Caballero Unai, Kim Sarah, Eraso Elena, Quindós Guillermo, Vozmediano Valvanera, Schmidt Stephan, Jauregizar Nerea
Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
Antibiotics (Basel). 2021 Mar 28;10(4):355. doi: 10.3390/antibiotics10040355.
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 . 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 infections.
是一种新兴的真菌病原体，在全球范围内引发严重的感染性疫情。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。克服这一问题的一个有价值的替代方法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对……的体外相互作用。使用棋盘法确定相互作用，并采用不同方法分析吸光度数据：分数抑菌浓度指数（FICI）、格雷科通用反应表面法和布利斯相互作用模型。所有模型均一致，表明艾沙康唑与棘白菌素的组合产生了总体协同相互作用。选择治疗范围内的广泛浓度来进行时间杀菌曲线实验。这些实验证实，艾沙康唑 - 棘白菌素组合比单一疗法更有效。低浓度（≥0.125 mg/L）的艾沙康唑与≥1 mg/L的棘白菌素组合可实现协同作用和抑菌活性。时间杀菌曲线表明，一旦实现协同作用，更高药物浓度的组合并不会提高抗真菌活性。这项工作为艾沙康唑与棘白菌素联合治疗……感染带来了有前景的结果。
