ACTIVITY OF VORICONAZOLE COMBINED WITH NEUTROPHILS OR MONOCYTES AGAINST ASPERGILLUS-FUMIGATUS - EFFECTS OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Voriconazole (VCZ) was tested for antifungal activity against Aspergil lus fumigatus hyphae alone or in combination with neutrophils or monoc ytes. Antifungal activity was measured as percent inhibition of hyphal growth in assays using the dye MTT (4,5-dimethylthiazol-2-yl)-2,5-dip henyltetrazolium bromide] or XXT [2,3-bis ro-5-sulfophenyl)-2H-tetrazo lium-5-carboxanilide]. With both assays, VCZ inhibited hyphal growth a t concentrations of <1 mu g/ml and was almost as active as amphoterici n B. VCZ (0.6 mu g/ml) was sporicidal, as was amphotericin B (0.4 mu g /ml). With both the MTT and XTT assays, neutrophils alone inhibited hy phae; when combined with VCZ, there was additive activity. Both granul ocyte colony-stimulating factor- and granulocyte-macrophage colony-sti mulating factor (GM-CSF)-treated polymorphonuclear neutrophils (PMN) h ad enhanced inhibition of hyphal growth, Moreover, such treatment of P MN also enhanced the collaboration of PMN with VCZ, Monocytes inhibite d hyphal growth. When VCZ was combined with monocytes or monocytes wer e treated with GM-CSF, inhibition was significantly increased, to simi lar levels, However, the combination of VCZ with GM-CSF treatment of m onocytes did not significantly increase the high-level inhibition by m onocytes with either agent alone.