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 Antonio 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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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

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Mycoses
Cell Wall
Mucor
Cryptococcus
Sensitivity and Specificity
Rhizopus
Aspergillosis
Candidiasis
Fusarium
Serum
polyglucosan
Therapeutics
Infection
Research
Invasive Fungal Infections
Neoplasms

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Multicenter clinical evaluation of the (1→3) β-D-glucan assay as an aid to diagnosis of fungal infections in humans. / Ostrosky-Zeichner, Luis; Alexander, Barbara D.; Kett, Daniel H.; Vazquez, Jose Antonio; Pappas, Peter G.; Saeki, Fumihiro; Ketchum, Paul A.; Wingard, John; Schiff, Robert; Tamura, Hiroshi; Finkelman, Malcolm A.; Rex, John H.

In: Clinical Infectious Diseases, Vol. 41, No. 5, 01.09.2005, p. 654-659.

Research output: Contribution to journalArticle

Ostrosky-Zeichner, L, Alexander, BD, Kett, DH, Vazquez, JA, Pappas, PG, Saeki, F, Ketchum, PA, Wingard, J, Schiff, R, Tamura, H, Finkelman, MA & Rex, JH 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, vol. 41, no. 5, pp. 654-659. https://doi.org/10.1086/432470
Ostrosky-Zeichner, Luis ; Alexander, Barbara D. ; Kett, Daniel H. ; Vazquez, Jose Antonio ; Pappas, Peter G. ; Saeki, Fumihiro ; Ketchum, Paul A. ; Wingard, John ; Schiff, Robert ; Tamura, Hiroshi ; Finkelman, Malcolm A. ; Rex, John H. / Multicenter clinical evaluation of the (1→3) β-D-glucan assay as an aid to diagnosis of fungal infections in humans. In: Clinical Infectious Diseases. 2005 ; Vol. 41, No. 5. pp. 654-659.
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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.",
author = "Luis Ostrosky-Zeichner and Alexander, {Barbara D.} and Kett, {Daniel H.} and Vazquez, {Jose Antonio} and Pappas, {Peter G.} and Fumihiro Saeki and Ketchum, {Paul A.} and John Wingard and Robert Schiff and Hiroshi Tamura and Finkelman, {Malcolm A.} and Rex, {John H.}",
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AU - Alexander, Barbara D.

AU - Kett, Daniel H.

AU - Vazquez, Jose Antonio

AU - Pappas, Peter G.

AU - Saeki, Fumihiro

AU - Ketchum, Paul A.

AU - Wingard, John

AU - Schiff, Robert

AU - Tamura, Hiroshi

AU - Finkelman, Malcolm A.

AU - Rex, John H.

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N2 - 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.

AB - 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.

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