{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:53Z","timestamp":1787009033383,"version":"build-2736575974"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Stichting Erasmus Trusfonds","award":["97030.2022.101.718"],"award-info":[{"award-number":["97030.2022.101.718"]}]},{"name":"Stichting Erasmus Trusfonds","award":["015.013.033"],"award-info":[{"award-number":["015.013.033"]}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"CSC","doi-asserted-by":"publisher","award":["202008520048"],"award-info":[{"award-number":["202008520048"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Eumycetoma is a neglected tropical fungal disease of the subcutaneous tissue that is currently not treatable with medication only. Standard itraconazole therapy is combined with surgical excision of the lesion. Recently, ibrexafungerp, a novel oral antifungal agent inhibiting 1,3-\u03b2-D-glucan synthesis, was approved by the United States Food and Drug Administration (FDA) for the treatment of vulvovaginal candidiasis. In this study we determined the in vitro activity and in vivo efficacy of ibrexafungerp in eumycetoma causative agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro activity of ibrexafungerp and itraconazole was determined against 30 Madurella and 7 Falciformispora isolates by standardized in vitro susceptibility assays. The in vivo efficacy of ibrexafungerp, itraconazole and the combination of ibrexafungerp and itraconazole was determined by measuring the 10 day survival in M. mycetomatis and F. senegalensis grain models in Galleria mellonella larvae. Grain number and size were determined in Grocott- and haematoxylin and eosin\u2013stained sections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ibrexafungerp inhibited the growth of Madurella and Falciformispora species with MICs ranging from 4 to 64 mg\/L and from 8 to 32 mg\/L, respectively. In G. mellonella larvae, ibrexafungerp was not toxic and prolonged the survival in M. mycetomatis-infected larvae 10 days after infection, but not in F. senegalensis-infected larvae. Combining ibrexafungerp with itraconazole prolonged the survival of M. mycetomatis- and F. senegalensis-infected larvae. Treatment with ibrexafungerp alone and in combination resulted in smaller grains in M. mycetomatis-infected larvae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ibrexafungerp showed in vitro activity and in vivo efficacy against the two most common eumycetoma causative agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf133","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T07:30:43Z","timestamp":1744702243000},"page":"1733-1741","source":"Crossref","is-referenced-by-count":5,"title":["Ibrexafungerp prolongs survival and reduces the eumycetoma grain size in\n                    <i>Galleria mellonella<\/i>\n                    infection models of two different causative agents of eumycetoma"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-2239","authenticated-orcid":false,"given":"Jingyi","family":"Ma","sequence":"first","affiliation":[{"name":"Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases , Dr. Molewaterplein 40, Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Eadie","sequence":"additional","affiliation":[{"name":"Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases , Dr. Molewaterplein 40, Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-4304","authenticated-orcid":false,"given":"Mickey","family":"Konings","sequence":"additional","affiliation":[{"name":"Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases , Dr. Molewaterplein 40, Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4922-7321","authenticated-orcid":false,"given":"Ahmed","family":"Fahal","sequence":"additional","affiliation":[{"name":"Mycetoma Research Centre , Khartoum ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Verbon","sequence":"additional","affiliation":[{"name":"Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases , Dr. Molewaterplein 40, Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-8783","authenticated-orcid":false,"given":"Wendy W J","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Erasmus MC, University Medical Center Rotterdam, Department of Medical Microbiology and Infectious Diseases , Dr. Molewaterplein 40, Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025060219525250700_dkaf133-B1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1093\/mmy\/myx061","article-title":"Closing the mycetoma knowledge gap","volume":"56","author":"van de Sande","year":"2018","journal-title":"Med Mycol"},{"key":"2025060219525250700_dkaf133-B2","volume-title":"Fungi Causing Eumycotic Mycetoma","author":"Ahmed","year":"2019"},{"key":"2025060219525250700_dkaf133-B3","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1080\/17460441.2022.2080195","article-title":"Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an Open Source Drug discovery approach","volume":"17","author":"Lim","year":"2022","journal-title":"Expert Opin Drug Discov"},{"key":"2025060219525250700_dkaf133-B4","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.clindermatol.2011.06.027","article-title":"Actinomycetoma and advances in its treatment","volume":"30","author":"Welsh","year":"2012","journal-title":"Clin Dermatol"},{"key":"2025060219525250700_dkaf133-B5","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/S1473-3099(15)00359-X","article-title":"Mycetoma: a unique neglected tropical disease","volume":"16","author":"Zijlstra","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2025060219525250700_dkaf133-B6","doi-asserted-by":"publisher","first-page":"e0003423","DOI":"10.1128\/cmr.00034-23","article-title":"An updated list of eumycetoma causative agents and their differences in grain formation and treatment response","volume":"37","author":"van de Sande","year":"2024","journal-title":"Clin Microbiol Rev"},{"key":"2025060219525250700_dkaf133-B7","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1093\/trstmh\/traa184","article-title":"In vitro susceptibility testing for black grain eumycetoma causative agents","volume":"115","author":"van de Sande","year":"2021","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2025060219525250700_dkaf133-B8","doi-asserted-by":"publisher","first-page":"e0003926","DOI":"10.1371\/journal.pntd.0003926","article-title":"A Madurella mycetomatis grain model in Galleria mellonella larvae","volume":"9","author":"Kloezen","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"2025060219525250700_dkaf133-B9","doi-asserted-by":"publisher","first-page":"myad070","DOI":"10.1093\/mmy\/myad070","article-title":"A Falciformispora senegalensis grain model in Galleria mellonella larvae","volume":"61","author":"Ma","year":"2023","journal-title":"Med Mycol"},{"key":"2025060219525250700_dkaf133-B10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0928-8244(03)00096-8","article-title":"A murine model of Madurella mycetomatis eumycetoma","volume":"37","author":"Ahmed","year":"2003","journal-title":"FEMS Immunol Med Microbiol"},{"key":"2025060219525250700_dkaf133-B11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/trstmh\/trac069","article-title":"Mycetoma management and clinical outcomes: the Mycetoma Research Center experience","volume":"117","author":"Musa","year":"2023","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2025060219525250700_dkaf133-B12","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.trstmh.2012.07.003","article-title":"Predictors of cure, amputation and follow-up dropout among patients with mycetoma seen at the Mycetoma Research Centre, University of Khartoum, Sudan","volume":"106","author":"Zein","year":"2012","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2025060219525250700_dkaf133-B13","doi-asserted-by":"publisher","first-page":"4882","DOI":"10.1021\/ja9944296","article-title":"Isolation and structural determination of enfumafungin, a triterpene glycoside antifungal agent that is a specific inhibitor of glucan synthesis","volume":"122","author":"Schwartz","year":"2000","journal-title":"J Am Chem Soc"},{"key":"2025060219525250700_dkaf133-B14","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3390\/antibiotics9090539","article-title":"Ibrexafungerp: a novel oral triterpenoid antifungal in development for the treatment of Candida auris infections","volume":"9","author":"Ghannoum","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"2025060219525250700_dkaf133-B15","doi-asserted-by":"publisher","first-page":"e01692-19","DOI":"10.1128\/AAC.01692-19","article-title":"In vitro activity of ibrexafungerp, a novel glucan synthase inhibitor against Candida glabrata isolates with FKS mutations","volume":"63","author":"Nunnally","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B16","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1177\/10600280221091301","article-title":"Ibrexafungerp in the treatment of vulvovaginal candidiasis","volume":"57","author":"Barnes","year":"2023","journal-title":"Ann Pharmacother"},{"key":"2025060219525250700_dkaf133-B17","doi-asserted-by":"publisher","first-page":"e02429-19","DOI":"10.1128\/AAC.02429-19","article-title":"Combination therapy with ibrexafungerp (formerly SCY-078), a first-in-class triterpenoid inhibitor of (1\u21923)-beta-d-glucan synthesis, and isavuconazole for treatment of experimental invasive pulmonary aspergillosis","volume":"64","author":"Petraitis","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B18","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1128\/AAC.01546-09","article-title":"Madurella mycetomatis is not susceptible to the echinocandin class of antifungal agents","volume":"54","author":"van de Sande","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B19","doi-asserted-by":"publisher","first-page":"e02331-20","DOI":"10.1128\/JCM.02331-20","article-title":"A short-tandem-repeat assay (MmySTR) for studying genetic variation in Madurella mycetomatis","volume":"59","author":"Nyuykonge","year":"2021","journal-title":"J Clin Microbiol"},{"key":"2025060219525250700_dkaf133-B20","doi-asserted-by":"publisher","first-page":"729\u2013","DOI":"10.1093\/trstmh\/trae030","article-title":"The performance and costs of XTT, resazurin, MTS and luciferin as viability dyes in in vitro susceptibility testing of Madurella mycetomatis","volume":"118","author":"Ma","year":"2024","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2025060219525250700_dkaf133-B21","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1093\/mmy\/myx064","article-title":"Amphotericin B and terbinafine but not the azoles prolong survival in Galleria mellonella larvae infected with Madurella mycetomatis","volume":"56","author":"Kloezen","year":"2018","journal-title":"Med Mycol"},{"key":"2025060219525250700_dkaf133-B22","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.tips.2024.02.007","article-title":"Targeting Fks1 proteins for novel antifungal drug discovery","volume":"45","author":"Kumar","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"2025060219525250700_dkaf133-B23","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.3390\/jof8111121","article-title":"Ibrexafungerp, a novel triterpenoid antifungal in development for the treatment of mold infections","volume":"8","author":"Angulo","year":"2022","journal-title":"J Fungi (Basel)"},{"key":"2025060219525250700_dkaf133-B24","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3390\/jof7030163","article-title":"Ibrexafungerp: a first-in-class oral triterpenoid glucan synthase inhibitor","volume":"7","author":"Jallow","year":"2021","journal-title":"J Fungi (Basel)"},{"key":"2025060219525250700_dkaf133-B25","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1093\/ajhp\/zxac256","article-title":"Ibrexafungerp: a new triterpenoid antifungal","volume":"79","author":"Sucher","year":"2022","journal-title":"Am J Health Syst Pharm"},{"key":"2025060219525250700_dkaf133-B26","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.3390\/jof8101106","article-title":"EUCAST ibrexafungerp MICs and wild-type upper limits for contemporary Danish yeast isolates","volume":"8","author":"Jorgensen","year":"2022","journal-title":"J Fungi (Basel)"},{"key":"2025060219525250700_dkaf133-B27","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1128\/AAC.02145-13","article-title":"Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida species and Aspergillus species isolates","volume":"58","author":"Jim\u00e9nez-Ortigosa","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B28","doi-asserted-by":"publisher","first-page":"4308","DOI":"10.1128\/AAC.00234-15","article-title":"Antifungal activities of SCY-078 (MK-3118) and standard antifungal agents against clinical non-Aspergillus mold isolates","volume":"59","author":"Lamoth","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B29","doi-asserted-by":"publisher","first-page":"e00244-18","DOI":"10.1128\/AAC.00244-18","article-title":"Evaluation of the antifungal activity of the novel oral glucan synthase inhibitor SCY-078, singly and in combination, for the treatment of invasive aspergillosis","volume":"62","author":"Ghannoum","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B30","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1093\/jac\/dkaa102","article-title":"A multicentre study to optimize echinocandin susceptibility testing of Aspergillus species with the EUCAST methodology and a broth microdilution colorimetric method","volume":"75","author":"Meletiadis","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2025060219525250700_dkaf133-B31","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3109\/13693780802713497","article-title":"The effects of antifungal agents to conidial and hyphal forms of Aspergillus fumigatus","volume":"48","author":"van de Sande","year":"2010","journal-title":"Med Mycol"},{"key":"2025060219525250700_dkaf133-B32","doi-asserted-by":"publisher","first-page":"myad118","DOI":"10.1093\/mmy\/myad118","article-title":"The combination of manogepix and itraconazole is synergistic and inhibits the growth of Madurella mycetomatis in vitro but not in vivo","volume":"61","author":"Konings","year":"2023","journal-title":"Med Mycol"},{"key":"2025060219525250700_dkaf133-B33","doi-asserted-by":"publisher","first-page":"e0154523","DOI":"10.1128\/aac.01545-23","article-title":"Ibrexafungerp is efficacious in a neutropenic murine model of pulmonary mucormycosis as monotherapy and combined with liposomal amphotericin B","volume":"68","author":"Gebremariam","year":"2024","journal-title":"Antimicrob Agents Chemother"},{"key":"2025060219525250700_dkaf133-B34","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1128\/9781555817381.ch125","article-title":"Fungi causing eumycotic mycetoma","author":"Ahmed","year":"2015;","journal-title":"Manual of Clinical Microbiology. 11th edn. Wiley,"},{"key":"2025060219525250700_dkaf133-B35","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1093\/jac\/dkx010","article-title":"The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp","volume":"72","author":"Marcos-Zambrano","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2025060219525250700_dkaf133-B36","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1016\/j.micinf.2007.05.015","article-title":"Melanin biosynthesis in Madurella mycetomatis and its effect on susceptibility to itraconazole and ketoconazole","volume":"9","author":"van de Sande","year":"2007","journal-title":"Microbes Infect"},{"key":"2025060219525250700_dkaf133-B37","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1111\/bjd.14025","article-title":"Amphotericin B but not itraconazole is able to prevent grain formation in experimental Madurella mycetomatis mycetoma in mice","volume":"173","author":"van de Sande","year":"2015","journal-title":"Br J Dermatol"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1733\/63032651\/dkaf133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/80\/6\/1733\/63032651\/dkaf133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T19:52:57Z","timestamp":1748893977000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/80\/6\/1733\/8122731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,4,30]]},"published-print":{"date-parts":[[2025,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkaf133","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,4,30]]}}}