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Largest Steroid Injection Outbreak Kills 55 People

Larry Hand

Jun 26, 2013

 

In the largest reported outbreak of infections associated with epidural or intraarticular injections of steroids, 741 cases of infections and 55 deaths occurred among more than 13,000 persons injected with a potentially contaminated drug, according to an article published online June 26 in the American Journal of Pathology.

A pathologic review of 40 cases (16 fatal) of confirmed infection of Exserophilum rostratum, a dark-colored mold that rarely infects humans, has established that immunohistochemistry analysis is a highly sensitive method for detecting Exserophilumin formalin-fixed, paraffin-embedded tissue samples.

Jana M. Ritter, DVM, from the Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, and colleagues conducted the pathologic review of clinical samples that included cerebrospinal fluid, joint fluid, and tissues, all obtained at biopsy or autopsy.

The CDC began receiving nationwide reports in September 2012 of fungal meningitis in patients who had received injections traced (through an extensive multistate, epidemiological and laboratory investigation) to 3 contaminated lots (>17,000 vials) of preservative-free methylprednisolone acetate from a single compounding pharmacy. By May 6, 2013, 55 deaths associated with this outbreak had occurred in 20 states.

Tissue samples received by the CDC between October 11, 2012, and January 24, 2013, from 7 states were used for the current review.

For 36 of the 40 review cases, the site of injection has been reported as follows: lumbar spine (n = 22), cervicothoracic spine (n = 5), sacroiliac joint (n = 5), or hip joint (n = 4). Although 11 cases had meningitis only and 6 had both meningitis and injection-site infection, all meningitis-only cases were fatal and had shorter intervals between injection and tissue collection compared with other cases (P = .009). Nineteen patients had paraspinal infection, and 4 patients had peripheral joint infection.

Especially for elderly people, epidural and intraarticular steroid injections are often administered for treatment of joint, back, and neck pain, although infections are rare. In this pathologic review, 93% of patients were aged 50 years or older, and 65% were women. For the 38 patients for whom it was reported, the interval between injection and tissue collection ranged from 12 to 120 days (median, 52 days).

For most cases for which a cause could be established, evidence pointed toExserophilum infection. Immunohistochemistry of tissue samples revealed the fungus in 100% of the review cases, although other test methods were also used.

In most cases, meningitis was the cause of death. The concurrent inoculation of steroids and fungus apparently led to extensive hemorrhage and tissue decay in the brain after the contaminant was transported by cerebrospinal fluid to the meninges and blood vessels within the brain.

"The observation of abundant fungi in the adventitial and perivascular tissues, but relatively few fungi in arterial lumens, suggests migration of fungus into, rather than out of, vessels at this location. This further supports the hypothesis thatExserohilum migrates from lumbar spine to brain through the [cerebrospinal fluid], with subsequent vascular invasion, rather than migration through the vasculature," Dr. Ritter and colleagues write.

The authors have disclosed no relevant financial relationships.

Am J Pathol. Published online June 26, 2013.