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唑类抗真菌药物与甲氨蝶呤体外抗白念珠菌协同作用。

In vitro synergy of azole antifungals and methotrexate against Candida albicans.

机构信息

Department of Dermatology, The 2nd Hospital of Harbin Medical University, Harbin 150080, China.

Microscopy Core Facility, Westlake University, Hangzhou 310024, China.

出版信息

Life Sci. 2019 Oct 15;235:116827. doi: 10.1016/j.lfs.2019.116827. Epub 2019 Aug 31.

DOI:10.1016/j.lfs.2019.116827
PMID:31479680
Abstract

OBJECTIVE

This study aims to evaluate the effective of azoles and MTX for patients with invasive candidiasis.

METHODS

We used the disk diffusion assay and the checkerboard assay to evaluate the in vitro interactions between MTX and antifungals. In addition, we used the transmission electron microscopy to observe the ultrastructure of the effect of MTX and fluconazole on Candida albicans.

RESULTS

The rates of synergy for the combination of MTX with fluconazole (FLC), itraconazole (ITC), and voriconazole (VRZ) were 91.3%, 65.2%, and 87% in checkerboard testing. No antagonism was found between methotrexate and azole antifungals in any of the strains. Furthermore, MTX treated C. albicans showed extensive cell wall vacuolations and the inhibition of blastospores growth, as observed using transmission electron microscopy. There was an apparent destruction of the cell membrane and cell wall resulting in the destruction of cytoplasm, a phenomenon observed when MTX was combined with azoles.

CONCLUSION

This study provides evidence that the combination of azoles and MTX is effective for patients with invasive candidiasis, which on the other hand, will reduce the side effects of the drugs.

摘要

目的

本研究旨在评估唑类药物和甲氨蝶呤对侵袭性念珠菌病患者的疗效。

方法

我们使用了纸片扩散法和棋盘试验来评估 MTX 和抗真菌药物之间的体外相互作用。此外,我们还使用透射电子显微镜观察 MTX 和氟康唑对白色念珠菌的超微结构的影响。

结果

在棋盘试验中,MTX 与氟康唑(FLC)、伊曲康唑(ITC)和伏立康唑(VRZ)联合的协同率分别为 91.3%、65.2%和 87%。在任何菌株中,MTX 与唑类抗真菌药物之间均未发现拮抗作用。此外,透射电子显微镜观察显示,MTX 处理后的白色念珠菌表现出广泛的细胞壁空泡化和芽生孢子生长的抑制。当 MTX 与唑类药物联合使用时,观察到细胞膜和细胞壁明显破坏,导致细胞质破坏。

结论

本研究提供了证据表明,唑类药物和 MTX 的联合治疗对侵袭性念珠菌病患者有效,另一方面,这将降低药物的副作用。

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