{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:24:02Z","timestamp":1787009042053,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T00:00:00Z","timestamp":1578268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Eumycetoma is currently treated with a combination of itraconazole therapy and surgery, with limited success. Recently, olorofim, the lead candidate of the orotomides, a novel class of antifungal agents, entered a Phase II trial for the treatment of invasive fungal infections. Here we determined the activity of olorofim against Madurella mycetomatis, the main causative agent of eumycetoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Activity of olorofim against M. mycetomatis was determined by in silico comparison of the target gene, dihydroorotate dehydrogenase (DHODH), and in vitro susceptibility testing. We also investigated the in vitro interaction between olorofim and itraconazole against M. mycetomatis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>M. mycetomatis and Aspergillus fumigatus share six out of seven predicted binding residues in their DHODH DNA sequence, predicting susceptibility to olorofim. Olorofim demonstrated excellent potency against M. mycetomatis in vivo with MICs ranging from 0.004 to 0.125\u2009mg\/L and an MIC90 of 0.063\u2009mg\/L. Olorofim MICs were mostly one dilution step lower than the itraconazole MICs. In vitro interaction studies demonstrated that olorofim and itraconazole work indifferently when combined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated olorofim has potent in vitro activity against M. mycetomatis and should be further evaluated in vivo as a treatment option for this disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz529","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T07:09:24Z","timestamp":1575443364000},"page":"936-941","source":"Crossref","is-referenced-by-count":44,"title":["Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim"],"prefix":"10.1093","volume":"75","author":[{"given":"Wilson","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Eadie","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickey","family":"Konings","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Rijnders","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H","family":"Fahal","sequence":"first","affiliation":[{"name":"Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D","family":"Oliver","sequence":"first","affiliation":[{"name":"F2G Ltd, Eccles, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Birch","sequence":"first","affiliation":[{"name":"F2G Ltd, Eccles, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Verbon","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"van de Sande","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, The 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