title: Fungal infections associated with contaminated methylprednisolone in Tennessee.
abstract: BACKGROUND
  We investigated an outbreak of fungal infections of the central nervous system that occurred among patients who received epidural or paraspinal glucocorticoid injections of preservative-free methylprednisolone acetate prepared by a single compounding pharmacy.
  
  
  METHODS
  Case patients were defined as patients with fungal meningitis, posterior circulation stroke, spinal osteomyelitis, or epidural abscess that developed after epidural or paraspinal glucocorticoid injections. Clinical and procedure data were abstracted. A cohort analysis was performed.
  
  
  RESULTS
  The median age of the 66 case patients was 69 years (range, 23 to 91). The median time from the last epidural glucocorticoid injection to symptom onset was 18 days (range, 0 to 56). Patients presented with meningitis alone (73%), the cauda equina syndrome or focal infection (15%), or posterior circulation stroke with or without meningitis (12%). Symptoms and signs included headache (in 73% of the patients), new or worsening back pain (in 50%), neurologic symptoms (in 48%), nausea (in 39%), and stiff neck (in 29%). The median cerebrospinal fluid white-cell count on the first lumbar puncture among patients who presented with meningitis, with or without stroke or focal infection, was 648 per cubic millimeter (range, 6 to 10,140), with 78% granulocytes (range, 0 to 97); the protein level was 114 mg per deciliter (range, 29 to 440); and the glucose concentration was 44 mg per deciliter (range, 12 to 121) (2.5 mmol per liter [range, 0.7 to 6.7]). A total of 22 patients had laboratory confirmation of Exserohilum rostratum infection (21 patients) or Aspergillus fumigatus infection (1 patient). The risk of infection increased with exposure to lot 06292012@26, older vials, higher doses, multiple procedures, and translaminar approach to epidural glucocorticoid injection. Voriconazole was used to treat 61 patients (92%); 35 patients (53%) were also treated with liposomal amphotericin B. Eight patients (12%) died, seven of whom had stroke.
  
  
  CONCLUSIONS
  We describe an outbreak of fungal meningitis after epidural or paraspinal glucocorticoid injection with methylprednisolone from a single compounding pharmacy. Rapid recognition of illness and prompt initiation of therapy are important to prevent complications. (Funded by the Tennessee Department of Health and the Centers for Disease Control and Prevention.).
authors.affiliation: Division of Communicable and Environmental Diseases and Emergency Preparedness, Tennessee Department of Health, 1st Fl., Cordell Hull Bldg., 425 5th Ave. N., Nashville, TN 37243, USA. marion.kainer@tn.gov
authors.forename: Marion A
authors.initials: MA
authors.lastname: Kainer
authors.forename: David R
authors.initials: DR
authors.lastname: Reagan
authors.forename: Duc B
authors.initials: DB
authors.lastname: Nguyen
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wiese
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wise
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ward
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Park
authors.forename: Meredith L
authors.initials: ML
authors.lastname: Kanago
authors.forename: Jane
authors.initials: J
authors.lastname: Baumblatt
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Schaefer
authors.forename: Brynn E
authors.initials: BE
authors.lastname: Berger
authors.forename: Ellyn P
authors.initials: EP
authors.lastname: Marder
authors.forename: Jea-Young
authors.initials: JY
authors.lastname: Min
authors.forename: John R
authors.initials: JR
authors.lastname: Dunn
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Dreyzehner
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001203:Ascomycota / Q000302:isolation & purification*; D001228:Aspergillosis / Q000175:diagnosis / Q000453:epidemiology; 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 / Q000009:adverse effects; D007278:Injections, Spinal / Q000009:adverse effects; D008297:Male; D016921:Meningitis, Fungal / Q000175:diagnosis / Q000453:epidemiology*; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D010594:Pharmacies; D012307:Risk Factors; D013714:Tennessee / Q000453:epidemiology
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone