A Randomized Trial Comparing Fluconazole With Amphotericin B For The Treatment Of Candidemia In Patients Without Neutropenia.
Rex, John H.; Bennett, John E.; Sugar, Alan M.; Pappas, Peter G.; van der Horst, Charles M.; Edwards, John E.; Washburn, Ronald G.; Scheld, W. Michael; Karchmer, Adolf W.; Dine, Alan P.; Levenstein, Marcia J.; Webb, C. Douglas.
[Article] New England Journal of Medicine. 331(20):1325-1330, November 17, 1994.

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Background: Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia.

Methods: To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count greater/= 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment.

Results: Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent; P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B.

Conclusions: In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia. (N Engl J Med 1994;331:1325-30.)

Owned, published, and (C) copyrighted, 1994, by the MASSACHUSETTS MEDICAL SOCIETY