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Interaction Between Amorolfine and Voriconazole Against Fusarium species
Mycopathologia ( IF 5.5 ) Pub Date : 2021-06-05 , DOI: 10.1007/s11046-021-00568-8
Qin Liu 1 , Si Jiang 1 , Kaiping Zheng 1 , Jiquan Song 1 , Pin Liang 1
Affiliation  

Fusarium species represent a range of fungal pathogens capable of causing diverse mycotic diseases. Relative to antibacterial drugs, few effective antifungal agents have been developed to date, and all are subject to significant limitations. As such, there is an urgent need to design novel antifungal treatments for infections caused by Fusarium spp. Herein, 15 clinical isolates, including 5 Fusarium oxysporum and 10 Fusarium solani strains, were analyzed to explore the relative inhibitory effects of different combinations of amorolfine (AMO) and voriconazole (VOR) on the growth of these fungal pathogens. These analyses were conducted by measuring minimal inhibitory concentration (MIC) values for these antifungal agents in a broth microdilution assay and by using an in vivo model of Fusarium-infected Galleria mellonella. These experiments revealed that in isolation, AMO and VOR exhibited MIC values ranging from 4 to 16 μg/mL and 2 to 8 μg/mL, respectively. However, these effective MIC values fell to 1–2 μg/mL and 0.5–2 μg/mL, respectively, when AMO and VOR were administered in combination with one another, exhibiting synergistic activity against 73.3% of analyzed Fusarium strains. Subsequent in vivo analyses conducted using the G. mellonella model further confirmed that combination VOR + AMO treatment was associated with significantly improved larval survival following Fusarium spp. infection. Together, these results serve as the first published evidence demonstrating that VOR and AMO exhibit synergistic activity against infections caused by Fusarium spp., indicating that they may represent an effective approach to antifungal disease treatment.



中文翻译:

阿莫罗芬和伏立康唑对镰刀菌的相互作用

镰刀菌属代表了一系列能够引起多种真菌病的真菌病原体。相对于抗菌药物,迄今为止开发出的有效抗真菌药物很少,而且都受到很大的限制。因此,迫切需要为镰刀菌属引起的感染设计新的抗真菌治疗方法。其中临床分离株15株,其中尖孢镰刀菌5株,茄病镰刀菌10株分析菌株,以探讨阿莫罗芬 (AMO) 和伏立康唑 (VOR) 的不同组合对这些真菌病原体生长的相对抑制作用。这些分析是通过在肉汤微量稀释试验中测量这些抗真菌剂的最小抑菌浓度 (MIC) 值并使用镰刀菌感染的大蜡螟的体内模型进行的。这些实验表明,单独地,AMO 和 VOR 的 MIC 值分别为 4 至 16 μg/mL 和 2 至 8 μg/mL。然而,当 AMO 和 VOR 相互组合使用时,这些有效 MIC 值分别降至 1-2 μg/mL 和 0.5-2 μg/mL,对 73.3% 的分析镰刀菌表现出协同活性菌株。随后使用大蜡螟模型进行的体内分析进一步证实,VOR + AMO 联合治疗与镰刀菌感染后幼虫存活率显着提高有关。感染。总之,这些结果是首次发表的证据,证明 VOR 和 AMO 对镰刀菌引起的感染表现出协同活性,表明它们可能代表了一种有效的抗真菌疾病治疗方法。

更新日期:2021-06-05
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