What is the treatment for Aspergillus meningitis with complications such as hydrocephalus and brain abscess?

From the Guidelines

The treatment for Aspergillus meningitis with complications like hydrocephalus and brain abscess requires aggressive antifungal therapy combined with neurosurgical interventions, with voriconazole as the first-line antifungal agent, as recommended by the Infectious Diseases Society of America 1.

Key Considerations

• Voriconazole is typically started with a loading dose of 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours, with transition to oral therapy (200-300 mg twice daily) when clinically stable.
• Treatment duration is typically 6-12 months, guided by clinical and radiological improvement.
• For severe cases or voriconazole-resistant infections, liposomal amphotericin B (3-5 mg/kg/day IV) may be used, often in combination with voriconazole.

Neurosurgical Management

• Hydrocephalus requires CSF diversion procedures such as ventriculoperitoneal shunting or external ventricular drainage.
• Brain abscesses often need surgical drainage or excision, especially for large (>2.5 cm) or accessible lesions.

Monitoring and Adjunctive Therapy

• Regular monitoring includes neuroimaging (MRI every 2-4 weeks initially), CSF analysis, and therapeutic drug monitoring for voriconazole (target trough levels: 2-5 μg/mL).
• Corticosteroids may be used briefly to reduce inflammation and intracranial pressure but should be used cautiously as they can worsen fungal infections.

Rationale

The aggressive approach is necessary because Aspergillus meningitis has high mortality rates, and the fungus can be difficult to eradicate from the central nervous system due to the blood-brain barrier limiting antifungal penetration, as highlighted in studies 1.

From the FDA Drug Label

The efficacy of voriconazole compared to amphotericin B in the primary treatment of acute IA was demonstrated in 277 patients treated for 12 weeks in a randomized, controlled study (Study 307/602). Voriconazole was administered intravenously with a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by a maintenance dose of 4 mg/kg every 12 hours for a minimum of seven days. Therapy could then be switched to the oral formulation at a dose of 200 mg every 12 hours.

The treatment for Aspergillus meningitis with complications such as hydrocephalus and brain abscess is voriconazole. The recommended dosage is a loading dose of 6 mg/kg every 12 hours for the first 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours for a minimum of seven days, which can then be switched to an oral formulation at a dose of 200 mg every 12 hours 2.

• The efficacy of voriconazole in treating invasive aspergillosis, including CNS infections, has been demonstrated in a randomized, controlled study.
• Voriconazole has shown a satisfactory global response in 53% of treated patients compared to 32% of amphotericin B treated patients.
• A benefit of voriconazole compared to amphotericin B on patient survival at Day 84 was seen with a 71% survival rate on voriconazole compared to 58% on amphotericin B 2.

From the Research

Treatment Options for Aspergillus Meningitis

The treatment for Aspergillus meningitis with complications such as hydrocephalus and brain abscess involves a combination of antifungal medications and neurosurgical interventions.

• Voriconazole is considered the standard treatment for CNS aspergillosis, including Aspergillus meningitis, due to its superior efficacy and penetration into the central nervous system 3, 4, 5, 6.
• Liposomal amphotericin B is an alternative treatment option for patients who cannot tolerate voriconazole or have failed voriconazole treatment 3, 4, 6.
• Neurosurgical interventions, such as craniotomy, abscess resection, and ventricular shunt placement, may be necessary to manage complications like hydrocephalus and brain abscess 3, 4, 5.
• Posaconazole delayed-release tablets may be used as an alternative treatment option for invasive aspergillosis, including Aspergillus meningitis, although its use is currently indicated only for antifungal prophylaxis in high-risk patients 7.
• Itraconazole may also be used in combination with voriconazole for the treatment of Aspergillus meningitis 6.

Management of Complications

The management of complications like hydrocephalus and brain abscess is crucial in the treatment of Aspergillus meningitis.

• Neurosurgical procedures, such as ventriculostomy or ventricular shunt placement, may be necessary to manage hydrocephalus 3, 5.
• Abscess resection or drainage may be necessary to manage brain abscesses 3, 4, 5.
• Antifungal treatment should be continued for an extended period to ensure complete resolution of the infection 5.