Cryptococcus neoformans is a yeast-like fungus widely present in soil and in greater concentration in bird excreta. It causes disseminated disease ultimately in about 5% of persons with advanced HIV infection. It readily spreads from the lungs to the meninges and, less commonly to the bone marrow, genitourinary tract and skin. It is the most common life threatening AIDS related fungal infection and occurs most often in HIV - positive patients with CD4+ counts < 50/mm3. In this group of patients its most common manifestation is cryptococcal meningitis. Early diagnosis is usually dependent upon demonstration of cryptococcal antigen in the serum, India ink staining of the CSF, or culture of cryptococci from the cerebrospinal fluid.
The onset of cryptococcal meningitis is generally insidious. Fever and headache are often the only presenting signs. Nausea, vomiting and neck stiffness may be absent and focal neurological signs are uncommon. Patients with high initial CSF pressure, decreased CSF glucose, low leukocyte count, no cryptococcal antibody or high cryptococcal antigen titres tend to have a poor prognosis. Typical extraneural manifestations include skin lesions, pneumonia’s, pleural effusions and retinitis. Untreated, the disease runs a slowly progressive and ultimately fatal course.
Treatment
1st choice |
Amphotericin B (IV) (0.5-1.0 mg/kg IV for 6 weeks) + flucytosine (100 mg/kg in divided doses for 2 weeks)
followed by fluconazole (200 mg daily maintenance) |
2nd choice |
Amphotericin B (IV) + flucytosine (100 mg/kg in divided doses for 2 weeks)
followed by itraconazole (200 mg 2 x day maintenance) |
3rd choice |
Fluconazole (oral) throughout (400 mg daily for 12 weeks then 200 mg daily maintenance) |
4th choice |
Amphotericin B IV throughout (as above) |
All patients from whom cryptococci are isolated should be treated, even if they have no signs of infection, because of the high risk of meningitis and disseminated disease. Treatment with amphotericin B infused intravenously plus or minus flucytosine for two weeks followed by oral fluconazole is the treatment of choice. In mild disease (i.e. if there is no demonstrable CNS involvement) oral fluconazole may be used throughout. Itraconazole may be a suitable alternative in patients unable to take fluconazole. If azoles are unavailable, treatment with intravenous amphotericin B should continue for 6 weeks, followed by maintenance with intravenous amphotericin B once or twice a week. Patients should remain on maintenance therapy for life.
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