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 patients with acute leukemia.


METHODS
A randomized, controlled, multicenter trial.


METHODS
30 hematologic units in tertiary care or university hospitals.


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


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


METHODS
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).


CONCLUSIONS
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.
Menichetti
F
F
Istituto di Malattie Infettive, Università di Perugia, Italy.
Del Favero
A
A
Martino
P
P
Bucaneve
G
G
Micozzi
A
A
D'Antonio
D
D
Ricci
P
P
Carotenuto
M
M
Liso
V
V
Nosari
A M
AM
Barbui
T
T
Fasola
G
G
Mandelli
F
F
D000208:Acute Disease; D000284:Administration, Oral; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D010349:Patient Compliance; D016896:Treatment Outcome
D000666:Amphotericin B; D015725:Fluconazole