{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:31:25Z","timestamp":1792704685576,"version":"4.5.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"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>Fusarium spp. are moulds ubiquitously distributed in nature and only occasionally pathogenic for humans. Species of the Fusarium solani complex are the predominant keratitis-inducing pathogens, because they are endowed with proper virulence factors. These fungi can adhere to the cornea creating a biofilm and, with the help of enzymes and cytotoxins, penetrate the cornea. Whereas an intact cornea is hardly able to be invaded by Fusarium spp. in spite of appropriate virulence factors, these opportunistic fungi may profit from predisposing conditions, for example mechanical injuries. This can lead to a progressive course of corneal infection and may finally affect the whole eye up to the need for enucleation. Here, we present and discuss the clinical, microbiological and histopathological aspects of a particular case due to Fusarium tonkinense of the Fusarium solani complex with severe consequences in a patient without any obvious predisposing factors. A broad portfolio of antifungal agents was applied, both topically and systemically as well as two penetrating keratoplasties were performed. The exact determination of the etiologic agent of the fungal infection proved likewise to be very challenging.<\/jats:p>","DOI":"10.3390\/jof7121093","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Malignant Keratitis Caused by a Highly-Resistant Strain of Fusarium Tonkinense from the Fusarium Solani Complex"],"prefix":"10.3390","volume":"7","author":[{"given":"Jens","family":"Schrecker","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Rudolf Virchow Klinikum Glauchau, Virchowstra\u00dfe 18, D-08371 Glauchau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-8204","authenticated-orcid":false,"given":"Berthold","family":"Seitz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Saarland University Medical Center, Kirrbergstr. 100, D-66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-2237","authenticated-orcid":false,"given":"Tim","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Saarland University Medical Center, Kirrbergstr. 100, D-66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loay","family":"Daas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Saarland University Medical Center, Kirrbergstr. 100, D-66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Behrens-Baumann","sequence":"additional","affiliation":[{"name":"Emeritus, Department of Ophthalmology, Otto-von-Guericke-University Magdeburg, Eckenbornweg 5j, D-37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Auw-H\u00e4drich","sequence":"additional","affiliation":[{"name":"Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Kilianstr. 5, D-79106 Freiburg im Breisgau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Sch\u00fctt","sequence":"additional","affiliation":[{"name":"MVZ Labor Limbach and Colleagues, Im Breitspiel 16, D-69126 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kerl","sequence":"additional","affiliation":[{"name":"MVZ Labor Limbach and Colleagues, Im Breitspiel 16, D-69126 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Rentner-Andres","sequence":"additional","affiliation":[{"name":"Limbach Analytics GmbH, Arotop Laboratories, Dekan-Laiststr. 9, D-55129 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-2517","authenticated-orcid":false,"given":"Herbert","family":"Hof","sequence":"additional","affiliation":[{"name":"MVZ Labor Limbach and Colleagues, Im Breitspiel 16, D-69126 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s12600-015-0484-z","article-title":"DNA sequence-based identification of Fusarium: Current status and future directions","volume":"43","author":"Ward","year":"2015","journal-title":"Phytoparasitica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3767\/persoonia.2018.41.06","article-title":"Removing chaos from confusion: Assigning names to common human and animal pathogens in neocosmospora","volume":"41","author":"Crous","year":"2018","journal-title":"Pers. Mol. Phylogeny Evol. Fungi"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3767\/persoonia.2019.43.04","article-title":"Back to the roots: A reappraisal of Neocosmospora","volume":"43","author":"Lombard","year":"2019","journal-title":"Pers. Mol. Phylogeny Evol. Fungi"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00810-20","DOI":"10.1128\/mSphere.00810-20","article-title":"No to Neocosmospora: Phylogenomic and practical reasons for continued inclusion of the Fusarium solani species complex in the genus Fusarium","volume":"5","author":"Aoki","year":"2020","journal-title":"mSphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1094\/PHYTO-08-20-0330-LE","article-title":"Phylogenomic analysis of a 55.1 kb 19-gene dataset resolves a monophyletic Fusarium that includes the Fusarium solani Species Complex","volume":"111","author":"Geiser","year":"2021","journal-title":"Phytopathology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"S\u00e1enz, V., Alvarez-Moreno, C., Pape, P.L., Restrepo, S., Guarro, J., and Ram\u00edrez, A.M.C. (2020). A one health perspective to recognize Fusarium as important in clinical practice. J. Fungi, 6.","DOI":"10.3390\/jof6040235"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hof, H. (2020). The medical relevance of Fusarium spp.. J. Fungi, 6.","DOI":"10.3390\/jof6030117"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Walther, G., Zimmermann, A., Theuersbacher, J., Kaerger, K., von Lilienfeld-Toal, M., Roth, M., Kampik, D., Geerling, G., and Kurzai, O. (2021). Eye infections caused by filamentous fungi: Spectrum and antifungal susceptibility of the prevailing agents in Germany. J. Fungi, 7.","DOI":"10.3390\/jof7070511"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1001\/jama.296.8.953","article-title":"Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution","volume":"296","author":"Chang","year":"2006","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1001\/jama.295.24.2867","article-title":"An outbreak of Fusarium keratitis associated with contact lens wear in Singapore","volume":"295","author":"Khor","year":"2006","journal-title":"J. Am. Med. Assoc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1128\/JCM.00649-17","article-title":"Fusarium keratitis in Germany","volume":"55","author":"Walther","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","first-page":"462","article-title":"Fusarium keratitis with dramatic outcome","volume":"114","author":"Emrani","year":"2017","journal-title":"Ophthalmologe"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1128\/AAC.01618-06","article-title":"Universal in vitro antifungal resistance of genetic clades of the Fusarium solani species complex","volume":"51","author":"Azor","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103802","DOI":"10.1016\/j.micpath.2019.103802","article-title":"Fungal keratitis: Pathogenesis, diagnosis and prevention","volume":"138","author":"Niu","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E5","DOI":"10.3314\/mmj.16-00024","article-title":"Epidemiological study of Fusarium species causing invasive and superficial fusariosis in Japan","volume":"58","author":"Muraosa","year":"2017","journal-title":"Med. Mycol. J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Subcommittee on Antifungal Susceptibility Testing of the ESCMID European Committee for Antimicrobial Susceptibility Testing (2008). EUCAST Technical Note on the method for determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds. Clin. Microbiol. Infect., 14, 982\u2013984.","DOI":"10.1111\/j.1469-0691.2008.02086.x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1001\/archopht.125.6.789","article-title":"Antimicrobial Susceptibility of Fusarium, Aspergillus, and Other Filamentous Fungi Isolated From Keratitis","volume":"125","author":"Lalitha","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103802","DOI":"10.1155\/2019\/6395840","article-title":"Antifungal susceptibilities of Fusarium and Aspergillus isolates from corneal scrapings","volume":"2019","author":"Manikandan","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.3389\/fmicb.2018.01052","article-title":"South Indian isolates of the Fusarium solani species complex from clinical and environmental samples: Identification, antifungal susceptibilities, and virulence","volume":"9","author":"Homa","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s00347-019-0871-9","article-title":"The German keratomycosis registry: Initial results of a multicenter survey","volume":"116","author":"Roth","year":"2019","journal-title":"Ophthalmologe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s11046-016-0042-3","article-title":"Fungal Keratitis in North India: Spectrum of Agents, Risk Factors and Treatment","volume":"181","author":"Ghosh","year":"2016","journal-title":"Mycopathologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/j.ophtha.2006.05.035","article-title":"Spectrum of Fungal Keratitis in North China","volume":"113","author":"Xie","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_23","unstructured":"Bugnicourt, F., and Guilliermond, A. (1939). Les Fusarium et Cylindrocarpon de L\u2019indochine, P. Lechevalier."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/00362177385190241","article-title":"Mycotic keratitis; 5 cases caused by unusual fungi","volume":"11","author":"Laverde","year":"1973","journal-title":"Sabouraudia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/BF03053157","article-title":"Cylindrocarpon species associated with mycotic keratitis","volume":"94","author":"Booth","year":"1985","journal-title":"Proc. Plant Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1128\/JCM.00533-07","article-title":"Phylogenetic diversity and microsphere array-based genotyping of human pathogenic fusaria, including isolates from the multistate contact lens-associated U.S. keratitis outbreaks of 2005 and 2006","volume":"45","author":"Sarver","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1099\/00222615-41-3-204","article-title":"An in-vitro study of the sterol content and toxin production of Fusarium isolates from mycotic keratitis","volume":"41","author":"Raza","year":"1994","journal-title":"J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s12550-009-0020-4","article-title":"Gliotoxin in Aspergillus fumigatus: An example that mycotoxins are potential virulence factors","volume":"25","author":"Hof","year":"2009","journal-title":"Mycotoxin Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1439-0507.2007.01455.x","article-title":"Mycotoxins: Pathogenicity factors or virulence factors?","volume":"51","author":"Hof","year":"2008","journal-title":"Mycoses"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.idcr.2015.10.004","article-title":"Adventitious sporulation in Fusarium: The yeast that were not","volume":"3","author":"Lockwood","year":"2016","journal-title":"IDCases"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1080\/00275514.1973.12019559","article-title":"Dimorphism in a Pathogenic Fusarium","volume":"65","author":"Kidd","year":"1973","journal-title":"Mycologia"},{"key":"ref_32","first-page":"754","article-title":"Keratomycosis\u2013Therapy standards and new developments","volume":"232","author":"Finis","year":"2015","journal-title":"Klin. Mon. Fur Augenheilkd."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00347-015-0206-4","article-title":"Confocal microscopy for the diagnostics of fungal keratitis","volume":"113","author":"Daas","year":"2016","journal-title":"Ophthalmologe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s00347-016-0270-4","article-title":"Confocal microscopy as an early relapse marker after keratoplasty due to Fusarium solani keratitis","volume":"114","author":"Daas","year":"2017","journal-title":"Ophthalmologe"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Alfaro Rangel, R., Szentm\u00e1ry, N., Lepper, S., Milioti, G., Daas, L., Langenbucher, A., and Seitz, B. (2021). Large-diameter penetrating keratoplasties are mostly due to very severe infectious keratitis and cannot always prevent secondary enucleation. Klin. Mon. F\u00fcr Augenheilkd., 6\u201313.","DOI":"10.1055\/a-1396-4787"},{"key":"ref_36","first-page":"1","article-title":"Fusarium: Molecular Diversity and Intrinsic Drug Resistance","volume":"12","author":"Meis","year":"2016","journal-title":"PLoS Pathog."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1128\/AAC.02456-15","article-title":"International evaluation of MIC distributions and epidemiological cutoff value (ECV) definitions for Fusarium species identified by molecular methods for the CLSI broth microdilution method","volume":"60","author":"Colombo","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.1016\/S1473-3099(20)30784-2","article-title":"Global guideline for the diagnosis and management of rare mould infections: An initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiolo","volume":"21","author":"Hoenigl","year":"2021","journal-title":"Lancet. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6393","DOI":"10.1074\/jbc.M707821200","article-title":"Natamycin Blocks Fungal Growth by Binding Specifically to Ergosterol without Permeabilizing the Membrane *","volume":"283","author":"Hendrik","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1128\/AAC.01794-09","article-title":"Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol","volume":"54","author":"Jones","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s00347-015-0111-x","article-title":"Prolonged topical natamycin 5 % therapy before and after keratoplasty for Fusarium keratitis","volume":"113","author":"Cvetkova","year":"2016","journal-title":"Ophthalmologe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1111\/bph.14024","article-title":"Principles of pharmacology in the eye","volume":"174","author":"Awwad","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_43","first-page":"457","article-title":"Extraocular fluid dynamics: How best to apply topical ocular medication","volume":"74","author":"Fraunfelder","year":"1977","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_44","first-page":"539","article-title":"Anti-infective drug therapy in ophthalmology\u2014Part 1: Bacterial infections","volume":"221","year":"2004","journal-title":"Klin. Mon. Fur Augenheilkd."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/ICO.0000000000001812","article-title":"Efficacy of Luliconazole against broad-range filamentous fungi Including Fusarium solani species complex causing fungal keratitis","volume":"38","author":"Todokoro","year":"2019","journal-title":"Cornea"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1055\/a-1478-4248","article-title":"New Antimycotics in the Pipeline\u2014For Ophthalmology Too?","volume":"238","year":"2021","journal-title":"Klin. Mon. F\u00fcr Augenheilkd."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ajo.2008.02.023","article-title":"Evaluation of Intrastromal Injection of Voriconazole as a Therapeutic Adjunctive for the Management of Deep Recalcitrant Fungal Keratitis","volume":"146","author":"Prakash","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s15010-012-0273-2","article-title":"The efficacy of voriconazole in 24 ocular Fusarium infections","volume":"41","author":"Troke","year":"2013","journal-title":"Infection"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/jac\/dkaa516","article-title":"Do high MICs predict the outcome in invasive fusariosis?","volume":"76","author":"Nucci","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3201\/eid0701.700149","article-title":"Disseminated Neocosmospora vasinfecta infection in a patient with acute nonlymphocytic leukemia","volume":"7","author":"Cornely","year":"2001","journal-title":"Emerg. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1007\/s10792-018-0930-2","article-title":"Keratomycosis due to Tintelnotia destructans refractory to common therapy treated successfully with systemic and local terbinafine in combination with polyhexamethylene biguanide","volume":"39","author":"Tammer","year":"2019","journal-title":"Int. Ophthalmol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/12\/1093\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:45Z","timestamp":1760169105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/7\/12\/1093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,18]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jof7121093"],"URL":"https:\/\/doi.org\/10.3390\/jof7121093","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,18]]}}}