Meningitis Outbreak: Pharmacy Violated License

Oct. 12, 2012— -- The compounding pharmacy at the center of the fungal meningitis outbreak was not following the requirements of its state license, according to a spokeswoman for the Massachusetts Department of Public Health.

The New England Compounding Center in Framingham, Mass., shipped more than 17,000 vials of a steroid -- now implicated in the outbreak -- to pain clinics in 23 states.

But Dr. Madeleine Biondolillo, director of the state's Bureau of Health Care Safety and Quality, said the company was meant to make up drugs only in response to a doctor's prescription for an individual patient.

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"This organization chose to apparently violate the licensing regulations under which they were allowed to operate," Biondolillo told reporters in a telephone news conference Thursday.

FDA spokeswoman Dr. Deborah Autor told MedPage Today the agency has legal remedies available, including the ability to seize products and to lay criminal charges, but she did not elaborate further.

A 2006 warning letter to the company, charging it was acting more like a drug manufacturing firm than a compounding pharmacy, elicited assurances that patient safety was being protected and that applicable laws and regulations were being obeyed, Autor said.

If the current investigation proves otherwise, she said, " we will hold people accountable appropriately."

She added that the agency has had its eye on the company for some time. "We've been there repeatedly," she said.

The company has now recalled all three lots of the contaminated steroid, used mainly to control back pain, as well as all of its other products, and is no longer carrying on production.

But "we are not out of the woods yet," said Dr. Todd Weber, the CDC's incident manager for the outbreak.

State and local health officials have now contacted more than 12,000 of the estimated 14,000 people exposed to the steroid, which is thought to be contaminated by one or more species of fungus.

But Weber told reporters that the incubation period for fungi can be very long, so both patients and their doctors will need to be vigilant for several more weeks.

The CDC is now reporting 170 cases in 10 states of fungal infection associated with the steroid, preservative-free methylprednisolone acetate, including 14 deaths.

That's an increase of 33 cases and two deaths from Wednesday.

Weber said one of the new cases did not involve meningitis, but was an apparent joint infection that arose after the steroid was injected into the ankle. He said the case is still under investigation.

There is evidence of fungal infection of the central nervous system in at least 25 patients, the CDC says, with the most common pathogen being exserohilum.

"Historically, fungal meningitis is very rare," Weber said, "and exserohilum has not been seen previously as a cause of fungal meningitis."

"This is new territory for public health and the clinical community," he added.

In cases of confirmed fungal meningitis, the CDC is recommending routine empiric treatment protocols to cover the possibility of bacterial infection, with the addition of broad-spectrum antifungal agents for the fungus.

Specifically, the agency is recommending intravenous voriconazole (VFEND), preferably at a dose of 6.0 mg/kg every 12 hours, combined with daily intravenous liposomal amphotericin B, preferably at a dose of 7.5 mg/kg.

The agency added that the dose of amphotericin B can be reduced to 5.0 mg/kg if physicians are concerned about the potential for nephrotoxicity, especially in older patients.

A liter of normal saline before the infusion is another way to minimize the risk of nephrotoxicity, the agency noted.

In cases where people have been exposed but remain without symptoms, the CDC is not recommending antifungal prophylaxis, but patients should be monitored closely for the onset of symptoms, with a low level of suspicion for a lumbar puncture to detect changes in the cerebrospinal fluid (CSF).

The agency is also not recommending empiric antifungal treatment for patients with symptoms but normal CSF.

The clinical recommendations may change as more information becomes available, Weber said.