Antifungal Dosing in Critically Ill Patients

Abstract

This article reviews appropriate dosing for antifungals and emphasizes factors specific to the critically ill patient, along with drug pharmacokinetics and pharmacodynamics. The rationale for doses of the echinocandins (caspofungin, micafungin, anidulafungin), triazoles (fluconazole, voriconazole, itraconazole, posaconazole), amphotericin B (including lipid formulations), and flucytosine are discussed.

Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients

“…The safety of fluconazole is illustrated in the Infectious Diseases Society of America treatment guidelines for cryptococcal diseases, in which doses of up to 2000 mg/day are recommended. 33 The simulated AUC values at a CLcr of 100 mL/min and a dose of 800 mg/day ranged from 475 to 1908 (5th to 90th percentiles) lg h/mL (data not shown). Moreover, the high interpatient variability in Vd indicates the wide time range to reach the steady state.…”

“…These results suggest that the dosage of fluconazole should be higher than that recommended by the package insert for critically ill patients with a CLcr of 100 mL/min. The safety of fluconazole is illustrated in the Infectious Diseases Society of America treatment guidelines for cryptococcal diseases, in which doses of up to 2000 mg/day are recommended (33). The simulated AUC values at a CLcr of 100 mL/min and a dose of 800 mg/day ranged from 475 to 1908 (5th to 90th percentiles) μg h/mL (data not shown).…”