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Most isolates are resistant to fluconazole, and many, to other drug classes, with acquired resistance to all clinically available antifungal drugs reported. Antifungal resistance is rising alongside increasing case counts, threatening a sparse antifungal toolbox with multidrug and pan-resistant isolates that may cause untreatable infections. In this minireview, we examine the recent literature investigating the mechanisms and evolutionary patterns of resistance in clinical isolates of\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      to each antifungal utilized to combat these infections. We propose a refined model of\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      drug resistance by separating the multidrug resistance paradigm into distinct resistance challenges for each drug class. We examine how the emergence of unique resistance patterns to each drug may suggest therapeutic options even for currently available antifungals. Resistance to fluconazole is driven by drug target mutations with clade-specific representation and more diverse acquired mutations in drug efflux regulators. Recent structural insights into the context of these mutations may suggest vulnerabilities to other triazoles even in fluconazole-resistant strains. Acquired resistance to echinocandins, amphotericin B, and the pyrimidine analog flucytosine is rare but can emerge under antifungal therapy through conserved resistance mechanisms. The reportedly higher amphotericin B resistance rate in\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      relative to other\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      species remains poorly understood and may be linked to unexplored intrinsic resistance mechanisms. We suggest that close examination and further investigation of these mechanisms may inform better therapeutic practice and may offer treatment solutions for this multidrug-resistant pathogen.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01062-24","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:03:21Z","timestamp":1773666201000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Deciphering the multidrug resistance paradigm in\n                    <i>Candida auris<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-8352","authenticated-orcid":false,"given":"Darian J.","family":"Santana","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-070X","authenticated-orcid":false,"given":"Nicholas C.","family":"Cauldron","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gq02987","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-0679","authenticated-orcid":true,"given":"P. David","family":"Rogers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02r3e0967","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital","place":["Memphis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5778-960X","authenticated-orcid":false,"given":"Christina A.","family":"Cuomo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gq02987","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.3767\/persoonia.2024.52.02"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6901a2"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","unstructured":"U.S. Centers for Disease Control and Prevention. 2019. 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