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

Abstract

Objectives The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four β-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 β-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 β-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 β-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the β-lactam dosages in clinical practice.