title: Influence of sustained low-efficiency diafiltration (SLED-f) on interstitial fluid concentrations of fluconazole in a critically ill patient: Use of microdialysis.
abstract: Acute kidney injury is a common complication in critically ill patients, and hybrid techniques including sustained low-efficiency dialysis/diafiltration (SLED-f) are being increasingly utilised in intensive care units. Most fungal infections occur in the interstitial fluid (ISF) of tissues and successful treatment of a fungal infection relies on the ability of an antifungal agent to achieve adequate concentrations at the site of infection. Tissue distribution of antimicrobials is impaired in critically ill patients owing to a variety of disease-related physiological changes, e.g. sepsis. Fluconazole is a widely used antifungal agent used to treat Candida spp. infections in critically ill patients. The implications for ISF concentrations of enhanced elimination during renal replacement therapy have not yet been reported for fluconazole. The aim of this single-patient case report was to describe the influence of SLED-f on subcutaneous (SC) ISF concentrations of fluconazole and the implications for achieving pharmacokinetic/pharmacodynamic targets. Serial blood and ISF samples were collected at pre- and post-filter ports within the SLED-f circuit and subcutaneously inserted microdialysis probe, respectively. Fluconazole concentrations were measured using a validated chromatography method. The SC ISF-to-plasma partition coefficient of fluconazole in this patient was 0.91, indicating rapid equilibrium. SC ISF fluconazole concentrations consistently decreased after initiating SLED-f. The majority of the fluconazole was eliminated from the SC ISF as a result of redistribution. Considering the extensive tissue re-distribution of fluconazole and observed elimination from tissue compartments, higher doses may be required to treat deep-seated fungal infections.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia. Electronic address: mahi716@yahoo.com.
authors.forename: Mahipal G
authors.initials: MG
authors.lastname: Sinnollareddy
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, SA, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, SA, Australia.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Peake
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D002845:Chromatography; D016638:Critical Illness; D045604:Extracellular Fluid / Q000737:chemistry*; D015725:Fluconazole / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D017551:Microdialysis; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy; D006435:Renal Dialysis / Q000379:methods*; D040521:Subcutaneous Tissue / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: Critically ill patients; Extended daily diafiltration; Fluconazole; Interstitial fluid concentration; Microdialysis; Sustained low-efficiency diafiltration