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Evaluation of serum (1 → 3)-β-d-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors

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Abstract

Purpose

We investigated the clinical performance of (1 → 3)-β-d-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings.

Methods

BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls.

Results

We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected.

Conclusion

Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.

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Acknowledgments

We thank Dr. Andrea Ardizzoni for the critical reading of the manuscript and suggestions.

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Authors and Affiliations

  1. Dipartimento Interaziendale Integrato di Medicina di Laboratorio e Anatomia Patologica, Struttura Complessa di Microbiologia e Virologia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy

    P. Pini, C. Bettua & C. Venturelli

  2. Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy

    P. Pini

  3. Dipartimento di Medicina Diagnostica, Clinica e di Sanità Pubblica, Istituti Biologici, Università di Modena e Reggio Emilia, Via Campi 287, 41125, Modena, Italy

    C. F. Orsi & Elisabetta Blasi

  4. Dipartimento di Scienze della Salute, Università di Milano, Polo Universitario San Paolo, Milan, Italy

    C. F. Orsi

  5. Dipartimento Attività Integrata di Oncologia, Ematologia e Patologie dell’Apparato Respiratorio, Ematologia, Azienda Ospedaliero-Universitaria Policlinico, Università di Modena e Reggio Emilia, Modena, Italy

    F. Forghieri, S. Bigliardi, L. Faglioni & M. Luppi

  6. Dipartimento Attività Integrata di Oncologia, Ematologia e Patologie dell’Apparato Respiratorio, Malattie dell’Apparato Respiratorio, Università di Modena e Reggio Emilia, Modena, Italy

    F. Luppi

  7. Divisione di Anestesiologia e Terapia Intensiva, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy

    L. Serio & M. Girardis

  8. Dipartimento Attività Integrata di Medicine, Medicina d’Urgenza e Specialità Mediche, Malattie infettive, Università di Modena e Reggio Emilia, Modena, Italy

    M. Codeluppi & C. Mussini

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  1. P. Pini
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  2. C. Bettua
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Correspondence to Elisabetta Blasi.

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All the procedures performed in the study, which involved human participants, were in accordance with the ethical standards of the institutional research committee (no. 53/11) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Pini, P., Bettua, C., Orsi, C.F. et al. Evaluation of serum (1 → 3)-β-d-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors. Infection 44, 223–233 (2016). https://doi.org/10.1007/s15010-015-0849-8

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