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  • Title: Plasma exposure of free linezolid and its ratio to minimum inhibitory concentration varies in critically ill patients.
    Author: Yagi T, Naito T, Doi M, Nagura O, Yamada T, Maekawa M, Sato S, Kawakami J.
    Journal: Int J Antimicrob Agents; 2013 Oct; 42(4):329-34. PubMed ID: 23988716.
    Abstract:
    The clinical implications of free linezolid monitoring have not been fully clarified in critically ill patients. The aim of this study was to evaluate the variability in pharmacokinetics of free linezolid and its relationship with susceptibility to meticillin-resistant Staphylococcus aureus (MRSA) in critically ill patients. Twenty critically ill MRSA-infected patients receiving intravenous linezolid were enrolled. Blood specimens were collected by 12-h sampling after dosing at Day 7. The medians (interquartile range) of the minimum free concentration, area under the concentration-time curve of total and free linezolid from 0 to 24 h (AUC(0-24) and fAUC(0-24), respectively) and percentage bound were 9.9 μg/mL (5.2-15 μg/mL), 495 μgh/mL (291-695 μgh/mL), 385 μgh/mL (242-528 μgh/mL) and 23% (15-28%), respectively. The medians of the AUC(0-24) and fAUC(0-24) to minimum inhibitory concentration ratios (AUC/MIC and fAUC/MIC) were 248 (144-347) and 192 (109-264), respectively. Two patients failed to achieve adequate levels of AUC/MIC and fAUC/MIC for linezolid. The percentage bound of linezolid in hypoalbuminaemic patients was significantly lower than in non-hypoalbuminaemic patients. A significant correlation was observed between fAUC(0-24) and creatinine clearance. In addition, the fAUC(0-24) was correlated with the minimum free concentration. In conclusion, the plasma level of free linezolid was variable in critically ill patients with renal dysfunction and hypoalbuminaemia. This finding suggests that the monitoring of free linezolid is necessary in critically ill patients.
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