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EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates

Ibrexafungerp is a novel triterpenoid antifungal that inhibits glucan synthase and thus fungal cell wall synthesis. We examined the in vitro activity against contemporary clinical yeast, investigated inter-laboratory and intra-laboratory variability, suggested wild-type upper-limit values (WT-UL), a...

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Autores principales: Jørgensen, Karin M., Astvad, Karen M. T., Hare, Rasmus K., Arendrup, Maiken C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605171/
https://www.ncbi.nlm.nih.gov/pubmed/36294671
http://dx.doi.org/10.3390/jof8101106
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author Jørgensen, Karin M.
Astvad, Karen M. T.
Hare, Rasmus K.
Arendrup, Maiken C.
author_facet Jørgensen, Karin M.
Astvad, Karen M. T.
Hare, Rasmus K.
Arendrup, Maiken C.
author_sort Jørgensen, Karin M.
collection PubMed
description Ibrexafungerp is a novel triterpenoid antifungal that inhibits glucan synthase and thus fungal cell wall synthesis. We examined the in vitro activity against contemporary clinical yeast, investigated inter-laboratory and intra-laboratory variability, suggested wild-type upper-limit values (WT-UL), and compared in vitro activity of ibrexafungerp to five licensed antifungals. Susceptibility to ibrexafungerp and comparators was investigated prospectively for 1965 isolates (11,790 MICs) and repetitively for three QC strains (1764 MICs) following the EUCAST E.Def 7.3.2 method. Elevated ibrexafungerp/echinocandin MICs prompted FKS sequencing. Published ibrexafungerp EUCAST MIC-distributions were retrieved and aggregated for WT-UL determinations following EUCAST principles. Ibrexafungerp MICs were ≤2 mg/L except against C. pararugosa, Cryptococcus and some rare yeasts. Modal MICs (mg/L) were 0.06/0.125/0.25/0.5/0.5/0.5/0.5/1/2 for C. albicans/C. dubliniensis/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis/S. cerevisiae/C. guilliermondii/C. lusitaniae and aligned within ±1 dilution with published values. The MIC ranges for QC strains were: 0.06–0.25/0.5–1/0.125–0.5 for CNM-CL-F8555/ATCC6258/ATCC22019. The WT-UL (mg/L) were: 0.25/0.5/1/1/2 for C. albicans/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis. Adopting these, non-wild-type rates were 0.3%/0.6%/0%/8%/3% for C. albicans/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis and overall lower than for comparators except amphotericin B. Five/six non-wild-type C. albicans/C. glabrata were echinocandin and Fks non-wild-type (F641S, F659del or F659L). Eight C. parapsilosis and three C. tropicalis non-wild-type isolates were echinocandin and Fks wild-type. Partial inhibition near 50% in the supra-MIC range may explain variable MICs. Ibrexafungerp EUCAST MIC testing is robust, although the significance of paradoxical growth for some species requires further investigation. The spectrum is broad and will provide an oral option for the growing population with azole refractory infection.
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spelling pubmed-96051712022-10-27 EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates Jørgensen, Karin M. Astvad, Karen M. T. Hare, Rasmus K. Arendrup, Maiken C. J Fungi (Basel) Article Ibrexafungerp is a novel triterpenoid antifungal that inhibits glucan synthase and thus fungal cell wall synthesis. We examined the in vitro activity against contemporary clinical yeast, investigated inter-laboratory and intra-laboratory variability, suggested wild-type upper-limit values (WT-UL), and compared in vitro activity of ibrexafungerp to five licensed antifungals. Susceptibility to ibrexafungerp and comparators was investigated prospectively for 1965 isolates (11,790 MICs) and repetitively for three QC strains (1764 MICs) following the EUCAST E.Def 7.3.2 method. Elevated ibrexafungerp/echinocandin MICs prompted FKS sequencing. Published ibrexafungerp EUCAST MIC-distributions were retrieved and aggregated for WT-UL determinations following EUCAST principles. Ibrexafungerp MICs were ≤2 mg/L except against C. pararugosa, Cryptococcus and some rare yeasts. Modal MICs (mg/L) were 0.06/0.125/0.25/0.5/0.5/0.5/0.5/1/2 for C. albicans/C. dubliniensis/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis/S. cerevisiae/C. guilliermondii/C. lusitaniae and aligned within ±1 dilution with published values. The MIC ranges for QC strains were: 0.06–0.25/0.5–1/0.125–0.5 for CNM-CL-F8555/ATCC6258/ATCC22019. The WT-UL (mg/L) were: 0.25/0.5/1/1/2 for C. albicans/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis. Adopting these, non-wild-type rates were 0.3%/0.6%/0%/8%/3% for C. albicans/C. glabrata/C. krusei/C. parapsilosis/C. tropicalis and overall lower than for comparators except amphotericin B. Five/six non-wild-type C. albicans/C. glabrata were echinocandin and Fks non-wild-type (F641S, F659del or F659L). Eight C. parapsilosis and three C. tropicalis non-wild-type isolates were echinocandin and Fks wild-type. Partial inhibition near 50% in the supra-MIC range may explain variable MICs. Ibrexafungerp EUCAST MIC testing is robust, although the significance of paradoxical growth for some species requires further investigation. The spectrum is broad and will provide an oral option for the growing population with azole refractory infection. MDPI 2022-10-20 /pmc/articles/PMC9605171/ /pubmed/36294671 http://dx.doi.org/10.3390/jof8101106 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jørgensen, Karin M.
Astvad, Karen M. T.
Hare, Rasmus K.
Arendrup, Maiken C.
EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title_full EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title_fullStr EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title_full_unstemmed EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title_short EUCAST Ibrexafungerp MICs and Wild-Type Upper Limits for Contemporary Danish Yeast Isolates
title_sort eucast ibrexafungerp mics and wild-type upper limits for contemporary danish yeast isolates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605171/
https://www.ncbi.nlm.nih.gov/pubmed/36294671
http://dx.doi.org/10.3390/jof8101106
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