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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?
Author(s) -
Pea Federico,
Cojutti Pier Giorgio,
Baraldo Massimo
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12797
Subject(s) - cmin , linezolid , dosing , medicine , therapeutic drug monitoring , population , cmax , pharmacology , drug , pharmacokinetics , staphylococcus aureus , vancomycin , biology , environmental health , bacteria , genetics
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 Cr CL C ‐G estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124–1.904, p = 0.005). Linezolid underexposure was significantly associated with Cr CL 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 Cr CL C ‐G ( R 2 = 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.