Infections have developed in one joint each in two individuals who were injected with fungus-contaminated methylprednisolone acetate in the weeks or months preceding the ongoing outbreak, according to a teleconference hosted Oct. 16 by the Food and Drug Administration and the Centers for Disease Control and Prevention.
The indications for those joint injections were not discussed at the briefing, but rheumatologists commonly use methylprednisolone injections in joints affected by rheumatoid arthritis or osteoarthritis to reduce inflammation and ease pain.
Dr. Tom Chiller, a medical epidemiologist at the Division of Foodborne, Waterborne and Environmental Diseases at the CDC, noted that both infected joints were ankles that had been injected with fungus-contaminated methylprednisolone acetate manufactured by the New England Compounding Center (NECC) in Framingham, Mass. That plant has been shut down because inspection by the FDA showed that the conditions were unsterile.
Neither culture nor polymerase chain reaction of synovial fluid aspirated from the infected ankles has grown any fungus. However, because bacteria and crystals have been ruled out as a cause of these two cases of septic arthritic and both patients received intra-articular injections with the contaminated steroid solution, investigators feel certain the patients have fungal joint infections, according to Dr. Chiller.
Three kinds of fungus have been identified in patients with fungal infections associated with the contaminated NECC products. Aspergillus was identified as the cause of the index case of fungal meningitis. Two types of black mold have been cultured from meningitis patients: Exserohilum rostratum and Cladosporium.
In total, as of Oct. 16, there have been 233 confirmed cases of fungal infection in people who received injections, usually epidural, of contaminated steroid in solution, according to Dr. Melissa Schaefer, medical officer in the Division of Healthcare Quality Promotion at the CDC’s National Center for Emerging and Zoonotic Infectious Diseases. Among these people there have been 15 deaths, all from meningitis.
One particularly challenging aspect of this outbreak for rheumatologists is the length of incubation of septic arthritis because of a fungus.
The FDA has advised physicians who used NECC products dated May 21, 2012 or later, to contact their patients to check on their well being. Most of the patients given epidural injections with the contaminated solution are likely to present within 1-2 weeks.
The latency period of a fungus infection in a joint, however, may be months, according to Dr. Peter G. Pappas, professor of medicine in the division of infectious diseases at the University of Alabama at Birmingham, who participated in the CDC teleconference.
Patients with septic arthritis often limp into the office months after the onset of symptoms to seek medical care, he said.
The CDC has revised its treatment guidance for septic arthritis in cases of suspected fungal infection Dr. Chiller said that in cases of suspected fungal septic arthritis, the CDC now recommends empiric treatment with voriconazole (Vfend), beginning with a loading dose of 6 mg/kg every 12 hours for two doses, followed by 4 mg/kg every 12 hours for the duration of treatment. A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily should be considered in addition to voriconazole in patients with severe joint infection and/or clinical instability. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity. Providers and patients should be aware of and monitor for potential adverse effects of amphotericin B formulations.
The CDC plans to update the guidance on diagnosing fungal septic arthritis on Oct. 17 or 18.
The source of the outbreak is NECC, a compounding pharmacy that operated in violation of the law on a number of levels.