What is Cryptococcal (Fungal) Meningitis?

From the Guidelines

Cryptococcal meningitis is a serious fungal infection of the brain and spinal cord membranes (meninges) caused primarily by the yeast Cryptococcus neoformans or Cryptococcus gattii, and treatment typically involves a three-phase approach: induction therapy with amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day 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 or until immune function improves significantly, as recommended by the Infectious Diseases Society of America 1.

Key Points

• Cryptococcal meningitis predominantly affects individuals with weakened immune systems, particularly those with HIV/AIDS, organ transplant recipients on immunosuppressive medications, and patients with other immunocompromising conditions.
• Symptoms include severe headache, fever, neck stiffness, sensitivity to light, confusion, nausea, and vomiting.
• If left untreated, cryptococcal meningitis can lead to brain damage and death.
• Early diagnosis through lumbar puncture and cryptococcal antigen testing is crucial for improving outcomes in this potentially fatal infection.
• The treatment approach may vary depending on the patient's immune status, with HIV-infected patients requiring a more aggressive treatment regimen 1.
• Immunosuppressive management may require sequential or step-wise reductions in immunosuppressants, with consideration of lowering the corticosteroid dose first 1.
• Control of intracranial pressure is critical in patients with cryptococcal meningitis, and may require repeated lumbar punctures or other interventions to relieve pressure 1.

Treatment Recommendations

• Induction therapy: amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day divided in four doses) for at least two weeks.
• Consolidation therapy: fluconazole 400-800 mg daily for 8 weeks.
• Maintenance therapy: fluconazole 200 mg daily for at least one year or until immune function improves significantly.
• Alternative regimens may be considered for patients who are intolerant of first-line treatments or have specific underlying conditions, such as renal dysfunction or HIV infection 1.

From the FDA Drug Label

Cryptococcal meningitis: In a multicenter study comparing fluconazole (200 mg/day) to amphotericin B (0. 3 mg/kg/day) for treatment of cryptococcal meningitis in patients with AIDS, a multivariate analysis revealed three pretreatment factors that predicted death during the course of therapy: abnormal mental status, cerebrospinal fluid cryptococcal antigen titer greater than 1:1024, and cerebrospinal fluid white blood cell count of less than 20 cells/mm3 Cryptococcal meningitis: The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily Cryptococcal meningitis: For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily.

Cryptococcal meningitis is a fungal infection caused by the Cryptococcus neoformans fungus that affects the brain and spinal cord.

• It is a serious and potentially life-threatening condition, especially in people with weakened immune systems, such as those with AIDS.
• The recommended treatment for acute cryptococcal meningitis typically involves antifungal medications, such as fluconazole, which is administered orally or intravenously 2, 2, 2.
• The dosage and duration of treatment may vary depending on the severity of the infection and the patient's response to therapy.

From the Research

Definition and Overview of Cryptococcal Meningitis

• Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system (CNS) 3, 4.
• It is caused by Cryptococcus infecting the meninges and/or brain parenchyma, with symptoms including fever, headache, neck stiffness, and visual disturbances 4.
• The infection can affect both immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection or organ transplantation, and immunocompetent people 4.

Management and Treatment

• The management of cryptococcal meningitis involves initial combination antifungal therapy, following the principles of induction, consolidation, and maintenance therapy, as well as aggressive management of elevated intracranial pressure (ICP) 3.
• Combination antifungal therapy with amphotericin B plus flucytosine is generally indicated for patients with and without AIDS 3, 5.
• The timing of the initiation of highly active antiretroviral therapy (HAART) is also important, with recent prospective trials suggesting that initiation of HAART is optimal for management of patients with AIDS and cryptococcal meningitis 3.

Clinical Manifestations and Outcomes

• Without treatment, patients with cryptococcal meningitis may have a mortality rate of up to 100% after hospital admission 4.
• Even after receiving therapy, CM patients may still suffer from problems such as difficulty to cure, poor prognosis, and high mortality 4.
• Clinical outcomes of CM are frequently unsatisfactory due to limited drug choices, severe adverse reactions, drug resistance, etc. 4.
• Recent advances in diagnosis and management have improved long-term survival, including point of care testing, targeted screening and treatment programs, and optimal initial management with amphotericin and flucytosine 6.