In vitro and in vivo activities of SCH 56592 (posaconazole), a new triazole antifungal agent, against Aspergillus and Candida

SCH 56592 (posaconazole), a new triazole antifungal agent, was tested in vitro, and its activity was compared to that of itraconazole against 39 Aspergillus strains and to that of fluconazole against 275 Candida and 9 Cryptococcus strains. The SCH 56592 MICs for Aspergillus ranged from less than or equal to 0.002 to 0.5 mu g/ml, and those of itraconazole ranged from less than or equal to 0.008 to 1 mu g/ml. The SCH 56592 MICs for Candida and Cryptococcus strains ranged from less than or equal to 0.004 to 16 mu g/ml, and those of fluconazole ranged from less than or equal to 0.062 to >64 mu g/ml. SCH 56592 showed excellent activity against Aspergillus fumigatus and Aspergillus flavus in a pulmonary mouse infection model. When administered therapeutically, the 50% protective doses (PD(50)s) of SCH 56592 ranged from 3.6 to 29.9 mg/kg of body weight, while the PD(50)s of SCH 56592 administered prophylactically ranged from 0.9 to 9.0 mg/kg; itraconazole administered prophylactically was ineffective (PD(50)s, >75 mg/kg). SCH 56592 was also very efficacious against fluconazole-susceptible, -susceptible dose-dependent, or -resistant Candida albicans strains In immunocompetent or immunocompromised mouse models of systemic infection. The PD(50)s of SCH 56592 administered therapeutically ranged from 0.04 to 15.6 mg/kg, while the PD(50)s of SCH 56592 administered prophylactically ranged from 1.5 to 19.3 mg/kg. SCH 56592 has excellent potential for therapy against serious Aspergillus or Candida infections.