Preventing Fungal Infection in Neutropenic Patients with Acute Leukemia: Fluconazole Compared with Oral Amphotericin B

  1. Francesco Menichetti, MD;
  2. Albano Del Favero, MD;
  3. Piero Martino, MD;
  4. Giampaolo Bucaneve, MD;
  5. Alessandra Micozzi, MD;
  6. Domenico D'Antonio, MD;
  7. Paolo Ricci, MD;
  8. Mario Carotenuto, MD;
  9. Vincenzo Liso, MD;
  10. Anna Maria Nosari, MD;
  11. Tiziano Barbui, MD;
  12. Giampiero Fasola, MD;
  13. Franco Mandelli, MD; and
  14. The GIMEMA Infection Program*
  1. From Istituto di Malattie Infettive and Istituto di Clinica Medica 1, Universita di Perugia; Istituto di Ematologia, Universita “La Sapienza” Roma; Divisione di Ematologia, Ospedale Pescara; Istituto di Ematologia, Universita di Bologna; Divisione di Ematologia, Ospedale S. Giovanni Rotondo; Istituto di Ematologia, Universita di Bari; Divisione Talamona, Ospedale Niguarda, Milano; Divisione di Ematologia, Ospedale di Bergamo; Cattedra di Ematologia, Ospedale di Udine. Requests for Reprints: Francesco Menichetti, MD, Istituto di Malattie Infettive, Universita di Perugia, Ospedale Policlinico Monteluce, 06122 Perugia, Italy. Grant Support: By grants from Pfizer, Italy; and by contract N. 92.02177.39/115.19159 with Consiglio Nazionale delle Ricerche.

    Abstract

    Objective: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia.

    Design: A randomized, controlled, multicenter trial.

    Setting: 30 hematologic units in tertiary care or university hospitals.

    Patients: 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia.

    Intervention: Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours.

    Measurements: An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B.

    Results: Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, −0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, −0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01).

    Conclusion: Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

    *Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. See Appendix for additional investigators in the study and end of text for participating institutions and current author addresses.

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    1. Ann Intern Med June 1, 1994 vol. 120 no. 11 913-918
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