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唑类衍生物与氯胺酮协同作用对 spp. 对氟康唑耐药性的影响。

Synergistic effects of ketamine and azole derivatives on spp. resistance to fluconazole.

机构信息

Department of Clinical & Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceara, Fortaleza, CE, 60430-1160, Brazil.

Christus University Center (UNICHRISTUS), Fortaleza, CE, 60160-230, Brazil.

出版信息

Future Microbiol. 2020 Feb;15:177-188. doi: 10.2217/fmb-2019-0082. Epub 2020 Feb 20.

Abstract

The emergence of spp. with resistance to antifungal molecules, mainly the azole class, is an increasing complication in hospitals around the globe. In the present research, we evaluated the synergistic effects of ketamine with two azole derivatives, itraconazole and fluconazole, on strains of spp. to fluconazole. The drug synergy was evaluated by quantifying the fractional inhibitory concentration index and by fluorescence microscopy and flow cytometry techniques. Our achievements showed a synergistic effect between ketamine in addition to the two antifungal agents (fluconazole and itraconazole) against planktonic cells and biofilms of spp. This combination promoted alteration of membrane integrity, generation of reactive oxygen species, damage to and DNA and externalization of phosphatidylserine.

摘要

spp. 对抗真菌分子(主要是唑类)的耐药性的出现,是全球医院日益复杂的问题。在本研究中,我们评估了氯胺酮与两种唑类衍生物伊曲康唑和氟康唑联合使用对氟康唑耐药的 spp. 菌株的协同作用。通过量化部分抑制浓度指数以及荧光显微镜和流式细胞术技术来评估药物协同作用。我们的研究结果表明,氯胺酮与两种抗真菌药物(氟康唑和伊曲康唑)联合使用对 spp. 的浮游细胞和生物膜具有协同作用。这种组合促进了膜完整性的改变、活性氧的产生、DNA 的损伤以及磷脂酰丝氨酸的外化。

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