What laboratory tests should be done on cerebrospinal fluid (CSF) to rule out meningitis?

Laboratory Tests for Diagnosing Meningitis in Cerebrospinal Fluid

A comprehensive panel of CSF tests including cell count with differential, glucose, protein, Gram stain, culture, and PCR should be performed to rule out meningitis. 1

Essential CSF Tests for Meningitis Diagnosis

First-line Tests (Must be performed)

• CSF appearance: Assess for turbidity, cloudiness, or purulence (suggestive of bacterial meningitis) 1
• Cell count with differential:
  • Bacterial meningitis typically shows >100 cells/μL with neutrophil predominance
  • Viral meningitis typically shows 5-1000 cells/μL with lymphocyte predominance
  • Tuberculous/fungal meningitis typically shows 5-500 cells/μL with lymphocyte predominance 1
• Glucose measurement:
  • Very low in bacterial meningitis (<2.6 mmol/L)
  • CSF:plasma glucose ratio <0.36 has 93% sensitivity for bacterial meningitis 1
• Protein measurement:
  • Elevated in bacterial meningitis (>0.6 g/L)
  • Markedly elevated in tuberculous meningitis 1
• Gram stain: Rapid identification with 60-90% sensitivity and 97% specificity for bacterial meningitis 1
• Culture: Gold standard for bacterial identification (70-85% sensitivity if antibiotics not given prior) 1

Second-line Tests (Based on clinical suspicion)

• CSF lactate: High sensitivity (93%) and specificity (96%) for distinguishing bacterial from viral meningitis if measured before antibiotics; cutoff of 35 mg/dL 1
• PCR testing:
  • For bacterial pathogens: 87-100% sensitivity, 98-100% specificity
  • Particularly valuable when antibiotics given before lumbar puncture 1
  • Can detect common pathogens (S. pneumoniae, N. meningitidis, H. influenzae, S. agalactiae, L. monocytogenes) 1, 2
  • For viral pathogens: HSV, VZV, enterovirus 1
• 16S ribosomal RNA PCR: For broad bacterial detection when specific pathogens aren't identified 1

Diagnostic Algorithm

1. Collect CSF (ideally before antibiotics)
2. Perform immediate tests:
   • Visual inspection for appearance
   • Gram stain (most rapid diagnostic test)
   • Cell count with differential
   • Glucose and protein measurements
   • Lactate measurement (if available)
3. Send for culture (results in 24-48 hours)
4. Order PCR testing based on clinical suspicion and initial results

Interpretation of Results

Parameter	Bacterial	Viral	Tuberculous	Fungal
Appearance	Turbid/cloudy	Clear	Clear/cloudy	Clear/cloudy
WBC (cells/μL)	>100	5-1000	5-500	5-500
Cell type	Neutrophils	Lymphocytes	Lymphocytes	Lymphocytes
Protein (g/L)	Elevated	Mildly elevated	Markedly elevated	Elevated
Glucose	Very low	Normal/slightly low	Very low	Low
CSF:plasma glucose	<0.36	Normal/slightly low	Very low	Low

Important Considerations

• Timing matters: CSF sterilization occurs within 2-4 hours of antibiotic administration, but analysis may still be helpful up to 48 hours after starting antibiotics 1
• False negatives: Prior antibiotic therapy can reduce Gram stain sensitivity by ~20% 1
• Sample volume: Larger volumes (10-15 mL) improve detection rates, especially for tuberculous or fungal meningitis 3
• Cytospin technique: Can increase bacterial detection on Gram stain up to 100-fold 1

Common Pitfalls to Avoid

1. Delaying lumbar puncture: If meningitis is suspected, perform LP promptly (unless contraindicated)
2. Not checking plasma glucose: Always measure plasma glucose simultaneously to calculate CSF:plasma glucose ratio
3. Insufficient sample volume: Collect adequate CSF volume (ideally 10-15 mL) for all required tests
4. Relying on a single test: No single test has 100% sensitivity; use multiple tests in combination
5. Misinterpreting results after antibiotics: Pre-treatment with antibiotics can alter CSF findings, particularly reducing culture yield and shifting cell differential from neutrophilic to lymphocytic

By following this comprehensive approach to CSF testing, clinicians can rapidly diagnose or exclude meningitis, identify the causative pathogen, and initiate appropriate treatment to reduce morbidity and mortality.