Diagnostic Approach to Rule Out Meningitis
To rule out meningitis, perform a lumbar puncture with CSF analysis including cell count with differential, protein, glucose (with simultaneous blood glucose), Gram stain, and culture—this remains the definitive diagnostic test, as CSF leukocyte count has the highest diagnostic accuracy (AUC 0.95) for differentiating bacterial meningitis from other diagnoses. 1
Clinical Assessment and Timing
When to Suspect Meningitis
The classic triad of fever, headache, and neck stiffness is commonly present, but no single clinical sign appears in all patients 1. Even in the absence of classic symptoms, CSF examination is strongly recommended when bacterial meningitis is suspected 1.
Critical Time-Sensitive Actions
- Initiate empiric antibiotics within one hour of presentation in suspected bacterial meningitis, regardless of whether cranial imaging or lumbar puncture has been performed 1
- Obtain blood cultures before administering antibiotics (positive in 40-90% depending on organism) 1
- Do not delay antibiotic therapy while awaiting diagnostic studies 1
Indications for CT Imaging Before Lumbar Puncture
Perform cranial CT before LP only in selected high-risk patients: 1
- Glasgow Coma Scale score <10 (severely altered mental status)
- Focal neurologic deficits
- New-onset seizures
- Severe immunocompromised state
- Papilledema
- Signs of severe sepsis or rapidly evolving rash
- Continuous or uncontrolled seizures
Important caveat: Inability to visualize the fundus is NOT a contraindication to LP 1. The risk of herniation from LP is difficult to establish causally, as brain herniation also occurs during the natural disease course 1.
CSF Analysis: Key Diagnostic Parameters
Primary Diagnostic Tests (Obtain in ALL Patients)
Strongly recommended tests: 1
- CSF leukocyte count and differential (most important single parameter)
- CSF protein concentration
- CSF glucose with simultaneous blood glucose
- CSF Gram stain
- CSF culture
CSF Findings That Rule Out Bacterial Meningitis
The following CSF parameters have high negative predictive value: 1, 2, 3
- CSF/blood glucose ratio >0.36 (93% sensitivity and specificity for ruling out bacterial meningitis) 1, 2
- CSF glucose >2.6 mmol/L (unlikely to be bacterial meningitis) 1
- CSF protein <0.6 g/L (unlikely to be bacterial disease) 1
- CSF lactate <35 mg/dL (<2 mmol/L) (93% sensitivity and 96% specificity for ruling out bacterial meningitis when antibiotics have not been given) 1, 4
Typical CSF Patterns by Etiology
| Parameter | Bacterial | Viral | Normal |
|---|---|---|---|
| WCC (cells/μL) | >100 (typically) | 5-1000 | <5 |
| Cell type | Neutrophils | Lymphocytes* | n/a |
| Protein (g/L) | Raised | Mildly raised | <0.4 |
| Glucose (mmol/L) | Very low | Normal/slightly low | 2.6-4.5 |
| CSF/plasma glucose ratio | Very low (<0.36) | Normal/slightly low | >0.66 |
| Appearance | Turbid, purulent | Clear | Clear |
*May be neutrophilic early in enteroviral meningitis 1
Microbiological Diagnostics
Gram Stain
- Sensitivity: 50-99% depending on organism and prior antibiotics 1
- Specificity: 97-100% 1
- Organism-specific sensitivity: S. pneumoniae 90%, N. meningitidis 70-90%, H. influenzae 50%, L. monocytogenes 33% 1
- Cytospin centrifugation increases yield up to 100-fold 1
CSF Culture
- Gold standard for diagnosis 1
- Sensitivity: 70-85% in untreated patients 1
- CSF sterilization occurs within 2 hours for meningococci and 4 hours for pneumococci after antibiotic administration 1, 5
- CSF analysis remains helpful up to 48 hours after starting antibiotics 1, 5
PCR Testing
When CSF culture is negative, PCR has additive diagnostic value: 1
- Sensitivity: 87-100% 1
- Specificity: 98-100% 1
- Remains positive even after antibiotic administration 5
- If organism-specific PCR is negative, 16S ribosomal RNA PCR can detect most bacteria (lower specificity) 1, 5
Latex Agglutination
- Not recommended except in large outbreak situations where rapid PCR is unavailable 1, 5
- Has been largely surpassed by PCR 1
Serum Markers
Serum procalcitonin (PCT) and C-reactive protein (CRP) can help differentiate bacterial from viral meningitis but cannot distinguish bacterial meningitis from other bacterial infections like sepsis: 1, 6
- Combined PCT and CSF protein has AUC 0.998 (100% sensitivity, 97.1% specificity) for bacterial meningitis 6
- PCT alone: AUC 0.951 6
- CSF protein alone: AUC 0.996 6
Critical Pitfalls to Avoid
Do not assume viral meningitis based solely on lymphocytic predominance—approximately 10% of bacterial meningitis presents with lymphocyte predominance, and partially treated bacterial meningitis commonly shows this pattern 1, 5
Meningitis can occur without pleocytosis—in rare cases (particularly immunocompromised patients), CSF WBC may be normal despite culture-proven bacterial meningitis 1, 8. If meningitis is suspected clinically, administer empiric antibiotics regardless of initial WBC count 8
Do not rely on negative CSF culture alone to exclude bacterial meningitis in partially treated patients—use PCR, blood cultures, and CSF parameters (glucose, protein, lactate) in combination 5
Blood cultures are critical adjuncts—positive in 71% of cases when CSF cultures are negative, particularly after antibiotic pretreatment 8
Consider nasopharyngeal swabs for meningococci—may be positive in up to 50% of patients even when blood and CSF cultures are negative after antibiotic treatment 1, 5
Algorithmic Approach to Rule Out Meningitis
- Clinical suspicion → Obtain blood cultures immediately
- Assess for CT indications (GCS <10, focal deficits, new seizures, severe immunocompromise)
- If present → Start antibiotics, then CT, then LP when safe
- If absent → Proceed directly to LP
- Perform LP → Send CSF for: cell count/differential, protein, glucose (with simultaneous blood glucose), Gram stain, culture, PCR
- Calculate CSF/blood glucose ratio:
- If antibiotics given before LP → Still perform LP (helpful up to 48 hours), add PCR testing, rely on CSF parameters and blood cultures 5