PREVENTING FUNGAL INFECTION IN NEUTROPENIC PATIENTS WITH ACUTE-LEUKEMIA - FLUCONAZOLE COMPARED WITH ORAL AMPHOTERICIN-B

Objective: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic pat ients with acute leukemia. Design: A randomized, controlled, multicent er trial. Setting: 30 hematologic units in tertiary care or university hospitals. Patients: 820 consecutive, afebrile, adult patients with a cute leukemia and chemotherapy-induced neutropenia. Intervention: Pati ents were randomly assigned to receive fluconazole, 150 mg, as a once- daily capsule, or amphotericin B suspension, 500 mg every 6 hours. Mea surements: An intention-to-treat analysis was done for 820 patients: 4 20 treated with fluconazole and 400 treated with oral amphotericin B. Results: Definite systemic fungal infection occurred in 2.6% of flucon azole recipients and 2.5% of amphotericin B recipients; suspected syst emic fungal infection requiring the empiric use of intravenous amphote ricin B occurred in 16% of fluconazole recipients and 21% of oral amph otericin B recipients, a difference of 5 percentage points (95% CI for difference, - 0.02% to 10%; P = 0.07). Superficial fungal infection w as 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 isolat es in systemic and superficial fungal infection was similar in both gr oups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with f luconazole compared with 72% of those treated with amphotericin B susp ension, a difference of 18 percentage points (CI for difference, 13% t o 23%). Side effects were documented less frequently in fluconazole th an in amphotericin B recipients (1.4% compared with 7%, a difference o f 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). Concl usion: 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.