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