Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group.
Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.
Wolff
S N
SN
Vanderbilt University, Nashville, TN 37232-5505, USA.
Fay
J
J
Stevens
D
D
Herzig
R H
RH
Pohlman
B
B
Bolwell
B
B
Lynch
J
J
Ericson
S
S
Freytes
C O
CO
LeMaistre
F
F
Collins
R
R
Pineiro
L
L
Greer
J
J
Stein
R
R
Goodman
S A
SA
Dummer
S
S
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000633:toxicity; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000633:toxicity; D016026:Bone Marrow Transplantation; D056486:Chemical and Drug Induced Liver Injury; D016001:Confidence Intervals; D005260:Female; D005334:Fever / Q000139:chemically induced; D015725:Fluconazole / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control*; D009503:Neutropenia / Q000382:microbiology; D009656:North America; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000139:chemically induced; D013534:Survival
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole