{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T08:31:35Z","timestamp":1788078695023,"version":"build-2784847793"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JMI Laboratories and supported by Pfizer Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017\u20132020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and\/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC50\/90, 2\/&gt;8 mg\/L) inhibited 59.6% and 71.2% of all Mucorales isolates at \u22642 mg\/L and \u22644 mg\/L, respectively. Among comparators, amphotericin B (MIC50\/90, 0.5\/1 mg\/L) displayed the highest activity, followed by posaconazole (MIC50\/90, 0.5\/8 mg\/L). Voriconazole (MIC50\/90, &gt;8\/&gt;8 mg\/L) and the echinocandins (MIC50\/90, &gt;4\/&gt;4 mg\/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at \u22644 mg\/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27; MIC50\/90, 1\/&gt;8 mg\/L), Lichtheimia spp. (n = 11; MIC50\/90, 4\/8 mg\/L), and Mucor spp. (n = 8; MIC50, &gt;8 mg\/L) isolates, respectively. Posaconazole MIC50\/90 values against Rhizopus, Lichtheimia, and Mucor species were 0.5\/8 mg\/L, 0.5\/1 mg\/L, and 2\/- mg\/L, respectively; amphotericin B MIC50\/90 values were 1\/1 mg\/L, 0.5\/1 mg\/L, and 0.5\/- mg\/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.<\/jats:p>","DOI":"10.3390\/jof9020241","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T02:42:33Z","timestamp":1676256153000},"page":"241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2734-3754","authenticated-orcid":false,"given":"Cecilia G.","family":"Carvalhaes","sequence":"first","affiliation":[{"name":"JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Rhomberg","sequence":"additional","affiliation":[{"name":"JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Huband","sequence":"additional","affiliation":[{"name":"JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Pfaller","sequence":"additional","affiliation":[{"name":"JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"name":"JMI Laboratories, 345 Beaver Kreek Centre, North Liberty, IA 52317, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global guideline for the diagnosis and management of mucormycosis: An initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium","volume":"19","author":"Cornely","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/myc.13148","article-title":"Breakthrough invasive fungal infections: Who is at risk?","volume":"63","author":"Jenks","year":"2020","journal-title":"Mycoses"},{"key":"ref_3","first-page":"29","article-title":"Diabetes mellitus as the major risk factor for mucormycosis in Mexico: Epidemiology, diagnosis, and outcomes of reported cases","volume":"56","author":"Walsh","year":"2017","journal-title":"Med. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/13693780500464930","article-title":"The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus","volume":"44","author":"Chakrabarti","year":"2006","journal-title":"Med. Mycol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13608","DOI":"10.1111\/tid.13608","article-title":"Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study","volume":"23","author":"Rinaldi","year":"2021","journal-title":"Transpl. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/sj.bmt.1705754","article-title":"Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole","volume":"40","author":"Trifilio","year":"2007","journal-title":"Bone Marrow Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Raffaelli, F., Tanzarella, E.S., De Pascale, G., and Tumbarello, M. (2022). Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients. J. Fungi, 8.","DOI":"10.3390\/jof8040415"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s15010-021-01670-1","article-title":"COVID-19 and mucormycosis superinfection: The perfect storm","volume":"49","author":"Alhumaid","year":"2021","journal-title":"Infection"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/myc.13335","article-title":"ECMM\/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries","volume":"64","author":"Rudramurthy","year":"2021","journal-title":"Mycoses"},{"key":"ref_10","unstructured":"Singh, N.K., Hage, N., Ramamourthy, B., and Kappagantu, K.M. (Infect. Disord.\u2013Drug Targets, 2022). COVID 19 associated Rhino- Orbital- Cerebral Mucormycosis: A proposed Classification and Treatment Strategies, Infect. Disord.\u2013Drug Targets, ahead of print."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/phar.1652","article-title":"Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent","volume":"35","author":"Rybak","year":"2015","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S1473-3099(16)00071-2","article-title":"Isavuconazole treatment for mucormycosis: A single-arm open-label trial and case-control analysis","volume":"16","author":"Marty","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","unstructured":"FDA, U. (2022, November 15). CRESEMBA\u00ae (isavuconazonium sulfate) prescribing information, Available online: http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/207500Orig1s000lbl.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s11046-012-9551-x","article-title":"Significance of molecular identification and antifungal susceptibility of clinically significant yeasts and moulds in a global antifungal surveillance program","volume":"174","author":"Pfaller","year":"2012","journal-title":"Mycopathologia"},{"key":"ref_15","unstructured":"(2018). Interpretive Criteria for Identification of Bacteria and Fungi by Targeted DNA Sequencing (Standard No. CL.S.I. M18Ed2)."},{"key":"ref_16","unstructured":"(2017). Reference Method for Broth Dilution Antifungal Susceptbility Testing of Yeasts (Standard No. CL.S.I. M27Ed4)."},{"key":"ref_17","unstructured":"(2018). Reference Method for Broth Dilution Antifungal Susceptibilty Testing of Filamentous Fungi (Standard No. CL.S.I. M38Ed3)."},{"key":"ref_18","unstructured":"(2020). Performance Standards for Antifungal Susceptibility Testing of Filamentous Fungi (Standard No. CL.S.I. M61Ed2)."},{"key":"ref_19","unstructured":"WHO (2022, November 15). WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240060241."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/432579","article-title":"Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases","volume":"41","author":"Roden","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/1469-0691.12371","article-title":"ESCMID\u2020 and ECMM\u2021 joint clinical guidelines for the diagnosis and management of mucormycosis 2013","volume":"20","author":"Cornely","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/1469-0691.12563","article-title":"Epidemiology of mucormycosis in Europe","volume":"20","author":"Petrikkos","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3767\/003158513X665070","article-title":"DNA barcoding in Mucorales: An inventory of biodiversity","volume":"30","author":"Walther","year":"2013","journal-title":"Persoonia\u2014Mol. Phylogeny Evol. Fungi"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.3201\/eid2709.210934","article-title":"Multicenter Epidemiologic Study of Coronavirus Disease\u2013Associated Mucormycosis, India","volume":"27","author":"Patel","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1111\/j.1469-0691.2010.03456.x","article-title":"Zygomycosis in Europe: Analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007","volume":"17","author":"Skiada","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Imbert, S., Portejoie, L., Pfister, E., Tauzin, B., Revers, M., Uthurriague, J., Hernandez-Grande, M., Lafon, M.-E., Jubert, C., and Issa, N. (2023). A Multiplex PCR and DNA-Sequencing Workflow on Serum for the Diagnosis and Species Identification for Invasive Aspergillosis and Mucormycosis. J. Clin. Microbiol., 61.","DOI":"10.1128\/jcm.01409-22"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/cid\/ciab1066","article-title":"Evaluation of Serum Mucorales Polymerase Chain Reaction (PCR) for the Diagnosis of Mucormycoses: The MODIMUCOR Prospective Trial","volume":"75","author":"Millon","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Walther, G., Wagner, L., and Kurzai, O. (2019). Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa. J. Fungi, 5.","DOI":"10.3390\/jof5040106"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01886-17","DOI":"10.1128\/JCM.01886-17","article-title":"Species Identification and Delineation of Pathogenic Mucorales by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry","volume":"56","author":"Shao","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/JCM.06133-11","article-title":"Antifungal Susceptibility and Phylogeny of Opportunistic Members of the Order Mucorales","volume":"50","author":"Vitale","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3767\/persoonia.2020.44.03","article-title":"A new species concept for the clinically relevant Mucor circinelloides complex","volume":"44","author":"Wagner","year":"2020","journal-title":"Persoonia\u2014Mol. Phylogeny Evol. Fungi"},{"key":"ref_32","unstructured":"EUCAST (2022, November 01). Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Yeasts European Committee on Antimicrobial Susceptibility Testing Definitive Document E.DEF 7.3.2; April 2020. Available online: https:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/AFST\/Files\/EUCAST_E_Def_7.3.2_Yeast_testing_definitive_revised_2020.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/jac\/dkr375","article-title":"The Deferasirox\u2013AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: A randomized, double-blinded, placebo-controlled trial","volume":"67","author":"Spellberg","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1016\/S0399-077X(08)73003-8","article-title":"AMBIZYGO: \u00e9tude de phase II de l\u2019efficacit\u00e9 d\u2019une posologie initiale \u00e9lev\u00e9e d\u2019amphot\u00e9ricine B liposomale (AmBisome\u00ae) [10 mg\/kg\/j] dans le traitement des zygomycoses","volume":"38","author":"Lanternier","year":"2008","journal-title":"Med. Mal. Infect."},{"key":"ref_35","first-page":"760","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":"Patterson","year":"2015","journal-title":"Lancet"},{"key":"ref_36","unstructured":"Gmb H, B.P.D. (2022, November 01). Cresemba (isavuconazole). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/cresemba."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1179\/joc.2009.21.3.272","article-title":"In Vitro Antifungal Activity of Isavuconazole against 345 Mucorales Isolates Collected at Study Centers in Eight Countries","volume":"21","author":"Verweij","year":"2009","journal-title":"J. Chemother."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","unstructured":"Borman, A., Fraser, M., Patterson, Z., Palmer, M., and Johnson, E. (2021). In Vitro Antifungal Drug Resistance Profiles of Clinically Relevant Members of the Mucorales (Mucoromycota) Especially with the Newer Triazoles. J. Fungi, 7.","DOI":"10.3390\/jof7040271"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7882","DOI":"10.1128\/AAC.02107-15","article-title":"Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species","volume":"59","author":"Chowdhary","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1128\/AAC.50.1.286-293.2006","article-title":"Multiple-Dose Pharmacokinetics and Safety of the New Antifungal Triazole BAL4815 after Intravenous Infusion and Oral Administration of Its Prodrug, BAL8557, in Healthy Volunteers","volume":"50","author":"Roos","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s15010-017-1042-z","article-title":"Pharmacokinetics of antifungal drugs: Practical implications for optimized treatment of patients","volume":"45","author":"Bellmann","year":"2017","journal-title":"Infection"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/imj.15592","article-title":"Consensus guidelines for the diagnosis and management of invasive fungal disease due to moulds other than Aspergillus in the haematology\/oncology setting, 2021","volume":"51","author":"Butters","year":"2021","journal-title":"Intern. Med. J."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Lamoth, F., and Kontoyiannis, D.P. (2019). Therapeutic Challenges of Non- Aspergillus Invasive Mold Infections in Immunosuppressed Patients. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.01244-19"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/2\/241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:31:15Z","timestamp":1760121075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/2\/241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,11]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jof9020241"],"URL":"https:\/\/doi.org\/10.3390\/jof9020241","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,11]]}}}