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Antimicrobial Agents and Chemotherapy, October 1998, p. 2630-2632, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro and In Vivo Efficacy of the Triazole TAK-187 against Cryptococcus neoformans

Wiley A. Schell,1,2 Gisele Madeira Duboc De Almeida,3 Richard K. Dodge,4 Kenji Okonogi,5 and John R. Perfect1,2,*

Division of Infectious Diseases, Department of Medicine, Duke University Medical Center,1 Veterans Affairs Medical Center,2 and Duke Cancer Center Biostatistics,4 Durham, North Carolina; Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil3; and Takeda Chemical Industries, Ltd., Osaka, Japan5

Received 12 December 1997/Returned for modification 16 July 1998/Accepted 3 August 1998

Multiple isolates of Cryptococcus neoformans, including those with fluconazole resistance, were tested to assess the in vitro activity of the new triazole TAK-187. MICs of TAK-187 were at least eightfold lower than those of fluconazole, and fungicidal concentrations for most isolates were 4 µg/ml or less. TAK-187 also was evaluated as intermittent therapy using two dosages in a rabbit model of experimental cryptococcal meningitis. Compared to daily treatment with fluconazole, as little as two doses of TAK-187 given 7 days apart were found to be effective. Plasma and cerebrospinal fluid TAK-187 concentrations were many times higher than MICs and fungicidal concentrations. Based upon its therapeutic efficacy and long half-life in the rabbit model, TAK-187 should be investigated for intermittent dosing in treatment or suppression of cryptococcal infections in humans.

* Corresponding author. Mailing address: Box 3353, Duke Medical Center, Durham, NC 27710. Phone: (919) 684-4016. Fax: (919) 684-8902. E-mail: Perfe001{at}MC.DUKE.EDU.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2630-2632, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Miller, J. L., Schell, W. A., Wills, E. A., Toffaletti, D. L., Boyce, M., Benjamin, D. K. Jr., Bartroli, J., Perfect, J. R. (2004). In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans. Antimicrob. Agents Chemother. 48: 384-387 [Abstract] [Full Text]  
  • Andriole, V. T. (1999). Current and future antifungal therapy: new targets for antifungal agents. J Antimicrob Chemother 44: 151-162 [Abstract] [Full Text]  


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