{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:31:31Z","timestamp":1790685091787,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aspergillus fumigatus is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in A. fumigatus has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a Galleria mellonella model of invasive infection due to azole-susceptible or azole-resistant A. fumigatus isolates. We also sought to describe the pharmacokinetics of VRZ in the G. mellonella model. G. mellonella larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of A. fumigatus. Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible A. fumigatus isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a Cmin (24 h) between 0.11 and 11.30 mg\/L, depending on the dose. In conclusion, G. mellonella is a suitable model for testing the efficacy of antifungal agents against A. fumigatus.<\/jats:p>","DOI":"10.3390\/jof7121012","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"1012","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["In Vivo Efficacy of Voriconazole in a Galleria mellonella Model of Invasive Infection Due to Azole-Susceptible or Resistant Aspergillus fumigatus Isolates"],"prefix":"10.3390","volume":"7","author":[{"given":"Sana","family":"Jemel","sequence":"first","affiliation":[{"name":"Dynamic, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"Facult\u00e9 de M\u00e9decine de Tunis, Universit\u00e9 Tunis EL Manar, Tunis 1007, Tunisia"},{"name":"UR17SP03, Centre Hospitalo-Universitaire La Rabta, Jabbari, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-6979","authenticated-orcid":false,"given":"Jacques","family":"Guillot","sequence":"additional","affiliation":[{"name":"Dynamic, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"Dermatology, Parasitology-Mycology Department, Ecole Nationale V\u00e9t\u00e9rinaire de Nantes, Oniris, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalthoum","family":"Kallel","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Tunis, Universit\u00e9 Tunis EL Manar, Tunis 1007, Tunisia"},{"name":"UR17SP03, Centre Hospitalo-Universitaire La Rabta, Jabbari, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9gory","family":"Jouvion","sequence":"additional","affiliation":[{"name":"Dynamic, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"Unit\u00e9 de Neuropathologie Exp\u00e9rimentale, Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8740-5136","authenticated-orcid":false,"given":"Elise","family":"Brisebard","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Neuropathologie Exp\u00e9rimentale, Institut Pasteur, 75015 Paris, France"},{"name":"Laboratoire d\u2019Histopathologie, Universit\u00e9 de Lyon, VetAgro-Sup, 69280 Marcy l\u2019Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Billaud","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie APHP, H\u00f4pital Europ\u00e9en Georges Pompidou, 75015 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jullien","sequence":"additional","affiliation":[{"name":"Service de Pharmacologie APHP, H\u00f4pital Europ\u00e9en Georges Pompidou, 75015 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Paris, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-2665","authenticated-orcid":false,"given":"Fran\u00e7oise","family":"Botterel","sequence":"additional","affiliation":[{"name":"Dynamic, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2817-3830","authenticated-orcid":false,"given":"Eric","family":"Dannaoui","sequence":"additional","affiliation":[{"name":"Dynamic, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, Universit\u00e9 Paris Est Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"Unit\u00e9 de Parasitologie-Mycologie, Service de Microbiologie, APHP, H\u00f4pital Europ\u00e9en Georges Pompidou, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00140-18","DOI":"10.1128\/CMR.00140-18","article-title":"Aspergillus fumigatus and Aspergillosis in 2019","volume":"33","author":"Latge","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/myc.13341","article-title":"A review of significance of Aspergillus detection in airways of ICU COVID-19 patients","volume":"64","author":"Pasquier","year":"2021","journal-title":"Mycoses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1007\/s00134-020-06091-6","article-title":"Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: An expert opinion","volume":"46","author":"Verweij","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1056\/NEJMra2027424","article-title":"Aspergillus Infections","volume":"385","author":"Thompson","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165rv113","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_6","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa020191","article-title":"Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis","volume":"347","author":"Herbrecht","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.cmi.2018.11.027","article-title":"Triazole resistance in Aspergillus fumigatus: Recent insights and challenges for patient management","volume":"25","author":"Lestrade","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.drup.2015.08.001","article-title":"International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus","volume":"21\u201322","author":"Verweij","year":"2015","journal-title":"Drug Resist. Updates"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1128\/CMR.00095-16","article-title":"Molecular tools for the detection and deduction of azole antifungal drug resistance phenotypes in Aspergillus species","volume":"30","author":"Dudakova","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20150460","DOI":"10.1098\/rstb.2015.0460","article-title":"Clinical implications of globally emerging azole resistance in Aspergillus fumigatus","volume":"371","author":"Meis","year":"2016","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.bbadis.2013.03.008","article-title":"Invertebrate models of fungal infection","volume":"1832","author":"Arvanitis","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1473-3099(06)70686-7","article-title":"Role of mini-host models in the study of medically important fungi","volume":"7","author":"Chamilos","year":"2007","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1080\/21505594.2021.1893945","article-title":"Galleria mellonella as a screening tool to study virulence factors of Aspergillus fumigatus","volume":"12","author":"Durieux","year":"2021","journal-title":"Virulence"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"7","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jemel, S., Guillot, J., Kallel, K., Botterel, F., and Dannaoui, E. (2020). Galleria mellonella for the evaluation of antifungal efficacy against medically important fungi, a narrative review. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030390"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kavanagh, K., and Sheehan, G. (2018). The use of Galleria mellonella larvae to identify novel antimicrobial agents against fungal species of medical interest. J. Fungi, 4.","DOI":"10.3390\/jof4030113"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jchromb.2017.01.036","article-title":"An ultra performance liquid chromatography-tandem mass spectrometry method for the therapeutic drug monitoring of isavuconazole and seven other antifungal compounds in plasma samples","volume":"1046","author":"Toussaint","year":"2017","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7866","DOI":"10.1128\/AAC.01594-15","article-title":"Fitness studies of azole-resistant strains of Aspergillus fumigatus","volume":"59","author":"Valsecchi","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3201\/eid2106.140717","article-title":"Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus","volume":"21","author":"Arendrup","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/jac\/dkv446","article-title":"Identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis","volume":"71","author":"Rivkin","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/jac\/dky455","article-title":"In vivo evaluation of the antifungal activity of sertraline against Aspergillus fumigatus","volume":"74","author":"Montoya","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ijantimicag.2015.07.007","article-title":"In vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of Aspergillus fumigatus infection","volume":"46","author":"Forastiero","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00241-18","DOI":"10.1128\/AAC.00241-18","article-title":"Insight into the significance of Aspergillus fumigatus cyp51A polymorphisms","volume":"62","author":"Monteiro","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"836","DOI":"10.3389\/fmicb.2020.00836","article-title":"Minocycline and fluconazole have a synergistic effect against Cryptococcus neoformans both in vitro and in vivo","volume":"11","author":"Kong","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/21505594.2015.1045183","article-title":"Galleria mellonella as a host model to study Aspergillus terreus virulence and amphotericin B resistance","volume":"6","author":"Maurer","year":"2015","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ijantimicag.2013.11.001","article-title":"Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection","volume":"43","author":"Hill","year":"2014","journal-title":"Int. J. Antimicrob. Agents"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/12\/1012\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:36:05Z","timestamp":1760168165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/12\/1012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,26]]},"references-count":27,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jof7121012"],"URL":"https:\/\/doi.org\/10.3390\/jof7121012","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,26]]}}}