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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 Positive Predictive Value as a function of varying Disease Prevalence.The positive predictive value of two sequential β-D-Glucan test results ≥80 pg/ml is plotted relative to increasing invasive candidiasis prevalence. Sensitivity and specificity have been fixed at 100% and 75%, respectively.
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pone-0042282-g002: β-D-Glucan Positive Predictive Value as a function of varying Disease Prevalence.The positive predictive value of two sequential β-D-Glucan test results ≥80 pg/ml is plotted relative to increasing invasive candidiasis prevalence. Sensitivity and specificity have been fixed at 100% and 75%, respectively.

Mentions: Composite definitions for proven or probable IFI were used as the “gold standard” for assessments of test performance. BDG had an overall sensitivity, specificity, positive, and negative predictive value of 100%, 50%, 17.6%, and 100%, respectively, when the a priori threshold of ≥60 pg/ml was used to define a positive test. Table 3. displays BDG test characteristics based on varying cut-offs. BDG performed best when 2 sequential specimens with values ≥80 pg/ml were required for a positive result (SN 100%, SP 75%, PPV 30%, and NPV 100%). This modified definition reduced the false positive rate (i.e. 1-specificity) from 50% using the ≥60 pg/ml threshold to 25%, without affecting clinical sensitivity. PPV was also calculated as a function of IC prevalence using the sensitivity and specificity estimates associated with the optimized test cut-off (Figure 2). Modest improvements in the PPV where observed when the disease prevalence was increased from 10% to 20%.


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 Positive Predictive Value as a function of varying Disease Prevalence.The positive predictive value of two sequential β-D-Glucan test results ≥80 pg/ml is plotted relative to increasing invasive candidiasis prevalence. Sensitivity and specificity have been fixed at 100% and 75%, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0042282-g002: β-D-Glucan Positive Predictive Value as a function of varying Disease Prevalence.The positive predictive value of two sequential β-D-Glucan test results ≥80 pg/ml is plotted relative to increasing invasive candidiasis prevalence. Sensitivity and specificity have been fixed at 100% and 75%, respectively.
Mentions: Composite definitions for proven or probable IFI were used as the “gold standard” for assessments of test performance. BDG had an overall sensitivity, specificity, positive, and negative predictive value of 100%, 50%, 17.6%, and 100%, respectively, when the a priori threshold of ≥60 pg/ml was used to define a positive test. Table 3. displays BDG test characteristics based on varying cut-offs. BDG performed best when 2 sequential specimens with values ≥80 pg/ml were required for a positive result (SN 100%, SP 75%, PPV 30%, and NPV 100%). This modified definition reduced the false positive rate (i.e. 1-specificity) from 50% using the ≥60 pg/ml threshold to 25%, without affecting clinical sensitivity. PPV was also calculated as a function of IC prevalence using the sensitivity and specificity estimates associated with the optimized test cut-off (Figure 2). Modest improvements in the PPV where observed when the disease prevalence was increased from 10% to 20%.

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