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?

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 (Cmin) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of Cmin was set between 2 and 7 mg/L (underexposure, Cmin < 2 mg/L; overexposure, Cmin > 7 mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid Cmin. One thousand and forty-nine patients had 2484 linezolid Cmin assessed during treatment with conventional doses. Median (IQR) linezolid Cmin was 5.08 mg/L (2.78–8.52 mg/L). Linezolid Cmin 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 CrCLC-G estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124–1.904, p = 0.005). Linezolid underexposure was significantly associated with CrCLC-G estimates >100 mL/min. (OR 3.046; 95% CI 2.234–4.152, p < 0.001). Linezolid Cmin was not correlated linearly with CrCLC-G (R2 = 0.061). Variability in renal function explained only partially the very wide interindividual linezolid Cmin variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients.