{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T20:24:01Z","timestamp":1777321441650,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["HOROS W1253-B24"],"award-info":[{"award-number":["HOROS W1253-B24"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number of antifungal medications available for treating IFIs, and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, are increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity, namely, manogepix, rezafungin, ibrexafungerp, and olorofim, against 100 isolates of Aspergillus section Terrei, containing amphotericin-B (AmB)-wildtype\/non-wildtype and azole-susceptible\/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against the tested isolates, exhibiting geometric mean (GM) and minimum effective concentration (MEC)\/minimum inhibitory concentration (MIC) ranges, respectively, as follows: manogepix (0.048 mg\/L, 0.032\u20130.5 mg\/L), rezafungin (0.020 mg\/L, 0.016\u20130.5 mg\/L), ibrexafungerp (0.071 mg\/L, 0.032\u20132 mg\/L), and olorofim (0.008 mg\/L, 0.008\u20130.032 mg\/L). In terms of MIC90\/MEC90, olorofim had the lowest values (0.008 mg\/L), followed by rezafungin (0.032 mg\/L), manogepix (0.125 mg\/L), and ibrexafungerp (0.25 mg\/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species.<\/jats:p>","DOI":"10.3390\/jof9060649","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T02:02:15Z","timestamp":1686103335000},"page":"649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals"],"prefix":"10.3390","volume":"9","author":[{"given":"Roya","family":"Vahedi-Shahandashti","sequence":"first","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-4438","authenticated-orcid":false,"given":"Jos","family":"Houbraken","sequence":"additional","affiliation":[{"name":"Westerdijk Fungal Biodiversity Institute, 3584 CT Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Birch","sequence":"additional","affiliation":[{"name":"F2G Ltd., Manchester M30 0LX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2946-7785","authenticated-orcid":false,"given":"Cornelia","family":"Lass-Fl\u00f6rl","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: Human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20150462","DOI":"10.1098\/rstb.2015.0462","article-title":"Medical mycology and fungal immunology: New research perspectives addressing a major world health challenge","volume":"371","author":"Gow","year":"2016","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrd.2017.46","article-title":"The antifungal pipeline: A reality check","volume":"16","author":"Perfect","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"i5","DOI":"10.1093\/jac\/dkx028","article-title":"Changes in the epidemiological landscape of invasive mould infections and disease","volume":"72","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Neal, C.O., Richardson, A.O., Hurst, S.F., Tortorano, A.M., Viviani, M.A., Stevens, D.A., and Balajee, S.A. (2011). Global population structure of Aspergillus terreus inferred by ISSR typing reveals geographical subclustering. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-203"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lass-Fl\u00f6rl, C. (2018). Treatment of infections due to Aspergillus terreus species complex. J. Fungi., 4.","DOI":"10.3390\/jof4030083"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103247","DOI":"10.1016\/j.fgb.2019.103247","article-title":"Antifungal resistance in Aspergillus terreus: A current scenario","volume":"131","year":"2019","journal-title":"Fungal Genet. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1093\/jac\/dku241","article-title":"Invasive aspergillosis caused by Aspergillus terreus: An emerging opportunistic infection with poor outcome independent of azole therapy","volume":"69","author":"Hachem","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101310","DOI":"10.1016\/j.mycmed.2022.101310","article-title":"Trends in the prevalence of amphotericin B-resistance (AmBR) among clinical isolates of Aspergillus species","volume":"32","author":"Fakhim","year":"2022","journal-title":"J. Med. Mycol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Stewart, E.R., and Thompson, G.R. (2016). Treatment of primary pulmonary aspergillosis: An assessment of the evidence. J. Fungi., 2.","DOI":"10.3390\/jof2030025"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3380","DOI":"10.1128\/AAC.00383-13","article-title":"Population-based survey of filamentous fungi and antifungal resistance in Spain (FILPOP Study)","volume":"57","author":"Mellado","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1093\/infdis\/jis442","article-title":"In vivo emergence of Aspergillus terreus with reduced azole susceptibility and a Cyp51a M217I alteration","volume":"206","author":"Arendrup","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fmicb.2018.00516","article-title":"Azole-Resistance in Aspergillus terreus and related species: An emerging problem or a rare phenomenon?","volume":"9","author":"Zoran","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e0227421","DOI":"10.1128\/aac.02274-21","article-title":"Aspergillus terreus and the interplay with amphotericin B: From resistance to tolerance?","volume":"66","author":"Dietl","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vahedi-Shahandashti, R., and Lass-Fl\u00f6rl, C. (2020). Novel antifungal agents and their activity against Aspergillus species. J. Fungi., 6.","DOI":"10.3390\/jof6040213"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): A phase 3, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet Lond Engl."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00073-19","DOI":"10.1128\/AAC.00073-19","article-title":"EUCAST Susceptibility Testing of Isavuconazole: MIC Data for Contemporary Clinical Mold and Yeast Isolates","volume":"63","author":"Astvad","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s40265-021-01611-0","article-title":"The Antifungal pipeline: Fosmanogepix, ibrexafungerp, olorofim, opelconazole, and rezafungin","volume":"81","author":"Hoenigl","year":"2021","journal-title":"Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1128\/AAC.00291-11","article-title":"In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds","volume":"55","author":"Miyazaki","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1128\/AAC.00731-11","article-title":"E1210, a New broad-spectrum antifungal, suppresses Candida albicans hyphal growth through inhibition of glycosylphosphatidylinositol biosynthesis","volume":"56","author":"Watanabe","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e02068-16","DOI":"10.1128\/AAC.02068-16","article-title":"Preclinical pharmacokinetics and pharmacodynamic target of SCY-078, a first-in-class orally active antifungal glucan synthesis inhibitor, in murine models of disseminated candidiasis","volume":"61","author":"Wring","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12809","DOI":"10.1073\/pnas.1608304113","article-title":"F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase","volume":"113","author":"Oliver","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1093\/jac\/dkx177","article-title":"In vitro activity of the novel antifungal compound F901318 against difficult-to-treat Aspergillus isolates","volume":"72","author":"Buil","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"776.e1","DOI":"10.1016\/j.cmi.2017.04.012","article-title":"A prospective international Aspergillus terreus survey: An EFISG, ISHAM and ECMM joint study","volume":"23","author":"Risslegger","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.simyco.2020.05.002","article-title":"Classification of Aspergillus, Penicillium, Talaromyces and related genera (Eurotiales): An overview of families, genera, subgenera, sections, series and species","volume":"95","author":"Houbraken","year":"2020","journal-title":"Stud. Mycol."},{"key":"ref_26","unstructured":"Arendrup, M.C., Guinea, J., Cuenca-Estrella, M., Meletiadis, J., Mouton, J.W., Lagrou, K., Howard, S.J., and the Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) (2023, February 02). Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Conidia Form-ing Moulds. EUCAST Definitive Document DEF 9.3.2. Available online: https:\/\/www.aspergillus.org.uk\/wpcontent\/uploads\/2016\/03\/EUCAST_E_Def_9_3_Mould_testing_definitive_0.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/318483","article-title":"Aspergillosis case-fatality rate: Systematic review of the literature","volume":"32","author":"Lin","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gintjee, T.J., Donnelley, M.A., and Thompson, G.R. (2020). Aspiring antifungals: Review of current antifungal pipeline developments. J. Fungi., 6.","DOI":"10.3390\/jof6010028"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41579-022-00720-1","article-title":"Tackling the emerging threat of antifungal resistance to human health","volume":"20","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.2147\/IDR.S367082","article-title":"Multicenter Italian study on \u201cin Vitro activities\u201d of isavuconazole, voriconazole, amphotericin B, and caspofungin for Aspergillus species: Comparison between SensititreTM YeastOneTM and MIC Test Strip","volume":"15","author":"Bazaj","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S436","DOI":"10.1093\/infdis\/jix210","article-title":"Azole-resistant aspergillosis: Epidemiology, molecular mechanisms, and treatment","volume":"216","author":"Chowdhary","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vahedi-Shahandashti, R., Hahn, L., Houbraken, J., and Lass-Fl\u00f6rl, C. (2023). Aspergillus section Terrei and antifungals: From broth to agar-based susceptibility testing methods. J. Fungi., 9.","DOI":"10.3390\/jof9030306"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41579-019-0322-2","article-title":"Drug resistance and tolerance in fungi","volume":"18","author":"Berman","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jgar.2021.04.012","article-title":"Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018\u20132019)","volume":"26","author":"Pfaller","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"ofac492.1665","DOI":"10.1093\/ofid\/ofac492.1665","article-title":"2043. In vitro activity of manogepix against 2,810 fungal isolates from the SENTRY surveillance program (2020-2021) stratified by infection type","volume":"9","author":"Huband","year":"2022","journal-title":"Open Forum. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1093\/jac\/dkz022","article-title":"In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies","volume":"74","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0038022","DOI":"10.1128\/aac.00380-22","article-title":"The combination treatment of fosmanogepix and liposomal amphotericin b is superior to monotherapy in treating experimental invasive mold infections","volume":"66","author":"Gebremariam","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e01572-18","DOI":"10.1128\/AAC.01572-18","article-title":"Pharmacodynamic evaluation of rezafungin (CD101) against Candida auris in the neutropenic mouse invasive candidiasis model","volume":"62","author":"Lepak","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1093\/jac\/dky280","article-title":"Rezafungin (CD101) demonstrates potent in vitro activity against Aspergillus, including azole-resistant Aspergillus fumigatus isolates and cryptic species","volume":"73","author":"Wiederhold","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1128\/AAC.01588-12","article-title":"In vitro activity of a new oral glucan synthase inhibitor (MK-3118) tested against Aspergillus spp. by CLSI and EUCAST broth microdilution methods","volume":"57","author":"Pfaller","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","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":"Paderu","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","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":"ref_43","doi-asserted-by":"crossref","first-page":"e00487-18","DOI":"10.1128\/AAC.00487-18","article-title":"EUCAST determination of olorofim (F901318) susceptibility of mold species, method validation, and MICs","volume":"62","author":"Astvad","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/jac\/dkz078","article-title":"In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies","volume":"74","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1093\/jac\/dky329","article-title":"Dihydroorotate dehydrogenase inhibitor olorofim exhibits promising activity against all clinically relevant species within Aspergillus section Terrei","volume":"73","author":"Lackner","year":"2018","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/6\/649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:49:06Z","timestamp":1760125746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/6\/649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,6]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jof9060649"],"URL":"https:\/\/doi.org\/10.3390\/jof9060649","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,6]]}}}