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.).