Improving cefazolin exposure in critically ill children using a population pharmacokinetic model.

Abstract

Population pharmacokinetics (PK) models may be effective in improving antibiotic exposure with individualized dosing. The aim of the study is to assess cefazolin exposure using a population PK model in critically ill children. We conducted a single-centre observational study including children under 18 years old who had cefazolin plasma monitoring before and after a cefazolin model implementation. The first concentration at steady state of each cefazolin course was analysed. The optimal exposure was defined by concentration values ranging from free concentration over four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval to total trough or plateau concentration under 100 mg. L-1. A total of 58 patients were included, of whom 39 and 19 children received conventional dosing or model-informed dosing, respectively. Median [range] age was 2.3 [0.1-17]years old, and median weight was 14.2 [2.9-72]kg. There were more continuous infusions (CI) in the model group than in the conventional group (n= 19/19 [100%] vs. n= 23/39 [59%]). Compared to conventional dosing, model-informed dosing provided more optimal exposure (n= 17/39 [44%] vs. n= 15/19 [79%], P= .01) and less underexposure (n= 18/39 [46%] vs. n= 2/19 [10%], P= .008), without increasing overexposure (n= 4/39 [10%] vs. n= 2/19 [11%], P= 1). Moreover, the time to C-reactive protein decrease by 50% was significantly shorter in the model group than the conventional group (3 [0.5-13] vs. 4 [1-34]; P= .045). Use of individualized cefazolin model-informed dosing improves critically ill children's exposure. Further studies are needed to assess the clinical benefit of cefazolin PK model application.