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Antimicrobial Agents and Chemotherapy, September 1998, p. 2371-2374, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Efficacy of Nikkomycin Z in the Treatment of Murine Histoplasmosis

John R. Graybill,1,2,* Laura K. Najvar,2 Rosie Bocanegra,2 Richard F. Hector,3 and Michael F. Luther1

Audie Murphy Memorial Veterans Hospital,1 University of Texas Health Science Center,2 San Antonio, Texas 78284, and Shaman Pharmaceuticals, South San Francisco, California 940803

Received 29 December 1997/Returned for modification 30 January 1998/Accepted 10 June 1998

Immune-competent ICR and BALB/c athymic (nude) mice were infected intravenously with Histoplasma capsulatum and treated with either fluconazole or nikkomycin Z or 5% dextrose (controls). In immune-competent ICR mice, fluconazole and nikkomycin Z both prolonged survival when given at 5 mg/kg of body weight twice daily. When administered in doses as low as 2.5 mg/kg twice daily, nikkomycin Z reduced fungal counts in both the spleen and liver. When both drugs were combined, there was no antagonism, and in combined therapy spleen and liver counts were reduced more than for either drug alone. However, nikkomycin Z had no effect on brain fungal burden. In nude mice fluconazole and nikkomycin Z had an additive effect in prolongation of survival and reduction of liver and spleen burden. Nikkomycin Z is well tolerated, is at least as effective as fluconazole, and may interact beneficially with fluconazole for treatment of murine histoplasmosis.

* Corresponding author. Mailing address: Division of Infectious Diseases (111F), Audie Murphy Memorial Veterans Hospital, 7400 Merton Minter Blvd., San Antonio, TX 78284.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2371-2374, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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