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Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data.

ABSTRACT: Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural modification in its parent molecule anidulafungin, rezafungin has acquired unique chemical stability conferring prolonged pharmacokinetics, as well as an administration advantage in the clinical setting compared to other drugs in the same class. Rezafungin displays potent in vitro activity against a wide spectrum of fungal pathogens, which is reflected in robust in vivo efficacy and/or pharmacodynamic studies using various animal models as well as in promising clinical trials data. This review describes in vivo characterization of rezafungin using animal models, current status of clinical development and key findings from these studies.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC7712954 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data.

Zhao Yanan Y Perlin David S DS

Journal of fungi (Basel, Switzerland) 20200928 4

Rezafungin is a novel echinocandin drug being developed as a first-line option for treatment and prevention of invasive fungal infections. As a result of a structural modification in its parent molecule anidulafungin, rezafungin has acquired unique chemical stability conferring prolonged pharmacokinetics, as well as an administration advantage in the clinical setting compared to other drugs in the same class. Rezafungin displays potent in vitro activity against a wide spectrum of fungal pathogen ...[more]

PMID: 32998224

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Project description:We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. Candida (n?=?1,904 isolates; 6 species), Cryptococcus neoformans (n?=?73), Aspergillus fumigatus (n?=?183), and Aspergillus flavus (n?=?45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of Candida albicans isolates (MIC50/90, 0.03/0.06??g/ml), 95.7% of Candida glabrata isolates (MIC50/90, 0.06/0.12??g/ml), 97.4% of Candida tropicalis isolates (MIC50/90, 0.03/0.06??g/ml), 100.0% of Candida krusei isolates (MIC50/90, 0.03/0.06??g/ml), and 100.0% of Candida dubliniensis isolates (MIC50/90, 0.06/0.12??g/ml) at ?0.12??g/ml. All (329/329 [100.0%]) Candida parapsilosis isolates (MIC50/90,1/2??g/ml) were inhibited by rezafungin at ?4??g/ml. Fluconazole resistance was detected among 8.6% of C. glabrata isolates, 12.5% of C. parapsilosis isolates, 3.2% of C. dubliniensis isolates, and 2.6% of C. tropicalis isolates. The activity of rezafungin against these 6 Candida spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT Candida isolates. Good activity against C. neoformans was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against A. fumigatus and A. flavus These in vitro data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

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Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data.

Publications

Review of the Novel Echinocandin Antifungal Rezafungin: Animal Studies and Clinical Data.

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