瑞扎芬净对耳念珠菌的活性。

Activity of rezafungin against Candida auris.

作者信息

Locke Jeffrey B, Andes David, Flanagan Shawn, Redell Mark, Ong Voon, Aram Jalal A, Pappas Peter G, Castanheira Mariana, Thompson George R

机构信息

Cidara Therapeutics, Inc., San Diego, CA, USA.

University of Wisconsin-Madison, Madison, WI, USA.

出版信息

J Antimicrob Chemother. 2025 Apr 30;80(6):1482-93. doi: 10.1093/jac/dkaf124.

Abstract

The increasing prevalence of candidemia and invasive candidiasis infections caused by Candida auris represents a global health risk. Such infections are difficult to treat as they are often multidrug-resistant and are linked to high rates of mortality. Rezafungin is a second-generation echinocandin with antifungal activity against a range of Candida species, including wild type, and azole- and some echinocandin-resistant isolates. Its stability and prolonged half-life permit less frequent dosing compared with other echinocandins, leading to high front-loaded exposures and potential earlier mycological clearance from infection sites. These properties make rezafungin a candidate for the treatment of candidemia and invasive candidiasis infections due to C. auris. Accordingly, this narrative review article describes available evidence for the activity and effectiveness of rezafungin against C. auris isolates and infections. To date, the activity of rezafungin against C. auris isolates and infections has been demonstrated in in vitro and in vivo non-clinical experiments, and in pharmacokinetic/pharmacodynamic target attainment estimations utilizing clinical data. With similar potency to other echinocandins, rezafungin demonstrates in vitro and in vivo activity that is comparable to or better than that seen with other echinocandins, and similar to that for rezafungin in other Candida species. Like other echinocandins, its activity is reduced in fks-mutant isolates. Although there is currently a dearth of data on the therapeutic activity of rezafungin against C. auris, it is reasonable that rezafungin may be a viable choice for treating candidemia and invasive candidiasis caused by C. auris. Further clinical investigations are necessary.

摘要

耳念珠菌引起的念珠菌血症和侵袭性念珠菌感染的患病率不断上升,这是一个全球健康风险。此类感染难以治疗,因为它们往往具有多重耐药性,且死亡率很高。瑞扎芬净是一种第二代棘白菌素,对一系列念珠菌具有抗真菌活性,包括野生型以及对唑类和一些棘白菌素耐药的分离株。与其他棘白菌素相比,其稳定性和较长的半衰期允许减少给药频率,从而导致高初始暴露量,并有可能更早地从感染部位清除真菌。这些特性使瑞扎芬净成为治疗耳念珠菌引起的念珠菌血症和侵袭性念珠菌感染的候选药物。因此,这篇叙述性综述文章描述了瑞扎芬净针对耳念珠菌分离株和感染的活性及有效性的现有证据。迄今为止,瑞扎芬净针对耳念珠菌分离株和感染的活性已在体外和体内非临床实验以及利用临床数据进行的药代动力学/药效学目标达成估计中得到证实。瑞扎芬净与其他棘白菌素具有相似的效力,其体外和体内活性与其他棘白菌素相当或更好,并且与瑞扎芬净对其他念珠菌属的活性相似。与其他棘白菌素一样,其在fks突变分离株中的活性降低。尽管目前关于瑞扎芬净针对耳念珠菌的治疗活性的数据匮乏,但瑞扎芬净可能是治疗耳念珠菌引起的念珠菌血症和侵袭性念珠菌病的可行选择,这是合理的。还需要进一步的临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a295/12129586/7c4f546e2753/dkaf124f1.jpg

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