{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:23:33Z","timestamp":1792113813077,"version":"4.4.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T00:00:00Z","timestamp":1408665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>A multistate fungal meningitis outbreak started in September of 2012 which spread in 20 states of the United States. The outbreak has been fatal so far, and has affected 751 individuals with 64 deaths among those who received contaminated spinal injections manufactured by a Compounding Center located in Massachusetts. In a preliminary study, Food and Drug Administration (FDA) investigated the outbreak in collaboration with Centers for Disease Control and Prevention (CDC), state and local health departments, and identified four fungal and several bacterial contaminations in the recalled unopened injection vials. This follow-up study was carried out to assess DNA sequencing of the ITS1 region of rRNA gene for rapid identification of fungal pathogens during public health outbreak investigations. A total of 26 environmental swabs were collected from several locations at the manufacturing premises of the Compounding Center known to have caused the outbreak. The swab samples were initially examined by conventional microbiologic protocols and a wide range of fungal species were recovered. Species-identification of these microorganisms was accomplished by nucleotide sequencing of ITS1 region of rRNA gene. Analysis of data confirmed 14 additional fungal species in the swabs analyzed.<\/jats:p>","DOI":"10.3390\/pathogens3030732","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T10:32:33Z","timestamp":1408703553000},"page":"732-742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic Characterization of Fungi Isolated from the Environmental Swabs collected from a Compounding  Center Known to Cause Multistate Meningitis Outbreak  in United States Using ITS Sequencing"],"prefix":"10.3390","volume":"3","author":[{"given":"Irshad","family":"Sulaiman","sequence":"first","affiliation":[{"name":"Southeast Regional Laboratory, U.S. Food and Drug Administration, 60, Eighth Street NE, Atlanta, GA 30309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Southeast Regional Laboratory, U.S. Food and Drug Administration, 60, Eighth Street NE, Atlanta, GA 30309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Simpson","sequence":"additional","affiliation":[{"name":"Southeast Regional Laboratory, U.S. Food and Drug Administration, 60, Eighth Street NE, Atlanta, GA 30309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Kerdahi","sequence":"additional","affiliation":[{"name":"Southeast Regional Laboratory, U.S. Food and Drug Administration, 60, Eighth Street NE, Atlanta, GA 30309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,8,22]]},"reference":[{"key":"ref_1","unstructured":"Food and Drug Administration (2004). Federal Food, Drug, and Cosmetic Act. As Amended through December 31, 2004, U.S. Department of Health and Human Services, Government Printing Office."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Centers for Disease Control and Prevention (2012). Multistate outbreak of fungal infection associated with injection of methylprednisolone acetate solution from a single compounding pharmacy - United States, 2012. MMWR, 61, 839\u2013842.","DOI":"10.1016\/j.annemergmed.2012.12.012"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMra1212617","article-title":"Fungal infections associated with contaminated methylprednisolone injections","volume":"368","author":"Kauffman","year":"2013","journal-title":"New Eng. J. Med."},{"key":"ref_4","unstructured":"Multistate Outbreak of Fungal Meningitis and Other Infections, Available online:http:\/\/www.fda.gov\/Drugs\/DrugSafety\/FungalMeningitis\/default.htm and http:\/\/www.cdc.gov\/hai\/outbreaks\/meningitis.html."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1128\/CMR.12.3.454","article-title":"Developments in Fungal Taxonomy","volume":"12","author":"Guarro","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1128\/JCM.39.11.4042-4051.2001","article-title":"Polymorphic internal transcribed spacer region 1 DNA sequences identify medically important yeasts","volume":"39","author":"Chen","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4137\/EBO.S653","article-title":"Intraspecific ITS Variability in the Kingdom Fungi as Expressed in the International Sequence Databases and Its Implications for Molecular Species Identification","volume":"4","author":"Nilsson","year":"2008","journal-title":"Evol. Bioinform. Online"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1073\/pnas.1117018109","article-title":"Fungal Barcoding Consortium. Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi","volume":"109","author":"Schoch","year":"2012","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_9","unstructured":"FDA\u2019s Bacteriological Analytical Manual (BAM). Available online:http:\/\/www.fda.gov\/Food\/FoodScienceResearch\/LaboratoryMethods\/ucm2006949.htm."},{"key":"ref_10","unstructured":"Murray, P.R., Baron, J.H., Pfaller, M.A., Jorgensen, J.H., and Yolken, R.H. (2003). Manual of Clinical Microbiology, American Society for Microbiology. [8th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1128\/AEM.65.4.1578-1583.1999","article-title":"Phylogenetic analyses of Cryptosporidium parasites based on small subunit ribosomal RNA gene locus","volume":"65","author":"Xiao","year":"1999","journal-title":"Appl. Env. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1550-7408.2003.tb00642.x","article-title":"A molecular biologic study of Enterocytozoon bieneusi in HIV-infected patients in Lima, Peru","volume":"50","author":"Sulaiman","year":"2003","journal-title":"J. Euk. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/AEM.69.8.4495-4501.2003","article-title":"Molecular characterization of microsporidia indicates that wild mammals harbor host-adapted Enterocytozoon spp. as well as human pathogenic Enterocytozoon bieneusi","volume":"69","author":"Sulaiman","year":"2003","journal-title":"Appl. Env. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s00436-003-1049-5","article-title":"Molecular characterization of Enterocytozoon bieneusi in cattle indicates that only some isolate have zoonotic potentials","volume":"93","author":"Sulaiman","year":"2004","journal-title":"Parasitol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.4315\/0362-028X.JFP-11-242","article-title":"Development of a PCR-RFLP protocol for rapid detection and differentiation of four cockroach vectors (Group I \u201cDirty 22\u201d Species) responsible for food contamination and spreading of foodborne pathogens: A public health importance","volume":"74","author":"Sulaiman","year":"2011","journal-title":"J. Food Protec."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.4315\/0362-028X.JFP-12-098","article-title":"Multilocus genetic characterization of two ant vectors (Group II \u201cDirty 22\u201d species) known to contaminate food and food products and spread foodborne pathogens","volume":"75","author":"Sulaiman","year":"2012","journal-title":"J. Food Protec."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.meegid.2013.07.015","article-title":"Genetic characterization of human-pathogenic Cyclospora cayetanensis parasites from three endemic regions at the 18S ribosomal RNA locus","volume":"22","author":"Sulaiman","year":"2014","journal-title":"Infec. Genet. Evol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/yea.320091106","article-title":"Nucleotide sequence analysis of the 5.8S rDNA and adjacent ITS2 region of Candida albicans and related species","volume":"9","author":"Lott","year":"1993","journal-title":"Yeast"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1128\/JCM.37.12.3957-3964.1999","article-title":"Phylogeny and PCR identification of clinically important Zygomycetes based on nuclear ribosomal-DNA sequence data","volume":"37","author":"Voigt","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1128\/JCM.38.6.2302-2310.2000","article-title":"Identification of medically important yeasts using PCR-based detection of DNA sequence polymorphisms in the internal transcribed spacer 2 region of the rRNA genes","volume":"38","author":"Chen","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jdermsci.2005.01.010","article-title":"Genetic identification and detection of human pathogenic Rhizopus species; a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene","volume":"39","author":"Nagao","year":"2005","journal-title":"J. Dermatol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1128\/AEM.00692-07","article-title":"Analysis of fungal flora in indoor dust by ribosomal DNA sequence analysis, quantitative PCR, and culture","volume":"74","author":"Meklin","year":"2008","journal-title":"Appl. Env. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1128\/JCM.02262-10","article-title":"Simultaneous detection and identification of Aspergillus and mucorales species in tissues collected from patients with fungal rhinosinusitis","volume":"49","author":"Zhao","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1128\/JCM.43.7.3324-3333.2005","article-title":"Multilocus DNA Sequence Comparisons Rapidly Identify Pathogenic Molds","volume":"43","author":"Rakeman","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/JCM.01750-09","article-title":"Internal transcribed spacer region sequence heterogeneity in Rhizopus microsporus: Implications for molecular diagnosis in clinical microbiology laboratories","volume":"48","author":"Woo","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2166\/wst.1998.0529","article-title":"Fungi as environmental microbiological indicators","volume":"38","author":"Mendes","year":"1998","journal-title":"Water Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1365-2222.1977.tb01485.x","article-title":"Fungal antigens as a source of sensitization and respiratory disease in Scottish malt workers","volume":"7","author":"Blyth","year":"1977","journal-title":"Clin. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1023\/A:1006815429916","article-title":"Two cases of cutaneous phaeohyphomycosis by Alternaria alternata and Alternaria tenuissima","volume":"137","author":"Romano","year":"1997","journal-title":"Mycopathologia"},{"key":"ref_29","first-page":"249","article-title":"Molecular diagnosis and epidemiology of fungal infections","volume":"36","author":"Reiss","year":"1998","journal-title":"Med. Mycol."},{"key":"ref_30","first-page":"334","article-title":"Molecular confirmation of invasive infection caused by Chaetomium globosum","volume":"58","author":"Paterson","year":"2005","journal-title":"Clin. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3109\/13693786.2010.499521","article-title":"Two new species of Mucor from clinical samples","volume":"49","author":"Alvarez","year":"2011","journal-title":"Med. Mycol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diagmicrobio.2012.03.007","article-title":"Chronic fungal meningitis caused by Aureobasidium proteae","volume":"73","author":"Hatvani","year":"2012","journal-title":"Diag. Microbiol. Infec. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jaci.2003.11.021","article-title":"Sampling for indoor fungi","volume":"113","author":"Portnoy","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1081-1206(10)60982-9","article-title":"Health effects of indoor fungi","volume":"94","author":"Portnoy","year":"2005","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1016\/j.scitotenv.2010.07.005","article-title":"Can we use indoor fungi as bioindicators of indoor air quality? Historical perspectives and open questions","volume":"408","author":"Cabral","year":"2010","journal-title":"Sci. Total Environ."},{"key":"ref_36","unstructured":"Sulaiman, I.M., Jacobs, E., Chatman, L., Simpson, S., and Kerdahi, K. (2013, January 18\u201321). The First Report on Molecular Characterization of Environmental Swab Samples Collected from Compounding Center known to cause 2012 Fungal Meningitis Outbreak. proceedings of the ASM 113th General Meeting, Denver, CO, USA."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/3\/3\/732\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:15:08Z","timestamp":1760217308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/3\/3\/732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,22]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,9]]}},"alternative-id":["pathogens3030732"],"URL":"https:\/\/doi.org\/10.3390\/pathogens3030732","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,22]]}}}