MSG-01

A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting

Luis Ostrosky-Zeichner, Shmuel Shoham, Jose Antonio Vazquez, Annette Reboli, Robert Betts, Michelle A. Barron, Mindy Schuster, Marc A. Judson, Sanjay G. Revankar, Juan Pablo Caeiro, Julie E. Mangino, David Mushatt, Roger Bedimo, Alison Freifeld, Minh Hong Nguyen, Carol A. Kauffman, William E. Dismukes, Andrew O. Westfall, Jeanna Beth Deerman, Craig Wood & 2 others Jack D. Sobel, Peter G. Pappas

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P =. 14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.

Original languageEnglish (US)
Pages (from-to)1219-1226
Number of pages8
JournalClinical Infectious Diseases
Volume58
Issue number9
DOIs
StatePublished - Jan 1 2014

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caspofungin
Invasive Candidiasis
Sodium Glutamate
Critical Care
Placebos
Intensive Care Units
Incidence
Therapeutics
Glucans
Mortality
Parenteral Nutrition
Immunosuppressive Agents
Pancreatitis
Dialysis
Length of Stay
Steroids
Clinical Trials
Anti-Bacterial Agents
Morbidity
Safety

Keywords

  • ICU
  • caspofungin
  • invasive candidiasis
  • preemptive therapy
  • prophylaxis

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)
  • Medicine(all)

Cite this

MSG-01 : A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. / Ostrosky-Zeichner, Luis; Shoham, Shmuel; Vazquez, Jose Antonio; Reboli, Annette; Betts, Robert; Barron, Michelle A.; Schuster, Mindy; Judson, Marc A.; Revankar, Sanjay G.; Caeiro, Juan Pablo; Mangino, Julie E.; Mushatt, David; Bedimo, Roger; Freifeld, Alison; Nguyen, Minh Hong; Kauffman, Carol A.; Dismukes, William E.; Westfall, Andrew O.; Deerman, Jeanna Beth; Wood, Craig; Sobel, Jack D.; Pappas, Peter G.

In: Clinical Infectious Diseases, Vol. 58, No. 9, 01.01.2014, p. 1219-1226.

Research output: Contribution to journalArticle

Ostrosky-Zeichner, L, Shoham, S, Vazquez, JA, Reboli, A, Betts, R, Barron, MA, Schuster, M, Judson, MA, Revankar, SG, Caeiro, JP, Mangino, JE, Mushatt, D, Bedimo, R, Freifeld, A, Nguyen, MH, Kauffman, CA, Dismukes, WE, Westfall, AO, Deerman, JB, Wood, C, Sobel, JD & Pappas, PG 2014, 'MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting', Clinical Infectious Diseases, vol. 58, no. 9, pp. 1219-1226. https://doi.org/10.1093/cid/ciu074
Ostrosky-Zeichner, Luis ; Shoham, Shmuel ; Vazquez, Jose Antonio ; Reboli, Annette ; Betts, Robert ; Barron, Michelle A. ; Schuster, Mindy ; Judson, Marc A. ; Revankar, Sanjay G. ; Caeiro, Juan Pablo ; Mangino, Julie E. ; Mushatt, David ; Bedimo, Roger ; Freifeld, Alison ; Nguyen, Minh Hong ; Kauffman, Carol A. ; Dismukes, William E. ; Westfall, Andrew O. ; Deerman, Jeanna Beth ; Wood, Craig ; Sobel, Jack D. ; Pappas, Peter G. / MSG-01 : A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. In: Clinical Infectious Diseases. 2014 ; Vol. 58, No. 9. pp. 1219-1226.
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abstract = "Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7{\%} (14/84) and 9.8{\%} (10/102), respectively, for prophylaxis (P =. 14), and 30.4{\%} (31/102) and 18.8{\%} (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.",
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T2 - A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting

AU - Ostrosky-Zeichner, Luis

AU - Shoham, Shmuel

AU - Vazquez, Jose Antonio

AU - Reboli, Annette

AU - Betts, Robert

AU - Barron, Michelle A.

AU - Schuster, Mindy

AU - Judson, Marc A.

AU - Revankar, Sanjay G.

AU - Caeiro, Juan Pablo

AU - Mangino, Julie E.

AU - Mushatt, David

AU - Bedimo, Roger

AU - Freifeld, Alison

AU - Nguyen, Minh Hong

AU - Kauffman, Carol A.

AU - Dismukes, William E.

AU - Westfall, Andrew O.

AU - Deerman, Jeanna Beth

AU - Wood, Craig

AU - Sobel, Jack D.

AU - Pappas, Peter G.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P =. 14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.

AB - Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P =. 14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P =. 04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234.

KW - ICU

KW - caspofungin

KW - invasive candidiasis

KW - preemptive therapy

KW - prophylaxis

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DO - 10.1093/cid/ciu074

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JO - Clinical Infectious Diseases

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