Sub-therapeutic initial ?-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations.
Chest. 2011 Dec 22;
Authors: Udy AA, Varghese JM, Altukroni M, Briscoe S, McWhinney B, Ungerer J, Lipman J, Roberts JA
Abstract
Abstract BACKGROUND:?-lactams are routinely employed as empirical therapy in critical illness, with extended concentrations above the minimum inhibitory concentration (MIC) of the infecting organism, required for effective treatment. Changes in renal function in this setting can significantly impact on the probability of achieving such targets. METHODS:Analysis of trough plasma drug concentrations obtained via therapeutic drug monitoring (TDM), compared with renal function, in critically ill patients receiving empirical ?-lactam therapy. Drug concentrations were measured by means of high performance liquid chromatography, and corrected for protein binding. Therapeutic levels were defined as ? MIC, and ? 4 × MIC (maximum bacterial eradication) respectively. Renal function was assessed by means of an 8-hour creatinine clearance (CL(CR)). RESULTS:Fifty-two concurrent trough concentrations and CL(CR) measures were employed in analysis. Piperacillin was the most frequent ?-lactam prescribed (48%), while empirical cover and Staphylococcus spp. were the most common indications for therapy (62%). Most patients were mechanically ventilated on the day of study (85%), although only 25% were receiving vasopressors. In only 58% (n=30) was the trough drug concentration ? MIC, falling to 31% (n=16) when using 4 × MIC as the target. CL(CR) values ? 130ml/min/1.73m(2) were associated with trough concentrations < MIC in 82% (p<0.001), and < 4 × MIC in 72% (p<0.001). CL(CR) remained a significant predictor of sub-therapeutic concentrations in multivariate analysis. CONCLUSION:Elevated CL(CR) appears to be an important predictor of sub-therapeutic ?-lactam concentrations, and suggests an important role in identifying such patients in the intensive care unit.
PMID: 22194591 [PubMed - as supplied by publisher]