A Randomized Trial Comparing Fluconazole with Amphotericin B for the Treatment of Candidemia in Patients without Neutropenia

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 ≥ 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., There has been substantial controversy over the treatment of patients with candidemia. Descriptions of transient candidemia caused by venous catheters¹ led initially to the conclusion that some episodes might not require treatment. Recent data have, however, documented mortality rates of 46 to 75 percent for a wide variety of patients with candidemia,²–⁷ and the excess mortality attributable to candidemia has been estimated at 38 percent⁸. These data have led to recommendations that all patients with candidemia receive some form of antifungal therapy⁹. Amphotericin B has long been the mainstay of treatment, but its toxicity – which complicates…