Cerebrospinal Fluid Analysis in Meningitis
Cerebrospinal fluid (CSF) analysis remains the cornerstone diagnostic procedure for meningitis, with the CSF leukocyte count being the most reliable diagnostic parameter for differentiating bacterial meningitis from other diagnoses. 1
Timing of Lumbar Puncture
- Perform lumbar puncture (LP) as soon as possible in suspected meningitis
- Do not delay antibiotics for LP - administer antibiotics within one hour of arrival if meningitis is suspected 2
- LP can still yield positive cultures if performed within 4 hours of antibiotic administration 3
- CSF sterilization may occur within 2 hours for meningococci and 4 hours for pneumococci 1
Contraindications to Immediate LP
LP should be delayed (but antibiotics should not be delayed) if any of the following are present:
- Signs of severe sepsis or rapidly evolving rash
- Respiratory or cardiac compromise
- Anticoagulant therapy/thrombocytopenia
- Infection at LP site
- Focal neurological signs
- Papilledema
- Continuous or uncontrolled seizures
- Glasgow Coma Scale ≤12 1
CSF Collection and Analysis
Collection
- Collect adequate volume (at least 22 mL can be safely removed from adults) 1
- Measure opening pressure (typically elevated >20 cm CSF in bacterial meningitis) 1
- Use pre-prepared LP packs with all necessary sampling tubes to increase diagnostic yield 1
Essential CSF Tests
- Cell count and differential
- Protein and glucose concentrations
- Gram stain
- Culture 1
Additional Tests
- PCR for bacterial and viral pathogens (especially if antibiotics given before LP)
- CSF lactate (good sensitivity/specificity for differentiating bacterial from aseptic meningitis)
- Blood cultures (should be collected before antibiotics) 1
Interpretation of CSF Findings
Typical Patterns:
| Parameter | Bacterial Meningitis | Viral Meningitis | Fungal Meningitis |
|---|---|---|---|
| Appearance | Turbid | Clear | Clear/slightly turbid |
| WBC count | 1000-5000/mm³ | 50-1000/mm³ | 40-400/mm³ |
| Cell type | Predominantly neutrophils | Predominantly lymphocytes | Predominantly lymphocytes |
| Protein | High (>100 mg/dL) | Normal/slightly elevated | Elevated |
| Glucose | Low (<40 mg/dL) | Normal/slightly low | Low |
| CSF:blood glucose ratio | <0.4 | >0.5 | <0.5 |
Important Caveats
- 10% of bacterial meningitis cases may have fewer than 100 cells/mm³ 1
- Early viral meningitis may have neutrophil predominance 1
- Partially treated bacterial meningitis may show lymphocyte predominance 1
- Meningitis can occur in the absence of pleocytosis, particularly with bacterial pathogens 4
Diagnostic Methods
Gram Stain
- Sensitivity varies by organism: 90% for S. pneumoniae, 86% for H. influenzae, 75% for N. meningitidis, 50% for gram-negative bacilli, and ~33% for L. monocytogenes 1
- Specificity is approximately 97% 1
- Yield decreases by ~20% if antibiotics given before LP 1
CSF Culture
- Gold standard for diagnosis (70-85% sensitive without prior antibiotics) 1
- Positive in 73% of cases when LP performed within 4 hours of antibiotics vs. only 11% when performed later 3
- No positive cultures found when LP performed >8 hours after antibiotics 3
PCR Testing
- Highly recommended if antibiotics given before LP
- Sensitivity 87-100% and specificity 98-100% 1
- Particularly valuable for viral pathogens and partially treated bacterial meningitis
- 16S ribosomal RNA PCR can detect almost all bacteria but has lower specificity 1
Other Tests
- CSF-CRP has shown 95% sensitivity and 86% specificity for differentiating bacterial from aseptic meningitis in infants 5
- Latex agglutination has limited incremental value and is not routinely recommended 1
Treatment Approach
Empiric Antibiotics
- Start immediately after blood cultures (or after LP if performed promptly)
- Adults <60 years: Ceftriaxone 2g IV q12h or Cefotaxime 2g IV q6h plus Vancomycin
- Adults ≥60 years or immunocompromised: Add Ampicillin 2g IV q4h (for Listeria coverage) 1, 2
Adjunctive Therapy
- Dexamethasone 10mg IV q6h for 4 days (start before or with first antibiotic dose) 2
Special Considerations
- Consider repeat LP if initial CSF is normal but clinical suspicion remains high 6
- In cases with negative cultures but strong clinical suspicion, molecular diagnostic tests should be pursued 3
- If CT scanning is needed before LP, do not delay antibiotics - administer before imaging 1
Remember that meningitis is a medical emergency, and treatment should never be delayed for diagnostic procedures. The most important factor affecting outcome is the prompt administration of appropriate antibiotics.