Optimizing dosing of antibiotics in critically ill patients

Suzanne L. Parker, Fekade B. Sime, Jason A. Roberts

Recent studies suggest that contemporary antibiotic dosing is unlikely to achieve best outcomes for critically ill patients because of extensive pharmacokinetic variability and altered pharmacodynamics. Dose adaptation is considered quite challenging because of unpredictable dose-exposure relationships. Consequently, individualization of antibiotic dosing has been advocated. Herein, we describe recent developments in the optimization of antibiotic dosing in the critically ill. Conventional doses of many antibiotics frequently result in sub or supratherapeutic exposures in the critically ill. Clinical studies continue to illustrate that dose-exposure relationships are highly variable in severely ill patients. Dose optimization based on pharmacokinetic/pharmacodynamic principles can effectively improve antibiotic exposure. Therapeutic drug monitoring (TDM) with adaptive feedback is likely to be the most robust approach to optimize dosing for individual patients. This more accurate approach to dosing is made possible with the user-friendly dosing software that is emerging. The scope of TDM is broadening from the traditional focus on prevention of toxicity, to include optimization of antibiotic exposure thereby improving patient outcomes. However, the evidence relating TDM practice with improved clinical outcome remains limited. Well designed, multicentre, randomized controlled studies are warranted.