Cryptococcal meningitis can be a life-threatening fungal infection in patients who are positive for human immunodeficiency virus (HIV) infection. In the past, the treatment of choice was amphotericin B and flucytosine, but flucytosine has had toxic effects in patients with acquired immunodeficiency syndrome. Newer oral triazole antifungal drugs, such as fluconazole and itraconazole, have been developed as alternatives to the traditional therapies. Van der Horst and colleagues studied the effectiveness of different combinations of antifungal medications in patients with a first episode of AIDS-associated cryptococcal meningitis.
In phase one of the study, 381 patients were given amphotericin B combined with flucytosine or placebo. Phase two consisted of consolidation therapy with either fluconazole or itraconazole. After two weeks, cerebrospinal fluid cultures were negative in 202 patients (60 percent) who received amphotericin B with flucytosine and in 179 patients (51 percent) who received amphotericin B alone. The clinical status of the two groups was similar. At this time, 306 patients were considered stable or improved and judged eligible for the second phase of the study. In phase two of the study, 151 patients were given fluconazole and 155 received itraconazole for an additional eight weeks.
At the conclusion of phase two, cultures of cerebrospinal fluid were negative in 72 percent of the patients treated with fluconazole and in 60 percent of the patients treated with itraconazole. However, cultures were not obtained in 39 patients in the fluconazole group and in 54 patients in the itraconazole group. Sixty-eight percent of patients treated with fluconazole and 70 percent of patients treated with itraconazole were asymptomatic after phase two. Similar percentages in both groups had unchanged or improved scores on the Mini-Mental State Examination.
The authors recommend that initial treatment of AIDS-associated cryptococcal meningitis consist of higher-dose amphotericin B in combination with flucytosine for two weeks, followed by eight weeks of fluconazole. The addition of flucytosine to amphotericin B during the first two weeks of therapy, followed by treatment with fluconazole for the next eight weeks, was independently associated with cerebrospinal fluid sterilization and may prevent relapse. In this study, the addition of lower-than-typical doses of flucytosine to amphotericin B for the first two weeks of treatment did not increase the efficacy of treatment or the incidence of toxic effects. Itraconazole is a suitable alternative for patients who are unable to tolerate fluconazole.