Disclosure: Dr. Talan is a paid consultant for BioFire Diagnostics and has advised on the development of new assays and collaborative research on meningitis and septic arthritis.

Back in the 1980s, texts stated that the administration of antibiotics should not be delayed beyond 30 minutes in cases of suspected bacterial meningitis. Doctors who weren’t fast enough were being sued.

This never seemed practical or possible. In fact, my very first research study from that time assessed time from triage to antibiotics for 122 ED patients admitted for presumed bacterial meningitis.¹

We found that the median time to the first dose of antibiotics was three hours and that only one patient received antibiotics within 30 minutes. We also found that diagnosis was not always obvious based on so-called classic symptoms. The reality was that patients presented with a range of complaints compatible with not only meningitis but also other diagnoses. The process of sorting that out could take time. “Delays” came not from laziness or lunch breaks but from the necessity of a proper diagnostic investigation.

Decades later, the diagnostic pathway for meningitis has changed little. The only significant change is the ability to obtain a pre-lumbar puncture (LP) CT of the brain nearly instantaneously. This lessens the angst of deferring antibiotics until the post-CT LP is completed, allowing for unambiguous bacterial identification and susceptibly testing.

However, we’ve recently seen an advance in the diagnostic pathway for meningitis as more hospital labs offer rapid molecular testing of the cerebrospinal fluid (CSF) for emergency department use. The BioFire FilmArray Meningitis/Encephalitis Panel detects nucleic acids from common bacterial and viral pathogens with a high degree of accuracy, providing results within one to two hours (see Table 1).² Currently, the BioFire CSF assay is the only FDA–approved molecular test available that detects a full range of pathogens. 

There are several test features that will improve management of ED patients with suspected meningitis.

Confident Diagnoses Reduces Hospital Admissions

Viral meningitis is far more common than bacterial meningitis. Because of the imperfect accuracy of standard CSF results in discriminating bacterial versus viral causes (particularly for patients pretreated with antibiotics), patients with a low likelihood of bacterial meningitis are often hospitalized for observation while awaiting final CSF culture results. The BioFire assay can confirm viral meningitis—most commonly due to enterovirus (EV) or other viruses. This can allow confident ED discharge. (Little-known fact: As many as 30 percent of patients found to have EV meningitis by molecular testing have normal CSF parameters.) Human herpesvirus-6 (roseola), the most common viral cause of childhood febrile seizures, is also included in the assay. The panel does not test for all possible viral pathogens (eg, flu, HIV), which account for a small number of cases.

Ruling in viral causes is one thing, but what about ruling out bacterial ones? Even when the test does not affirmatively identify a virus, in a clinically stable, non-immunocompromised patient presenting with acute symptoms, a negative CSF molecular panel should be reassuring enough to permit ED discharge, provided the patient received no prior antibiotics and has low-risk CSF parameter findings. The BioFire assay has near-perfect sensitivity to rule out typical bacterial meningitis pathogens. Of course, there are also noninfectious causes of meningitis to consider (eg, cancer, lupus, medication reactions, etc.) and symptoms of viral meningitis can last weeks. Patients should have close primary care follow-up to make sure that subacute but nonemergent problems do not go undiagnosed.

Test Can Remain Positive After Antibiotic Pretreatment

Table1: BioFire Film Array
Meningitis/Encephalitis Panel

Whether you get anxious while awaiting head CT results and slip in a dose of ceftriaxone or have a patient who has taken oral antibiotics, bacterial DNA can still be detected in many (not all) cases by the BioFire assay, even though some bacteria may not grow on traditional media.³ Although antibiotic susceptibilities are not currently available, rapid bacterial identification, sometimes even in the face of prior antibiotics, allows more targeted treatment and, in the case of meningococcal infection, public health notification and close-contact prophylaxis or, alternatively, reassurance to the staff.

The BioFire assay has limitations. First, it does not test for some common causes of encephalitis, like West Nile or the emerging Eastern equine encephalitis virus. As with other polymerase chain reaction assays, the test may be negative in early herpes simplex virus encephalitis. Second, while false negatives are rare for typical bacteria in non-pretreated patients, false positives occasionally occur, such as with pneumococcus, which is thought to be due to specimen contamination during specimen handling (your sterile technique counts). As with any test, the result should be correlated with all available epidemiological, clinical, and lab data. Third, caution should be exercised in patients with subacute symptoms since, for example, tuberculosis and fungi other than Cryptococcus are not included in the panel. Caution should also be exercised in immunocompromised patients, for whom the risk of misdiagnosis is higher and a greater range of pathogens must be considered. For example, the current standard cryptococcal antigen test appears to be more sensitive for this pathogen than the BioFire test. Fourth, the assay does not test for staphylococcal species and gram-negative pathogens that are sometimes seen in neurosurgery-related infections. Finally, the test is an additional expense—the manufacturer’s charge is $130 per cartridge after purchase of the FilmArray system (which can also run stat respiratory, pneumonia, gastrointestinal, and blood panels) for about $50,000. It is best targeted for stat use after standard CSF test results are back and diagnostic uncertainly remains.

Acknowledgement: Dr. Talan thanks his residents, Dr. Randy Lee and Dr. Cameron Harrison, for their review and suggestions on this article. 

Dr. Talan is professor of emergency medicine/medicine-infectious diseases at the David Geffen School of Medicine at UCLA in Los Angeles and the University of Iowa in Iowa City.

References

1. Talan DA, Guterman JJ, Overturf GD, et al. Analysis of the emergency department management of bacterial meningitis. Ann Emerg Med. 1989;18:856-862.
2. Leber Al, Everhart K, Balada-Llasat J-M, et al. Multicenter evaluation of BioFire FilmArray Meningitis/Encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol. 2016;54(9):2251-2261.
3. Mina Y, Schechner V, Savion M, et al. Clinical benefits of FilmArray meningitis-encephalitis PCR assay in partially-treated bacterial meningitis in Israel. BMC Infect Dis. 2019;19(1):713.