title: Low but sufficient anidulafungin exposure in critically ill patients.
abstract: The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive Candida infection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of the Candida species were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (Cmax), and minimum concentration of drug in plasma (Cmin) were 69.8 ± 24.1 mg · h/liter, 4.7 ± 1.4 mg/liter, and 2.2 ± 0.8 mg/liter, respectively. The MIC values of all cultured Candida species were below the EUCAST MIC breakpoints. The exposure to anidulafungin in relation to the MIC that was determined appeared sufficient in all patients. The anidulafungin exposure was low in our critically ill patients. However, combined with the low MICs of the isolated Candida strains, the lower exposure observed in comparison to the exposure in the general patient population resulted in favorable AUC/MIC ratios, based on EUCAST data. No correlation was observed between anidulafungin exposure and disease severity or plasma protein concentrations. In patients with less-susceptible Candida albicans or glabrata strains, we recommend considering determining the anidulafungin exposure to ensure adequate exposure. (This trial has been registered at ClinicalTrials.gov under registration no. NCT01047267.).
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands.
authors.forename: Marjolijn J P
authors.initials: MJ
authors.lastname: van Wanrooy
authors.forename: Michael G G
authors.initials: MG
authors.lastname: Rodgers
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.forename: Jan P
authors.initials: JP
authors.lastname: Arends
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zijlstra
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000368:Aged; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D016638:Critical Illness; D054714:Echinocandins / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D000077612:Anidulafungin