Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill Intensive Care Unit patients

Severely ill Intensive Care Unit (ICU) patients have an increased risk of developing multiresistant Gram-positive infections, largely due to the inappropriate use of antimicrobials. In this study, the pharmacokinetic/pharmacodynamic (PK/PD) profile of linezolid, an antibiotic against Gram-positive infections, was characterised in eight critically ill patients admitted to the ICU. Remarkable variation amongst patients in the PK parameters of linezolid was observed, including a 5-7-fold difference in peak serum concentration (C(max)) (mean +/- standard deviation 15.70 +/- 6.58 mg/L) and 12-h area under the serum concentration-time curve (AUC(0-12)) (96.73 +/- 56.45 mg h/L), although the minimum inhibitory concentration (MIC) was similar amongst patients. In particular, variation amongst patients was found in the ratio of AUC(0-24)/MIC (range 31.66-216.82, mean 96.73) and the percentage of time that the serum concentration exceeded the MIC (T > MIC) (range 53.4-100%), two parameters used to predict linezolid efficacy. These variations highlight the importance of individual monitoring of linezolid PK/PD properties in critically ill patients. Furthermore, it was observed that regardless of AUC(0-24)/MIC and T > MIC values, the clinical and microbiological responses of patients were primarily affected by the individual's pathophysiological condition. In summary, these findings point to highly variable PK/PD properties of linezolid in severely ill patients, providing the rationale for targeting linezolid dosage to each individual patient's specific properties. An optimal dosage regimen based on individual PK/PD properties and pathophysiological conditions will help reduce the occurrence of resistance in Gram-positive bacteria. (C) 2011 Published by Elsevier B.V. and the International Society of Chemotherapy.