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

The antifungal activity of voriconazole (VCZ) was tested against Candi da albicans in the absence or presence of polymorphonuclear neutrophil s (PMN) or monocytes. In some experiments, VCZ was compared to flucona zole (FCZ). On a weight basis, VCZ was 10-fold more efficacious than F CZ against C. albicans Sh27. Against an FCZ-resistant isolate, VCZ at 1 mu g/ml produced the same fungistasis as FCZ at 20 mu g/ml. VCZ at 0 .1 mu g/ml collaborated with PMN for enhanced killing to the same exte nt as FCZ at 1.0 mu g/ml. Granulocyte-colony-stimulating factor (G-CSF ) enhanced the candidacidal activity of PMN, and it increased the coll aboration of PMN with VCZ for killing. Granulocyte-macrophage (GM)-CSF also significantly enhanced both the killing by PMN and the collabora tion of PMN with VCZ for killing. VCZ collaborated with monocytes for enhanced killing of C. albicans Sh27, and GM-CSF increased this collab oration. 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-activa ted PMN and monocytes have enhanced collaboration with VCZ compared to that of unstimulated phagocytes with VCZ.