title: Fungal infections associated with contaminated methylprednisolone injections.
abstract: BACKGROUND
  Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy.
  
  
  METHODS
  Three lots of methylprednisolone acetate were recalled by the pharmacy; examination of unopened vials later revealed fungus. Notification of all persons potentially exposed to implicated methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. We collected clinical data on standardized case-report forms, and we tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing.
  
  
  RESULTS
  By October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249); 40 patients (5%) had a stroke.
  
  
  CONCLUSIONS
  Analysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.
authors.affiliation: From the Epidemic Intelligence Service, Scientific Education and Professional Development Program Office (R.M.S., S.G., A.P.), Division of Foodborne, Waterborne, and Environmental Diseases (R.M.S., A.P., A.A.C., K.B., J.R.H., M.E.B., B.J.P.), Division of Healthcare Quality Promotion (M.K.S., M.W., J.J., J.T.W.), and Division of High-Consequence Pathogens and Pathology (D.B.), Centers for Disease Control and Prevention, Atlanta; the Tennessee Department of Health, Nashville (M.A.K., A.D.W.); the Michigan Department of Community Health, Bureau of Epidemiology, Lansing (J. Finks, J. Fiedler); the Indiana State Department of Health, Indianapolis (J.D., C.F.); the Virginia Department of Health, Richmond (E.F., L.G.); the Maryland Department of Health and Mental Hygiene, Baltimore (A.C.); the New Jersey Department of Health, Trenton (B.C.); the Florida Department of Health, Tallahassee (A.R.); and the North Carolina Division of Public Health, Raleigh (S.G.).
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Smith
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Schaefer
authors.forename: Marion A
authors.initials: MA
authors.lastname: Kainer
authors.forename: Matthew
authors.initials: M
authors.lastname: Wise
authors.forename: Jennie
authors.initials: J
authors.lastname: Finks
authors.forename: Joan
authors.initials: J
authors.lastname: Duwve
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fontaine
authors.forename: Alvina
authors.initials: A
authors.lastname: Chu
authors.forename: Barbara
authors.initials: B
authors.lastname: Carothers
authors.forename: Amy
authors.initials: A
authors.lastname: Reilly
authors.forename: Jay
authors.initials: J
authors.lastname: Fiedler
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wiese
authors.forename: Christine
authors.initials: C
authors.lastname: Feaster
authors.forename: Lex
authors.initials: L
authors.lastname: Gibson
authors.forename: Stephanie
authors.initials: S
authors.lastname: Griese
authors.forename: Anne
authors.initials: A
authors.lastname: Purfield
authors.forename: Angela A
authors.initials: AA
authors.lastname: Cleveland
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Benedict
authors.forename: Julie R
authors.initials: JR
authors.lastname: Harris
authors.forename: Mary E
authors.initials: ME
authors.lastname: Brandt
authors.forename: Dianna
authors.initials: D
authors.lastname: Blau
authors.forename: John
authors.initials: J
authors.lastname: Jernigan
authors.forename: J Todd
authors.initials: JT
authors.lastname: Weber
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use; D001203:Ascomycota / 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; D055256:Infectious Disease Incubation Period; D007278:Injections, Spinal / Q000009:adverse effects; D008297:Male; D016921:Meningitis, Fungal / Q000188:drug therapy / Q000453:epidemiology*; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011634:Public Health; D020521:Stroke / Q000453:epidemiology / Q000382:microbiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D005938:Glucocorticoids; D008775:Methylprednisolone