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Antimicrobial Agents and Chemotherapy, April 1998, p. 907-910, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activity of Voriconazole, a New Triazole, Combined with Neutrophils or Monocytes against Candida albicans: Effect of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

Shefali Vora,1 Nayanatara Purimetla,1 Elmer Brummer,1,2,* and David A. Stevens1,2

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center and California Institute for Medical Research, San Jose,1 and Stanford University School of Medicine, Stanford,2 California

Received 15 August 1997/Returned for modification 20 October 1997/Accepted 27 January 1998

The antifungal activity of voriconazole (VCZ) was tested against Candida albicans in the absence or presence of polymorphonuclear neutrophils (PMN) or monocytes. In some experiments, VCZ was compared to fluconazole (FCZ). On a weight basis, VCZ was 10-fold more efficacious than FCZ against C. albicans Sh27. Against an FCZ-resistant isolate, VCZ at 1 µg/ml produced the same fungistasis as FCZ at 20 µg/ml. VCZ at 0.1 µg/ml collaborated with PMN for enhanced killing to the same extent as FCZ at 1.0 µg/ml. Granulocyte-colony-stimulating factor (G-CSF) enhanced the candidacidal activity of PMN, and it increased the collaboration of PMN with VCZ for killing. Granulocyte-macrophage (GM)-CSF also significantly enhanced both the killing by PMN and the collaboration of PMN with VCZ for killing. VCZ collaborated with monocytes for enhanced killing of C. albicans Sh27, and GM-CSF increased this collaboration. Taken together, these data show that VCZ is more potent than FCZ against C. albicans isolates, alone and in collaboration with PMN or monocytes for enhanced killing. In addition, G-CSF- or GM-CSF-activated PMN and monocytes have enhanced collaboration with VCZ compared to that of unstimulated phagocytes with VCZ.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, 751 S. Bascom Ave., San Jose, CA 95128-2699. Phone: (408) 998-4556. Fax: (408) 998-2723. E-mail: e.brummer{at}juno.com.

Antimicrobial Agents and Chemotherapy, April 1998, p. 907-910, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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