Caroline Helwick

October 17, 2012

NEW ORLEANS — The fungal meningitis outbreak strikes fear in the hearts of many anesthesiologists, who depend on compounding pharmacies to meet many of their needs, according to a presentation here at Anesthesiology 2012: American Society of Anesthesiologists (ASA) 2012 Annual Meeting.

The current count of cases related to products from the New England Compounding Center stands at 247 cases, with 19 deaths occurring across 15 states.

"This is a very scary time. The goal of the panel was to present the facts and clarify any misperceptions concerning the outbreak of fungal meningitis," said ASA Committee on Communications chair John F. Dombrowski, MD, who moderated the panel. Dr. Dombrowski is director of the Washington (DC) Pain Center.

"There are 1.1 million people receiving some type of back injections, and right now we are seeing that some of those people are sick and some are, unfortunately, dying. We wanted to get the clearest science, the most recent data, out there so our members will have less fear," he told Medscape Medical News.

Although patients are very concerned, clinicians also fear that they may be unknowingly inflicting harm, Dr. Dombrowski said. "I worry whether I might be harming my patients because I don't know where my medications are coming from."

Although the fungal meningitis outbreak seems limited to products from the New England Compounding Center, "we get the idea that maybe there are other medications out there that we don't know about," he said. "We are always under the assumption, incorrectly it seems, that the drugs we get will be up to standards, but if they do not come from the manufacturer and need to be compounded, we need to look at the data from that particular lab."

Infectious Disease Risks and Compounded Drugs

James P. Rathmell, MD, of Harvard Medical School, Boston, said that compounding pharmacies "are here to stay," and that is certainly the case in the area of pain medicine.

Compounding pharmacies compensate for drug shortages, providing drug formulations not supplied by pharmaceutical manufacturing companies (especially preservative-free steroids and complex drug combinations, including drugs for topical and intrathecal drug delivery), and such compounding can reduce the cost of drugs.

Dr. Rathmell emphasized the need to use compounding pharmacies for intrathecal drug delivery, because there are no FDA-approved agents. "These are not manufactured, so we simply need to get these from compounding pharmacies," he said.

The infectious disease risks associated with injection therapies are "small," Dr. Rathmell said, both for superficial and deep infection, including neuraxial infections such as epidural abscess and meningitis. Although it is not possible to discern the actual incidence from available published data, estimates range from approximately 1 in 10,000 to 1 in 100,000 injections.

Know Where Your Drugs Come From

Although Dr. Rathmell indicated that the current outbreak is "unique," Steven Gayer, MD, MBA, who holds appointments in both anesthesiology and ophthalmology at the University of Miami School of Medicine, pointed out that "tainted injectables" are actually not a new entity.

Over the past decade, there have been other deaths from fungal contamination of epidural methylprednisolone from a compounding pharmacy in South Carolina and from exposure to Serratia-contaminated betamethasone epidural injections in California. In addition, a Michigan pharmacy recalled more than 900 vials of contaminated methylprednisolone, and other reports surfaced of contaminated triamcinolone and brilliant blue G dye from compounding pharmacies in Florida, he said.

In 2011, an outbreak of Streptococcus endophthalmitis with intravitreal injections of bevacizumab caused functional loss of vision in 11 of 12 exposed patients in South Florida. The FDA traced the problem to poor sterile techniques, inadequate documentation, insufficient testing and monitoring of equipment, multiple vial punctures, and distribution problems from the compounding pharmacy.

"The lesson we learned from the endophthalmitis outbreak in Miami was to use manufacturers' products where feasible," Dr. Gayer said, "and carefully assess any compounding pharmacy you use."

The compounding pharmacy should comply with the Unites States Pharmacopoeia (USP) Chapter 797 guidelines for safe practices. State health department inspection reports should be made available, and companies that deny requests to view them should be avoided, he added.

Companies should provide sterility test results with each batch, he continued. "Periodic testing does not help if there is a problem with a particular batch that was not tested," Dr. Gayer noted.

Clinicians can use the International Academy of Compounding Pharmacists' Assessment Tool for evaluating the pharmacies with which they do business, he added.

Be Cognizant of the Symptoms

Session attendees were particularly interested in being able to recognize the infection among persons they may have unknowingly exposed to the contaminants from drugs produced by the New England Compounding Center.

Mark R. Abbruzzese, MD, an infectious disease specialist at Georgetown University and MedStar Georgetown University Hospital in Washington, DC, emphasized, "This is an unusual disease, and if you don't think of it, you will never see it."

The infectious organisms are Exserohilum rostratum and Aspergillus fumigatus. All infections occurred after May 21, 2012, and should be suspected in patients with unknown causes of meningitis, stroke without data from the cerebrospinal fluid (CSF), or the occurrence of a spinal osteo, epidural abscess, or progressive joint destruction of unknown cause, he said.

The challenge is that symptoms are subacute and nonspecific, but there is one interesting and consistent presentation in this particular population: nausea. Although serologies may be useful, lumbar puncture is required for diagnosis, Dr. Abbruzzese pointed out.

The Centers for Disease Control and Prevention recommends obtaining a large volume of CSF, sending 10 mL to the Department of Health, and keeping 10 mL for stains, cultures, and Aspergillus galactomannan assay. Blood and distant sites should be cultured because the infection spreads contiguously.

The main treatment options are voriconazole, amphotericin B, and caspofungin. The optimal treatment duration is unknown, but patients are likely to need treatment "more like months or years, not weeks," and are at risk for reactivation of latent disease or subclinical infection, Dr. Abbruzzese said.

Dr. Dombrowski, Dr. Rathmell, Dr. Gayer, and Dr. Abbruzzese have disclosed no relevant financial relationships.

Anesthesiology 2012: American Society of Anesthesiologists (ASA) 2012 Annual Meeting. Presented October 15, 2012.