Treatment of Experimental Murine Aspergillosis with BAY n7133

BAY n7133, a recently developed imidazole antifungal drug, was evaluated in experimental murine aspergillosis. BALB/c mice were challenged with conidia of Aspergillus fumigatus by either the intravenous or the intranasal route. One day after challenge, oral treatment with BAY n7133, ketoconazole, or a placebo control was begun BAY n7133 was well absorbed after oral administration and penetrated all tissues evaluated. There was some evidence for accelerated inactivation of the drug after prolonged therapy. BAY n7133 and ketoconazole both markedly inhibited the growth of mycelia of A fumigatus in vitro. However, only BAY n7133 prolonged the survival time of infected mice. Prolonged survival was associated with a significant reduction in counts of A fumigatus in the lungs. BAY n7133 appeared to be slightly less effective than amphotericin B. In studies with combined drugs, BAY n7133 appeared to add modestly to the benefit conferred by amphotericin B. BAY n7133 seems promising for the treatment of aspergillosis, a disease in which ketoconazole has not been particularly effective.