A Randomized and Blinded Multicenter Trial of High-Dose Fluconazole plus Placebo versus Fluconazole plus Amphotericin B as Therapy for Candidemia and Its Consequences in Nonneutropenic Subjects

• Published in: Clinical infectious diseases Vol. 36; no. 10; pp. 1221 - 1228
• Main Authors: Rex, John H., Pappas, Peter G., Karchmer, Adolf W., Sobel, Jack, Edwards, John E., Hadley, Susan, Brass, Corstiaan, Vazquez, Jose A., Chapman, Stanley W., Horowitz, Harold W., Zervos, Marcus, McKinsey, David, Lee, Jeannette, Babinchak, Timothy, Bradsher, Robert W., Cleary, John D., Cohen, David M., Danziger, Larry, Goldman, Mitchell, Goodman, Jesse, Hilton, Eileen, Hyslop, Newton E., Kett, Daniel H., Lutz, Jon, Rubin, Robert H., Scheld, W. Michael, Schuster, Mindy, Simmons, Bryan, Stein, David K., Washburn, Ronald G., Mautner, Linda, Chu, Teng-Chiao, Panzer, Helene, Rosenstein, Rebecca B., Booth, Jenia
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15.05.2003; University of Chicago Press
• Subjects: Adult; Amphotericin B - adverse effects; Amphotericin B - therapeutic use; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; Antifungals; Blood; Candida - drug effects; Candidemia; Candidiasis - drug therapy; Candidiasis - physiopathology; Catheterization; Catheters; Cultural groups; Dosage; Double-Blind Method; Drug Therapy, Combination; Female; Fluconazole - adverse effects; Fluconazole - therapeutic use; Fungemia - drug therapy; Fungemia - physiopathology; Humans; Infections; Infectious diseases; Logistic regression; Major Articles; Male; Middle Aged; Neutropenia - etiology; Placebos; Treatment Outcome
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/374850

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (± standard error) Acute Physiology and Chronic Health Evaluation II score (16.8 ± 0.6 vs. 15.0 ± 0.7; P = .039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P = .08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P = .043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P = .02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.