What is the recommended diagnostic workup and treatment for patients with suspected central nervous system (CNS) infections, including the use of cerebrospinal fluid (CSF) cultures?

CSF Cultures in CNS Infections: Diagnostic Approach

Core Diagnostic Testing

CSF culture remains essential for bacterial meningitis diagnosis and should be obtained alongside Gram stain, cell count with differential, glucose, and protein in all patients with suspected CNS infection. 1, 2

Standard CSF Panel

• Cell count with differential identifies inflammatory patterns: bacterial meningitis typically shows ≥2,000 WBCs/μL or ≥1,180 neutrophils/μL, while viral infections show lymphocytic pleocytosis (5-1,000 cells/μL) 2

• Glucose concentration <35 mg/dL or CSF-to-blood ratio <0.23 strongly suggests bacterial infection 2

• Protein concentration >220 mg/dL indicates infection or inflammation 2

• Gram stain has 60-80% sensitivity in untreated patients but drops to 40-60% after antibiotic administration 1

• Bacterial culture remains the gold standard for identifying causative organisms and guiding antimicrobial therapy 1

Critical Collection Requirements

• Collect ≥5 mL of CSF for standard testing; 8-10 mL improves sensitivity for mycobacterial and fungal cultures 1, 2

• Process within 30 minutes to prevent cellular degradation 2

• Do not refrigerate CSF as this compromises viability of fastidious organisms 1

• Discard the first tube for microbiology studies due to highest contamination risk 2

Blood Cultures Are Mandatory

Obtain 2-4 blood cultures before antibiotics in all suspected bacterial meningitis cases, as blood cultures are positive in 50-80% of bacterial meningitis and may be the only positive culture if antibiotics were given before lumbar puncture 1

When Culture Fails: Molecular Testing

PCR Multiplex Panels

Multiplex PCR demonstrates 96.3% sensitivity and 100% specificity compared to culture, with particular value in antibiotic-pretreated patients where culture sensitivity drops dramatically. 3, 4

• Enterovirus PCR has replaced viral culture with >95% sensitivity for viral meningitis/encephalitis 1

• HSV-1/HSV-2 PCR has >95% sensitivity and specificity for HSV encephalitis, far exceeding culture (<5% yield) 1, 2

• Bacterial PCR panels detect S. pneumoniae, H. influenzae, and N. meningitidis in culture-negative cases, especially after antibiotic exposure 3, 4

When to Use PCR

PCR is particularly valuable when:

• Antibiotics were administered before CSF collection 3, 4
• Gram stain and culture are negative but clinical suspicion remains high 1
• Viral encephalitis is suspected (HSV, enterovirus, VZV) 1, 2
• Immunocompromised patients require broader pathogen detection 1, 2

Immunocompromised Patients Require Expanded Testing

In immunocompromised patients, perform CSF culture plus cryptococcal antigen, AFB smear and culture, fungal culture, and PCR for HSV, VZV, CMV, EBV, and JC virus regardless of CSF cell count. 1, 2

• CSF may be acellular despite active infection in severely immunocompromised patients 1

• Cryptococcal antigen has >90% sensitivity and specificity, superior to India ink stain 1

• AFB culture sensitivity for tuberculous meningitis is only 25-70%, requiring large volumes (≥5 mL) and prolonged incubation 1

Chronic Meningitis (≥4 Weeks Symptoms)

For subacute presentations, prioritize:

• Mycobacterial culture (6 mL minimum) with AFB smear 1, 2
• Fungal cultures for Cryptococcus, Coccidioides, Histoplasma 1
• Syphilis serology (CSF VDRL/RPR) 2
• Toxoplasma serology/PCR in immunocompromised patients 2

Critical Timing Issues

Never Delay Antibiotics for Imaging or Culture

If bacterial meningitis is suspected and lumbar puncture is delayed for any reason (including CT scan), start empirical antibiotics for S. pneumoniae immediately after obtaining blood cultures. 1, 2

• Gram stain sensitivity drops from 60-80% to 40-60% after antibiotic administration 1
• Culture may become negative within 2-4 hours of appropriate antibiotics 3, 4
• PCR remains positive longer than culture after antibiotic treatment 3, 4

Repeat Lumbar Puncture When Initial Testing Is Non-Diagnostic

If initial CSF is non-diagnostic but clinical suspicion persists, repeat lumbar puncture at 24-48 hours, particularly for HSV encephalitis where initial CSF may be normal in 5-10% of cases. 2

Device-Associated Infections

For patients with ventriculostomy catheters or shunt systems:

• Sample CSF from the device reservoir when fever or altered mental status develops 1, 2
• Remove and culture the catheter tip if meningitis signs develop 1, 2
• Sample both device and lumbar space if CSF flow is obstructed 1, 2

Common Pitfalls to Avoid

• Insufficient volume collection is a leading cause of false-negative results, especially for mycobacterial and fungal cultures 2

• Bacterial antigen testing is not recommended except in antibiotic-pretreated patients with negative Gram stain and culture 1

• PCR cannot replace culture entirely: unusual pathogens like Bacillus cereus, MSSA, and M. tuberculosis may be missed by standard multiplex panels 3

• Normal CSF cell count does not exclude infection in immunocompromised patients 1, 2

• Hemorrhagic contamination interferes with interpretation; use proper collection technique 2