What labs and tests are recommended for diagnosing and managing meningitis?

Laboratory Evaluation for Meningitis

Lumbar puncture with comprehensive CSF analysis is the cornerstone of meningitis diagnosis and should include opening pressure, cell count with differential, glucose (with concurrent plasma glucose), protein, lactate, Gram stain, culture, and PCR testing for pathogens. 1, 2

Pre-Lumbar Puncture Considerations

Delay LP if any of these features are present: 1

• Signs of severe sepsis or rapidly evolving rash
• Respiratory or cardiac compromise
• Anticoagulant therapy or known thrombocytopenia
• Infection at the LP site
• Focal neurological signs (requires neuroimaging first)
• Papilloedema (inability to see fundus is NOT a contraindication)
• Continuous or uncontrolled seizures (requires neuroimaging first)
• GCS ≤12 (requires neuroimaging first, though LP may be safe at lower consciousness levels)

Obtain blood cultures before or concurrent with LP, as they are positive in 71% of cases when meningitis occurs without CSF pleocytosis and can be the only positive diagnostic test. 3

Essential CSF Studies

Immediate Analysis Required:

Opening Pressure 1, 2

• Must be measured (unless sitting position used, which artificially elevates pressure)
• Typically elevated >20 cm CSF in bacterial meningitis

Cell Count with Differential 1, 2

• Bacterial: typically >100 cells/mm³ with neutrophil predominance, though 10% have <100 cells/mm³ early in disease 1
• Viral: typically 5-1000 cells/mm³ with lymphocyte predominance (though neutrophils may predominate early in enteroviral disease) 1
• Critical pitfall: Absence of pleocytosis does NOT exclude meningitis—bacterial meningitis can occur with normal CSF white cell count, particularly early in disease or in immunocompromised patients 3

CSF Glucose with Simultaneous Plasma Glucose 1, 4

• CSF:plasma glucose ratio is the most precise single indicator for bacterial meningitis 4
• Ratio <0.36 has 93% sensitivity and specificity for bacterial meningitis 1, 4
• If plasma glucose unavailable: CSF glucose >2.6 mmol/L unlikely to be bacterial meningitis 1
• Normal ratio is approximately 0.66 (two-thirds) 1

CSF Protein 1

• CSF protein <0.6 g/L makes bacterial meningitis unlikely 1
• Elevated in bacterial meningitis, normal to mildly elevated in viral meningitis 1, 2

CSF Lactate 1

• 93% sensitivity and 96% specificity for distinguishing bacterial from viral meningitis if obtained BEFORE antibiotics 1
• Cutoff of 35 mg/dL has best sensitivity 1
• Sensitivity drops to <50% after antibiotic administration 1
• High negative predictive value makes it useful to rule out bacterial meningitis and guide antibiotic discontinuation 1

Gram Stain 1

• Sensitivity 50-99% (organism and prior antibiotic dependent), specificity 97-100% 1
• Cytospin centrifugation increases yield 1

Culture 1

• Gold standard with 70-85% sensitivity when no prior antibiotics given 1
• CSF may sterilize within 2 hours for meningococci, 4 hours for pneumococci after antibiotic administration 1
• CSF analysis may still be diagnostically helpful up to 48 hours after starting antibiotics 1

PCR Testing 1, 2, 5

• Sensitivity 87-100%, specificity 98-100% 1, 2
• Especially valuable after antibiotic administration 1, 2, 5
• Multiplex PCR platforms can detect multiple pathogens simultaneously 1, 5
• Particularly useful in S. pneumoniae meningitis with prior antibiotics—four of five patients with exclusively positive PCR results had received antibiotics before LP 5
• 16S ribosomal RNA PCR available if pathogen-specific PCR negative, though lower specificity 1

Volume Requirements

Collect at least 22 mL of CSF from adults to ensure adequate volume for all necessary tests, as CSF is produced at approximately 15 mL/hour. 1

Additional Blood Tests

Blood Cultures 3

• Perform in all suspected meningitis cases
• Positive in 71% of culture-proven meningitis cases, even when CSF shows no pleocytosis 3

Plasma Glucose 1, 4

• Essential for calculating CSF:plasma glucose ratio, the most accurate single predictor of bacterial meningitis 4

Special Circumstances

Nasopharyngeal Swabs for Meningococcal Disease 1

• Positive in up to 50% of meningococcal disease cases
• May remain positive after blood/CSF cultures sterilize with antibiotics 1
• Important for surveillance and vaccine coverage determination when PCR-only diagnosis made 1
• Do NOT perform for pneumococcal disease (multiple strains carried asymptomatically, unclear relationship to invasive strain) 1

Traumatic LP Correction 1

• Use 1:1000 correction factor (1 WBC per 1000 RBCs) to adjust for blood contamination 1

Common Pitfalls to Avoid

• Never exclude meningitis based solely on normal CSF cell count—bacterial meningitis occurs without pleocytosis in documented cases, with 31% mortality in bacterial cases 3
• Do not rely on CSF glucose alone without plasma glucose—the ratio is far more accurate than isolated CSF glucose 4
• Do not skip CSF lactate if LP performed before antibiotics—it has superior diagnostic accuracy and can guide safe antibiotic discontinuation 1
• Do not delay antibiotics waiting for LP if contraindications exist—LP remains diagnostically useful for days after antibiotic initiation 1
• Lymphocytic predominance does NOT exclude bacterial meningitis (occurs with Listeria and partially treated bacterial meningitis) 1
• Neutrophilic predominance does NOT confirm bacterial meningitis (occurs early in enteroviral meningitis) 1