Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients

  • P. Phillips
  • S. Shafran
  • G. Garber
  • C. Rotstein
  • F. Smaill
  • I. Fong
  • I. Salit
  • M. Miller
  • K. Williams
  • J. M. Conly
  • J. Singer
  • S. Ioannou
  • for the Canadian Candidemia Study Group
Article

DOI: 10.1007/BF01726360

Cite this article as:
Phillips, P., Shafran, S., Garber, G. et al. Eur. J. Clin. Microbiol. Infect. Dis. (1997) 16: 337. doi:10.1007/BF01726360

Abstract

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1∶:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due toCandida glabrata orCandida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p=0.39; one-sided 95% Cl, −8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p=0.66: one-sided 95% Cl, −12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p=0.52; chi-square test) and remained similar throughout the course of follow-up. Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Copyright information

© MMV Medizin Verlag GmbH Munchen 1997

Authors and Affiliations

  • P. Phillips
    • 1
  • S. Shafran
    • 2
  • G. Garber
    • 3
  • C. Rotstein
    • 4
  • F. Smaill
    • 5
  • I. Fong
    • 6
  • I. Salit
    • 7
  • M. Miller
    • 8
  • K. Williams
    • 9
  • J. M. Conly
    • 9
    • 10
  • J. Singer
    • 11
  • S. Ioannou
    • 12
  • for the Canadian Candidemia Study Group
  1. 1.Division of Infectious DiseasesSt. Paul's Hospital and the University of British ColumbiaVancouverCanada
  2. 2.Division of Infectious DiseasesUniversity of Alberta, 2E4.11 Walter MacKenzie CentreEdmontonCanada
  3. 3.Division of Infectious Diseases, Ottawa General HospitalUniversity of OttawaOttawaCanada
  4. 4.Division of Infectious Diseases, McMaster Medical UnitHenderson General HospitalHamiltonCanada
  5. 5.Division of Infectious DiseasesMcMaster University Medical CentreHamiltonCanada
  6. 6.St. Michael's HospitalTorontoCanada
  7. 7.Division of Infectious DiseasesToronto General HospitalTorontoCanada
  8. 8.Department of Medical MicrobiologyJewish General HospitalMontrealCanada
  9. 9.Division of Infectious DiseasesRoyal University HospitalSaskatoonCanada
  10. 10.Toronto HospitalTorontoCanada
  11. 11.Department of Health Care and EpidemiologyUniversity of British ColumbiaVancouverCanada
  12. 12.Pfizer Canada, Inc.Point ClaireCanada