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Journal of Antimicrobial Chemotherapy (1999) 44, 827-829
© 1999 The British Society for Antimicrobial Chemotherapy

Brief report

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans

Mohammad Ashraf Hossain, Shigefumi Maesaki, Kotaro Mitsutake, Hiroshi Kakeya, Eisuke Sasaki, Kazunori Tomono, Takayoshi Tashiro and Shigeru Kohno*,

Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC90s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 ± 0.21 log10 cfu/g), as compared with fluconazole (7.77 ± 0.07 log10 cfu/g) and control (7.79 ± 0.1 log10 cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 ± 0.62 ng/ml) than in plasma (2.16 ± 0.86 ng/mL), and this was maintained for 12 h after administration.

* Corresponding author. Tel: +81-95-849-7271; Fax: +81-95-849-7285; E-mail: sk1227{at}net.nagasaki-u.ac.jp


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