Management of False Positive Streptococcus pneumoniae on BioFire Meningoencephalitis Panel
A positive S. pneumoniae result on the BioFire ME panel should be interpreted in the context of CSF parameters, clinical presentation, and culture results—if the CSF profile is normal (glucose >34 mg/dL, protein <120 mg/dL, WBC <100 cells/mm³) and the patient lacks clinical features of bacterial meningitis, the result is likely a false positive from nasopharyngeal carriage contamination and antimicrobial therapy should be discontinued. 1
Understanding the Clinical Context
The BioFire FilmArray ME panel has high sensitivity (100% for S. pneumoniae in most studies) but variable positive predictive value depending on the organism 2, 3. S. pneumoniae is asymptomatically carried in the nasopharynx, and PCR can detect DNA from colonizing strains that are not causing invasive disease 1. This is a critical distinction from N. meningitidis, where nasopharyngeal isolates often match invasive strains 1.
Key Diagnostic Algorithm
Step 1: Review CSF Parameters
Compare the CSF findings against established thresholds for bacterial meningitis 1:
- Glucose <34 mg/dL (99% certainty for bacterial meningitis) 1
- CSF:blood glucose ratio <0.23 (99% certainty for bacterial meningitis) 1
- Protein >120 mg/dL (99% certainty for bacterial meningitis) 1
- WBC >12,000 cells/mm³ (99% certainty for bacterial meningitis) 1
- Neutrophil count >11,000 cells/mm³ (99% certainty for bacterial meningitis) 1
If none of these criteria are met, the positive PCR result is highly likely to be false positive 1, 3.
Step 2: Assess Clinical Presentation
Evaluate for signs and symptoms of bacterial meningitis 1:
- Altered mental status
- Fever with nuchal rigidity
- Focal neurologic deficits
- Seizures
- Signs of increased intracranial pressure
A patient who is clinically well or improving without antibiotics is unlikely to have true bacterial meningitis 3.
Step 3: Correlate with Culture Results
- CSF culture remains the gold standard with 70-85% sensitivity in untreated patients 1
- Blood cultures should be obtained as they may be positive even when CSF culture is negative 1
- If cultures remain negative at 48-72 hours AND CSF parameters are normal, this strongly supports a false positive PCR 3
Management Recommendations
When to Treat as True Positive
Continue empirical antibiotics (ceftriaxone 2g IV q12h or cefotaxime 2g IV q6h) if 1:
- Any of the CSF parameters meet bacterial meningitis criteria above
- Clinical presentation consistent with bacterial meningitis
- Patient received antibiotics prior to lumbar puncture (PCR may be the only positive test) 4, 3
Notably, 27.4% of confirmed bacterial meningitis cases would have no pathogen identified without the BioFire panel, particularly in antibiotic-pretreated patients 3.
When to Consider False Positive
Discontinue antibiotics if ALL of the following are present 3:
- Normal CSF parameters (glucose, protein, cell count all within normal limits)
- Negative CSF Gram stain 1
- Negative CSF and blood cultures at 48-72 hours
- Patient clinically well or improving without antibiotics
- No prior antibiotic exposure before lumbar puncture
Critical Pitfalls to Avoid
Do not rely solely on PCR specificity statistics (98-100%) 1—these are calculated against culture, not clinical disease. The positive predictive value for S. pneumoniae varies from 48.9% to 100% depending on the clinical setting 3, 5.
S. agalactiae (Group B Streptococcus) has the highest false positive rate on the BioFire panel, accounting for one-third of false positives in one large study 3. However, S. pneumoniae false positives do occur, particularly when CSF parameters are normal 3.
Prior antibiotic administration is the most important confounder—it sterilizes CSF cultures within 2-4 hours but does not immediately clear bacterial DNA 1, 4. In this scenario, the combination of positive PCR with abnormal CSF parameters should be treated as true bacterial meningitis 4, 3.
Special Considerations
Multiplex PCR platforms should be evaluated by each laboratory before routine use, as recommended by UK guidelines 1. The BioFire panel demonstrated 100% specificity compared to culture in validation studies 2, 3, but real-world performance shows variable positive predictive values 3.
If uncertainty remains, err on the side of treating bacterial meningitis given the high mortality and morbidity of untreated disease 1. A short course of empirical antibiotics (48-72 hours) while awaiting culture results and clinical evolution is safer than premature discontinuation in ambiguous cases 3.