title: Clinical findings for fungal infections caused by methylprednisolone injections.
abstract: BACKGROUND
  Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections.
  
  
  METHODS
  We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification.
  
  
  RESULTS
  Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis.
  
  
  CONCLUSIONS
  The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Chiller
authors.forename: Monika
authors.initials: M
authors.lastname: Roy
authors.forename: Duc
authors.initials: D
authors.lastname: Nguyen
authors.forename: Alice
authors.initials: A
authors.lastname: Guh
authors.forename: Anurag N
authors.initials: AN
authors.lastname: Malani
authors.forename: Robert
authors.initials: R
authors.lastname: Latham
authors.forename: Sheree
authors.initials: S
authors.lastname: Peglow
authors.forename: Tom
authors.initials: T
authors.lastname: Kerkering
authors.forename: David
authors.initials: D
authors.lastname: Kaufman
authors.forename: Jevon
authors.initials: J
authors.lastname: McFadden
authors.forename: Jim
authors.initials: J
authors.lastname: Collins
authors.forename: Marion
authors.initials: M
authors.lastname: Kainer
authors.forename: Joan
authors.initials: J
authors.lastname: Duwve
authors.forename: David
authors.initials: D
authors.lastname: Trump
authors.forename: Carina
authors.initials: C
authors.lastname: Blackmore
authors.forename: Christina
authors.initials: C
authors.lastname: Tan
authors.forename: Angela A
authors.initials: AA
authors.lastname: Cleveland
authors.forename: Tara
authors.initials: T
authors.lastname: MacCannell
authors.forename: Atis
authors.initials: A
authors.lastname: Muehlenbachs
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brandt
authors.forename: John A
authors.initials: JA
authors.lastname: Jernigan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D001100:Arachnoiditis / Q000453:epidemiology* / Q000382:microbiology / Q000401:mortality; D001203:Ascomycota / Q000235:genetics / Q000302:isolation & purification; D001232:Aspergillus fumigatus / Q000302:isolation & purification; D004196:Disease Outbreaks; D004339:Drug Compounding; D004340:Drug Contamination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007268:Injections, Epidural; D007278:Injections, Spinal; D008297:Male; D016921:Meningitis, Fungal / Q000453:epidemiology* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020521:Stroke / Q000453:epidemiology* / Q000382:microbiology / Q000401:mortality; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D005938:Glucocorticoids; D008775:Methylprednisolone