On Sept 18, infectious disease specialist April Pettit reported an unusual laboratory result to the Tennessee Department of Health. She had ordered extra tests on the spinal fluid of a patient with meningitis who was not responding to antibiotics, and the results showed that a rare fungus had infected his nervous system.
The finding came too late to save the patient's life but within a week it connected his illness to a dozen other anomalous cases scattered across the country, outlining a blossoming outbreak of fungal meningitis produced by one of the most damaging breakdowns of US drug safety in the past decade.
The US Centers for Disease Control and Prevention (CDC) ultimately confirmed that the pathogens originated at the New England Compounding Center (NECC) in Framingham, MA. NECC was licensed as a compounding pharmacy, a facility that traditionally combines appropriate ingredients to create drugs that meet the needs of individual patients.
Beginning on May 21, NECC prepared and shipped three lots of the steroid methylprednisolone acetate to health-care providers in 23 states, which would be administered in spinal injections or peripheral joint injections to an estimated 14 000 people over the next 4 months. An unknown number of the doses were contaminated with the black mould Exserohilum rostratum and other pathogens.
The outbreak posed unique difficulties for those attempting to track and treat it. Identifying cases proved difficult even after the outbreak was recognised because fungus grows very slowly and screening tests are not always sensitive enough to detect it.
Physicians were also in uncharted territory as they tried to determine the optimum treatment for those afflicted, because the primary fungal pathogen had never before been known to cause meningitis. And many of the individuals exposed were elderly people vulnerable to infection, and the immunosuppressant effects of the steroid that carried the contaminant may have further compromised their cellular immunity. By Oct 29, 354 cases had been reported nationally of which 25 had died.
The number of people stricken was exceptional but the outbreak was not unprecedented. In 2007, the Food and Drug Administration (FDA) claimed it was aware of more than 200 adverse events involving compounded drugs since 1990.
In 2002, five cases of fungal meningitis in North Carolina were linked to compounded doses of the same steroid implicated in this year's outbreak, administered by the same spinal procedure. Last year, bacterial contamination of a supplement killed nine people in Alabama.
Once NECC was identified as the source and state and federal authorities began to investigate the facility, any mystery of how the contamination occurred quickly dropped away. A review of the pharmacy's records revealed that over the past year its clean rooms had repeatedly tested positive for bacteria or mould at levels that should have triggered remedial measures, yet no corrective actions had been taken.
Investigators also documented “a systemic failure” by the pharmacy to use sterilisation equipment for enough time to ensure the drugs it produced were safe. And NECC repeatedly shipped drugs—including two of the three lots of steroid implicated in the outbreak—before receiving laboratory results that confirmed their sterility.