Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates: SENTRY Program 2016-2018.

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Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates: SENTRY Program 2016-2018.

Antimicrob Agents Chemother. 2020 Feb 03;:

Authors: Pfaller MA, Carvalhaes C, Messer SA, Rhomberg PR, Castanheira M

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

PMID: 32015043 [PubMed - as supplied by publisher]