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Pharmacokinetic issues for antibiotics in the critically ill patient

Section Editor(s): Dellinger, R Phillip MD, FCCMRoberts, Jason A. B Pharm (Hons); Lipman, Jeffrey FJFICM, MD

doi: 10.1097/CCM.0b013e3181961bff
Continuing Medical Education Article: Concise Definitive Review

Objective: To discuss the altered pharmacokinetic properties of selected antibiotics in critically ill patients and to develop basic dose adjustment principles for this patient population.

Data Sources: PubMed, EMBASE, and the Cochrane-Controlled Trial Register.

Study Selection: Relevant papers that reported pharmacokinetics of selected antibiotic classes in critically ill patients and antibiotic pharmacodynamic properties were reviewed. Antibiotics and/or antibiotic classes reviewed included aminoglycosides, β-lactams (including carbapenems), glycopeptides, fluoroquinolones, tigecycline, linezolid, lincosamides, and colistin.

Data Synthesis: Antibiotics can be broadly categorized according to their solubility characteristics which can, in turn, help describe possible altered pharmacokinetics that can be caused by the pathophysiological changes common to critical illness. Hydrophilic antibiotics (e.g., aminoglycosides, β-lactams, glycopeptides, and colistin) are mostly affected with the pathphysiological changes observed in critically ill patients with increased volumes of distribution and altered drug clearance (related to changes in creatinine clearance). Lipophilic antibiotics (e.g., fluoroquinolones, macrolides, tigecycline, and lincosamides) have lesser volume of distribution alterations, but may develop altered drug clearances. Using antibiotic pharmacodynamic bacterial kill characteristics, altered dosing regimens can be devised that also account for such pharmacokinetic changes.

Conclusions: Knowledge of antibiotic pharmacodynamic properties and the potential altered antibiotic pharmacokinetics in critically ill patients can allow the intensivist to develop individualized dosing regimens. Specifically, for renally cleared drugs, measured creatinine clearance can be used to drive many dose adjustments. Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring.

Research Fellow (JR), the University of Queensland, Pharmacy Department, Royal Brisbane and Women’s Hospital, Herston, Australia; and Professor (JL), University of Queensland and Royal Brisbane and Women’s Hospital, Herston, Australia.

Supported, in part, by the Australian and New Zealand College of Anesthetists, Society of Hospital Pharmacists of Australia, the Queensland State Government—Smart State Initiative, Royal Brisbane and Women’s Hospital Research Foundation and the Australian National Health and Medical Research Council (519702). Supported by the Australian National Health and Medical Research Council (JAR) (409931).

Dr. Lipman holds consultancies with AstraZeneca and Wyeth. Mr. Roberts has not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins