Antifungal drug dosing adjustment in critical patients with invasive fungal infections

Critically ill patients suffer from invasive fungal infections, mainly due to Candida spp., but also to Aspergillus spp., Cryptococcus spp. and other more rare yeasts or filamentous fungi. These infections are prevented or treated with various antifungal agents belonging to one of the following classes: polyenes (mainly amphotericin B formulations with liposomal amphotericin B as the most frequently used compound), azoles (fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole) or echinocandins (caspofungin, micafungin and anidulafungin). Administration of these agents may be challenging due to various factors in patients hospitalized in the intensive care unit (ICU). Such factors frequently found in these patients are renal and liver insufficiencies, extreme ages (prematurely born infants or elderly patients), obesity, thermal injury, other co-morbidities, and interactions with many simultaneously administered other drugs. In addition, sepsis itself may cause such hemodynamic changes resulting in increased clearance of antifungal agents. The use of continuous renal replacement therapy and extracorporeal membrane oxygenation needs special attention when antifungal agents are administered. It is very important that the physicians caring for these patients are aware of the impact of such factors on the pharmacokinetics and pharmacodynamics of the antifungal agents administered in the ICU. In addition, they should be aware of the adverse effects of these agents that they administer on the biology and physiology of host’s various organs and the metabolism of other co-administered drugs occurring through these organs. This knowledge may lead to optimization of dosing of the antifungal agents and other interacting medications in order to maximize antifungal effect in the care of critically ill patients.