Just over 5 months after the first symptoms were reported in what turned out to be a fatal multistate fungal meningitis outbreak, a preliminary report in the December 20 issue of the New England Journal of Medicine assessed the scope of the incident so far.
The fungal meningitis outbreak is associated with contaminated vials of methylprednisolone compounded at Massachusetts-based New England Compounding Center. Compounding pharmacies produce medications that are not commercially available in order to meet the individual needs of patients for whom commercial drugs are not appropriate. The three lots of steroids associated with the meningitis outbreak, which were contaminated with mold, were first produced in May of this year and shipped to physicians and health facilities at 76 locations in 23 states. Physicians inject the steroids into a patient’s spine, or in some cases a joint, to treat severe chronic pain.
By December 10, there were 590 reported cases of infection in 19 states and 37 deaths associated with exposure to the steroid. The NEJM report described the morbidity and mortality of the outbreak as “substantial.”
“We think this is most likely the largest outbreak of iatrogenic fungal meningitis that’s been reported in the US,” said Rachel Smith, MD, MPH, who is an epidemiologist at CDC and an author of the report.
Detailed data were available for 386 of the reported cases. These cases were analyzed in the preliminary report. While not all case patients were diagnosed with meningitis, each received the contaminated steroid and later had one or more of the conditions considered associated with the steroid, such as an infection at the site of injection.
Among these 386 patients, 300, or 78%, were diagnosed with meningitis. Thirty-three patients, or 9%, had a stroke. Patients ranged in age from 16 to 92, with a median age of 64. They had from one to six injections, though most had only one. While the incubation period for infection ranged from 0 to 120 days, most infected patients experienced symptoms about 20 days after exposure.
Investigators found the mold Exserohilum rostratum in the spinal fluid of 100 patients. Additional patient specimens showed evidence of other fungi.
The report, however, is only a “snapshot” of a moment in the outbreak, Smith says.
“It’s important to remember that we have not seen all the cases yet. In the last 2 weeks we’ve had about 80 new infections reported to us,” she said.
The majority of these 80 cases were spinal and paraspinal infections associated with the contaminated steroids. Reports of meningitis infections have declined.
“These localized spinal and paraspinal infections could still be very serious infections, and we want people to be aware that those are happening. People who were exposed to this contaminated steroid may still be at risk for some of these localized spinal and paraspinal infections,” Smith said.
The outbreak has health professionals and patients alike asking what is an appropriate level of state and federal regulation of compounding pharmacies. FDA, which regulates commercial mass manufacture of pharmaceuticals, has not thus far overseen compounding pharmacies, although it has limited authority to take action in some circumstances. State regulation of compounding pharmacies varies widely from one state to the next. In interviews with pharmacist.com, some pharmacists have expressed hope the outbreak will bring more regulations, while others say they fear over-regulation.
As noted in editorials in NEJM and JAMA, this was not the first outbreak of meningitis associated with contaminated steroids produced at a compounding pharmacy. Nor is this the first time an outbreak has led to a call for broader oversight of compounding.
Shortly after a 2002 meningitis outbreak, according to the editorial in JAMA, the Kansas City Star quoted a pharmacist as saying, “It is just a matter of time before somebody makes a grossly contaminated product and scores of people die. … People will then be asking, ‘Why did this happen?’”
Ten years later, it has happened again. Some, while recognizing the need for compounded pharmaceuticals, are again pointing to FDA regulation of compounding pharmacies as the solution to the problem.
“We believe that the best way to balance the need for ‘designer therapeutics’ from these pharmacies with the need for product safety,” wrote NEJM editors, “is to give [FDA] broader powers to monitor and control the agents produced by such pharmacies and any adverse events that are associated with them.”