Pharmacokinetic/pharmacodynamic considerations for the optimization of antimicrobial delivery in the critically ill.
OBJECTIVE
Antimicrobials are very commonly used drugs in the intensive care setting. Extensive research has been conducted in recent years to describe their pharmacokinetics/pharmacodynamics in order to maximize the pharmacological benefit and patient outcome. Translating these new findings into clinical practice is encouraged.


RESULTS
This article will discuss mechanistic data on factors causing changes in antimicrobial pharmacokinetics in critically ill patients, such as the phenomena of augmented renal clearance as well as the effects of hypoalbuminemia, renal replacement therapy, and extracorporeal membrane oxygenation. Failure to achieve clinical cure has been correlated with pharmacokinetics/pharmacodynamics target nonattainment, and a recent meta-analysis suggests an association between dosing strategies aimed at optimizing antimicrobial pharmacokinetics/pharmacodynamics with improvement in clinical cure and survival. Novel dosing strategies including therapeutic drug monitoring are also now being tested to address challenges in the optimization of antimicrobial pharmacokinetics/pharmacodynamics.


CONCLUSIONS
Optimization of antimicrobial dosing in accordance with pharmacokinetics/pharmacodynamics targets can improve survival and clinical cure. Dosing regimens for critically ill patients should aim for pharmacokinetics/pharmacodynamics target attainment by utilizing altered dosing strategies including adaptive feedback using therapeutic drug monitoring.
aBurns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland bDepartment of Intensive Care Medicine cPharmacy Department, Alice Springs Hospital, Alice Springs, Northern Territory dDepartment of Intensive Care Medicine ePharmacy Department, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia fDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.
Danny
D
Tsai
Jeffrey
J
Lipman
Jason A
JA
Roberts
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D016638:Critical Illness / Q000628:therapy*; D054796:Drug Dosage Calculations; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D034141:Hypoalbuminemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007677:Kidney Function Tests; D008826:Microbial Sensitivity Tests; D017582:Renal Replacement Therapy / Q000379:methods*
D000900:Anti-Bacterial Agents