A Comparison of Amphotericin B Alone and Combined With Flucytosine in the Treatment of Cryptoccal Meningitis

N Engl J Med. 1979 Jul 19;301(3):126-31. doi: 10.1056/NEJM197907193010303.


We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amphotericin B / administration & dosage*
  • Amphotericin B / adverse effects
  • Cryptococcosis / blood
  • Cryptococcosis / drug therapy*
  • Cytosine / analogs & derivatives*
  • Drug Evaluation
  • Drug Therapy, Combination
  • Flucytosine / administration & dosage*
  • Flucytosine / adverse effects
  • Flucytosine / blood
  • Humans
  • Meningitis / blood
  • Meningitis / drug therapy*
  • Middle Aged
  • Prospective Studies
  • Time Factors


  • Amphotericin B
  • Cytosine
  • Flucytosine