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Antimicrobial Agents and Chemotherapy, July 1999, p. 1716-1718, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Activities of Sordarins in Murine Histoplasmosis

John R. Graybill,1,2,* Laura Najvar,1 Annette Fothergill,2 Rosie Bocanegra,1 and Federico Gomez de las Heras3

University of Texas Health Science Center1 and Veterans Administration Hospital,2 San Antonio, Texas, and Glaxo Wellcome SA, Tres Cantos, Madrid, Spain3

Received 30 December 1998/Returned for modification 26 February 1999/Accepted 23 April 1999

Sordarins are new antifungals which inhibit fungal protein synthesis by blocking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune-competent mice were infected intravenously with 106 to 108 CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after infection or intraperitoneally with amphotericin B during the same period. Protection was measured by increased rates of survival for 30 days after infection or reduction of lung or kidney tissue counts 9 days after infection. All three of the antifungal drugs tested were protective compared with controls. Sordarins were effective at doses as low as 2 mg/kg of body weight/day. This novel class of drugs compared favorably with amphotericin B and fluconazole for the treatment of histoplasmosis.

* Corresponding author. Mailing address: Infectious Diseases Service, South Texas Veterans Administration Hospital, 7400 Merton Minter Blvd., San Antonio, TX 78284. Phone: (210) 617-5111. Fax: (210) 614-6197. E-mail: graybill{at}uthSCSA.edu.

Antimicrobial Agents and Chemotherapy, July 1999, p. 1716-1718, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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