Pharmacokinetics and pharmacodynamics of Linezolid in burn patients

Burns induce complex physiological changes such as modification of distribution volume, increased clearance of elements and decrease of protein binding. The pharmacokinetics of many antibiotics may then be modified, which requires dose adjustment. We attempted to evaluate the pharmacokinetics of linezolid in burn patients at a standard dose of 600 mg intravenously thrice a day. A prospective study was conducted in a 20-bed adult burn ICU at a university-affiliated teaching hospital in Tunis. Thirteen adult burned patients with documented and/or suspected multi drug resistant (MDR) gram-positive bacterium-related infections were enrolled in the study. Our study suggests that linezolid dosing at 600mg thrice a day leads to adequate pharmacodynamic/pharmacokinetic exposure to linezolid with a Cmin > 2mg/l in 84.6% of cases, T > MIC in about 87.5% and AUC/MIC > 100 in 61.5% of cases. However, a high variability in linezolid serum concentrations with a substantial percentage of sub-therapeutic levels was observed in a few patients, 15% of cases. Therefore, therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in burned patients, to avoid the risk of treatment failure or of dose-dependent toxicity.