Antifungal Dosing Considerations in Patients Undergoing Continuous Renal Replacement Therapy

Abstract

The incidence of systemic fungal infections is increasing among patients admitted to the intensive care unit (ICU). Acute kidney injury (AKI) occurs in one third of ICU patients and approximately 5% require renal replacement therapy (RRT). Among those requiring RRT, continuous RRT (CRRT) is used in more than 70% of cases. This review aims to summarize antifungal dosing management in ICU patients receiving CRRT. For most antifungal agents, including new azoles such as posaconazole and isavuconazole, CRRT does not significantly affect antifungal pharmacokinetics (PK) mainly due to drug liver elimination and high protein binding. For fluconazole, increased dose is recommended during CRRT taking into account the type of CRRT mode (CVVHF or CVVHDF), membrane surface, and effluent and dialysis flow rates. A dose increase for itraconazole seems also necessary during CRRT; a dose decrease for flucytosine is probably necessary but data are too scarce to give a strong recommendation. In ICU patients receiving CRRT, no dosing adjustment is required for the majority of antifungal agents commonly used to treat invasive fungal infections (IFIs) excepted for fluconazole, itraconazole, and flucytosine. Due to high PK variability, therapeutic drug monitoring should be considered in ICU patients receiving CRRT.