COMMENTARY

Fungal Infection Outbreak: What Should Physicians Be Doing?

Tom M. Chiller, MD, MPHTM

Disclosures

October 31, 2012

Editorial Collaboration

Medscape &

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Hello. I am Dr. Tom Chiller, a medical epidemiologist at the Centers for Disease Control and Prevention (CDC). Today I am pleased to speak as part of the CDC Expert Video Commentary Series on Medscape.

As you probably are well aware, CDC, in collaboration with state and local health departments and the US Food and Drug Administration (FDA), is investigating a multistate fungal meningitis outbreak among patients who received contaminated steroid injections.

Several patients have suffered from strokes that are believed to have resulted from their infections. This investigation also includes possible fungal infections associated with injections into peripheral joints, such as a knees, shoulders, or ankles.

To date, all identified cases associated with this outbreak have received at least 1 of 3 lots of preservative-free methylprednisolone acetate (MPA) from the New England Compounding Center (NECC).

The fungal infections we are seeing associated with this outbreak are extremely rare. CDC has convened a panel of the nation's leading clinical fungal experts who are working with us to ensure that our diagnostic and treatment guidance is appropriate for identifying and treating patients who develop infections.

Today I want to give you an update on where we stand with respect to our clinical guidance.

First, here is what we know: To date, more than 300 cases have been reported to us, which includes 24 deaths across 17 states.

Of cases in which we have identified a fungus, most have been Exserohilum rostratum. One patient has been found to be infected with Aspergillus fumigatus and another with a Cladosporium species. These fungi are common in the environment but were not a recognized cause of meningitis before this outbreak. We are really in new territory when it comes to treatment and management of patients with Exserohilum infection.

CDC and FDA have also confirmed the presence of Exserohilum in 2 of the 3 unopened vials of MPA. We continue to test the third implicated lot of MPA as well as other NECC medications.

Of the approximately 14,000 patients who received injections from 1 of the 3 contaminated lots of MPA, nearly all have been contacted for further follow-up. Among people with meningitis for whom we have clinical information available, the onset of symptoms is typically 1-4 weeks following injection. However, we know that fungal infections can be slow to develop and that there are reports of longer periods of time between injection and onset of symptoms, so we need to monitor these patients for development of signs and symptoms for several months following the injection.

For patients who received epidural or paraspinal steroid injections with medication from any of the 3 recalled lots of MPA, we need to carefully clinically evaluate them. If they have any symptoms consistent with meningitis or posterior circulation stroke, cerebrospinal fluid (CSF) should be obtained for diagnosis unless contraindicated. We also encourage physicians to have a low threshold to obtain CSF in patients with mild signs and symptoms of meningitis because we are aware that some patients in this outbreak have presented with minimal symptoms. When obtaining CSF for diagnosis, we encourage that this be done at a site other than the site used for the steroid injection when possible.

At this time, CDC does not recommend initiation of antifungal treatment in people who received a contaminated steroid injection but who do not have any symptoms or in whom there is no laboratory evidence of infection. However, some patients may be at greater risk than others of developing fungal meningitis. Specific CDC analysis has shown that the greatest risk is in the first 6 weeks after injections.

Clinicians may consider the option of obtaining CSF in patients who received their last injection within the past 6 weeks (42 days) to look for evidence of meningitis before symptoms appear. From our analysis, we have seen that the more time that has passed since the date of the steroid injection, the lower the risk of developing disease.

For patients who are presenting with joint infections, clinicians should collect synovial fluid and/or synovial tissue, either by arthrocentesis or biopsy, and look for evidence of infection.

Let's shift gears and talk about treatment. If you have a patient who has evidence of fungal meningitis or joint infection, make sure you are following CDC's treatment recommendations.

At this time, CDC is recommending voriconazole, which is an effective agent for treating infections due to brown-black molds, such as Exserohilum, as well as infections due to Aspergillus species, and has good penetration into the central nervous system.

CDC continues to consult with national experts about treatment options for infections associated with this outbreak. As more information becomes available on patient management, we will continue to update the clinical community.

Please see the links below to stay up to date on the latest CDC guidance.

Finally, because this is an ongoing investigation, we continue to need your help. If you see patients with any suspected adverse events following use of NECC products, please report this to your state health department and FDA's MedWatch program at 1-800-332-1088 or FDA.gov/medwatch.

Thank you.

Web Resources

Guidance

Interim Treatment Guidance for Central Nervous System (CNS) and Parameningeal Infections Associated with Injection of Contaminated Steroid Products. Update: October 23, 2012.

Interim Treatment Guidance for Osteoarticular Infections Associated with Injection of Contaminated Steroid Products. Update: October 23, 2012.

Interim Guidance for Management of Asymptomatic Persons Exposed to Potentially Contaminated Steroid Products

Guidance on Management of Asymptomatic Patients Who Received Epidural or Paraspinal Injections with Contaminated Steroid Products. New: October 23, 2012.

Case Definitions

Case Definitions for Meningitis and Septic Arthritis. Update: October 24, 2012.

Diagnostic Testing

Diagnostic Testing for Septic Arthritis and Specimen Submission to CDC - Outbreak Associated with Injection of Potentially Contaminated Steroid Products. New: October 16, 2012.

Diagnostic Testing and Specimen Shipping for Central Nervous System and Parameningeal Infections. Update: October 19, 2012.

Tom M. Chiller, MD, MPHTM, became the associate director for epidemiologic science in the Division of Foodborne, Waterborne, and Environmental Diseases at the National Center for Emerging and Infectious Zoonotic Diseases (NCEZID) in June 2007. He also serves as the deputy chief of the Mycotic Diseases Branch.

Between 2003 and 2006, Dr. Chiller was chief of the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS) in CDC's Foodborne and Diarrheal Diseases Branch. He also served as CDC's lead for the Global Foodborne Infections Network, a World Health Organization program to build global capacity for enteric disease surveillance and response. In 2006, he became the epidemiology team lead in the Mycotic Diseases Branch and then shortly after assumed the role of deputy chief.

Dr. Chiller received his bachelor's degree from Dartmouth College and his medical and public health degrees from Tulane University. He completed a residency in internal medicine at University of Texas Southwestern, and then worked as an attending physician in HIV medicine. He completed a fellowship in infectious diseases and mycotics at Stanford University and then joined CDC to train in infectious disease epidemiology as an Epidemic Intelligence Service (EIS) officer in the Foodborne and Diarrheal Diseases Branch.

Dr. Chiller is board certified in infectious diseases and is a faculty member in the Division of Infectious Diseases at the Emory School of Medicine. He practices infectious diseases at the Veterans Affairs Hospital in Atlanta. He has authored numerous articles and book chapters and given many lectures on public health surveillance and infectious diseases. Dr. Chiller is fluent in Spanish, French, and German.

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