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Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model

BACKGROUND: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose admin...

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Autores principales: Hager, Christopher L, Larkin, Emily L, Long, Lisa A, Ghannoum, Mahmoud A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070025/
https://www.ncbi.nlm.nih.gov/pubmed/29897469
http://dx.doi.org/10.1093/jac/dky153
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author Hager, Christopher L
Larkin, Emily L
Long, Lisa A
Ghannoum, Mahmoud A
author_facet Hager, Christopher L
Larkin, Emily L
Long, Lisa A
Ghannoum, Mahmoud A
author_sort Hager, Christopher L
collection PubMed
description BACKGROUND: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. OBJECTIVES: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. METHODS: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 10(7)C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day. RESULTS: Rezafungin had significantly lower average log(10) cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log(10) cfu/g of tissue compared with micafungin-treated mice on day 10. CONCLUSIONS: Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.
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spelling pubmed-60700252018-08-08 Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model Hager, Christopher L Larkin, Emily L Long, Lisa A Ghannoum, Mahmoud A J Antimicrob Chemother Original Research BACKGROUND: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. OBJECTIVES: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. METHODS: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 10(7)C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day. RESULTS: Rezafungin had significantly lower average log(10) cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log(10) cfu/g of tissue compared with micafungin-treated mice on day 10. CONCLUSIONS: Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis. Oxford University Press 2018-08 2018-04-19 /pmc/articles/PMC6070025/ /pubmed/29897469 http://dx.doi.org/10.1093/jac/dky153 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Hager, Christopher L
Larkin, Emily L
Long, Lisa A
Ghannoum, Mahmoud A
Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title_full Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title_fullStr Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title_full_unstemmed Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title_short Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
title_sort evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated candida auris infection using an immunocompromised mouse model
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070025/
https://www.ncbi.nlm.nih.gov/pubmed/29897469
http://dx.doi.org/10.1093/jac/dky153
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