Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome1, 2

Abstract

<h3>Purpose</h3> Because of the increasing numbers of patients with acquired immunodeficiency syndrome AIDS) who will require treatment for cryptococcosis and because of the problems associated with long-term administration of intravenous amphotericin B, an alternative therapeutic approach in the form of an efficacious and easily administered oral antifungal drug would be of great benefit. Fluconazole, a new triazole antifungal agent, represents such an alternative. We therefore conducted an open, non-randomized trial of oral fluconazole as maintenance suppressive therapy of disseminated cryptococcosis in patients with AIDS. <h3>Patients and methods</h3> Twenty patients with AIDS, 19 of whom had cryptococcal meningitis, were studied. Patients were followed for up to 21 months. All patients received amphotericin B as primary therapy, from 20 to 257 days prior to entry (500 to 5,080 mg total dose). Eight also received flucytosine. After administration of amphotericin B for acute disseminated cryptococcosis, and prior to initiation of fluconazole therapy, <i>Cryptococcus neoformans</i> was isolated from the cerebrospinal fluid (CSF) in two patients and from the blood in one patient. Fluconazole was given once daily, in doses of 50 to 200 mg/day. <h3>Results</h3> Following initiation of fluconazole, results of CSF and blood cultures continued to be negative, except for the CSF culture in one patient who had a relapse in the 32nd week of therapy. Fluconazole therapy has been successfully continued in nine patients, for a median of 11 months (nine to 21 months). Seven patients died; five had no evidence of active cryptococcosis at the time of death. Two patients had a relapse, although the CSF culture showed growth of the fungus in only one patient. One patient was lost to follow-up after five months of therapy and one was unevaluable. Fluconazole had to be discontinued in only one patient in whom thrombocytopenia developed, and then resolved when the drug was stopped. <h3>Conclusion</h3> We conclude that oral fluconazole represents a significant advance in the management of cryptococcal meningitis and should be useful in the long-term suppressive therapy of this opportunistic infection in patients with AIDS.