title: A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients.
abstract: Fluconazole antifungal prophylaxis is standard care in allogeneic hematopoietic stem cell transplant (HSCT) recipients, but this drug lacks anti-Aspergillus activity, the primary cause of invasive fungal infection (IFI) in many transplantation centers. We performed a randomized trial to compare itraconazole vs fluconazole, for prevention of IFIs in patients with acute leukemia (AL) and HSCT recipients. One hundred and ninety-five patients were randomly assigned to either fluconazole or itraconazole antifungal prophylaxis, after stratification into high-risk and low-risk groups. Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia, or until amphotericin B treatment was started. IFI occurred in 11 (11%) of itraconazole, and in 12 (12%) fluconazole recipients. Invasive candidiasis (IC) developed in two (2%) itraconazole and one (1%) fluconazole recipients, while invasive aspergillosis (IA) developed in nine (9%) itraconazole and 11(11%) fluconazole recipients. There was no difference in the incidence of total IFI, IC and IA between the two study arms. However, there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis (3/9=33% vs 8/11=73%, P=0.095).
authors.affiliation: Infectious Diseases Unit, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. i_oren@rambam.health.gov.il
authors.forename: I
authors.initials: I
authors.lastname: Oren
authors.forename: J M
authors.initials: JM
authors.lastname: Rowe
authors.forename: H
authors.initials: H
authors.lastname: Sprecher
authors.forename: A
authors.initials: A
authors.lastname: Tamir
authors.forename: N
authors.initials: N
authors.lastname: Benyamini
authors.forename: L
authors.initials: L
authors.lastname: Akria
authors.forename: A
authors.initials: A
authors.lastname: Gorelik
authors.forename: N
authors.initials: N
authors.lastname: Dally
authors.forename: T
authors.initials: T
authors.lastname: Zuckerman
authors.forename: N
authors.initials: N
authors.lastname: Haddad
authors.forename: R
authors.initials: R
authors.lastname: Fineman
authors.forename: E J
authors.initials: EJ
authors.lastname: Dann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000517:prevention & control* / Q000628:therapy; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use*; D007938:Leukemia / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000628:therapy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D015725:Fluconazole