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

1 June 1994 | Volume 120 Issue 11 | Pages 913-918

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.

Author and Article Information

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.