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Antimicrobial Agents and Chemotherapy, September 1998, p. 2299-2303, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activity of Voriconazole Combined with Neutrophils or Monocytes against Aspergillus fumigatus: Effects of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

Shefali Vora,1 Sharda Chauhan,1 Elmer Brummer,1,2,3 and David A. Stevens1,2,3,*

California Institute for Medical Research1 and Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center,2 San Jose, and Stanford University School of Medicine, Stanford,3 California

Received 12 January 1998/Returned for modification 8 May 1998/Accepted 11 June 1998

Voriconazole (VCZ) was tested for antifungal activity against Aspergillus fumigatus hyphae alone or in combination with neutrophils or monocytes. Antifungal activity was measured as percent inhibition of hyphal growth in assays using the dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] or XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]. With both assays, VCZ inhibited hyphal growth at concentrations of <1 µg/ml and was almost as active as amphotericin B. VCZ (0.6 µg/ml) was sporicidal, as was amphotericin B (0.4 µg/ml). With both the MTT and XTT assays, neutrophils alone inhibited hyphae; when combined with VCZ, there was additive activity. Both granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated polymorphonuclear neutrophils (PMN) had enhanced inhibition of hyphal growth. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. Monocytes inhibited hyphal growth. When VCZ was combined with monocytes or monocytes were treated with GM-CSF, inhibition was significantly increased, to similar levels. However, the combination of VCZ with GM-CSF treatment of monocytes did not significantly increase the high-level inhibition by monocytes with either agent alone.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, CA 95128-2699. Phone: (408) 885-4313. Fax: (408) 885-4306. E-mail: stevens{at}leland.stanford.edu.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2299-2303, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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