Dose finding in aspergillosis

Invasive aspergillosis (IA) continues to represent a significant challenge for physicians in charge of immunocompromised patients. Voriconazole, caspofungin, itraconazole, and the different formulations of amphotericin B (AmB) are all approved for therapy of IA. To collect information on the effect of high dose of antifungals in the treatment of IA, data from the available medical literature were reviewed. For AmB there are no data demonstrating any better clinical activity of doses higher than standard. For liposomal-AmB preliminary data seem to show that high doses are not more efficacious than the standard dose, and it is probably more toxic. Anecdotal data of itraconazole suggest that high dosages might be feasible and it has been associated with good clinical results. Unpublished data about voriconazole suggest the absence of any better activity of high plasma concentrations. For caspofungin the efficacy of higher dosage did not seem to be better than that obtained with the traditional dosage. Prospective studies are required, because many confounding factors may obscure the effects of the higher dosages when data are retrieved retrospectively.