Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Antimicrob Agents Chemother. 2013 Apr;57(4):1625-31. doi: 10.1128/AAC.01573-12. Epub 2013 Jan 14.
Given the high protein binding rates of antifungal drugs and the effect of serum proteins on Aspergillus growth, we investigated the in vitro pharmacodynamics of amphotericin B, voriconazole, and three echinocandins in the presence of human serum, assessing both inhibitory and fungicidal effects. In vitro inhibitory (IC) and fungicidal (FC) concentrations against 5 isolates of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus were determined with a CLSI M38-A2-based microdilution method using the XTT methodology after 48 h of incubation at 35 °C with a medium supplemented with 50% human serum. In the presence of serum, the IC and FC of amphotericin B and the IC of echinocandins were increased (1.21- to 13.44-fold), whereas voriconazole IC and FC were decreased (0.22- to 0.90-fold). The amphotericin B and voriconazole FC/IC ratios did not change significantly (0.59- to 2.33-fold) in the presence of serum, indicating that the FC increase was due to the IC increase. At echinocandin concentrations above the minimum effective concentration (MEC), fungal growth was reduced by 10 to 50% in the presence of human serum, resulting in complete inhibition of growth for some isolates. Thus, the in vitro activities of amphotericin B and echinocandins were reduced, whereas that of voriconazole was enhanced, in the presence of serum. These changes could not be predicted by the percentage of protein binding, indicating that other factors and/or secondary mechanisms may account for the observed in vitro activities of antifungal drugs against Aspergillus species in the presence of serum.
鉴于抗真菌药物的高蛋白结合率以及血清蛋白对曲霉生长的影响，我们研究了两性霉素 B、伏立康唑和三种棘白菌素在人血清存在下的体外药效学，评估了抑制和杀菌作用。采用 CLSI M38-A2 基于微量稀释法，使用 XTT 方法，在 35°C 下孵育 48 小时，用补充有 50%人血清的培养基，测定了 5 株烟曲霉、黄曲霉和土曲霉对两性霉素 B、伏立康唑和三种棘白菌素的体外抑制（IC）和杀菌（FC）浓度。在血清存在的情况下，两性霉素 B 和棘白菌素的 IC 以及伏立康唑的 IC 增加了（1.21 至 13.44 倍），而伏立康唑的 IC 和 FC 降低了（0.22 至 0.90 倍）。血清存在时，两性霉素 B 和伏立康唑的 FC/IC 比值变化不大（0.59 至 2.33 倍），表明 FC 的增加是由于 IC 的增加。在棘白菌素浓度高于最小有效浓度（MEC）时，在人血清存在下，真菌生长减少 10%至 50%，导致一些分离株的生长完全受到抑制。因此，在血清存在的情况下，两性霉素 B 和棘白菌素的体外活性降低，而伏立康唑的体外活性增强。这些变化不能通过蛋白结合百分比来预测，表明其他因素和/或次级机制可能解释了在血清存在下抗真菌药物对曲霉属的体外活性。
