title: Pharmacokinetic evaluation of fluconazole in critically ill patients.
abstract: BACKGROUND
  Invasive candidiasis has emerged over the last few decades as an increasingly important nosocomial problem for the critically ill, affecting around 2% of intensive care unit patients. Although poor outcomes associated with invasive candidiasis among critically ill patients may relate to severe underlying disease processes and delayed institution of antifungal therapy, inadequate dosing of antifungal agents may also contribute.
  
  
  METHODS
  This drug evaluation provides a critical appraisal of the published literature pertaining to the pharmacokinetics of fluconazole in critically ill, obese or severely burned patients, including those receiving acute renal replacement therapy. The pharmacodynamics of fluconazole is also covered, as well as the likely clinical implications for optimal dosing and the toxicity of fluconazole. Last, variations in fluconazole susceptibility patterns of Candida spp. are also discussed.
  
  
  CONCLUSIONS
  Recently, there has been an increased but geographically variable prevalence of non-albicans Candida spp., causing invasive candidiasis and an overall trend towards reduced fluconazole susceptibility. The pathophysiological changes of critical illness, coupled with a lack of dose finding studies, support the use of local susceptibility patterns to guide fluconazole dosing until such time as pharmacokinetic-pharmacodynamic information to guide optimal fluconazole dosing strategies and pharmacodynamic targets becomes available.
authors: The Queen Elizabeth Hospital, Pharmacy Department, Adelaide, Australia.
authors: Mahipal
authors: M
authors: Sinnollareddy
authors: Sandra L
authors: SL
authors: Peake
authors: Michael S
authors: MS
authors: Roberts
authors: E Geoffrey
authors: EG
authors: Playford
authors: Jeffrey
authors: J
authors: Lipman
authors: Jason A
authors: JA
authors: Roberts
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D058365:Candidiasis, Invasive / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D016638:Critical Illness; D004341:Drug Evaluation; D015725:Fluconazole / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole