The principal diseases to be considered in diagnosis are tuberculous meningitis; granulomatous cerebral vasculitis (normal glucose values in CSF); unidentifiable forms of viral meningoencephalitis (normal CSF glucose values); sarcoidosis; and lymphomatosis or carcinomatosis of meninges (neoplastic cells in CSF).
Treatment In patients without HIV, this consists of intravenous administration of amphotericin B, given in a dose of 0.7 to 1.0 mg/kg/d, or 3–4 mg/kg/d of liposomal amphotericin. Intrathecal administration of the drug in addition to the intravenous route appears not to be essential. Administration of the drug should be discontinued if the blood urea nitrogen reaches 40 mg/dL and resumed when it descends to normal levels. Renal tubular acidosis also frequently complicates amphotericin B therapy. The addition of flucytosine (100 mg/kg/d) to amphotericin B results in fewer failures or relapses, more rapid sterilization of the CSF, and less nephrotoxicity than the use of amphotericin B alone. Both medications are usually continued for at least 6 weeks—longer if CSF cultures remain positive.
However, this regimen, which has a success rate of 75 to 85 percent in immunocompetent patients, has proven to be much less effective in patients with HIV. The recommended treatment in these circumstances is amphotericin supplemented by flucytosine for 2 weeks. Subsequently, fluconazole, an oral triazole antifungal agent, is given (or less preferably, oral itraconazole), for up to 1 year or indefinitely to prevent relapse (Saag et al; Powderly et al). The medication can be discontinued if the CD4 exceeds 100/mm3 and HIV viral load is suppressed. The optimum use of these drugs has not been settled, and some trials have yielded ambiguous results in both HIV and other patients. Details of a randomized trial in HIV comparing amphotericin as above to a regimen of additional flucytosine is given by Day and colleagues. They showed no advantage to an initial regimen of both drugs over amphotericin alone.
Mortality from cryptococcal meningoencephalitis, even in the absence of HIV or other disease, is high.
Candidiasis is probably the most frequent opportunistic fungus infection. The notable antecedents of Candida sepsis are severe burns and the use of total parenteral nutrition, especially in children. Urine, blood, skin, and particularly the heart (myocardium and valves) and lungs (alveolar proteinosis) are the usual sites of primary infection. No special features distinguish this fungal infection from others; meningitis, meningoencephalitis, and cerebral abscess, usually multiple and small, are the main modes of clinical presentation. Generally, the CSF contains several hundred (up to 2,000) cells/mm3. Yeast can be seen on direct microscopy in half the cases. Even with treatment (intravenous amphotericin B), the prognosis is grave.