Open AccessCD101: a novel long‐acting echinocandin
Author(s) -
Zhao Yanan,
Perez Winder B.,
JiménezOrtigosa Cristina,
Hough Grayson,
Locke Jeffrey B.,
Ong Voon,
Bartizal Ken,
Perlin David S.
Publication year - 2016
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12640
Subject(s) - echinocandin , micafungin , candida albicans , caspofungin , echinocandins , pharmacology , mutant , biology , microbiology and biotechnology , antifungal , potency , invasive candidiasis , in vitro , amphotericin b , biochemistry , fluconazole , gene
Summary CD101 is a novel echinocandin drug being developed to treat severe fungal infections including invasive candidiasis. We have performed a series of studies to evaluate the antifungal properties of CD101 against both echinocandin‐susceptible and ‐resistant Candida strains. Antifungal susceptibility testing performed on a collection of 95 Candida strains including 30 caspofungin‐resistant isolates containing fks mutations demonstrated comparable antifungal potency of CD101 relative to micafungin (MCF) across different Candida species. Comparable kinetic inhibition of glucan synthase activity was also observed for CD101 and MCF on both wild‐type (WT) and resistant fks mutant Candida strains. Similarly, both drugs yielded nearly identical values for a mutant prevention concentration. In a murine model of invasive candidiasis, CD101 displayed better or at least comparable efficacy relative to MCF in treating WT or fks mutant Candida albicans . An exceptional long‐lived pharmacokinetic profile was observed in mice following a single dose of CD101. Collectively, CD101 has great potential not only in treating invasive Candida infections but also in preventing emergence of resistance to currently approved echinocandin drugs.