Suboptimal plasma concentrations with posaconazole suspension as prophylaxis in critically ill COVID-19 patients at risk of Covid-associated pulmonary aspergillosis

Abstract

What is known and objective: The safety and efficacy of different antifungal agents in the prophylaxis of invasive fungal infection in patients with haematological disorders are known. We comment on the poor bioavailability of posaconazole suspension to suggest that it is not useful in critically ill COVID patients. Comment: The increased mortality and high incidence of COVID-associated pulmonary aspergillosis (CAPA) might justify administration of off-label posaconazole for preventing CAPA, being the only drug officially registered for prophylaxis of fungal infections. We decided to initiate off-label posaconazole prophylaxis in COVID-19 patients, who were mechanically ventilated and exposed to high-dose steroids for progressive pulmonary disease or ARDS. We found that posaconazole suspension was inadequate. Very low trough levels were observed after administration, and the dose adjustments necessary for the therapeutic drug monitoring (TDM) of the drug in our critically ill ICU patients were not useful. What is new and conclusion: Posaconazole suspension should not be used to prevent CAPA in COVID-19 patients on high-dose steroid therapy.