Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial.
OBJECTIVE
To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis.


METHODS
Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses.


METHODS
Los Angeles County-University of Southern California Medical Center.


METHODS
Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis.


RESULTS
Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27).


CONCLUSIONS
Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.
Los Angeles County Hospital, California.
R A
RA
Larsen
M A
MA
Leal
L S
LS
Chan
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000302:isolation & purification; D004359:Drug Therapy, Combination; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D005437:Flucytosine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008581:Meningitis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic
D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine