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评估新型棘白菌素类药物瑞他康唑在免疫抑制小鼠模型中治疗播散性耳念珠菌感染的疗效。

Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model.

机构信息

Center for Medical Mycology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

出版信息

J Antimicrob Chemother. 2018 Aug 1;73(8):2085-2088. doi: 10.1093/jac/dky153.

Abstract

BACKGROUND

Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration.

OBJECTIVES

Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis.

METHODS

Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 107C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day.

RESULTS

Rezafungin had significantly lower average log10 cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log10 cfu/g of tissue compared with micafungin-treated mice on day 10.

CONCLUSIONS

Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.

摘要

背景

由于其多药耐药性,已经报告了多例耳念珠菌感染病例,死亡率很高。瑞他康唑(以前称为 CD101)是一种新型棘白菌素,具有增强的稳定性和药代动力学特性,可实现高血浆药物暴露,并允许每周给药一次。

目的

使用播散性念珠菌病的小鼠模型评估瑞他康唑治疗播散性耳念珠菌感染的疗效。

方法

在感染前 3 天和感染后 1 天对小鼠进行免疫抑制。在感染当天,通过尾静脉将 3×107 个耳念珠菌芽生孢子接种到小鼠体内。将小鼠随机分为四组(n=20):瑞他康唑 20mg/kg、两性霉素 B 0.3mg/kg、米卡芬净 5mg/kg 和载体对照组。感染后 2 小时给予治疗。瑞他康唑在第 3 天和第 6 天额外给药,总共给药 3 次,而其余组每天给药,总共给药 7 次。每组各有 5 只小鼠在研究的第 1、4、7 和 10 天被处死。从每组的每只小鼠中取出肾脏,以确定每天的 cfu 数。

结果

在所有收获肾脏的日子里,与两性霉素 B 和载体处理的小鼠相比,瑞他康唑组的平均对数 10cfu/g 组织明显较低。此外,与米卡芬净治疗的小鼠相比,瑞他康唑治疗的小鼠在第 10 天的平均对数 10cfu/g 组织明显较低。

结论

我们的研究结果表明,瑞他康唑在播散性念珠菌病模型中对耳念珠菌具有强大的抗真菌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7835/6070025/70a89473ddd3/dky153f1.jpg

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