John, LLH; Thomson, DD; Bicanic, T; Hoenigl, M; Brown, AJP; Harrison, TS; Bignell, EM
(2023)
Heightened Efficacy of Anidulafungin When Used in Combination with Manogepix or 5-Flucytosine against Candida auris In Vitro.
Antimicrob Agents Chemother, 67 (6).
e0164522.
ISSN 1098-6596
https://doi.org/10.1128/aac.01645-22
SGUL Authors: Bicanic, Tihana Harrison, Thomas Stephen
Abstract
Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high proportion of C. auris isolates that display antifungal resistance severely limits treatment options. Combination therapies provide a possible strategy by which to enhance antifungal efficacy and prevent the emergence of further resistance. Therefore, we examined drug combinations using antifungals that are already in clinical use or are undergoing clinical trials. Using checkerboard assays, we screened combinations of 5-flucytosine and manogepix (the active form of the novel antifungal drug fosmanogepix) with anidulafungin, amphotericin B, or voriconazole against drug resistant and susceptible C. auris isolates from clades I and III. Fractional inhibitory concentration indices (FICI values) of 0.28 to 0.75 and 0.36 to 1.02 were observed for combinations of anidulafungin with manogepix or 5-flucytosine, respectively, indicating synergistic activity. The high potency of these anidulafungin combinations was confirmed using live-cell microfluidics-assisted imaging of the fungal growth. In summary, combinations of anidulafungin with manogepix or 5-flucytosine show great potential against both resistant and susceptible C. auris isolates.
Item Type: |
Article
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Additional Information: |
© 2023 American Society for Microbiology. All Rights Reserved.
For the purpose of open access, the author has applied a 'Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. The research data supporting this publication are provided within this paper or in the supplementary information accompanying this publication. |
Keywords: |
Candida auris, anidulafungin, antifungal combination, flucytosine, manogepix, synergy, Antifungal Agents, Anidulafungin, Flucytosine, Candida auris, Candida, Microbial Sensitivity Tests, Candida, Flucytosine, Antifungal Agents, Microbial Sensitivity Tests, Anidulafungin, Candida auris, Candida auris, antifungal combination, anidulafungin, flucytosine, manogepix, synergy, anidulafungin, antifungal combination, Candida auris, flucytosine, manogepix, synergy, 0605 Microbiology, 1108 Medical Microbiology, 1115 Pharmacology and Pharmaceutical Sciences, Microbiology |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Antimicrob Agents Chemother |
ISSN: |
1098-6596 |
Language: |
eng |
Dates: |
Date | Event |
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15 June 2023 | Published | 10 May 2023 | Published Online | 20 March 2023 | Accepted |
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Publisher License: |
Publisher's own licence |
Projects: |
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PubMed ID: |
37162367 |
Web of Science ID: |
WOS:000984975500001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/115483 |
Publisher's version: |
https://doi.org/10.1128/aac.01645-22 |
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