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β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study.

Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD - PLoS ONE (2012)

Bottom Line: BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001).Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001).Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America. kim.hanson@hsc.utah.edu

ABSTRACT

Background: Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

Methods: Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

Results: Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

Conclusions: BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

Trial registration: Clinical Trials.gov NCT00672841.

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Related in: MedlinePlus

β-D-Glucan Concentrations Over Time in Subjects Receiving Preemptive versus No Antifungal Therapy.The antifungal treatment effect on glucan concentration over time was modeled as a linear trend. Abbreviations: 0 = subjects in the standard care group with at least one positive BDG test, but no systemic antifungal treatment; 2 = subjects in active surveillance group that were treated with preemptive anidulafungin; SE = standard error of the estimated glucan concentration slope.
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pone-0042282-g003: β-D-Glucan Concentrations Over Time in Subjects Receiving Preemptive versus No Antifungal Therapy.The antifungal treatment effect on glucan concentration over time was modeled as a linear trend. Abbreviations: 0 = subjects in the standard care group with at least one positive BDG test, but no systemic antifungal treatment; 2 = subjects in active surveillance group that were treated with preemptive anidulafungin; SE = standard error of the estimated glucan concentration slope.

Mentions: Receipt of preemptive antifungal therapy had a significant effect on median glucan concentrations (p<0.001). However, BDG levels declined in both antifungal treated as well as untreated subjects over time (Figure 3). The slope of the decline was steeper for subjects receiving preemptive as compared to no antifungal therapy (slope −2.7 [SE 1.5] vs. −0.2 [SE 0.5]). The slope difference did not reach statistical significance (one sided p-value 0.06).


β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study.

Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD - PLoS ONE (2012)

β-D-Glucan Concentrations Over Time in Subjects Receiving Preemptive versus No Antifungal Therapy.The antifungal treatment effect on glucan concentration over time was modeled as a linear trend. Abbreviations: 0 = subjects in the standard care group with at least one positive BDG test, but no systemic antifungal treatment; 2 = subjects in active surveillance group that were treated with preemptive anidulafungin; SE = standard error of the estimated glucan concentration slope.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412848&req=5

pone-0042282-g003: β-D-Glucan Concentrations Over Time in Subjects Receiving Preemptive versus No Antifungal Therapy.The antifungal treatment effect on glucan concentration over time was modeled as a linear trend. Abbreviations: 0 = subjects in the standard care group with at least one positive BDG test, but no systemic antifungal treatment; 2 = subjects in active surveillance group that were treated with preemptive anidulafungin; SE = standard error of the estimated glucan concentration slope.
Mentions: Receipt of preemptive antifungal therapy had a significant effect on median glucan concentrations (p<0.001). However, BDG levels declined in both antifungal treated as well as untreated subjects over time (Figure 3). The slope of the decline was steeper for subjects receiving preemptive as compared to no antifungal therapy (slope −2.7 [SE 1.5] vs. −0.2 [SE 0.5]). The slope difference did not reach statistical significance (one sided p-value 0.06).

Bottom Line: BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001).Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001).Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America. kim.hanson@hsc.utah.edu

ABSTRACT

Background: Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.

Methods: Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.

Results: Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.

Conclusions: BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.

Trial registration: Clinical Trials.gov NCT00672841.

Show MeSH
Related in: MedlinePlus