Fungal meningitis from injection of contaminated steroids: a compounding problem.

INJECTIONS OF CONTAMINATED STEROIDS LEAD TO A deadly outbreak of meningitis. Investigations reveal that a compounding pharmacy manufactured the steroids under unacceptable conditions. Newspaper reports document significant gaps in oversight by state and federal agencies, and public health officials call for stronger controls. The year is 2002. According to the San Francisco Chronicle, “the case of Doc’s Pharmacy illustrates how doctors, as well as their patients, are unaware of the risks inherent in pharmacy compounding.” Not long after, the Kansas City Star reviews a series of compounding-related injuries and deaths from across the country. A pharmaceutical industry executive is quoted by the paper 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?’” Almost exactly a decade later, at the end of September 2012, the Maryland Department of Health and Mental Hygiene receives a call from the Centers for Disease Control and Prevention (CDC). Seven Maryland outpatient facilities have received suspect lots of methylprednisolone acetate injection from the New England Compounding Center. Working with these facilities and other clinicians to identify affected patients reveals that at least 17 Marylanders have meningitis and 1 has died. As of October 25, this outbreak has reached 18 states, causing 328 cases of serious fungal infection, including 323 cases of meningitis, 5 cases of peripheral joint infection, and 24 deaths. Thousands of additional patients have undergone lumbar punctures and other invasive diagnostic procedures. Tens of thousands are living in fear that they could become seriously ill at any moment. Managing the crisis has required an intensive response by federal, state, and local public health officials. With an evolving spectrum of fungal illness caused by Exserohilum and potentially Aspergillus, Cladosporium, and other species, CDC experts have developed and modified working case definitions, diagnostic recommendations, and treatment guidelines. The CDC’s emergency operations center has assisted states in contacting thousands of patients. The Food and Drug Administration (FDA) has focused its attention on the conditions at the New England Compounding Center, overseeing an increasing series of recalls. On October 18, the FDA announced that unopened vials from implicated lots tested positive for Exserohilum, the same fungus identified in meningitis cases. Health departments across the nation have coordinated local activities in emergency response mode. These efforts include investigating reports of possible cases, providing guidance to physicians on diagnosis and treatment, sharing information with the CDC and with other states, and analyzing data to better define the risk associated with exposure. State health departments have also organized outreach to scores of clinics and tens of thousands of exposed patients to assess symptoms, encourage vigilance, and answer questions. There are many questions. Patients already affected with chronic pain syndromes ask how they can identify new or worsening symptoms and endure the stress of medical evaluation and the complicated logistics of the health care system. Physicians want to know whether it is possible to reassure anxious callers who may have received one of the more than 3000 products made by the New England Compounding Center, when few clinics are able to track which lots were administered to specific patients. And everyone wants to know: Why did this happen? According to the International Association for Compounding Pharmacists, there are an estimated 7500 compounding pharmacies in the United States, and 1% to 3% of all prescriptions are compounded. Unlike pharmaceutical manufacturers, compounding pharmacies do not have to demonstrate the safety and efficacy of their products or adhere to manufacturing and labeling standards. Only about 2% participate in the industry’s voluntary accreditation program.