title: Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock.
abstract: Antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD) are important considerations, particularly in critically ill patients with severe sepsis and septic shock. The pathophysiologic changes that occur in these conditions can have a major effect on pharmacokinetic parameters, which in turn could result in failure to achieve pharmacodynamic targets for antimicrobials thus adversely affecting clinical outcome. This paper discusses the pathophysiologic changes that occur during severe sepsis and septic shock and the consequent effects on antimicrobial PK and PD. The effect of PK/PD on specific antimicrobial classes is discussed and a rational framework for antimicrobial dosing is provided. Knowledge of PK/PD properties of antimicrobials can be used to personalize dosing regimens not only to maximize antimicrobial activity but also to minimize toxicity and reduce the development of antimicrobial resistance.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Level 7 Block 6, Royal Brisbane & Women's Hospital, Brisbane Queensland 4029, Australia.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Varghese
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016638:Critical Illness / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents