What is the treatment for aspergillosis meningitis?

Treatment of Aspergillosis Meningitis

Voriconazole is the primary treatment of choice for aspergillosis meningitis, administered at 6 mg/kg IV every 12 hours for 1 day, followed by 4 mg/kg IV every 12 hours. 1

Primary Treatment Regimen

First-line Therapy:

• Voriconazole:
  • Loading dose: 6 mg/kg IV every 12 hours for 1 day
  • Maintenance dose: 4 mg/kg IV every 12 hours
  • Can transition to oral therapy (200 mg every 12 hours) after clinical improvement 1, 2
  • For pediatric patients: 5-7 mg/kg IV every 12 hours 1

Duration of Treatment:

• Minimum of 6-12 weeks
• Continue throughout the period of immunosuppression
• Treatment should be continued until resolution or stabilization of all clinical and radiographic manifestations 1

Alternative Treatment Options

For patients who cannot tolerate voriconazole or have refractory disease:

1. Liposomal Amphotericin B (L-AMB):

   • Dosage: 3-5 mg/kg/day IV 1
   • Consider when voriconazole is contraindicated or not tolerated 1

2. Amphotericin B lipid complex (ABLC):

   • Dosage: 5 mg/kg/day IV 1

3. Posaconazole:

   • Initial: 200 mg QID
   • After stabilization: 400 mg BID orally 1
   • Recent evidence shows non-inferiority to voriconazole for invasive aspergillosis with fewer treatment-related adverse events 3

4. Isavuconazole:

   • Loading: 200 mg every 8 hours for 6 doses
   • Maintenance: 200 mg daily 4

5. Echinocandins (caspofungin, micafungin):

   • Not recommended as primary monotherapy
   • May be effective in salvage therapy 1
   • Caspofungin: 70 mg day 1 IV, then 50 mg/day IV thereafter 1

Therapeutic Considerations

Monitoring:

• Regular clinical evaluation of all symptoms and signs
• Serial neuroimaging (CT or MRI) at regular intervals
• Consider monitoring serum galactomannan levels (increasing levels signify poor prognosis) 1
• Therapeutic drug monitoring for voriconazole is recommended 1

Surgical Intervention:

• Surgical resection should be considered for accessible lesions
• Particularly important for decompression in cases with significant mass effect 1, 5

Special Considerations:

• CNS aspergillosis has the highest mortality among all patterns of invasive aspergillosis 1
• Be aware of potential drug interactions, especially with anticonvulsants 1
• Early initiation of antifungal therapy while diagnostic evaluation is conducted is critical 1

Diagnostic Approach

• CSF analysis may reveal Aspergillus antigen or DNA 6, 7
• Galactomannan assay in CSF can aid diagnosis 7
• Neuroimaging (MRI preferred) to identify characteristic lesions 5
• Culture and histopathology when possible 2

Common Pitfalls and Caveats

• Delayed diagnosis and treatment are associated with high mortality 7
• Conventional amphotericin B deoxycholate (D-AMB) causes significant nephrotoxicity and infusion-related reactions and is not recommended as primary therapy 1
• Aspergillus meningitis may present with subtle symptoms and can be mistaken for tuberculous meningitis or other CNS infections 5
• Patients with underlying immunosuppression (hematologic malignancies, transplantation, prolonged steroid use) are at highest risk 1
• For patients requiring subsequent immunosuppression after successful treatment, secondary prophylaxis should be initiated to prevent recurrence 1

Remember that early and aggressive treatment is essential for improving outcomes in this life-threatening infection.