What are the diagnostic tests for Neisseria (N.) meningitis?

Diagnostic Tests for Neisseria Meningitidis

The most important diagnostic tests for N. meningitidis infection are CSF Gram stain, CSF culture, and PCR, with PCR having the highest sensitivity (91-100%) especially when antibiotics have been administered prior to testing. 1

Primary Diagnostic Approach

CSF Analysis

• Lumbar Puncture: Essential first step for all patients with suspected meningitis unless contraindicated 2

  • Contraindications requiring CT before LP: 2
    • Immunocompromised state
    • History of CNS disease
    • New onset seizure within 1 week
    • Papilledema
    • Abnormal level of consciousness
    • Focal neurologic deficits

• CSF Characteristics in Bacterial Meningitis: 2

  • Elevated opening pressure (200-500 mm H₂O)
  • Cloudy appearance
  • Elevated WBC count (1,000-5,000 cells/mm³, range 100-110,000)
  • Neutrophil predominance (80-95%)
  • Low glucose (<40 mg/dL in 50-60% of cases)
  • CSF:serum glucose ratio <0.4
  • Elevated protein

Specific Tests for N. meningitidis

1. Gram Stain 2, 1

   • Sensitivity: 75% for N. meningitidis
   • Specificity: 97% for bacterial meningitis
   • Factors affecting sensitivity:
     • Bacterial concentration (25% positive at 10³ CFU/mL, 97% at >10⁵ CFU/mL)
     • Prior antibiotic use reduces sensitivity by ~20%
     • Cytospin techniques can increase sensitivity up to 100-fold
   • Appearance: Gram-negative diplococci

2. CSF Culture 2, 1

   • Sensitivity: 82% for N. meningitidis without prior antibiotics
   • Gold standard for definitive identification
   • Limitations: Takes up to 48 hours for results
   • Allows for antibiotic susceptibility testing

3. PCR 2, 1

   • Sensitivity: 91-100% for N. meningitidis
   • Specificity: 96%
   • Advantages:
     • Remains positive after antibiotic administration
     • Rapid results compared to culture
     • Can detect non-viable organisms
   • Clinical utility: Particularly valuable when antibiotics have been administered prior to testing

4. Latex Agglutination 2, 1

   • Sensitivity: 22-93% for N. meningitidis
   • Specificity: 99.4%
   • Not routinely recommended due to limited incremental value over Gram stain and culture
   • May be useful in patients pretreated with antibiotics with negative Gram stain and culture

5. Blood Cultures 2

   • Sensitivity: 40-60% for N. meningitidis
   • Should always be obtained before antibiotic administration

Diagnostic Algorithm

1. Immediate steps:

   • Assess for contraindications to immediate LP
   • If contraindications present, obtain blood cultures and start empiric antibiotics, then perform CT followed by LP if safe
   • If no contraindications, perform immediate LP

2. CSF testing sequence:

   • Gram stain (most rapid test)
   • Culture (gold standard)
   • PCR (especially if antibiotics given)
   • Consider latex agglutination only if Gram stain negative and antibiotics given prior to LP

3. Interpretation:

   • Positive Gram stain showing gram-negative diplococci strongly suggests N. meningitidis
   • Positive culture confirms diagnosis
   • Positive PCR confirms diagnosis even with negative culture

Important Considerations

• Prior antibiotic administration significantly reduces the yield of Gram stain and culture but has less impact on PCR 2, 1

• Distinguishing features: N. meningitidis may be difficult to distinguish from other Neisseria species or Moraxella catarrhalis on microscopy alone 1

• Timing is critical: Antibiotics should be administered within one hour of presentation if meningitis is suspected, regardless of whether imaging is performed before LP 2

• Avoid diagnostic delays: Do not delay antibiotic administration for diagnostic testing in suspected cases 2

• Pitfall: Relying solely on latex agglutination has poor sensitivity (7%) in culture-negative meningitis 2

By following this diagnostic approach, clinicians can rapidly identify N. meningitidis infection, allowing for prompt targeted therapy and improved patient outcomes.