Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin.

Author(s): Delattre IK, Musuamba FT, Verbeeck RK, Dugernier T, Spapen H, Laterre PF, Wittebole X, Cumps J, Taccone FS, Vincent JL, Jacobs F, Wallemacq PE

Affiliation(s): Unit of Clinical Biochemistry, Universite Catholique de Louvain, Avenue Hippocrate, 10, B-1200 Brussels, Belgium.

Publication date & source: 2010-04, Clin Biochem., 43(6):589-98. Epub 2009 Dec 28.

Publication type: Evaluation Studies; Research Support, Non-U.S. Gov't

OBJECTIVES: The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens. DESIGN AND METHODS: 69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem. A multivariate analysis was performed to predict the beta-lactam PK using AMK PK parameters estimated from TDM and using pathophysiological variables. RESULTS: An optimal prediction model was identified for each PK parameter of each beta-lactam. The best predictor of each model was one of the AMK PK parameters estimated from TDM. Other variables included colloid solution, renal and hepatic biomarkers, age and body weight. CONCLUSION: PK of the four beta-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the beta-lactam dosages in clinical practice. Copyright 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.