{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:28:30Z","timestamp":1785540510490,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014054","name":"Drugs for Neglected Diseases initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently treated with a combination of itraconazole and surgery. In an ongoing clinical study, the efficacy of fosravuconazole, the prodrug of ravuconazole, is being investigated. For both itraconazole and ravuconazole, no clinical breakpoints or epidemiological cut\u2010off values (ECV) to guide treatment are currently available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine tentative ECVs for itraconazole and ravuconazole in <jats:italic>Madurella mycetomatis<\/jats:italic>, the main causative agent of eumycetoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Minimal inhibitory concentrations (MICs) for itraconazole and ravuconazole were determined in 131 genetically diverse clinical <jats:italic>M. mycetomatis<\/jats:italic> isolates with the modified CLSI M38 broth microdilution method. The MIC distributions were established and used to determine ECVs with the ECOFFinder software. <jats:italic>CYP51A<\/jats:italic> sequences were sequenced to determine whether mutations occurred in this azole target gene, and comparisons were made between the different <jats:italic>CYP51A<\/jats:italic> variants and the MIC distributions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The MICs ranged from 0.008 to 1\u00a0mg\/L for itraconazole and from 0.002 to 0.125\u2009mg\/L for ravuconazole. The <jats:italic>M. mycetomatis<\/jats:italic> ECV for itraconazole was 1\u00a0mg\/L and for ravuconazole 0.064\u2009mg\/L. In the wild\u2010type population, two <jats:italic>CYP51A<\/jats:italic> variants were found for <jats:italic>M. mycetomatis<\/jats:italic>, which differed in one amino acid at position 499 (S499G). The MIC distributions for itraconazole and ravuconazole were similar between the two variants. No mutations linked to decreased susceptibility were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The proposed <jats:italic>M. mycetomatis<\/jats:italic> ECV for itraconazole is 1\u00a0mg\/L and for ravuconazole 0.064\u2009mg\/L.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13509","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T07:48:23Z","timestamp":1659167303000},"page":"1170-1178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Epidemiological cut\u2010off values for itraconazole and ravuconazole for <i>Madurella mycetomatis<\/i>, the most common causative agent of mycetoma"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-6149","authenticated-orcid":false,"given":"Bertrand","family":"Nyuykonge","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases Erasmus MC, University Medical Centre Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel E.","family":"Siddig","sequence":"additional","affiliation":[{"name":"Mycetoma Research Centre University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najwa Adam","family":"Mhmoud","sequence":"additional","affiliation":[{"name":"Mycetoma Research Centre University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9563-7108","authenticated-orcid":false,"given":"Borna A.","family":"Nyaoke","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi)  Nairobi Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard E.","family":"Zijlstra","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative (DNDi)  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Verbon","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases Erasmus MC, University Medical Centre Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Bakhiet","sequence":"additional","affiliation":[{"name":"Mycetoma Research Centre University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.","family":"Fahal","sequence":"additional","affiliation":[{"name":"Mycetoma Research Centre University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy W. 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