title: Preliminary laboratory report of fungal infections associated with contaminated methylprednisolone injections.
abstract: In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although Aspergillus fumigatus was recovered from the index case, Exserohilum rostratum was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials. Exserohilum rostratum was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (n=67 patients), Tennessee (n=26), Virginia (n=20), and Indiana (n=16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF. E. rostratum antifungal susceptibility MIC50 and MIC90 values were determined for voriconazole (1 and 2 μg/ml, respectively), itraconazole (0.5 and 1 μg/ml), posaconazole (0.5 and 1 μg/ml), isavuconazole (4 and 4 μg/ml), and amphotericin B (0.25 and 0.5 μg/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.
authors.affiliation: Mycotic Diseases Branch, National Center for Emerging, Zoonotic and Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. gyi2@cdc.gov
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
authors.forename: Cau D
authors.initials: CD
authors.lastname: Pham
authors.forename: Lalitha
authors.initials: L
authors.lastname: Gade
authors.forename: Naureen
authors.initials: N
authors.lastname: Iqbal
authors.forename: Christina M
authors.initials: CM
authors.lastname: Scheel
authors.forename: Angela A
authors.initials: AA
authors.lastname: Cleveland
authors.forename: Anne M
authors.initials: AM
authors.lastname: Whitney
authors.forename: Judith
authors.initials: J
authors.lastname: Noble-Wang
authors.forename: Tom M
authors.initials: TM
authors.lastname: Chiller
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Park
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Litvintseva
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brandt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology; D001203:Ascomycota / Q000187:drug effects / Q000302:isolation & purification*; D004196:Disease Outbreaks; D004340:Drug Contamination; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009181:Mycoses / Q000139:chemically induced* / Q000453:epidemiology*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D008775:Methylprednisolone