Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris
Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris
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DOI：
10.1016/j.ijantimicag.2020.106049
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发表时间：
2020-08-01
影响因子：
10.8
通讯作者：
Ishida, Kelly
中科院分区：
文献类型：
--
作者：
Barreto, Thayna Lopes;Rossato, Luana;Ishida, Kelly
目的：研究耳念珠菌（Candida auris，C. auris）是一种新兴的真菌物种，其能够发展多药耐药性并在全球范围内爆发侵袭性感染，具有高死亡率。增加C.本研究评估了米替福新（MFS）的疗效，米替福新在体外已证明具有广谱抗真菌作用。本研究的目的是：（i）评价MFS对念珠菌的体外抗真菌活性;耳炎临床分离株在嗜酸性和生物膜生活方式;和（ii）比较MFS在其游离形式和包封在藻酸盐纳米颗粒（MFS-AN）中的大蜡螟幼虫感染的C. auris.Methods:结果：MFS对大蜡螟幼虫感染模型的体外抑菌活性为1-4 μ g/mL，对大蜡螟幼虫感染模型的体外抑菌活性为1 μ g/mL，对大蜡螟幼虫感染模型的体外抑菌活性为1 μ g/mL，对大蜡螟幼虫感染模型的体外抑菌活性为1 μ g/mL。耳临床分离株。在生物膜形成期间（0.25-4 μ g/mL）和在预形成的生物膜上（16-32 μ g/mL）观察到MFS生物膜活性。此外，C.耳生物膜具有与从牙周细胞获得的那些相似的易感性。用游离MFS或MFS-AN处理大蜡螟幼虫，可显著提高感染大蜡螟幼虫的存活率和发病率。耳。此外，减少真菌负荷（0.5-1 log CFU/g）和肉芽肿形成时，观察到与未经处理的group.Conclusions相比：研究结果表明，无论是游离MFS和MFS-AN有潜力的治疗真菌感染所造成的新兴的C。耳。(C)2020 Elsevier B. V.和国际化疗学会。All rights reserved.
Objectives: Candida auris (C. auris) is an emerging fungal species that is able to develop multidrug resistance and outbreaks of invasive infections worldwide with high mortality rates. To increase the treatment options for C. auris infection this study assessed the efficacy of miltefosine (MFS), that has demonstrated a broad-spectrum antifungal action in vitro. This study aimed to: (i) evaluate the in vitro antifungal activity of MFS against C. auris clinical isolates in the planktonic and biofilm lifestyles; and (ii) compare the activity of MFS in its free form and encapsulated in alginate nanoparticles (MFS-AN) in Galleria mellonella larvae infected by C. auris.Methods: The antifungal susceptibility test was performed using broth microdilution method and the in vivo treatment in Galleria mellonella larval infection model.Results: MFS exhibited in vitro inhibitory effects at MICs ranging 1-4 mu g/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25-4 mu g/mL) and on pre-formed biofilms (16-32 mu g/mL). Moreover, the dispersed cells from C. auris biofilms had a similar susceptibility to those obtained for planktonic cells. Treatment with free MFS or MFS-AN resulted in significant improvements in the survival and morbidity rates of Galleria mellonella larvae infected by C. auris. In addition, reduction of fungal burden (0.5-1 log CFU/g) and granuloma formation were observed when compared with the untreated group.Conclusions: The findings suggest that both the free MFS and MFS-AN have potential for the treatment of fungal infections caused by the emerging C. auris. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.