What are the treatment options for central nervous system (CNS) infections caused by Streptococcus agalactiae, Candida, or enterovirus in patients, including neonates and immunocompromised individuals?

Treatment of CNS Infections Caused by Streptococcus agalactiae, Candida, and Enterovirus

For Streptococcus agalactiae (Group B Streptococcus) CNS infections in neonates, use ampicillin 150-200 mg/kg/day IV divided every 3-4 hours for bacterial meningitis, with dosing adjusted based on gestational and postnatal age; for Candida CNS infections, particularly in immunocompromised patients and neonates, use fluconazole or amphotericin B; and for enterovirus CNS infections, provide supportive care as no specific antiviral therapy is proven effective, though these infections can be severe and fatal. 1, 2, 3

Streptococcus agalactiae (Group B Streptococcus) CNS Infections

Neonatal Dosing Algorithm

For neonates ≤28 days postnatal age with bacterial meningitis:

• Gestational age ≤34 weeks AND postnatal age ≤7 days: 100 mg/kg/day divided every 12 hours 1
• Gestational age ≤34 weeks AND postnatal age 8-27 days: 150 mg/kg/day divided every 12 hours 1
• Gestational age >34 weeks AND postnatal age ≤28 days: 150 mg/kg/day divided every 8 hours 1

Older Children and Adults

• 150-200 mg/kg/day ampicillin IV in equally divided doses every 3-4 hours 1
• Initiate with IV drip therapy and continue with IM injections as appropriate 1

Treatment Duration

• Minimum 10 days for any Group A beta-hemolytic streptococcal infection to prevent acute rheumatic fever or glomerulonephritis 1
• Continue for minimum 48-72 hours beyond symptom resolution or bacterial eradication 1
• For uncomplicated non-CNS GBS infections in low-risk neonates, once-daily ceftriaxone IM may complete therapy after initial stabilization 4

Critical Pitfall

More rapid IV administration than 10-15 minutes for 1-2g doses may result in convulsive seizures 1

Candida CNS Infections

High-Risk Populations

Candida CNS infections predominantly affect neonates and immunocompromised patients, particularly those with CARD9 deficiency 5

Diagnostic Approach in Immunocompromised Patients

• Indian ink staining and/or cryptococcal antigen (CRAG) testing of CSF and serum for Cryptococcus neoformans (though this targets Cryptococcus, not Candida specifically) 3
• CSF examination for Coccidioides species and Histoplasma species should be considered depending on circumstances 3
• Perform CT before LP in patients with known severe immunocompromise 3

Treatment Options

Fluconazole is the primary antifungal for CNS candidiasis:

• 200 mg/day fluconazole was studied in cryptococcal meningitis in AIDS patients, though optimal doses for high-risk patients remain undetermined 2
• Amphotericin B (0.3 mg/kg/day) is an alternative 2
• For pediatric oropharyngeal candidiasis (not CNS but demonstrates efficacy): 2-3 mg/kg/day fluconazole achieved 86% clinical cure versus 46% with nystatin 2

Special Considerations

CARD9-deficient patients have critical susceptibility to CNS candidiasis due to impaired neutrophil recruitment and function 5. This represents the only molecule shown critical for CNS protection against Candida in humans 5.

Enterovirus CNS Infections

Clinical Severity

Enterovirus can cause severe, potentially fatal CNS disease in neonates, including myocarditis, hepatitis, and meningoencephalitis requiring intensive care 6. In one series, 2 of 3 neonates with severe enterovirus infection died, comparable to mortality from bacterial meningitis 6.

Diagnostic Testing

All patients with suspected viral encephalitis should have CSF PCR for enteroviruses 3

• CSF PCR sensitivity >95% for enterovirus encephalitis 3
• Culture sensitivity only 65-75% 3
• Throat and rectal swabs for enterovirus should be obtained, though positive results indicate carriage rather than definitive causation 3

Imaging Findings

Enterovirus may cause:

• Generalized parenchymal destruction 3
• Predominant brainstem involvement, occasionally spreading to cerebellar dentate nuclei 3
• Superior spread to thalami and basal ganglia 3

Treatment Approach

No specific antiviral therapy is proven effective for enterovirus CNS infections 3. Management is supportive, focusing on:

• Intensive care monitoring for severe manifestations (myocarditis, hepatitis, meningoencephalitis) 6
• Recognition that C-reactive protein values are significantly lower in enterovirus infection (9 mg/L) versus bacterial infection (62.3 mg/L), which may aid differentiation 6

Critical Diagnostic Pitfall

In immunocompromised patients, CSF may be acellular despite active enterovirus infection, so microbiological testing must proceed regardless of CSF cell count 3, 7. Enterovirus can cause subtle, subacute presentations in immunocompromised hosts 3.

Immunocompromised Patient Considerations

Encephalitis should be considered even if history is prolonged, clinical features are subtle, there is no fever, or CSF white cell count is normal 3. The broader diagnostic workup for immunocompromised patients includes CSF PCR for HSV 1 & 2, VZV, enteroviruses, EBV, CMV, and cultures for Listeria monocytogenes and Mycobacterium tuberculosis 3.