Therapeutic Drug Monitoring of Linezolid in Real-World Clinical Practice: Determinants of Exposure, Dose Optimization, and Hematological Toxicity.

Abstract

Introduction: Linezolid exhibits significant pharmacokinetic variability in hospitalized patients, which may lead to suboptimal exposure or toxicity. Therapeutic drug monitoring (TDM) has been proposed to optimize treatment, although real-world data under standardized dosing conditions remain limited. The objective was to evaluate linezolid exposure in routine clinical practice under standardized dosing conditions and to identify factors associated with overexposure, dose optimization, and hematological toxicity.

Methods: A retrospective observational study was conducted using a hospital-based TDM database. Only patients receiving linezolid 600 mg every 12 h were included. A single trough concentration (C_min) per patient was analyzed, defined as the first determination obtained at ≥48 h after treatment initiation. Exposure was categorized as subtherapeutic (<2 µg/mL), therapeutic (2-10 µg/mL), or supratherapeutic (>10 µg/mL). Logistic regression analyses were performed to identify factors associated with overexposure and thrombocytopenia.

Results: A total of 76 patients were included. The mean C_min was 4.75 ± 4.45 µg/mL (median 3.07; range 0.67-23.6). Subtherapeutic, therapeutic, and supratherapeutic exposure occurred in 26.3%, 60.5%, and 13.2% of patients, respectively, with 39.5% of patients outside the therapeutic range. Age was associated with higher exposure (odds ratio: 1.03 per year; p = 0.025), while renal function showed a nonsignificant trend. Thrombocytopenia occurred in approximately 5-6% of patients and showed a nonsignificant association with higher trough concentrations. TDM led to dose modification in a relevant proportion of patients.

Conclusion: Linezolid exposure shows substantial interindividual variability in hospitalized patients despite standardized dosing. A considerable proportion of patients present subtherapeutic or supratherapeutic concentrations. TDM may help identify patients at risk of underexposure or toxicity and support individualized dosing strategies, particularly in elderly patients and those with renal impairment.