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Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only avail...

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Autores principales: Ghannoum, Mahmoud, Arendrup, Maiken Cavling, Chaturvedi, Vishnu P., Lockhart, Shawn R., McCormick, Thomas S., Chaturvedi, Sudha, Berkow, Elizabeth L., Juneja, Deven, Tarai, Bansidhar, Azie, Nkechi, Angulo, David, Walsh, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559578/
https://www.ncbi.nlm.nih.gov/pubmed/32854252
http://dx.doi.org/10.3390/antibiotics9090539
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author Ghannoum, Mahmoud
Arendrup, Maiken Cavling
Chaturvedi, Vishnu P.
Lockhart, Shawn R.
McCormick, Thomas S.
Chaturvedi, Sudha
Berkow, Elizabeth L.
Juneja, Deven
Tarai, Bansidhar
Azie, Nkechi
Angulo, David
Walsh, Thomas J.
author_facet Ghannoum, Mahmoud
Arendrup, Maiken Cavling
Chaturvedi, Vishnu P.
Lockhart, Shawn R.
McCormick, Thomas S.
Chaturvedi, Sudha
Berkow, Elizabeth L.
Juneja, Deven
Tarai, Bansidhar
Azie, Nkechi
Angulo, David
Walsh, Thomas J.
author_sort Ghannoum, Mahmoud
collection PubMed
description Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.
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spelling pubmed-75595782020-10-29 Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections Ghannoum, Mahmoud Arendrup, Maiken Cavling Chaturvedi, Vishnu P. Lockhart, Shawn R. McCormick, Thomas S. Chaturvedi, Sudha Berkow, Elizabeth L. Juneja, Deven Tarai, Bansidhar Azie, Nkechi Angulo, David Walsh, Thomas J. Antibiotics (Basel) Review Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections. MDPI 2020-08-25 /pmc/articles/PMC7559578/ /pubmed/32854252 http://dx.doi.org/10.3390/antibiotics9090539 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ghannoum, Mahmoud
Arendrup, Maiken Cavling
Chaturvedi, Vishnu P.
Lockhart, Shawn R.
McCormick, Thomas S.
Chaturvedi, Sudha
Berkow, Elizabeth L.
Juneja, Deven
Tarai, Bansidhar
Azie, Nkechi
Angulo, David
Walsh, Thomas J.
Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title_full Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title_fullStr Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title_full_unstemmed Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title_short Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections
title_sort ibrexafungerp: a novel oral triterpenoid antifungal in development for the treatment of candida auris infections
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559578/
https://www.ncbi.nlm.nih.gov/pubmed/32854252
http://dx.doi.org/10.3390/antibiotics9090539
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