Vora S, Chauhan S, Brummer E, Stevens D A
California Institute for Medical Research, Department of Medicine, Stanford, California, USA.
Antimicrob Agents Chemother. 1998 Sep;42(9):2299-303. doi: 10.1128/AAC.42.9.2299.
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-carboxa nilide ]. With both assays, VCZ inhibited hyphal growth at concentrations of <1 microgram/ml and was almost as active as amphotericin B. VCZ (0.6 microgram/ml) was sporicidal, as was amphotericin B (0.4 microgram/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.
伏立康唑(VCZ)被单独或与中性粒细胞或单核细胞联合用于测试其对烟曲霉菌丝的抗真菌活性。抗真菌活性通过在使用染料MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐] 或XTT [2, 3-双(2-甲氧基-4-硝基-5-磺基苯基)-2H-四氮唑-5-羧基苯胺] 的试验中对菌丝生长的抑制百分比来衡量。在这两种试验中,伏立康唑在浓度<1微克/毫升时均能抑制菌丝生长,其活性几乎与两性霉素B相同。伏立康唑(0.6微克/毫升)具有杀孢子活性,两性霉素B(0.4微克/毫升)也是如此。在MTT和XTT试验中,单独的中性粒细胞就能抑制菌丝;与伏立康唑联合使用时,存在相加活性。粒细胞集落刺激因子和粒细胞-巨噬细胞集落刺激因子(GM-CSF)处理的多形核中性粒细胞(PMN)对菌丝生长的抑制作用均增强。此外,对PMN的这种处理还增强了PMN与伏立康唑的协同作用。单核细胞能抑制菌丝生长。当伏立康唑与单核细胞联合使用或单核细胞用GM-CSF处理时,抑制作用显著增强,达到相似水平。然而,伏立康唑与GM-CSF联合处理单核细胞并没有显著增加单核细胞单独使用任一药物时的高水平抑制作用。