β-D-glucan Surveillance with Preemptive Anidulafungin for Invasive Candidiasis in Intensive Care Unit Patients: A Randomized Pilot Study

Department of Medicine and Pathology, University of Utah, Salt Lake City, Utah, United States of America.
PLoS ONE (Impact Factor: 3.23). 08/2012; 7(8):e42282. DOI: 10.1371/journal.pone.0042282
Source: PubMed


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.
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.
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.
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.
Clinical NCT00672841.

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    • "A randomized controlled trial (RCT) comparing a DD-strategy that guided the administration of anidulafungin therapy based on a positive BDG result (>80 pg/ml; Fungitell assay) to the administration of anidulafungin empirically based on physician’s preference reported that BDG levels were significantly higher in those with an IFI versus those who had no IFI (117 vs. 28 pg/ml; p < 0.001) [58]. Analysis of test performance indicated that the use of two sequential BDG results >80 pg/ml had a sensitivity, specificity, PPV and NPV of 100 %, 75 %, 30 % and 100 %, respectively. "
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