Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
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DOI：
10.1093/jac/dky153
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发表时间：
2018-08-01
影响因子：
5.2
通讯作者：
Ghannoum, Mahmoud A.
中科院分区：
文献类型：
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作者：
Hager, Christopher L.;Larkin, Emily L.;Ghannoum, Mahmoud A.
背景：据报道，由于其耐多药性质，多例耳念珠菌感染病例的死亡率很高。 Rezafungin（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，可实现高血浆药物暴露并允许每周一次给药。目的：使用播散性念珠菌病小鼠模型评估雷扎芬净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，通过尾静脉给小鼠接种3x10(7)个耳念珠菌芽生孢子。将小鼠随机分为四组 (n = 20)：雷扎芬净 20 mg/kg、两性霉素 B 0.3 mg/kg、米卡芬净 5 mg/kg 和载体对照。感染后2小时进行治疗。在第 3 天和第 6 天额外给予 Rezafungin，总共 3 剂，而其余组每天接受治疗，总共 7 剂。在研究的第 1 天、第 4 天、第 7 天和第 10 天处死每组 5 只小鼠。从每只小鼠中取出肾脏以确定每天的 cfu 数量。结果：与两性霉素 B 和媒介物处理的小鼠相比，在收获肾脏的所有天中，Rezafungin 的平均 log(10) cfu/g 组织显着较低。此外，第 10 天，与米卡芬净治疗的小鼠相比，雷扎芬净治疗的小鼠组织的平均 log(10) cfu/g 显着降低。 结论：我们的研究结果表明，在播散性念珠菌病模型中，雷扎芬净对耳念珠菌具有有效的抗真菌活性。
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 3x10(7 ) C. 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 log(10) 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 log(10) 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.