Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome

N Engl J Med. 1989 Sep 21;321(12):794-9. doi: 10.1056/NEJM198909213211205.


We reviewed the records of 106 patients with cryptococcal infections and the acquired immunodeficiency syndrome (AIDS) treated at San Francisco General Hospital. We examined four issues: the efficacy of treatment with amphotericin plus flucytosine as compared with amphotericin alone, the efficacy of suppressive therapy, the prognostic clinical characteristics, and the course of nonmeningeal cryptococcosis. In 48 of the 106 patients (45 percent), cryptococcosis was the first manifestation of AIDS. Among the 89 patients with cryptococcal meningitis confirmed by culture, survival did not differ significantly between those treated with amphotericin plus flucytosine (n = 49) and those treated with amphotericin alone (n = 40). Flucytosine had to be discontinued in over half the patients because of cytopenia. Long-term suppressive therapy with either ketoconazole or amphotericin was associated with improved survival, as compared with survival in the absence of suppressive therapy (median survival, greater than or equal to 238 vs. 141 days; P less than 0.004). The only clinical features independently associated with a shorter cumulative survival were hyponatremia and a positive culture for cryptococcus from an extrameningeal source. The 14 patients with nonmeningeal cryptococcosis had a median survival (187 days) and rate of relapse (20 percent) similar to those in the patients with meningitis (165 days and 17 percent, respectively). From this retrospective study of cryptococcal infections in patients with AIDS we conclude that the addition of flucytosine to amphotericin neither enhances survival nor prevents relapse, but long-term suppressive therapy appears to benefit these patients.

Publication types

  • Comparative Study

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications*
  • Adult
  • Aged
  • Amphotericin B / administration & dosage*
  • Cryptococcosis* / drug therapy
  • Cryptococcosis* / mortality
  • Cryptococcus neoformans / isolation & purification
  • Drug Therapy, Combination
  • Female
  • Flucytosine / administration & dosage*
  • Flucytosine / adverse effects
  • Humans
  • Hyponatremia / complications
  • Ketoconazole / administration & dosage
  • Ketoconazole / therapeutic use
  • Male
  • Meningitis / drug therapy
  • Middle Aged
  • Pancytopenia / chemically induced
  • Prognosis
  • Recurrence


  • Amphotericin B
  • Flucytosine
  • Ketoconazole