What is the management of fungal meningitis?

From the Guidelines

Management of fungal meningitis requires prompt initiation of antifungal therapy tailored to the specific pathogen, with the goal of reducing morbidity, mortality, and improving quality of life. For cryptococcal meningitis, the most common form, treatment involves induction therapy with amphotericin B deoxycholate (0.7-1 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally divided in four doses) for at least two weeks, followed by consolidation therapy with fluconazole 400-800 mg daily for 8 weeks, and then maintenance therapy with fluconazole 200 mg daily for at least one year, as recommended by the Infectious Diseases Society of America 1. Some key points to consider in the management of fungal meningitis include:

• The use of liposomal amphotericin B (5 mg/kg/day IV) with or without flucytosine for 2-3 weeks, followed by fluconazole, for Candida meningitis, although the evidence for this is largely based on observational reports and case series 1.
• The importance of serial lumbar punctures to reduce intracranial pressure if opening pressure exceeds 25 cm H₂O, particularly in cryptococcal meningitis, to prevent long-term neurological sequelae and improve quality of life.
• The potential benefits of adjunctive corticosteroids in cases with significant inflammation, although these should be used cautiously due to the risk of immunosuppression and worsening of the underlying infection.
• The need for regular monitoring of renal function, electrolytes, and drug levels due to the nephrotoxicity of amphotericin B and the narrow therapeutic window of flucytosine, to minimize the risk of adverse effects and optimize treatment outcomes. Overall, the management of fungal meningitis requires a comprehensive approach that takes into account the specific pathogen, host immune status, and individual patient factors, with the goal of reducing morbidity, mortality, and improving quality of life, as supported by the most recent and highest quality evidence 1.

From the FDA Drug Label

The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative The recommended dosage of fluconazole tablets for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.

Management of Fungal Meningitis:

• The recommended initial treatment for acute cryptococcal meningitis is fluconazole 400 mg on the first day, followed by 200 mg once daily.
• The treatment duration is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative.
• For suppression of relapse of cryptococcal meningitis in patients with AIDS, the recommended dose is 200 mg once daily 2, 2.
• Key Considerations:
  • Dosage may be adjusted based on medical judgment of the patient’s response to therapy.
  • Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided.

From the Research

Management of Fungal Meningitis

• The management of fungal meningitis, particularly cryptococcal meningitis, involves the use of antifungal medications.
• Combination antifungal therapy with amphotericin B (AmB) as an induction therapy is recommended for the treatment of cryptococcal meningitis 3, 4.
• The use of flucytosine (5-FC) in combination with AmB has been shown to improve survival rates and reduce mortality compared to AmB alone 3, 4.
• A meta-analysis of prospective controlled studies found that the combination of AmB and 5-FC resulted in a 44% reduction in mortality at 2 weeks, and a significant improvement in early fungicidal activity 3.
• Another study found that triple therapy with AmB, 5-FC, and fluconazole was associated with a higher frequency of satisfactory outcomes and improved neurological function compared to dual therapy with AmB and 5-FC 5.
• The use of low-dose AmB (0.4 mg/kg) with flucytosine has been shown to be effective in treating cryptococcal meningitis, with a lower incidence of adverse events compared to high-dose AmB (0.7 mg/kg) 6.
• A study in a murine model of cryptococcal meningitis found that the combination of AmB and fluconazole was potent and effective, with or without the addition of flucytosine 7.

Treatment Options

• Amphotericin B (AmB) is a key component of induction therapy for cryptococcal meningitis.
• Flucytosine (5-FC) is often used in combination with AmB to improve survival rates and reduce mortality.
• Fluconazole may be used as an alternative to 5-FC, particularly in cases where 5-FC is not available or is contraindicated.
• Triple therapy with AmB, 5-FC, and fluconazole may be considered in certain cases, such as non-HIV and non-transplant associated cryptococcal meningitis 5.

Adverse Events

• The use of AmB and 5-FC can be associated with adverse events, such as neutropenia and other hematologic abnormalities.
• Low-dose AmB (0.4 mg/kg) with flucytosine may be better tolerated than high-dose AmB (0.7 mg/kg), with a lower incidence of adverse events 6.
• The combination of AmB and fluconazole may have a relatively safe profile compared to the combination of AmB and 5-FC 7.