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

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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.

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Authors and Affiliations

  1. Division of Infectious Diseases, St. Paul's Hospital and the University of British Columbia, 667-1081 Burrard Street, V6Z l Y6, Vancouver, British Columbia, Canada

    P. Phillips

  2. Division of Infectious Diseases, University of Alberta, 2E4.11 Walter MacKenzie Centre, 8440-112 Street, T6G 2B7, Edmonton, Alberta, Canada

    S. Shafran

  3. Division of Infectious Diseases, Ottawa General Hospital, University of Ottawa, 501 Smythe Road, K1H 8L6, Ottawa, Ontario, Canada

    G. Garber

  4. Division of Infectious Diseases, McMaster Medical Unit, Henderson General Hospital, 711 Concession Street, L8V 1C3, Hamilton, Ontario, Canada

    C. Rotstein

  5. Division of Infectious Diseases, McMaster University Medical Centre, 2N29-1200 Main Street West, L8N 3Z5, Hamilton, Ontario, Canada

    F. Smaill

  6. St. Michael's Hospital, 30 Bond Street, MSB 1W8, Toronto, Ontario, Canada

    I. Fong

  7. Division of Infectious Diseases, Toronto General Hospital, 101 College Street, College Wing, Ground Floor, Room 325, M5G 1L7, Toronto, Ontario, Canada

    I. Salit

  8. Department of Medical Microbiology, Jewish General Hospital, G-142, 3755 Cote-Ste-Catherine, H3T 1E2, Montreal, Quebec, Canada

    M. Miller

  9. Division of Infectious Diseases, Royal University Hospital, S7N 0X0, Saskatoon, Saskatchewan, Canada

    K. Williams & J. M. Conly

  10. Toronto Hospital, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada

    J. M. Conly

  11. Department of Health Care and Epidemiology, University of British Columbia, 5th floor - 1081 Burrard Street, V6Z 1 Y6, Vancouver, British Columbia, Canada

    J. Singer

  12. Pfizer Canada, Inc., P O Box 800, H9R 4V2, Point Claire, Quebec, Canada

    S. Ioannou

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Phillips, P., Shafran, S., Garber, G. et al. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Eur. J. Clin. Microbiol. Infect. Dis. 16, 337–345 (1997). https://doi.org/10.1007/BF01726360

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