Clinical findings for fungal infections caused by methylprednisolone injections

N Engl J Med. 2013 Oct 24;369(17):1610-9. doi: 10.1056/NEJMoa1304879.

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.).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use
  • Arachnoiditis / epidemiology*
  • Arachnoiditis / microbiology
  • Arachnoiditis / mortality
  • Ascomycota / genetics
  • Ascomycota / isolation & purification
  • Aspergillus fumigatus / isolation & purification
  • Disease Outbreaks*
  • Drug Compounding
  • Drug Contamination*
  • Female
  • Glucocorticoids* / administration & dosage
  • Humans
  • Injections, Epidural
  • Injections, Spinal
  • Male
  • Meningitis, Fungal / epidemiology*
  • Meningitis, Fungal / microbiology
  • Meningitis, Fungal / mortality
  • Meningitis, Fungal / pathology
  • Methylprednisolone* / administration & dosage
  • Middle Aged
  • Polymerase Chain Reaction
  • Stroke / epidemiology*
  • Stroke / microbiology
  • Stroke / mortality
  • United States / epidemiology
  • Young Adult

Substances

  • Antifungal Agents
  • Glucocorticoids
  • Methylprednisolone