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 ca ndidemia, but its use is complicated by its toxicity. More recently, f luconazole, a water-soluble triazole with activity against candida spe cies and little toxicity, has become available. We conducted a multice nter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. Methods. To be eligible, patients had to ha ve a positive blood culture for candida species, a neutrophil count gr eater than or equal to 500 per cubic millimeter, and no major immunode ficiency. Patients were randomly assigned to receive either amphoteric in B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazol e (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investig ators blinded to treatment assignment. Results. Of the 237 patients en rolled, 206 met all entry criteria. The most common diagnoses were ren al failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 pa tients treated with amphotericin B, 81 (79 percent) were judged to hav e been treated successfully, as were 72 of the 103 patients treated wi th fluconazole (70 percent; P = 0.22; 95 percent confidence interval f or the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluco nazole group; the species most commonly associated with failure was Ca ndida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters ap peared to be the most frequent source of candidemia. There was less to xicity with fluconazole than with amphotericin B. Conclusions. In pati ents without neutropenia and without major immunodeficiency, fluconazo le and amphotericin B are not significantly different in their effecti veness in treating candidemia.-