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新型口服葡聚糖合成酶抑制剂 SCY-078 对念珠菌属的浮游和黏附状态均具有体外活性。

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

机构信息

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.

出版信息

J Antimicrob Chemother. 2017 Jul 1;72(7):1969-1976. doi: 10.1093/jac/dkx010.

Abstract

OBJECTIVES

We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital.

METHODS

The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay.

RESULTS

SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P  <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P  <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment.

CONCLUSIONS

Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin.

摘要

目的

我们研究了 SCY-078(一种可口服的 1,3-β-D-葡聚糖合成抑制剂)、米卡芬净和氟康唑对最近入住一家大型欧洲医院的患者血液感染的浮游和固着形式的 178 株念珠菌和非念珠菌分离株的抗真菌活性。

方法

使用 EUCAST EDef 7.3 和 CLSI M27-A3 评估 SCY-078、米卡芬净和氟康唑对分离株浮游形式的体外活性。使用 XTT 还原测定法评估抗生物膜活性。

结果

SCY-078 和米卡芬净对念珠菌和非念珠菌分离株表现出强大的体外活性。这两种药物的体外活性相似,但 SCY-078 对近平滑念珠菌和非念珠菌分离株的 MIC 值明显低于米卡芬净,而米卡芬净对其余物种的 MIC 值明显较低(P<0.001)。相比之下,SCY-078 和米卡芬净对生物膜的活性基本相同,但除了光滑念珠菌外,米卡芬净的固着 MIC 值明显较低(P<0.001)。通过在抗真菌治疗后用扫描电子显微镜评估生物膜结构,证实了这些观察结果。

结论

我们的研究表明,SCY-078 对浮游和固着形式的侵袭性念珠菌分离株的高体外活性与米卡芬净相当。

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