Infectious Disease Alert Updates
Meningitis Diagnostics on Fire!
SOURCE: FDA News Release. http://www.fda.gov/NewsEvents/
Newsroom/PressAnnouncements/ ucm466360.htm.
I read this press release with delight, especially in light of a current clinical dilemma. A 23-year-old, previously health young woman was admitted just last week with acute meningitis, with 1 day of headache, nausea and vomiting, blurred vision, altered mental status, and meningismus. She had returned from a trip to Scotland with her mother two days earlier; that same evening, she had done some heavy partying at the bar with girlfriends for her birthday. Her mother thought her initial symptoms were from a hangover until she clearly worsened and was brought to the emergency department (ED). Her cerebrospinal fluid (CSF) was remarkable for a white cell count of 12,400, a protein of 763, and a glucose of 3. She began receiving empiric antimicrobials with IV vancomycin and ceftriaxone within 50 minutes of presentation to the ED, and a lumbar tap was performed. Her blood and CSF cultures remained negative, and imaging was unremarkable. Parenterally administered ampicillin 2 g Q4 hours was added to her regimen. After 5 days of steady clinical improvement and diminishing peripheral white blood count (24K → 16K), ampicillin was discontinued. Within 48 hours, her condition worsened, with increasing headache, nausea, dizziness, and increased white blood cells (WBC) to 24.9 cells/mm3. Repeat blood cultures, urinalysis, and radiographic studies were unremarkable. Now what?
The U.S. Food and Drug Administration gave de novo clearance on October 8 for the first CSF diagnostic “meningitis panel,” designed to simultaneously detect multiple nucleic acid targets for multiple pathogens causing central nervous system (CNS) infection. The BioFire FilmArray Meningitis/Encephalitis (ME) Panel (bioMerieux, Marcy-l’Etoile, France) is designed to rapidly (within 60 minutes) detect 14 different viral, bacterial, and yeast pathogens. After injection of hydration solution and the CSF sample into a packet, the instrument extracts and purifies nucleic acid in the sample, and then performs a nested multiplex PCR. The organism is identified by examination of the generated end-point melting curve, and the instrument automatically generates a report.
Table. Target Organisms
Bacteria
- Escherichia coli K1
- Haemophilus influenzae
- Listeria monocytogenes
- Neisseria meningitidis
- Streptococcus agalactiae
- Streptococcus pneumoniae
Viruses
- Cytomegalovirus
- Enterovirus
- Herpes simplex virus 1
- Herpes simplex virus 2
- Human herpesvirus 6
- Human parechovirus
- Varicella zoster virus
Fungus
- Cryptococcus neoformans/gattii
The assay was validated in a prospective study of CSF samples taken from 1560 patients with suspected meningitis/encephalitis, and the results were compared with those of standard methods, including cultures. Also evaluated were 150 test CSF samples from patients with recognized bacterial meningitis based on positive culture results, as well as 425 CSF samples “spiked” with microorganisms at varying concentrations. There was a high degree of agreement between the results of the FilmArray ME Panel and the conventional methods.
The test requires only 200 microliters of CSF. Despite its anticipated utility, the panel may generate some false-negative and false-positive results, and, similar to current PCR tests on CSF, may be overly sensitive, detecting low-grade up-regulation of HSV and VSV in CSF specimens of uncertain significance. In addition, the assay does not detect some organisms of interest, especially in immunocompromised hosts, such as EBV and JCV. Despite these limitations, this assay is bound to improve our ability to more rapidly detect bacterial and viral CNS pathogens, allowing for appropriate isolation, targeted therapy, and improvement in predicting outcomes. The FDA cautions that conventional test methods and cultures should still be performed in conjunction with this assay.
The assay is manufactured by a small company in Salt Lake City, UT, called BioFire Diagnostics, which merged with bioMerieux in January 2014. The BioFire website states that they began their search for better diagnostic tests “in a corner of an Idaho potato equipment facility.” In addition to the CNS panel, they are working on a blood panel, a gastrointestinal panel, and a comprehensive respiratory panel for the detection of 20 viral and bacterial targets.
Meningitis Diagnostics
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