{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:42:46Z","timestamp":1785433366578,"version":"3.56.0"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"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":[[2025,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The dihydroorotate dehydrogenase (DHODH) inhibitor olorofim has potent activity against most molds. Recent reports of\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      acquired resistance to olorofim and an agrochemical fungicide DHODH inhibitor warrant continuous monitoring of\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity of olorofim. We examined the activity of olorofim against a contemporary, large collection of molds and explored the impact of different dilution schemes used for the preparation of microdilution plates. In total, 3,550 isolates referred to Statens Serum Institut during 2020\u20132023 were analyzed. Isolates were identified with matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and\/or sequencing. MICs of olorofim, amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, and terbinafine were determined using EUCAST E.Def 9.4 and E.Def 11.0 protocols. Drug dilutions were prepared either using serial dilutions directly in the medium (Serial, 2020\u20132023) or according to the ISO standard 20776-1, with predilutions in DMSO before dilution in medium (introduced during 2023). For isolates with elevated MICs to azoles and olorofim,\n                      <jats:italic toggle=\"yes\">Cyp51A<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Hmg1,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PyrE<\/jats:italic>\n                      were sequenced as deemed relevant. Serial dilutions generated MICs 1\u20132 dilutions higher than the ISO dilutions for olorofim, voriconazole, and isavuconazole. Olorofim MICs were &lt;0.5 mg\/L (modal MICs 0.03\u20130.5 mg\/L) against most isolates of\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Fusarium<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Scedosporium<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Talaromyces<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Penicillium<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Paecilomyces<\/jats:italic>\n                      , and dermatophytes. Exceptions included isolates belonging to\n                      <jats:italic toggle=\"yes\">Aspergillus section Aspergillus,<\/jats:italic>\n                      to\n                      <jats:italic toggle=\"yes\">Fusarium dimerum<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Fusarium solani<\/jats:italic>\n                      species complexes, and some rare molds (MICs &gt; 1 mg\/L). Olorofim susceptibility was stable over the years and not affected by Cyp51A, Hmg1, or PyrE Q35L alterations. Olorofim maintained broad, potent\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity over the years against a contemporary collection of molds.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00353-25","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T12:16:52Z","timestamp":1750940212000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["EUCAST olorofim MICs for 3,550 Danish mold and dermatophyte isolates from 2020 to 2023"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-1509","authenticated-orcid":true,"given":"Joseph","family":"Meletiadis","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit of Mycology, Statens Serum Institut","place":["Copenhagen, Denmark"]},{"id":[{"id":"https:\/\/ror.org\/04gnjpq42","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Microbiology Laboratory, Attikon University Hospital, National and Kapodistrian University of Athens","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-5153","authenticated-orcid":false,"given":"Karin Meinike","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit of Mycology, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-2904","authenticated-orcid":false,"given":"Karen Marie Thyssen","family":"Astvad","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit of Mycology, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5451-5379","authenticated-orcid":false,"given":"Nissrine","family":"Abou-Chakra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit of Mycology, Statens Serum Institut","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-0144","authenticated-orcid":true,"given":"Maiken Cavling","family":"Arendrup","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0417ye583","id-type":"ROR","asserted-by":"publisher"}],"name":"Unit of Mycology, Statens Serum Institut","place":["Copenhagen, Denmark"]},{"id":[{"id":"https:\/\/ror.org\/03mchdq19","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Microbiology, Rigshospitalet","place":["Copenhagen, Denmark"]},{"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Medicine, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof10050345"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608304113"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-024-10143-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0289441"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01527-20"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00487-18"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2034485"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01542-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00073-19"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab088"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2343079"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa111"},{"key":"e_1_3_3_14_2","unstructured":"Guinea J Meletiadis J Arikan-Akdagli S Muehlethaler K Gunnar K Arendrup M Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committe for Antimicrobial Susceptibility Testing. 2022. EUCAST DEFINITIVE DOCUMENT E.DEF 9.4. Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. Available from: www.eucast.org. http:\/\/www.eucast.org"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.08.042"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01386-21"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00353-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00353-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:39:36Z","timestamp":1773178776000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00353-25"}},"subtitle":[],"editor":[{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,6]]}},"alternative-id":["10.1128\/aac.00353-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00353-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00353-25"}}