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

John H. Rex, Peter G. Pappas, Adolf W. Karchmer, Jack Sobel, John E. Edwards, Susan Hadley, Corstiaan Brass, Jose Antonio 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 & 15 others 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

Research output: Contribution to journalArticle

380 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1221-1228
Number of pages8
JournalClinical Infectious Diseases
Volume36
Issue number10
DOIs
StatePublished - May 15 2003
Externally publishedYes

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Candidemia
Fluconazole
Amphotericin B
Multicenter Studies
Placebos
Therapeutics
APACHE
Neutropenia
Candida
Infection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

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. / Rex, John H.; Pappas, Peter G.; Karchmer, Adolf W.; Sobel, Jack; Edwards, John E.; Hadley, Susan; Brass, Corstiaan; Vazquez, Jose Antonio; 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.

In: Clinical Infectious Diseases, Vol. 36, No. 10, 15.05.2003, p. 1221-1228.

Research output: Contribution to journalArticle

Rex, JH, Pappas, PG, Karchmer, AW, Sobel, J, Edwards, JE, Hadley, S, Brass, C, Vazquez, JA, Chapman, SW, Horowitz, HW, Zervos, M, McKinsey, D, Lee, J, Babinchak, T, Bradsher, RW, Cleary, JD, Cohen, DM, Danziger, L, Goldman, M, Goodman, J, Hilton, E, Hyslop, NE, Kett, DH, Lutz, J, Rubin, RH, Scheld, WM, Schuster, M, Simmons, B, Stein, DK, Washburn, RG, Mautner, L, Chu, TC, Panzer, H, Rosenstein, RB & Booth, J 2003, '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', Clinical Infectious Diseases, vol. 36, no. 10, pp. 1221-1228. https://doi.org/10.1086/374850
Rex, John H. ; Pappas, Peter G. ; Karchmer, Adolf W. ; Sobel, Jack ; Edwards, John E. ; Hadley, Susan ; Brass, Corstiaan ; Vazquez, Jose Antonio ; 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. / 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. In: Clinical Infectious Diseases. 2003 ; Vol. 36, No. 10. pp. 1221-1228.
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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.",
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AU - Goldman, Mitchell

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AU - Hyslop, Newton E.

AU - Kett, Daniel H.

AU - Lutz, Jon

AU - Rubin, Robert H.

AU - Scheld, W. Michael

AU - Schuster, Mindy

AU - Simmons, Bryan

AU - Stein, David K.

AU - Washburn, Ronald G.

AU - Mautner, Linda

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AU - Rosenstein, Rebecca B.

AU - Booth, Jenia

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