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Antimicrobial Agents and Chemotherapy, January 1998, p. 151-153, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Treatment of Histoplasmosis with MK-991 (L-743,872)

John R. Graybill,1,2,* Laura K. Najvar,1 Eleanor M. Montalbo,1 Francesco J. Barchiesi,1 Michael F. Luther,2 and Michael G. Rinaldi1,2

The University of Texas Health Science Center at San Antonio,1 and South Texas Veterans Health Care System, Audie Murphy Division,2 San Antonio, Texas 78284

Received 7 July 1997/Returned for modification 12 August 1997/Accepted 16 October 1997

BALB/c nu/+ immunocompetent and athymic (nu/nu) mice were infected intravenously with yeast cells of Histoplasma capsulatum. Mice were either given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survival or reduction in tissue counts. MK-991 was protective in immunocompetent mice, prolonging survival and reducing counts in spleen and livers at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modestly effective in athymic mice at a higher dose, 5 mg/kg/day. These studies suggest that MK-991 may be appropriate for clinical development in histoplasmosis.

* Corresponding author. Mailing address: South Texas Veterans Health Care System, Audie Murphy Division (111F), 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, January 1998, p. 151-153, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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