title: Pharmacokinetic issues for antibiotics in the critically ill patient.
abstract: 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.
  
  
  METHODS
  PubMed, EMBASE, and the Cochrane-Controlled Trial Register.
  
  
  METHODS
  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, beta-lactams (including carbapenems), glycopeptides, fluoroquinolones, tigecycline, linezolid, lincosamides, and colistin.
  
  
  RESULTS
  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, beta-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.
authors.affiliation: University of Queensland, Pharmacy Department, Royal Brisbane and Women's Hospital, Herston, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
mesh_terms: D000900:Anti-Bacterial Agents / Q000145:classification / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness; D006801:Humans; D018805:Sepsis / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents