What is the recommended treatment for a patient with a cerebrospinal fluid (CSF) fungal infection?

Treatment of Cerebrospinal Fluid Fungal Infections

For CSF fungal infections, liposomal amphotericin B (5 mg/kg daily) with or without flucytosine (25 mg/kg 4 times daily) is recommended as initial therapy, followed by step-down to fluconazole (400-800 mg daily) for susceptible isolates after clinical improvement.

Initial Treatment Based on Fungal Type

Candida CNS Infections

• First-line therapy:
  • Liposomal amphotericin B, 5 mg/kg IV daily 1
  • Consider adding flucytosine, 25 mg/kg orally 4 times daily 1
• Alternative initial therapy:
  • Amphotericin B deoxycholate, 1 mg/kg IV daily (if lipid formulation unavailable) 1
• Duration: Continue until all signs, symptoms, and CSF/radiological abnormalities have resolved 1

Cryptococcal Meningitis

• First-line therapy:
  • Liposomal amphotericin B, 5 mg/kg IV daily, plus flucytosine, 25 mg/kg orally 4 times daily for 2 weeks 1
  • For HIV patients: Continue treatment for at least 4-6 weeks 1
• Step-down therapy:
  • Fluconazole 400-800 mg (6-12 mg/kg) daily after clinical improvement 1
  • For HIV patients: Fluconazole 200 mg daily until CD4 >100/μL and undetectable HIV viral load for 3 months 1

Other Fungal CNS Infections

• Coccidioidomycosis:
  • Fluconazole 400-1200 mg daily 1
  • Note: For coccidioidal meningitis, treatment is lifelong 1
• Blastomycosis:
  • Liposomal amphotericin B, 5 mg/kg IV daily for 4-6 weeks 1
  • Step-down to fluconazole 800 mg daily, itraconazole 200 mg 2-3 times daily, or voriconazole 200-400 mg twice daily for at least 12 months 1

Management of Infected CNS Devices

• Removal of infected devices is mandatory:
  • Ventriculostomy drains, shunts, stimulators, and other CNS devices should be removed if at all possible 1
• If device cannot be removed:
  • Consider direct administration of amphotericin B through the device:
    • Amphotericin B deoxycholate: 0.01-0.5 mg in 2 mL 5% dextrose in water 1
    • Liposomal amphotericin B: Starting dose of 0.125-0.5 mg daily, with slow titration up to 2 mg maximum daily dose 2

Monitoring and Follow-up

• CSF analysis:

  • Monitor for clearance of fungal organisms
  • Follow CSF parameters (cell count, protein, glucose)
  • For cryptococcal meningitis: Monitor CSF opening pressure; if ≥250 mmH₂O, perform serial lumbar drainage to achieve closing pressure <200 mmH₂O 1

• Imaging:

  • Repeat neuroimaging to assess response to therapy
  • Continue treatment until radiological abnormalities have resolved 1

• Drug level monitoring:

  • For voriconazole: Monitor serum levels after 2 weeks of therapy 3
  • For itraconazole: Check serum levels after at least 2 weeks to ensure adequate drug exposure 1

Duration of Therapy

• Candida CNS infections: Continue until all signs, symptoms, and CSF/radiological abnormalities have resolved (typically at least 4-6 weeks) 1
• Cryptococcal meningitis: Minimum 4-6 weeks, with final duration depending on clinical response 1
• Coccidioidal meningitis: Lifelong therapy recommended 1
• Blastomycosis CNS: Minimum 12 months 1

Common Pitfalls and Caveats

1. Delayed diagnosis: Fungal CNS infections often present with nonspecific symptoms; maintain high index of suspicion in immunocompromised patients 4, 5

2. Inadequate duration: Premature discontinuation of therapy can lead to relapse; ensure complete resolution of clinical, CSF, and radiological abnormalities before stopping treatment 1

3. Failure to remove infected devices: Retention of infected CNS hardware significantly reduces cure rates; surgical removal should be prioritized whenever possible 1

4. Inadequate monitoring for drug toxicity:

   • Monitor renal function, electrolytes (especially potassium) with amphotericin B therapy 6
   • Monitor liver function with azole therapy 3
   • Monitor for visual disturbances with voriconazole 3

5. Management of increased intracranial pressure: Failure to address elevated intracranial pressure in cryptococcal meningitis can lead to poor outcomes; serial lumbar punctures may be necessary 1