A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital-wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

Abstract

A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (C_min ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of C_min was set between 2 and 7 mg/L (underexposure, C_min < 2 mg/L; overexposure, C_min > 7 mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid C_min . One thousand and forty-nine patients had 2484 linezolid C_min assessed during treatment with conventional doses. Median (IQR) linezolid C_min was 5.08 mg/L (2.78-8.52 mg/L). Linezolid C_min was within the desired range in 50.8% of cases (1262/2484). Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n = 401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid overexposure was significantly associated with CrCL_C-G estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly associated with CrCL_C-G estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p < 0.001). Linezolid C_min was not correlated linearly with CrCL_C-G (R² = 0.061). Variability in renal function explained only partially the very wide interindividual linezolid C_min variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients.