{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:35:59Z","timestamp":1790562959941,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The University of Sydney Infectious Diseases Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Global emergence of rapidly developing resistance to multiple antifungal drugs and high mortality pose challenges to the treatment of invasive Candida auris infections. New therapeutic approaches are needed, such as repurposing drugs including combination with antifungals. Statins have been reported to exert antifungal effects against various Candida species.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Our study investigated potential synergy between the statins (rosuvastatin and fluvastatin) and azoles (voriconazole, posaconazole and isavuconazole) on clinical isolates of C. auris.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Twenty-one clinical isolates of C. auris were obtained. Chequerboard assays based on the CLSI broth microdilution method were used to assess synergy based on FIC index (FICI) calculations of MICs of individual drugs and in combinations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Single drug geometric mean (GM) MICs of fluvastatin and rosuvastatin were \u2265128\u2005mg\/L in all 21 isolates. GM (range) MICs of posaconazole, voriconazole and isavuconazole were 0.259 (0.016\u20131\u2005mg\/L), 0.469 (0.016\u20132\u2005mg\/L) and 0.085 (0.004\u20131\u2005mg\/L), respectively. Combination of azoles with fluvastatin showed synergy in 70%\u201390% of C. auris isolates. In particular, voriconazole\/fluvastatin resulted in 16-fold reduction in voriconazole MIC and synergy in 14\/21 (67%) isolates. Posaconazole\/fluvastatin resulted in 8-fold reduction in posaconazole MIC and synergy in 19\/21 (90%) isolates.<\/jats:p>\n                  <jats:p>Combining rosuvastatin with the azoles also showed synergy against C. auris in 40%\u201360% of the isolates and additive effect in 40%\u201350%. None of the combinations was antagonistic.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results provide a rationale for pursuing in vivo synergy tests as well as clinical studies to explore tolerability, treatment outcomes, optimal dose and exposure targets.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad303","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T09:40:41Z","timestamp":1697103641000},"page":"2824-2829","source":"Crossref","is-referenced-by-count":14,"title":["Exploring synergy between azole antifungal drugs and statins for <i>Candida auris<\/i>"],"prefix":"10.1093","volume":"78","author":[{"given":"Catriona","family":"Halliday","sequence":"first","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital , Westmead, NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-5036","authenticated-orcid":false,"given":"Hannah Yejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney , A15 Science Rd , Camperdown, NSW 2006, Australia"},{"name":"Department of Pharmacy, Westmead Hospital , Westmead, NSW , Australia"},{"name":"The University of Sydney Infectious Diseases Institute (Sydney ID) , Westmead, NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enoch","family":"Tay","sequence":"additional","affiliation":[{"name":"Research Education Network, Western Sydney Local Health District, Westmead Hospital , Westmead, NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon C A","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital , Westmead, NSW , Australia"},{"name":"Sydney Medical School, Faculty of Medicine and Health, The University of Sydney , Camperdown, NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-0288","authenticated-orcid":false,"given":"Jan-Willem","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney , A15 Science Rd , Camperdown, NSW 2006, Australia"},{"name":"The University of Sydney Infectious Diseases Institute (Sydney ID) , Westmead, NSW , Australia"},{"name":"Westmead Hospital , Westmead, NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"2023120106054156400_dkad303-B1","author":"WHO","year":"2022"},{"key":"2023120106054156400_dkad303-B2","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1080\/22221751.2022.2125349","article-title":"Confirmation of fifth Candida auris clade by whole genome sequencing","volume":"11","author":"Spruijtenburg","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"2023120106054156400_dkad303-B3","doi-asserted-by":"crossref","first-page":"e01503-19","DOI":"10.1128\/JCM.01503-19","article-title":"Laboratory analysis of an outbreak of Candida auris in New York from 2016 to 2018: impact and lessons learned","volume":"58","author":"Zhu","year":"2020","journal-title":"J Clin Microbiol"},{"key":"2023120106054156400_dkad303-B4","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/jac\/dkx480","article-title":"A multicentre 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