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Infections Post Transplant

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

Bone Marrow Transplantation volume 25, pages 853–859 (2000)Cite this article

Abstract

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/μl. 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°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. Bone Marrow Transplantation (2000) 25 , 853–859.

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Authors and Affiliations

  1. Vanderbilt University, Nashville, TN, USA

    SN Wolff, J Greer, R Stein, SA Goodman & S Dummer

  2. Baylor University Medical Center, Dallas, TX, USA

    J Fay, R Collins & L Pineiro

  3. University of Louisville, Louisville, KY, USA

    D Stevens

  4. Jewish Hospital, Cincinnati, OH, USA

    RH Herzig

  5. Cleveland Clinic, Cleveland, OH, USA

    B Pohlman & B Bolwell

  6. West Virginia University, Morgantown, WV, USA

    J Lynch & S Ericson

  7. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    CO Freytes & F LeMaistre

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Wolff, S., Fay, J., Stevens, D. et al. 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. Bone Marrow Transplant 25, 853–859 (2000). https://doi.org/10.1038/sj.bmt.1702233

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