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.
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.
Rex
John H
JH
Division of Infectious Diseases, University of Texas Medical School, Houston, TX 77030, USA. john@rexweb.org
Pappas
Peter G
PG
Karchmer
Adolf W
AW
Sobel
Jack
J
Edwards
John E
JE
Hadley
Susan
S
Brass
Corstiaan
C
Vazquez
Jose A
JA
Chapman
Stanley W
SW
Horowitz
Harold W
HW
Zervos
Marcus
M
McKinsey
David
D
Lee
Jeannette
J
Babinchak
Timothy
T
Bradsher
Robert W
RW
Cleary
John D
JD
Cohen
David M
DM
Danziger
Larry
L
Goldman
Mitchell
M
Goodman
Jesse
J
Hilton
Eileen
E
Hyslop
Newton E
NE
Kett
Daniel H
DH
Lutz
Jon
J
Rubin
Robert H
RH
Scheld
W Michael
WM
Schuster
Mindy
M
Simmons
Bryan
B
Stein
David K
DK
Washburn
Ronald G
RG
Mautner
Linda
L
Chu
Teng-Chiao
TC
Panzer
Helene
H
Rosenstein
Rebecca B
RB
Booth
Jenia
J
D000328:Adult; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy* / Q000503:physiopathology; D002404:Catheterization; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D016469:Fungemia / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D016896:Treatment Outcome
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole