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Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1,3)-β-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease

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Abstract

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75–0.99]) and BG (0.856 [95% CI, 0.71–0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39–0.82) and 0.768 (95% CI, 0.63–0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

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Acknowledgements

This work was supported by grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, PI070107 (to A.d.P), PI070134 (to M.S.C.), and PI070376(to J.P. and M.D.M.); by a grant from the Department of Education, Universities and Research, Basque Government, IT-264-07 (to J.P. and M.D.M.); and by a Pfizer and Gilead independent investigation research grants to A.d.P. All the co-authors, with the exception of M. Finkelman, have no dual or conflicting interests. M. Finkelman is an employee of Associates of Cape Cod, Inc., the manufacturer of the Fungitell kit.

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Authors and Affiliations

  1. Department of Medical Microbiology, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, Madrid, 28041, Spain

    J. Acosta & A. del Palacio

  2. Medical Intensive Care Unit, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, Madrid, 28041, Spain

    M. Catalan & J.-C. Montejo

  3. Department of Internal Medicine, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, Madrid, 28041, Spain

    A. del Palacio-Pérez-Medel

  4. Clinical Epidemiology Unit, Hospital Universitario 12 de Octubre, Biomedical Research Institute (imas12), Avenida de Córdoba s/n, Madrid, 28041, Spain

    J. De-La-Cruz-Bértolo

  5. Department of Nursing, Universidad del País Vasco, Campus Universitario, Leioa, 48940, Spain

    M.-D. Moragues

  6. Department of Immunology, Microbiology, and Parasitology, School of Medicine and Dentistry, Universidad del País Vasco, Campus Universitario, Leioa, 48940, Spain

    J. Pontón

  7. Falmouth Technology Park, Associates of Cape Cod, Inc., East Falmouth, Massachusetts, 124 Bernard E. Saint Jean Drive, East Falmouth, MA, 02536-4445, USA

    M. A. Finkelman

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  1. J. Acosta
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  9. A. del Palacio
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Correspondence to A. del Palacio.

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This work is dedicated to the memory of Jose Ponton who passed away on 21 July 2010

Electronic supplementary materials

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Online Resource 1

Characteristics of patients with proven and probable IFD (n=23) (PDF 102 kb)

Online Resource 2

Performance of serum GM determination in invasive aspergillosis case patients (PDF 104 kb)

Online Resource 3

Performance of BG determination in serum (PDF 73 kb)

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Acosta, J., Catalan, M., del Palacio-Pérez-Medel, A. et al. Prospective study in critically ill non-neutropenic patients: diagnostic potential of (1,3)-β-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease. Eur J Clin Microbiol Infect Dis 31, 721–731 (2012). https://doi.org/10.1007/s10096-011-1365-0

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