Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia

Thomas J. Walsh, Robert W. Finberg, Carola Arndt, John Hiemenz, Cindy Schwartz, David Bodensteiner, Peter Pappas, Nita Seibel, Richard N. Greenberg, Stephen Dummer, Mindy Schuster, John S. Holcenberg, William E. Dismukes

Research output: Contribution to journalArticle

Abstract

Background: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. Methods: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. Results: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P

Original languageEnglish (US)
Pages (from-to)764-771
Number of pages8
JournalNew England Journal of Medicine
Volume340
Issue number10
DOIs
StatePublished - Mar 11 1999
Externally publishedYes

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Amphotericin B
Neutropenia
Fever
Mycoses
Therapeutics
Colony-Stimulating Factors
Chills
Poisons
Hypotension
Multicenter Studies
liposomal amphotericin B
Creatinine
Hypertension
Survival
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Walsh, T. J., Finberg, R. W., Arndt, C., Hiemenz, J., Schwartz, C., Bodensteiner, D., ... Dismukes, W. E. (1999). Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia. New England Journal of Medicine, 340(10), 764-771. https://doi.org/10.1056/NEJM199903113401004

Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia. / Walsh, Thomas J.; Finberg, Robert W.; Arndt, Carola; Hiemenz, John; Schwartz, Cindy; Bodensteiner, David; Pappas, Peter; Seibel, Nita; Greenberg, Richard N.; Dummer, Stephen; Schuster, Mindy; Holcenberg, John S.; Dismukes, William E.

In: New England Journal of Medicine, Vol. 340, No. 10, 11.03.1999, p. 764-771.

Research output: Contribution to journalArticle

Walsh, TJ, Finberg, RW, Arndt, C, Hiemenz, J, Schwartz, C, Bodensteiner, D, Pappas, P, Seibel, N, Greenberg, RN, Dummer, S, Schuster, M, Holcenberg, JS & Dismukes, WE 1999, 'Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia', New England Journal of Medicine, vol. 340, no. 10, pp. 764-771. https://doi.org/10.1056/NEJM199903113401004
Walsh, Thomas J. ; Finberg, Robert W. ; Arndt, Carola ; Hiemenz, John ; Schwartz, Cindy ; Bodensteiner, David ; Pappas, Peter ; Seibel, Nita ; Greenberg, Richard N. ; Dummer, Stephen ; Schuster, Mindy ; Holcenberg, John S. ; Dismukes, William E. / Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia. In: New England Journal of Medicine. 1999 ; Vol. 340, No. 10. pp. 764-771.
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AU - Walsh, Thomas J.

AU - Finberg, Robert W.

AU - Arndt, Carola

AU - Hiemenz, John

AU - Schwartz, Cindy

AU - Bodensteiner, David

AU - Pappas, Peter

AU - Seibel, Nita

AU - Greenberg, Richard N.

AU - Dummer, Stephen

AU - Schuster, Mindy

AU - Holcenberg, John S.

AU - Dismukes, William E.

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N2 - Background: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. Methods: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. Results: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P

AB - Background: In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. Methods: We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. Results: The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P

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