{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:45:09Z","timestamp":1791726309586,"version":"4.3.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:00:00Z","timestamp":1707264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"German Ministry of Health","award":["1369-240"],"award-info":[{"award-number":["1369-240"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,2,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Invasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged. Ibrexafungerp (IBX) is a new antifungal substance with potent anti-\n                    <jats:italic>Candida<\/jats:italic>\n                    activity. We challenged IBX with a library of 192 pheno-\/genotypically echinocandin-resistant\n                    <jats:italic>Candida<\/jats:italic>\n                    isolates, focusing on the substance susceptibility, its activity on certain\n                    <jats:italic>FKS<\/jats:italic>\n                    hotspot (HS) mutated strains, and applying WTULs (wild-type upper limits). Therefore, a 9-year-old strain and patient data collection provided by the German National Reference Center for Invasive Fungal Infections were analyzed. Species identification was confirmed through ITS-sequencing. Molecular susceptibility testing was performed by sequencing HS of the\n                    <jats:italic>FKS<\/jats:italic>\n                    gene. Anidulafungin (AND) and IBX EUCAST-broth-microdilution was conducted. The four most common echinocandin-resistance mediating mutations were found in\n                    <jats:italic>Candida glabrata<\/jats:italic>\n                    [112\/192 isolates; F659-(43\u00d7) and S663-(48\u00d7)] and\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    [63\/192 isolates; F641-(15\u00d7) and S645-(39\u00d7)]. Mutations at the HS-start sequence were associated with higher IBX MIC-values (F659 and F641 (MIC 50\/90 mg\/L: &gt;4\/&gt;4 and 2\/4 mg\/L) in comparison to AND (F659 and F641 (MIC 50\/90: 1\/4 and 0.25\/1 mg\/L). MIC-values in HS-center mutations were almost equal [MIC50\/90 in S663: 2\/4 (AND and IBX); in S645: 0.5\/1 (AND) and 0.25\/1 (IBX) mg\/L]. In total, 61 vs 78 of 192 echinocandin-resistant isolates may be classified as IBX wild type by applying WTULs, whereas the most prominent effect was seen in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    [48% (30\/63) vs 70% (44\/63)]. IBX shows\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity against echinocandin-resistant\n                    <jats:italic>Candida<\/jats:italic>\n                    and thus is an addition to the antifungal armory. However, our data suggest that this effect is more pronounced in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    and strains harboring mutations, affecting the HS-center.\n                  <\/jats:p>","DOI":"10.1128\/aac.01324-23","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T09:04:59Z","timestamp":1704963899000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["<i>In vitro<\/i>\n                    activity of ibrexafungerp against clinically relevant echinocandin-resistant\n                    <i>Candida<\/i>\n                    strains"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-5518","authenticated-orcid":false,"given":"Alexander Maximilian","family":"Aldejohann","sequence":"first","affiliation":[{"name":"Institute for Hygiene and Microbiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Menner","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Thielemann","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-1511","authenticated-orcid":true,"given":"Ronny","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grit","family":"Walther","sequence":"additional","affiliation":[{"name":"National Reference Center for Invasive Fungal Infections, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-2646","authenticated-orcid":true,"given":"Oliver","family":"Kurzai","sequence":"additional","affiliation":[{"name":"Institute for Hygiene and Microbiology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"National Reference Center for Invasive Fungal Infections, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"Geneva WHO. 2022. 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The European Committee on antimicrobial susceptibility testing. In Breakpoint tables for interpretation of Mics for antifungal agents, version 10.0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz287"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy358"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01674-13"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01725-21"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof7060491"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.02.006"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01692-19"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00027-12"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/LGT.0000000000000383"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01324-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01324-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T19:33:53Z","timestamp":1715801633000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01324-23"}},"subtitle":[],"editor":[{"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,7]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,7]]}},"alternative-id":["10.1128\/aac.01324-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01324-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,7]]},"assertion":[{"value":"2023-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01324-23"}}