https://orcid.org/0000-0001-9002-7052
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Nicole F Maranchick, Charles A Peloquin, Connie A Haley, Linezolid Dosing and Pharmacokinetics in North American Patients With Tuberculosis, Clinical Infectious Diseases, 2025;, ciaf027, https://doi.org/10.1093/cid/ciaf027
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Abstract
Linezolid is recommended in treatment regimens for rifampin- or multidrug-resistant tuberculosis (TB). However, considerable pharmacokinetic variability exists, and long-term use is limited by adverse effects. This study evaluates the pharmacokinetics of linezolid in patients with TB from an international therapeutic drug monitoring (TDM) service.
Linezolid trough, 2-hour, and 6-hour postdose clinical samples from across North America were tested by the University of Florida Infectious Disease Pharmacokinetics Laboratory. Total serum concentrations were measured using liquid chromatography–tandem mass spectrometry. TDM was performed, and measurements were compared to typical linezolid concentrations including a trough value of <2 μg/mL and peak value between 12 and 26 μg/mL.
From January 2019 to December 2023, 1604 linezolid samples from 500 patients and 817 unique TDM occasions were analyzed. Trough concentrations were measured on 670 samples (median, 1.19 [range, 0.00–20.06] μg/mL), and 232 troughs (34.6%) were >2 μg/mL. Among trough samples from linezolid dosing of 600 mg daily, 43.2% were >2 μg/mL. Of 600 peak samples, 264 (44%) were outside the typical range, most (89%) being subtherapeutic at <12 μg/mL.
High serum linezolid trough concentrations were measured in approximately one-third of samples and in >40% of those taking the recommended dose. More than 40% of peak concentrations were outside typical range, of which 89% were <12 μg/mL. This study demonstrates that TDM can be used to identify patients with serum linezolid concentrations outside of targeted ranges, allowing clinicians to make appropriate dose adjustments to improve outcomes.
