In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris.

In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris.
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艾沙康唑和棘白菌素对抗耳念珠菌的体外协同相互作用。

DOI:
10.3390/antibiotics10040355
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发表时间:
2021-03-28
期刊:
Antibiotics (Basel, Switzerland)
影响因子:
--
通讯作者:
Jauregizar N
Jauregizar N
中科院分区:
其他
文献类型:
--
作者:
Caballero U;Kim S;Eraso E;Quindós G;Vozmediano V;Schmidt S;Jauregizar N

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耳念珠菌是一种新出现的真菌病原体,在全球范围内引起严重的传染病暴发。处理这种病原体时的公共卫生问题主要是由于对当前抗真菌药物的敏感性降低。克服这个问题的一个有价值的替代方案是研究联合治疗的疗效。本研究的目的是确定艾沙康唑与棘白菌素类药物体外抗念珠菌的相互作用。耳。采用棋盘法测定相互作用,并采用不同方法分析吸光度数据:分数抑制浓度指数(FICI)、Greco通用响应面法和布利斯相互作用模型。所有的模型是一致的,并表明艾沙康唑与棘白菌素的组合导致整体协同相互作用。选择治疗范围内的广泛浓度范围来绘制时间-杀灭曲线。这些证实了艾沙康唑-棘白菌素联合治疗比单药治疗方案更有效。使用包括低浓度(≥0.125 mg/L)艾沙康唑和≥1 mg/L棘白菌素的组合实现了协同作用和真菌抑制活性。时间-杀菌曲线显示,一旦实现协同作用,较高药物浓度的组合并不能提高抗真菌活性。这项工作启动了关于艾沙康唑与棘白菌素联合治疗C。耳感染。
Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.
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