Can a patient still have meningitis if the BioFire (FilmArray) test on cerebrospinal fluid (CSF) is negative?

Negative BioFire Test on CSF Does Not Rule Out Meningitis

A negative BioFire FilmArray Meningitis/Encephalitis panel result on cerebrospinal fluid (CSF) does not definitively rule out meningitis, and patients may still have bacterial, viral, or fungal meningitis despite negative results. 1, 2

Understanding BioFire FilmArray Testing Limitations

• The BioFire FilmArray Meningitis/Encephalitis (ME) panel is a multiplex PCR test that can detect 14 common pathogens causing meningitis, but has inherent limitations in sensitivity that can lead to false-negative results 3
• PCR testing, including multiplex platforms like BioFire, has a sensitivity of 87-100% and specificity of 98-100%, meaning some cases will be missed 4
• Studies have shown that the BioFire ME panel may fail to detect pathogens identified by standard techniques, including West Nile virus and Histoplasma 1

Factors Affecting Test Sensitivity

• Low pathogen burden in CSF can lead to false-negative results, as demonstrated with cryptococcal meningitis where sensitivity drops to only 29% at low fungal burdens (0-99 CFU/mL) compared to 94% for higher burdens (≥100 CFU/mL) 2
• Prior antimicrobial therapy can reduce the detection of bacterial pathogens in CSF, potentially leading to false-negative results 4
• The panel only tests for specific pathogens and will miss uncommon or emerging pathogens not included in the panel 5

Clinical Decision Making with Negative BioFire Results

• CSF culture remains the gold standard for diagnosing bacterial meningitis, with diagnostic rates of 70-85% in cases where antibiotics have not been given prior to lumbar puncture 4
• When BioFire is negative but clinical suspicion remains high, additional testing should be considered:
  • Conventional CSF culture (which may detect organisms not included in the panel) 4
  • Pathogen-specific PCR tests for suspected organisms not covered by the panel 4
  • 16S ribosomal RNA PCR for bacterial pathogens that may be missed by targeted assays 4
  • Additional testing for tuberculosis, fungi, or other pathogens based on clinical presentation 5

Management Recommendations with Negative BioFire Results

• Empiric antimicrobial therapy should be continued in patients with clinical features suggestive of meningitis despite negative BioFire results, especially if CSF parameters are abnormal 4
• For suspected bacterial meningitis with negative BioFire results, recommended empiric therapy includes:
  • Ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours 4
  • Addition of ampicillin/amoxicillin 2g IV every 4 hours for patients aged 60 or over and immunocompromised patients (including those with diabetes or alcohol misuse) to cover Listeria monocytogenes 4
  • Consider vancomycin if penicillin-resistant pneumococci are suspected 4
• Duration of therapy should be guided by clinical response, CSF parameters, and results of additional diagnostic tests 6

Common Pitfalls to Avoid

• Prematurely discontinuing antimicrobial therapy based solely on a negative BioFire result when clinical suspicion remains high 6
• Failing to consider pathogens not included in the BioFire panel (such as tuberculosis, fungi, or rare bacterial causes) 2
• Not accounting for the timing of lumbar puncture in relation to symptom onset or antimicrobial administration, which can affect test sensitivity 4
• Overlooking the possibility of partially treated bacterial meningitis, which can present with lymphocytic predominance in CSF and negative molecular tests 4