Heightened Efficacy of Anidulafungin When Used in Combination with Manogepix or 5-Flucytosine against Candida auris In Vitro
dc.contributor.author | John, LLH | |
dc.contributor.author | Thomson, DD | |
dc.contributor.author | Bicanic, T | |
dc.contributor.author | Hoenigl, M | |
dc.contributor.author | Brown, AJP | |
dc.contributor.author | Harrison, TS | |
dc.contributor.author | Bignell, EM | |
dc.date.accessioned | 2023-06-13T12:54:09Z | |
dc.date.issued | 2023-05-10 | |
dc.date.updated | 2023-06-13T10:04:16Z | |
dc.description.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. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | National Institute for Health and Care Research (NIHR) | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Medical Research Foundation | en_GB |
dc.format.extent | e0164522- | |
dc.format.medium | Print-Electronic | |
dc.identifier.citation | Published online 10 May 2023 | en_GB |
dc.identifier.doi | https://doi.org/10.1128/aac.01645-22 | |
dc.identifier.grantnumber | MR/N006364/2 | en_GB |
dc.identifier.grantnumber | MR/V033417/1 | en_GB |
dc.identifier.grantnumber | MR/P501955/2 | en_GB |
dc.identifier.grantnumber | MR/S001824/1 | en_GB |
dc.identifier.grantnumber | BB/V017004/1 | en_GB |
dc.identifier.grantnumber | MR/M026663/2 | en_GB |
dc.identifier.grantnumber | MRF-160-0009-ELP-BICA-C0802 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/133375 | |
dc.identifier | ORCID: 0000-0003-1406-4251 (Brown, Alistair JP) | |
dc.identifier | ScopusID: 7408339455 (Brown, Alistair JP) | |
dc.identifier | ORCID: 0000-0001-7748-1920 (Bignell, Elaine M) | |
dc.identifier | ScopusID: 6602285504 (Bignell, Elaine M) | |
dc.language.iso | en | en_GB |
dc.publisher | American Society for Microbiology | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/37162367 | en_GB |
dc.rights | © 2023 American Society for Microbiology. This version is made available under the CC-BY 4.0 license: https://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.subject | Candida auris | en_GB |
dc.subject | anidulafungin | en_GB |
dc.subject | antifungal combination | en_GB |
dc.subject | flucytosine | en_GB |
dc.subject | manogepix | en_GB |
dc.subject | synergy | en_GB |
dc.title | Heightened Efficacy of Anidulafungin When Used in Combination with Manogepix or 5-Flucytosine against Candida auris In Vitro | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-06-13T12:54:09Z | |
dc.identifier.issn | 0066-4804 | |
exeter.place-of-publication | United States | |
dc.description | This is the author accepted manuscript. The final version is available from the American Society for Microbiology via the DOI in this record | en_GB |
dc.description | Data availability: The research data supporting this publication are provided within this paper or in the supplementary information accompanying this publication. | en_GB |
dc.identifier.eissn | 1098-6596 | |
dc.identifier.journal | Antimicrobial Agents and Chemotherapy | en_GB |
dc.relation.ispartof | Antimicrob Agents Chemother | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-03-20 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2023-05-10 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-06-13T12:48:47Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2023-06-13T12:54:16Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-05-10 |
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Except where otherwise noted, this item's licence is described as © 2023 American Society for Microbiology. This version is made available under the CC-BY 4.0 license: https://creativecommons.org/licenses/by/4.0/