Issues in the design and interpretation of antifungal drug trials in the critically ill.

Objective: Invasive fungal infections, such as invasive candidiasis and aspergillosis, are increasingly important in the critical care setting. This review will focus on clinical trials of antifungals in this setting and the methodological issues surrounding them.

Results: Critically ill patients have traditionally only comprised a fraction of the patients enrolled in clinical trials exploring antifungal use, but recently a few clinical trials with specific therapeutic approaches have focused on this subpopulation. Increased mortality and problems with diagnosis have fostered the development of new management strategies, such as prophylaxis, pre-emptive treatment, and empirical antifungal therapy.

Conclusions: Although there are limited data supporting preventive and early therapeutic strategies, their use is recommended in highly selected patients and settings. Although critically ill patients are under-represented in clinical trials of antifungals conducted for the purpose of licensing, most experts agree that it is reasonable to extrapolate from these data until specific trials are conducted.