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In Vivo Efficacy of Amphotericin B against Four Candida auris Clades

Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades...

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Autores principales: Forgács, Lajos, Borman, Andrew M., Kovács, Renátó, Balázsi, Dávid, Tóth, Zoltán, Balázs, Bence, Chun-Ju, Chiu, Kardos, Gábor, Kovacs, Ilona, Majoros, László
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144575/
https://www.ncbi.nlm.nih.gov/pubmed/35628754
http://dx.doi.org/10.3390/jof8050499
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author Forgács, Lajos
Borman, Andrew M.
Kovács, Renátó
Balázsi, Dávid
Tóth, Zoltán
Balázs, Bence
Chun-Ju, Chiu
Kardos, Gábor
Kovacs, Ilona
Majoros, László
author_facet Forgács, Lajos
Borman, Andrew M.
Kovács, Renátó
Balázsi, Dávid
Tóth, Zoltán
Balázs, Bence
Chun-Ju, Chiu
Kardos, Gábor
Kovacs, Ilona
Majoros, László
author_sort Forgács, Lajos
collection PubMed
description Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system.
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spelling pubmed-91445752022-05-29 In Vivo Efficacy of Amphotericin B against Four Candida auris Clades Forgács, Lajos Borman, Andrew M. Kovács, Renátó Balázsi, Dávid Tóth, Zoltán Balázs, Bence Chun-Ju, Chiu Kardos, Gábor Kovacs, Ilona Majoros, László J Fungi (Basel) Article Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system. MDPI 2022-05-11 /pmc/articles/PMC9144575/ /pubmed/35628754 http://dx.doi.org/10.3390/jof8050499 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
Forgács, Lajos
Borman, Andrew M.
Kovács, Renátó
Balázsi, Dávid
Tóth, Zoltán
Balázs, Bence
Chun-Ju, Chiu
Kardos, Gábor
Kovacs, Ilona
Majoros, László
In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title_full In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title_fullStr In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title_full_unstemmed In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title_short In Vivo Efficacy of Amphotericin B against Four Candida auris Clades
title_sort in vivo efficacy of amphotericin b against four candida auris clades
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144575/
https://www.ncbi.nlm.nih.gov/pubmed/35628754
http://dx.doi.org/10.3390/jof8050499
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