Population Pharmacokinetics and Target Attainment of Cefepime in Critically Ill Patients and Guidance for Initial Dosing

Antimicrob Agents Chemother. 2020 Jun 29;AAC.00745-20. doi: 10.1128/AAC.00745-20. Online ahead of print.

Abstract

Cefepime is commonly used in the intensive care unit (ICU) to treat bacterial infections. The time the free cefepime concentration above the minimum inhibitory concentration (fT>MIC) should be optimized to increase the efficacy of the regimen. We aim to optimize the exposure of cefepime in ICU patients using population pharmacokinetic (PK) modeling and simulations. Two datasets were included in this study. The first was a prospective study in pediatric patients who received cefepime 50 mg/kg and had extensive PK sampling. The second was retrospective data for adult ICU patients admitted to UFHealth-Shands hospital, received cefepime, and had cefepime concentration measured. The population PK model was developed and simulations were performed using Pmetrics. The target exposures were 100% fT>MIC and fT>4×MIC A total of 266 patients and the mean age was 3.9 years in pediatric and 55 years in adult group. More than half of patients were males. The mean (SD) creatinine clearance (CrCl) was 125 mL/min (93). The mean (SD) daily dose in adults was 4.9 g (1.6). Cefepime was well described by a two-compartment model with weight as a covariate on volume of distribution and elimination rate constant (ke) and CrCl and age group on ke At MIC of 8 mg/L, cefepime 4g loading dose as extended infusion followed by 6g continuous infusion was needed to achieve good target attainment. In conclusion, prolonged or continuous infusions will be needed to achieve optimal cefepime exposure in ICU patients. Given the observed variability, therapeutic drug monitoring can help individualize therapy.