Optimising cefepime dosing in intensive care: the pharmacokinetics of extended (prolonged) infusions.

Cefepime is a broad spectrum antibiotic used as part of the Alfred Intensive Care Unit (ICU) antibiotic guidelines at a dose of 1g every 12 hours in combination with other agents, higher doses are used (eg 2g every 12 hours) in many international centres. Conventional administration is via short infusion over a few minutes. However the antibacterial effect is dependent on adequate drug concentrations being maintained over most of the period between doses. Extended infusions have been shown in computer modelling to achieve this for cefepime. Clinically, extended infusions have been shown in intensive care patients to be more effective for other antibiotics of similar class to cefepime. This study will be a randomised controlled trial in intensive care patients which aims to compare the pharmacokinetic profile (blood concentrations of the drug over time) of conventional administration of cefepime over a few minutes at the dose of 1g every 12 hours (the dose routinely used in The Alfred ICU) and the higher dose of 2g every 12 hours against an extended infusion of 1g given over 6 hours every 12 hours. Cefepime blood concentration will be obtained from analysis of blood samples taken at predetermined time points over two 12 hour periods on Day 1 and Day 3 (steady state) of therapy. This will allow determination of the pharmacokinetic profile of cefepime in intensive care patients for each of the three dosing regimens. Comparison of these profiles will provide evidence of any advantage of extended infusions in intensive care patients leading to larger scale clinical investigations of this administration method.