Meningitis and parameningeal infections are extremely rare complications of epidural injection, with few cases reported.[1–3] Most often these infections are bacterial; rarely is a postepidural injection meningitis case caused by fungi, and when present, fungal infection is often diagnosed only after a patient fails to improve on antibiotic therapy. Diagnosis of fungal meningitis, particularly in cases caused by molds, is difficult because traditional diagnostic methods such as culture have a low yield.[4–6] Molecular methods such as polymerase chain reaction have been useful for detection in some cases, but currently remain in use only as research tools.
The clinical presentation of fungal meningitis is often indolent, with few patients displaying the classic meningeal signs of bacterial meningitis. Early in this outbreak, many patients with meningitis had only a few mild symptoms, but had CSF pleocytosis. Additionally, some of these patients either presented with, or later developed, a stroke in the posterior circulation (which supplies the cerebellum, midbrain, and brainstem), a finding described in one prior case series of fungal meningitis. Clinicians should be aware of the atypical presentation of meningitis in this outbreak, and should consider performing lumbar puncture if patients have mild symptoms and have received a steroid injection originating from one of the three implicated lots of MPA. Early identification and treatment of patients with fungal infections might reduce the risk for serious complications, such as stroke or death. It is possible that the lower case-fatality rate reported here compared with other case series might have resulted from intensive patient notification and earlier diagnosis and therapy; further investigation is needed.
Close follow-up of these patients is needed to understand important clinical questions, such as the optimal medications, dosage, and duration of treatment. To provide guidance on these important clinical issues, CDC, in consultation with experts in the diagnosis and treatment of fungal infections, has drafted interim treatment guidelines for infections associated with this outbreak. Current recommendations for treatment of central nervous system and parameningeal infections include consultation with an infectious disease physician and initiation of empiric antifungal therapy with high dose voriconazole and liposomal amphotericin B. Treatment duration is likely to be prolonged, on the order of months, and will need to be tailored to individual patients. Routine use of adjuvant steroids or intrathecal amphotericin B in treatment and postexposure prophylaxis or screening of asymptomatic persons by lumbar puncture currently are not recommended. These recommendations are subject to change as more information becomes available.
As of October 6, all products manufactured since January 1, 2012, have been recalled by NECC and should not be used. The FDA and Massachusetts Board of Registration in Pharmacy investigation into the NECC facility is ongoing and includes microbiologic testing of unopened vials of the three lots of MPA as well as additional NECC products. If not already completed, providers should contact all patients exposed to any of the three lots of MPA recalled on September 26 to inquire about symptoms. Patients who received epidural injection with medication from any of the three lots of MPA and who have symptoms of meningitis or posterior circulation stroke should be referred for diagnostic lumbar puncture, if not contraindicated. Patients with signs or symptoms of parameningeal infection or peripheral joint infection (e.g., increasing pain, redness, or swelling at the injection site) should be referred for diagnostic evaluation, which might include aspiration of fluid collections or joint aspiration. Although available preliminary data demonstrate incubation periods ranging from 4 to 42 days, the maximum incubation period for this infection is not known; therefore, asymptomatic but exposed patients should remain vigilant for symptoms and seek medical attention should symptoms develop. More guidance for patients and clinicians, including interim treatment guidelines, is available at https://www.cdc.gov/hai/outbreaks/meningitis.html.
Multistate Meningitis Outbreak Response Team: Doug Kernodle, MD, April C. Pettit, MD, Kathy Wilkerson, and the Fungal Infection Team, Vanderbilt Univ Medical Center. Carol A. Rauch, MD, Jonathan E. Schmitz, MD, Vanderbilt Univ School of Medicine. Megan Casey, MPH, Allegheny County Health Dept. Srihari Seshadri, MBBS, Barren River District Health Dept. Jon Rosenberg, MD, California Dept of Public Health. Stephanie R. Black, MD, Alicia Siston, PhD, Chicago Dept of Public Health. Michael O. Vernon, DrPh, Cook County Dept of Public Health. Wendy Chung MD, Dallas County Health and Human Svcs. Carina Blackmore, DVM, Tricia Foster, MPH, Florida Dept of Health. Christine Hahn, MD, Kathy Turner, PhD, Idaho Div of Public Health. Judith Conway, Kate Kelly-Shannon, Matthew Roberts, MPH, Kenneth Soyemi, MD, Illinois Dept of Public Health. Pamela Pontones, MA, Joan Duwve, MD, Indiana State Dept of Health. Kraig Humbaugh, MD, Kentucky Dept for Public Health. Clara Tyson, MSN, Los Angeles County Dept of Public Health. Amy Reilly, Meghan Gumke, Nathan Grossman, MD, Marion County Health Dept. Madeleine Biondolillo, MD, James D. Coffey, Jim Collins, MPH, Joseph Coyle, MPH, Kevin Cranston, Alfred DeMaria, MD, Jean Pontikas, Iyah Romm, Massachusetts Dept of Public Health. David Blythe, MD, Ruth Thompson, Lucy Wilson, Maryland Dept of Health and Mental Hygiene. Craig McMilllan, MD, Mendocino County Dept of Public Health. Jay Fiedler, MS, Jennie Finks, DVM, Shannon Johnson, MPH, Michigan Dept of Community Health. Kathryn Como-Sabetti, MPH, Richard Danila, PhD, Aaron DeVries, MD, Jane Harper, Ruth Lynfield, MD, Minnesota Dept of Health. Ihsan Azzam, MD, PhD, Patricia Rowley, MPH, Nevada Dept of Health and Human Svcs. Sharon Alroy-Preis, MD, New Hampshire Dept of Health and Human Svcs. Barbara Carothers, Barbara Montana, MD, Christina Tan, MD, Laura Taylor, PhD, New Jersey Dept of Health. Jean-Marie Maillard, MD, Zack Moore, MD, North Carolina Dept of Health and Human Svcs. Mary DiOrio, MD, Ohio Dept of Health. Mary Powell, MPH, Pennyrile District Health Dept. Virginia Dato, MD, Elizabeth Hunt, MPH, Erica E. Smith, MD, Lauren Torso, MPH, Pennsylvania Dept of Health. Caroline Banis, Dan Drociuk, MD, South Carolina Dept of Health and Environmental Control. Brynn E. Berger, MPH, Meredith L. Kanago, MSPH, Jea Young Min, PharmD, David Reagan, MD, PhD, Brenda Rue, Jennifer Ward, MS, Anita Kurian, DrPh, Tarrant County Public Health. Neil Pascoe, Texas Dept of State Health Svcs. Karen Haught, MD, Tulare County Dept of Public Health. Katie Kurkjian, DVM, Margaret Tipple, MD, David Trump, MD, Virginia Dept of Health. Danae Bixler, MD, Carrie A. Thomas, PhD, West Virginia Bur for Public Health. Susann E. Ahrabi-Fard, MS, Richard T. Heffernan, MPH, James J. Kazmierczak, DVM, Wisconsin Div of Public Health. Aaron Fleischauer, PhD, James Lando, MD, Jevon McFadden, MD, Doug Thoroughman, PhD, Tom Torok, MD, Career Epidemiology Field Officers, Office of Public Health Preparedness and Response; Tom Chiller, MD, Angela Cleveland, MPH, Martha Iwamoto, MD, Ana Litvenseva, PhD, Shawn Lockhart, PhD, Agam Rao, MD, Monika Roy, MD, Jonathan Yoder, MPH, Div of Foodborne, Waterborne, and Environmental Diseases, Shelley Magill, MD, PhD, Div of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Diseases; Anne Purfield, PhD, Jane Baumblatt, MD, Amanda Beaudoin, PhD, Jennifer Espiritu, MD, Stephanie Griese, MD, Michael Gronostaj, MD, Christina Mikosz, MD, Maria Said, MD, Alice Shumate, MD, EIS officers, CDC.
Morbidity and Mortality Weekly Report. 2012;61(41):839-842. © 2012 Centers for Disease Control and Prevention (CDC)