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In vitro activity of ibrexafungerp (SCY-078) against Candida auris Isolates as Determined by EUCAST methodology and comparison with activity against C. Albicans and C. Glabrata and with the activities of six comparator agents

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@article{903930f564a3402893ccf56491bc6c94,
title = "In vitro activity of ibrexafungerp (SCY-078) against Candida auris Isolates as Determined by EUCAST methodology and comparison with activity against C. Albicans and C. Glabrata and with the activities of six comparator agents",
abstract = "Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting glucan synthase. Candida auris is an emerging multidrug-resistant species that has caused outbreaks on five continents. We investigated the in vitro activity of ibrexafungerp against C. auris by applying EUCAST E.Def 7.3.1 methodology. C. albicans and C. glabrata, as well as anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole, and isavuconazole, were included as comparators. Three C. auris reference strains (CBS12372, CBS12373, and CBS10913) and 122 C. auris, 16 C. albicans, and 16 C. glabrata isolates were evaluated. C. albicans ATCC 64548, C. parapsilosis ATCC 22019, and C. krusei ATCC 6258 served as quality control strains. Echinocandin-resistant isolates were fks sequenced. MIC ranges and modal MIC and MIC 50 values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined according to EUCAST principles for setting ECOFFs. Nine repetitions of three QC strains and MICs for C. albicans and C. glabrata yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs, confirming a robust test performance. The ibrexafungerp MICs against C. auris isolates displayed a Gaussian distribution with a modal MIC (range) of 0.5 mg/liter (0.06 to 2 mg/liter), suggesting uniform susceptibility. Of 122 isolates, 8 were echinocandin resistant and harbored the S639F Fks1 alteration. All but one were fluconazole resistant, and the MIC distributions for voriconazole and isavuconazole were multimodal confirming variable susceptibility. Ibrexafungerp demonstrated promising activity against C. auris, including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the Clinical and Laboratory Standards Institute method, suggesting that a common clinical breakpoint may be appropriate.",
keywords = "Antifungal susceptibility, Antifungal susceptibility testing, C. auris, Echinocandin resistance, EUCAST, Fks mutation, Ibrexafungerp, SCY078",
author = "Arendrup, {Maiken Cavling} and J{\o}rgensen, {Karin Meinike} and Hare, {Rasmus Kr{\o}ger} and Anuradha Chowdhary",
note = "Copyright {\circledC} 2020 American Society for Microbiology.",
year = "2020",
month = "2",
day = "21",
doi = "10.1128/AAC.02136-19",
language = "English",
volume = "64",
pages = "e02136--19",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "3",

}

RIS

TY - JOUR

T1 - In vitro activity of ibrexafungerp (SCY-078) against Candida auris Isolates as Determined by EUCAST methodology and comparison with activity against C. Albicans and C. Glabrata and with the activities of six comparator agents

AU - Arendrup, Maiken Cavling

AU - Jørgensen, Karin Meinike

AU - Hare, Rasmus Krøger

AU - Chowdhary, Anuradha

N1 - Copyright © 2020 American Society for Microbiology.

PY - 2020/2/21

Y1 - 2020/2/21

N2 - Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting glucan synthase. Candida auris is an emerging multidrug-resistant species that has caused outbreaks on five continents. We investigated the in vitro activity of ibrexafungerp against C. auris by applying EUCAST E.Def 7.3.1 methodology. C. albicans and C. glabrata, as well as anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole, and isavuconazole, were included as comparators. Three C. auris reference strains (CBS12372, CBS12373, and CBS10913) and 122 C. auris, 16 C. albicans, and 16 C. glabrata isolates were evaluated. C. albicans ATCC 64548, C. parapsilosis ATCC 22019, and C. krusei ATCC 6258 served as quality control strains. Echinocandin-resistant isolates were fks sequenced. MIC ranges and modal MIC and MIC 50 values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined according to EUCAST principles for setting ECOFFs. Nine repetitions of three QC strains and MICs for C. albicans and C. glabrata yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs, confirming a robust test performance. The ibrexafungerp MICs against C. auris isolates displayed a Gaussian distribution with a modal MIC (range) of 0.5 mg/liter (0.06 to 2 mg/liter), suggesting uniform susceptibility. Of 122 isolates, 8 were echinocandin resistant and harbored the S639F Fks1 alteration. All but one were fluconazole resistant, and the MIC distributions for voriconazole and isavuconazole were multimodal confirming variable susceptibility. Ibrexafungerp demonstrated promising activity against C. auris, including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the Clinical and Laboratory Standards Institute method, suggesting that a common clinical breakpoint may be appropriate.

AB - Ibrexafungerp (SCY-078) is a novel first-in-class antifungal agent targeting glucan synthase. Candida auris is an emerging multidrug-resistant species that has caused outbreaks on five continents. We investigated the in vitro activity of ibrexafungerp against C. auris by applying EUCAST E.Def 7.3.1 methodology. C. albicans and C. glabrata, as well as anidulafungin, micafungin, amphotericin B, fluconazole, voriconazole, and isavuconazole, were included as comparators. Three C. auris reference strains (CBS12372, CBS12373, and CBS10913) and 122 C. auris, 16 C. albicans, and 16 C. glabrata isolates were evaluated. C. albicans ATCC 64548, C. parapsilosis ATCC 22019, and C. krusei ATCC 6258 served as quality control strains. Echinocandin-resistant isolates were fks sequenced. MIC ranges and modal MIC and MIC 50 values were determined. Wild-type upper limits (the upper MIC value where the wild-type distribution ends) were determined according to EUCAST principles for setting ECOFFs. Nine repetitions of three QC strains and MICs for C. albicans and C. glabrata yielded narrow MIC ranges with modal MICs in agreement with established EUCAST modal MICs, confirming a robust test performance. The ibrexafungerp MICs against C. auris isolates displayed a Gaussian distribution with a modal MIC (range) of 0.5 mg/liter (0.06 to 2 mg/liter), suggesting uniform susceptibility. Of 122 isolates, 8 were echinocandin resistant and harbored the S639F Fks1 alteration. All but one were fluconazole resistant, and the MIC distributions for voriconazole and isavuconazole were multimodal confirming variable susceptibility. Ibrexafungerp demonstrated promising activity against C. auris, including isolates resistant to echinocandins and/or other agents. The MICs were similar to those reported for the Clinical and Laboratory Standards Institute method, suggesting that a common clinical breakpoint may be appropriate.

KW - Antifungal susceptibility

KW - Antifungal susceptibility testing

KW - C. auris

KW - Echinocandin resistance

KW - EUCAST

KW - Fks mutation

KW - Ibrexafungerp

KW - SCY078

U2 - 10.1128/AAC.02136-19

DO - 10.1128/AAC.02136-19

M3 - Journal article

VL - 64

SP - e02136-19

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 3

ER -

ID: 59156450