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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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