2hr value below the expected range.


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

Heysell SK, Moore JL, Peloquin CA, Ashkin D, Houpt ER - Tuberc Respir Dis (Seoul) (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388904&req=5

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.
Mentions: Eight patients (80%) had TDM for at least one drug performed (maximum 6 drugs). Patients without TDM either died early (patient 2) or were transferred out of care (patient 6). Initial TDM was performed at a median of 6.5 weeks (minimum 2, maximum 14 weeks) after MDR-TB treatment initiation. Of the eight subjects with initial TDM, six (75%) had at least one follow-up concentration performed, though for some medications repeat testing was performed without dose adjustment (Figure 1). All dose increase or decrease led to C2hr increase or decrease respectively in subjects with follow-up samples, while follow-up C2hr concentrations were not significantly different if the dose was unchanged (Figure 1). Limited 6-hour concentrations for delayed absorption generally supported the 2-hour result (Table 2). For the medications most frequently checked (cycloserine, capreomycin, and moxifloxacin), no demographic characteristic was associated with a C2hr value below the expected range.

Bottom Line: Drug concentrations, measured at time of estimated peak (Cmax), were compared to expected ranges.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, 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.

No MeSH data available.


Related in: MedlinePlus