Multicenter clinical evaluation of the (1→3) β-D-glucan assay as an aid to diagnosis of fungal infections in humans

Luis Ostrosky-Zeichner, Barbara D. Alexander, Daniel H. Kett, Jose Vazquez, Peter G. Pappas, Fumihiro Saeki, Paul A. Ketchum, John Wingard, Robert Schiff, Hiroshi Tamura, Malcolm A. Finkelman, John H. Rex

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519 Scopus citations

Abstract

Background. Measurement of (1→3)-β-D-glucan (BG) has emerged as an adjunct diagnostic strategy for invasive fungal infections (IFI). Methods. Subjects at 6 clinical sites in the United States were enrolled as either fungal infection-negative subjects (n = 170) or subjects with proven or probable IFI according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria (n = 163). A central laboratory and 4 sites performed assays. A single sample was obtained per patient and was evaluated using an assay to detect serum BG derived from fungal cell walls (range, 0 to >7000 pg/mL). Results. At a cutoff of 60 pg/mL, the sensitivity and specificity of the assay were 69.9% and 87.1%, respectively, with a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 75.1%. At a cutoff value of 80 pg/mL, the sensitivity and specificity were 64.4% and 92.4%, respectively, with a PPV of 89% and an NPV of 73%. Of the 107 patients with proven candidiasis, 81.3% had positive results at a cutoff value of 60 pg/mL, and 77.6% had positive results at a cutoff value of 80 pg/mL. Of the 10 patients with aspergillosis, 80% had positive results at cutoff values of 60 and 80 pg/mL. The 3 subjects diagnosed with Fusarium species had positive results at a cutoff value of 60 pg/mL. Patients infected with Mucor or Rhizopus species (both of which lack BG) had negative results at both cutoff values, and of the 12 patients with Cryptococcus infection, 3 had positive results at a cutoff value of 60 pg/mL, and 2 had positive results at a cutoff value of 80 pg/mL. Of the subjects with proven positive results who were receiving antifungal therapy (n = 118), 72.9% had results positive for BG at a cutoff value of 60 pg/mL, and 69.5% had results positive for BG at a cutoff value of 80 pg/mL. The interlaboratory sample test r 2 was 0.93. Conclusion. Reproducible assay results with high specificity and high PPV in a multicenter setting demonstrate that use of an assay to detect serum BG derived from fungal cell walls is a useful diagnostic adjunct for IFI.

Original languageEnglish (US)
Pages (from-to)654-659
Number of pages6
JournalClinical Infectious Diseases
Volume41
Issue number5
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Ostrosky-Zeichner, L., Alexander, B. D., Kett, D. H., Vazquez, J., Pappas, P. G., Saeki, F., Ketchum, P. A., Wingard, J., Schiff, R., Tamura, H., Finkelman, M. A., & Rex, J. H. (2005). Multicenter clinical evaluation of the (1→3) β-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clinical Infectious Diseases, 41(5), 654-659. https://doi.org/10.1086/432470