Efficacy of oral saperconazole in systemic murine aspergillosis

Saperconazole is a fluorinated bis-triazole. Groups of ten 5-week-old female CD-1 mice were infected intravenously with 5.5 x 10(7) Aspergillus conidia. Saperconazole, dissolved in hydroxypropyl-beta-cyclodextrin (HPBC), was given orally twice a day for 11 days, beginning 1 day post-infection, at 50, 100 or 200 mg kg-1 day-1. At day 18 post-infection, survivors were killed and residual infection quantified in the kidneys. With Aspergillus fumigatus isolate 10AF, 70% given no therapy, 100% given daily oral HPBC and 40% given intraperitoneal amphotericin B at 3.3 mg kg-1 three times a week for 2 weeks died, whereas all mice given saperconazole survived. Each saperconazole regimen prolonged survival compared to untreated or HPBC treated mice (P < 0.01). Saperconazole at 200 mg kg-1 day-1 reduced colony forming units of aspergillus in kidneys more than 1000-fold compared to untreated or HPBC treated mice (P < 0.001) and saperconazole regimens were superior to amphotericin B therapy (P < 0.01). In another study of the same design with A. fumigatus isolate 15AF, 90% of untreated and 20% of mice treated with saperconazole at 50 mg kg-1 day-1 died; all others survived. Any saperconazole regimen prolonged survival (P < 0.001). Residual infection was also significantly reduced by all saperconazole regimens (P < 0.01). With Aspergillus terreus isolate 4AT, 80% of untreated mice, 50% of mice treated with saperconazole at 50 mg kg-1 day-1 and 10% of mice treated at 200 mg kg-1 day-1 died. Any saperconazole regimen prolonged survival (P < 0.05). Saperconazole at 100 and 200 mg kg-1 day-1 also reduced residual infection (P < 0.001). No adverse effects were noted in any study. Thus, saperconazole was efficacious in vivo against different Aspergillus isolates.