The Relevance of Drug Clearance to Antibiotic Dosing in Critically Ill Patients

Darren      M. Roberts

Abstract

To maximise the effect of an antibiotic it is necessary to pay careful attention to dosing. The maintenance dose is determined by antibiotic clearance which is usually determined in young healthy adults with normal physiology. Antibiotic clearance in critically ill patients may increase or decrease due to altered physiology and the treatments that are administered. Clearance may also vary significantly over time in patients with critical illness. Advancing age and comorbidities, in particular chronic kidney disease, can also decrease antibiotic clearance. Therefore, it is complicated and arguably impossible to suggest generic guidelines for the dosing of antibiotics in critically ill patients. Factors that influence clearance must be identified and accounted for in each patient for a rational approach to dose adjustment of antibiotics in patients with critical illness. The necessary changes can be predicted by understanding pharmacokinetic concepts. It is necessary to quantify organ function in patients at multiple time points because this can be used to estimate antibiotic clearance and guide dose selection. For example, creatinine clearance should be calculated but methods used in ambulatory patients may not apply to patients with critical illness. If possible, therapeutic drug monitoring should be conducted to ensure that antibiotic concentration targets are achieved and also to guide titration of subsequent doses. If blood sampling is carefully planned it may be possible to directly measure antibiotic clearance for dose adjustment. The purpose of this article is to review the concept of clearance and to highlight circumstances where antibiotic clearance may be altered in patients with critical illness. Strategies for dose modification of antibiotics in critically ill patients will be discussed.

Keywords: Clearance, antibiotic, critical illness, pathophysiology, pharmacokinetics, estimation, organ function in patients, particular chronic kidney disease, renal system, volume of distribution (Vd), glomerular filtration rate (GFR), multiple organ systems, macrolide antibiotic, hydrophilic antibiotics, Multiple-compartmental kinetics