We studied the efficacy of
itraconazole, a new oral
triazole, in 33 patients (32 were immunocompromised) with
cryptococcosis. Diagnoses included
cryptococcal meningitis (24 patients), cryptococcemia (19 patients), cryptococcuria (4 patients),
osteomyelitis (1 patient), pulmonary
cryptococcosis (1 patient), and soft-tissue
cryptococcosis (2 patients). Twenty-six patients had the
acquired immunodeficiency syndrome, and 4 were transplant recipients.
Therapy (200 mg two times per day) was monitored by clinical response, culture, and cryptococcal
antigen testing. Cryptococcemia was abolished in 10 (100%) of 10 assessable patients; clinical abnormalities also cleared. Thirteen (65%) of 20 assessable patients with
cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 5 (25%) had partial responses, and
therapy failed in 2 (10%). Ten (71%) of 14 patients with the
acquired immunodeficiency syndrome who had
meningitis and were treated with
itraconazole as their sole
therapy had complete responses, 3 (21%) had partial responses, and
therapy failed in 1 (7%). Partial responses or failures were all associated with the failure of previous
therapy, severe disease, low serum
itraconazole concentrations, or a resistant organism. Noncompliance was associated with relapse (4 patients).
Meningitis recrudesced in 3 (20%) of 15 patients who responded to
therapy. All 4 patients with pulmonary
cryptococcosis, soft-tissue
cryptococcosis, or
osteomyelitis responded to
therapy (100%). Cryptococcuria was abolished in 3 (60%) of 5 assessable patients. The median survival of the 20 patients with the
acquired immunodeficiency syndrome who had
meningitis exceeded 10.5 months at this writing. Overall results compare favorably with
amphotericin B therapy with or without
flucytosine. Forty of 44 isolates of Cryptococcus neoformans were susceptible in vitro to
itraconazole (minimum inhibitory concentration less than or equal to 3.13 mg/L), 3 were borderline (minimum inhibitory concentration, 6.25 mg/L), and 1 was resistant (minimum inhibitory concentration, 12.5 mg/L). As
itraconazole does not penetrate cerebrospinal fluid, the
meningitis results are noteworthy and suggest that meningeal and parenchymal penetration is critical.
Itraconazole is promising for the treatment of
cryptococcosis in patients with and without the
acquired immunodeficiency syndrome.