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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0042282

Publication Info

Hanson, Kimberly E, Christopher D Pfeiffer, Erika D Lease, Alfred H Balch, Aimee K Zaas, John R Perfect and Barbara D Alexander (2012). β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: a randomized pilot study. PloS one, 7(8). p. e42282. 10.1371/journal.pone.0042282 Retrieved from https://hdl.handle.net/10161/26034.

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Scholars@Duke

Zaas

Aimee Kirsch Zaas

Professor of Medicine

Medical education
Genomic applications for diagnosis of infectious diseases
Genomic applications for prediction of infectious diseases

Perfect

John Robert Perfect

James B. Duke Distinguished Professor of Medicine

Research in my laboratory focuses around several aspects of medical mycology. We are investigating antifungal agents (new and old) in animal models of candida and cryptococcal infections. We have examined clinical correlation of in vitro antifungal susceptibility testing and with in vivo outcome. Our basic science project examines the molecular pathogenesis of cryptococcal infections. We have developed a molecular foundation for C. neoformans, including transformation systems, gene disruptions, differential gene expression screens, and cloning pathogenesis genes. The goal of this work is to use C. neoformans as a model yeast system to identify molecular targets for antifungal drug development. There are a series of clinical trials in fungal infections which are being coordinated through this laboratory and my work also includes a series of antibiotic trials in various aspects of infections. Finally, we have now been awarded a NIH sponsored Mycology Unit for 5 years with 6 senior investigators which is focused on C. neoformans as a pathogenic model system, but will include multiple areas of medical mycology from diagnosis to treatment.

Alexander

Barbara Dudley Alexander

Professor of Medicine

Clinical research related to infectious complications of solid organ and bone marrow transplantation, with a particular interest in the treatment and rapid diagnosis of fungal disease. Training the next generation of Transplant Infectious Disease Physicians is a special focus of mine as the Principal Investigator of our Interdisciplinary T32 Training Program funded the NIH. 


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