Cryptococcus Neoformans

GENERAL PRINCIPLES

• The severity of infection depends on the degree of the patient's immunosuppression.

• Cryptococcal meningitis is the most frequent CNS fungal infection in AIDS patients.

DIAGNOSIS

• Patients with CNS infection usually present with headaches, fever, and possibly mental status changes, but presentation can be more subtle.

• Cryptococcal infection can also present as pulmonary or cutaneous disease.

• Diagnosis is based on LP results and on the determination of latex cryptococcal antigen, which is usually positive in the serum and the CSF.

• CSF opening pressure should always be measured to assess the possibility of elevated intracranial pressure.

TREATMENT

• Initial treatment is with liposomal amphotericin dosed at 3-4 mg/kg/d IV, and flucytosine, 25 mg/kg PO q6h for at least 2 weeks, followed by fluconazole, 400 mg PO daily for at least 8 weeks and then 200 mg PO daily, either lifelong or until immune reconstitution occurs. Fluconazole can be discontinued in those who are asymptomatic with regard to signs and symptoms of cryptococcosis and have a sustained increase (gt;6 months) in their CD4+ counts to #8805;200 cells#8725;#956;L.

• Repeat LPs (removing up to 30 mL CSF until the pressure is lt;20-25 cm H₂O) may be required to relieve elevated intracranial pressure.

• The 5-flucytosine level should be monitored during therapy to avoid toxicity.

• Alternative initial therapy is with amphotericin B deoxycholate, 0.7 mg/kg/d IV, and flucytosine, 25 mg/kg PO q6h.

• In persons who have persistent elevation of intracranial pressure, a temporary lumbar drain is indicated.