Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients.
Cryptococcal meningitis is an important cause of
central nervous system disease and death in patients with
AIDS. Although the introduction of
amphotericin B has greatly improved the prognosis of patients with
cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing. The discovery of the additive effects of
amphotericin B and
flucytosine in
cryptococcosis resulted in some improvement in efficacy and reduction in
amphotericin B-related toxicity. However, approximately 30% of patients with
cryptococcal meningitis still fail to respond to
therapy.
Ketoconazole has not proved useful in treating
cryptococcal meningitis. Accumulating evidence suggests that the antifungal
triazoles fluconazole,
itraconazole, and
SCH 39304 represent an advance in the treatment of
cryptococcal meningitis, particularly in
AIDS patients. Preliminary clinical trials in patients with and without
AIDS have indicated that
fluconazole and intraconazole are effective and well tolerated as either initial or maintenance
therapy. Two large comparative trials of
fluconazole and
amphotericin B in patients with
cryptococcal meningitis (mostly those with
AIDS) are under way.