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.

Abstract

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.

• Authors: John H Rex, Peter G Pappas, Adolf W Karchmer, Jack Sobel, John E Edwards, Susan Hadley, Corstiaan Brass, Jose A Vazquez, Stanley W Chapman, Harold W Horowitz, Marcus Zervos, David McKinsey, Jeannette Lee, Timothy Babinchak, Robert W Bradsher, John D Cleary, David M Cohen, Larry Danziger, Mitchell Goldman, Jesse Goodman, Eileen Hilton, Newton E Hyslop, Daniel H Kett, Jon Lutz, Robert H Rubin, W Michael Scheld, Mindy Schuster, Bryan Simmons, David K Stein, Ronald G Washburn, Linda Mautner, Teng-Chiao Chu, Helene Panzer, Rebecca B Rosenstein, Jenia Booth, National Institute of Allergy and Infectious Diseases Mycoses Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 36 Issue 10 Pg. 1221-8 (May 15 2003) ISSN: 1537-6591 [Electronic] United States
• PMID: 12746765 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antifungal Agents
• Amphotericin B
• Fluconazole

Topics

• Adult
• Amphotericin B (adverse effects, therapeutic use)
• Antifungal Agents (adverse effects, therapeutic use)
• Candida (drug effects)
• Candidiasis (drug therapy, physiopathology)
• Catheterization
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Fluconazole (adverse effects, therapeutic use)
• Fungemia (drug therapy, physiopathology)
• Humans
• Male
• Middle Aged
• Neutropenia (etiology)
• Treatment Outcome