Collabortion of Phagocytes with Voriconazole (VCZ) against Aspergillus fumigatus: Effect of G-CSF and GM-CSF.



The antifungal activity of VCZ against A. fumigatus conidia or germlings was measured. VCZ (0.06 micro g/ml) was cidal for conidia A. fumigatus in 24 or 48 h tests as judged by lack of germination and negative cultures. These results suggests prophylactic use of VCZ in patients that have a high risk for contracting asperillosis. By contrast, VCZ was only fungistatic for germlings as measured with the MTT and XTT assays. With the 24-well tissue culture plate MTT assay VCZ (0.5 micro g/ml) inhibited hyphal growth of 2 X 105} germlings/well by 50 +/- 7% (n=4) . Polymorphonuclear neutrophils (PMN) at E:T of 10:1 inhibited growth by 30% and PMN combined with VCZ produced an additive inhibition. Monocytes at E:T of 50:1 inhibited hyphal growth by 50%, VCZ (0.5 micro g/ml) by 58%, and combined the inhibition was 79%. In the presence of GM-CSF (500 U/ml) monocytes inhibited growth by 83%. In the 96-well microtest plate XTT assay (103} germlings/well) VCZ at 0.05 micro g/ml inhibited hyphal growth of isolate 96-92 by 34 +/- 5% (n=3) and isolate 92-270 by 67 +/- 7% (n=2). PMN collaborated with VCZ (0.01 to 0.10 micro g/ml) for significantly increased inhibition compared to either agent alone. In the presence of G-CSF (100 ng/ml) or GM-CSF (100 U/ml) inhibition by PMN 39 +/- 9% was significantly increased to 84 +/- 9% and 85 +/- 6%, respectively. This was significantly increased further by VCZ. These findings demonstrate the efficacy of VCZ against conidia and additive collaboration with phagocytes against hyphae.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th