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分析依维莫司与抗真菌药物联合抗暗色真菌的协同抗真菌活性。

Analysis of the synergistic antifungal activity of everolimus and antifungal drugs against dematiaceous fungi.

机构信息

Department of Medical Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.

Department of General Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, Hubei, China.

出版信息

Front Cell Infect Microbiol. 2023 Feb 22;13:1131416. doi: 10.3389/fcimb.2023.1131416. eCollection 2023.

Abstract

INTRODUCTION

Chromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition.

METHODS

In this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates.

RESULTS

These analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC.

DISCUSSION

Overall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.

摘要

简介

着色芽生菌病(CBM)是一种慢性真菌病,影响皮肤和黏膜,由暗色真菌引起,包括拟青霉属、瓶梗霉属和帚霉属。由于这种疾病的持续存在以及单一药物治疗的局限性,使得难以充分管理这种疾病。

方法

在这项研究中,采用微量稀释法研究了依维莫司(EVL)与伊曲康唑(ITC)、伏立康唑(VRC)、泊沙康唑(POS)和两性霉素 B(AMB)联合使用对一系列临床暗色真菌分离株的协同抗真菌活性。

结果

这些分析表明,EVL+POS 和 EVL+ITC 分别表现出优越的体外协同功效,分别抑制了 64%(14/22)和 59%(13/22)的测试菌株的生长。相比之下,仅 9%(2/22)的测试菌株的生长被 EVL+AMB 的组合抑制,而 EVL+VRC 的组合未观察到协同功效。

讨论

总体而言,这些发现表明 EVL 有希望成为一种新的药物,可以与现有的抗真菌药物协同联合使用,以提高其疗效,从而有助于治疗 CBM。

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