{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:18:09Z","timestamp":1791303489722,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Precise<jats:italic>FKS<\/jats:italic>mutation rates among<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>species are undefined because studies have not systematically screened consecutive, disease-causing isolates. The Sensititre YeastOne (SYO) assay measures echinocandin MICs against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>with less variability than reference broth microdilution methods. However, clinical breakpoint MICs may overstate caspofungin nonsusceptibility compared to other agents. Our objectives were to determine<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content><jats:italic>FKS<\/jats:italic>mutation rates by studying consecutive bloodstream isolates and to determine if discrepant susceptibility results were associated with<jats:italic>FKS<\/jats:italic>mutations.<jats:italic>FKS<\/jats:italic>hot spots were sequenced in echinocandin-intermediate and -resistant isolates and those from patients with breakthrough candidemia or \u22653 days of prior echinocandin exposure. Overall, 453 isolates from 384 patients underwent susceptibility testing; 16% were echinocandin intermediate or resistant. Intermediate susceptibility rates were higher for<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida glabrata<\/jats:named-content>than for other species (<jats:italic>P<\/jats:italic>&lt; 0.0001) and higher for caspofungin than for other agents (<jats:italic>P<\/jats:italic>&lt; 0.0001). Resistance rates were similar between agents.<jats:italic>FKS<\/jats:italic>mutations were detected in 5% of sequenced isolates and 2% of isolates overall. Corresponding rates among<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>isolates were 8% and 4%, respectively. Among<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>isolates, rates were 5% and &lt;1%, respectively. Mutations occurred exclusively with prior echinocandin exposure and were not detected in other species. Isolates with discrepant susceptibility results did not harbor<jats:italic>FKS<\/jats:italic>mutations. Mutation rates among isolates resistant to \u22652, 1, and 0 agents were 75%, 13%, and 0%, respectively. In conclusion,<jats:italic>FKS<\/jats:italic>mutations were uncommon among non-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. glabrata<\/jats:named-content>species, even with prior echinocandin exposure. Discrepancies in echinocandin susceptibility by SYO testing were not driven by mutations and likely reflect imprecise caspofungin clinical breakpoints.<\/jats:p>","DOI":"10.1128\/aac.01973-15","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T02:23:49Z","timestamp":1442888629000},"page":"7465-7470","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Rate of<i>FKS<\/i>Mutations among Consecutive Candida Isolates Causing Bloodstream Infection"],"prefix":"10.1128","volume":"59","author":[{"given":"Ryan K.","family":"Shields","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Hong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen G.","family":"Press","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Cumbie","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. William","family":"Pasculle","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius J.","family":"Clancy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"},{"name":"VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu407"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit136"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00027-12"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.3201\/eid2011.140685","article-title":"Drug-resistant Candida glabrata infection in cancer patients","volume":"20","author":"Farmakiotis D","year":"2014","unstructured":"Farmakiotis D, Tarrand JJ, Kontoyiannis DP. 2014. Drug-resistant Candida glabrata infection in cancer patients. Emerg Infect Dis 20:1833\u20131840.","journal-title":"Emerg Infect Dis"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv087"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00136-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04134-14"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00029-06"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-014-0286-5"},{"key":"e_1_3_2_11_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts, fourth informational supplement M27-S4","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Reference method for broth dilution antifungal susceptibility testing of yeasts, fourth informational supplement M27-S4, 4th ed. 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