Tainted steroids cause meningitis outbreak

Steroid injections are a common form of relief for severe back and neck pain. Instead of comfort, however, patients who recently received injections may be facing a graver issue: meningitis.

Methylprednisolone acetate, a steroid produced by the New England Compounding Center (NECC) in Framingham, Mass., is implicated in the nationwide outbreak of meningitis. The steroids are contaminated with the fungi Exserohilum, and 17,676 vials are believed to be in circulation.

Nineteen deaths and almost 250 cases of infection have been reported to this point across 15 states, including 16 infections and one death in Maryland. Seven out of the 76 clinics are believed to have received the tainted steroids are also in Maryland.

Meningitis is characterized by the inflammation of the meninges, which are membranes that protect the brain and spinal cord. Depending on the cause, meningitis can be classified as bacterial, fungal or chemical. The meningitis seen in the recent outbreak is of the fungal variety.

In the most common forms of meningitis, only bacteria and fungi that are able to traverse the blood-brain-barrier, the filter between the capillaries and the brain tissue, can cause an infection.

In the more rare process, a bacterium or fungus bypasses the blood-brain-barrier for a direct and troubling effect. Injections can be responsible for this kind of infection, as seen in the recent outbreak.

“If you inoculated directly [through] the meninges into the site of the infection, all of the microbes should be able to cause meningitis,” Kwang Sik Kim, professor and Director of the Eudowood Division of Pediatric Infectious Diseases at Hopkins Children’s Center, said.

Despite the widespread reach of the contaminated drugs’ distribution, a relatively small proportion of the 14,000 people who may have been exposed have actually been diagnosed with meningitis. There are several possible reasons for the disparity.

“It depends on the amount of the contamination and how much fungi have been inoculated,” Kim said. A larger dosage can increase the risk of contraction, and an older drug whose fungi have been sitting around replicating is more dangerous.

Other factors being examined are procedural. Injections into the epidural space should not puncture the dura matter membrane covering the spinal cord. When this occurs accidentally, however, it provides a direct route for the fungi to access the brain through the spinal fluid.

Fluoroscopy assists doctors in directing the needle without puncturing the dura. However, this technique is not used in all procedures, and injections administered by people other than physicians have been the topic of a growing debate.

Symptoms of the infection, which has also caused strokes in some patients, have emerged between one and four weeks after injection, sometimes longer.

The NECC recalled the contaminated steroids on Sept. 26, but the incident has raised serious questions about legal policies regarding compounding centers. In the past, compounding pharmacies have only combined medicines for specific patients. Under limited regulation, however, many have expanded relatively unchecked into small drug companies themselves. The Supreme Court overturned a legal definition of compounding proposed in 2002, and since then the FDS has shied away from the issue.

On Tuesday, the first FDA criminal investigators searched the NECC under warrant. The agency will scrutinize the situation to examine any possible breaches of federal law or unauthorized sale of drugs. The Centers for Disease Control and Prevention and the Massachusetts Board of Registration in Pharmacy also have investigations under way.

“Surely I think the blame has to go to the manufacturer. No doubt about it,” Kim said. Kim emphasizes that manufacturers of drugs that will bypass the blood-brain barrier (by injection, for example) ought to be extremely vigilant, given the increased threats that contamination holds. “If there’s any lapse in the manufacturing process, then there’s no guarantee that it will not happen again,” Kim said.

Kim said that, to his knowledge, no vials of the contaminated steroid or meningitis cases occurring as a result have been seen at Hopkins. However, he does state that contamination is a constant issue, and any unusual infections seen by doctors are always a warning sign to speak up.