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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Available from: Alfred Balch, Oct 07, 2015
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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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    ABSTRACT: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in the immunocompromised. The traditional diagnostic methods of culture and histological examination lack sensitivity and often only make a diagnosis late when the fungal burden is high, reducing the chances of cure even with the availability of new more potent and less toxic antifungal agents. New non-culture-based serological and PCR assays have been developed. These appear more sensitive and are able to make an earlier diagnosis as compared with traditional diagnostic methods. Early diagnosis is central to reducing IFI-related morbidity and mortality. This review describes the diagnostic potential of the new serological and PCR assays and outlines how these assays have been incorporated into algorithms to improve the management of IFI.
    Current Fungal Infection Reports 03/2013; 7(1):51-58. DOI:10.1007/s12281-012-0128-4
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    ABSTRACT: There are increasing numbers of patients at risk for invasive fungal infections (IFI). The early diagnosis of IFI’s is limited by the lack of sensitivity and delayed turn-around time of routine cultures. Delays in diagnosis are associated with poor outcomes, especially with immunocompromised hosts and patients within the intensive care unit (ICU). Over the last decade, fungal biomarkers such as galactomannan and 1,3-β-D-glucan (BDG) have been increasingly utilized for the early and accurate diagnosis of these infections. This review will evaluate the recent clinical data on the BDG assay, focusing on its ability to assist in the diagnosis of invasive candidiasis in the ICU, and also whether BDG kinetics can predict the prognosis of the patient. Similarly, this review will evaluate BDG in invasive Aspergillus and Pneumocystis jiroveci diagnosis and prognosis, as well as the current limitations of the assay.
    Current Fungal Infection Reports 03/2012; 7(1). DOI:10.1007/s12281-012-0118-6
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    ABSTRACT: Invasive fungal infections present a great challenge in modern medicine. The recent devel-opment of serologic markers represents a clear advance in the field. Two serological tests have been developed: (1,3)-β-D glucan and Aspergillus galactomannan. This review discusses highlights of both tests.ResumenLas infecciones invasoras por hongos representan un gran reto para la medicina moderna. El reciente desarrollo de marcadores serológicos representa un claro avance en este campo. Se han desarrollados dos pruebas serológicas: (1,3)-β-d-glucano y galactomanano de Aspergillus. Esta revisión recoge los aspectos más destacados de cada una de las pruebas.
    Infectio 12/2012; 16:59–63. DOI:10.1016/S0123-9392(12)70028-0
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