Antibiotic dosing for critically ill patients that is derived from other patient groups is likely to be suboptimal because of significant antibiotic pharmacokinetic changes, particularly in terms of drug volume of distribution and clearance. Organ support techniques including renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) increase the pharmacokinetic variability. This article reviews the recently published antibiotic pharmacokinetic data associated with burns patients, those receiving continuous RRT (CRRT), sustained low-efficiency dialysis (SLED) and ECMO.
These groups develop increases in volume of distribution that necessitate the use of higher initial doses to rapidly achieve therapeutic antibiotic concentrations. Burns patients have supranormal drug clearances requiring more frequent administration of antibiotics. Patients receiving CRRT or SLED have variable drug clearances related to different equipment and RRT settings at different institutions. ECMO presents a different challenge because there is such a dearth of data with higher than standard doses potentially required, even in the presence of end-organ failure.
In the context of such variable pharmacokinetics, a guideline approach to dosing remains elusive because of insufficient available data and, therefore, use of therapeutic drug monitoring should be considered advantageous where possible.
aBurns, Trauma and Critical Care Research Centre, University of Queensland
bDepartment of Intensive Care Medicine
cPharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
Correspondence to Professor Jeffrey Lipman, Burns, Trauma and Critical Care Research Centre, Level 3, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, QLD 4029, Australia. Tel: +61 73 646 1852; fax: +61 73 646 3542; e-mail: firstname.lastname@example.org