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Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial

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An Erratum to this article was published on 17 July 2015

Abstract

Purpose

Presepsin is a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity. We evaluated the relation between its circulating concentration, host response, appropriateness of antibiotic therapy, and mortality in patients with severe sepsis.

Methods

Plasma presepsin was measured 1, 2, and 7 days after enrollment of 997 patients with severe sepsis or septic shock in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial. They were randomized to albumin or crystalloids. We tested with univariate and adjusted models the association of single measurements of presepsin or changes over time with clinical events, organ dysfunctions, appropriateness of antibiotic therapy, and ICU or 90-day mortality.

Results

Presepsin concentration at baseline (946 [492–1,887] ng/L) increased with the SOFA score, the number of prevalent organ dysfunctions or failures, and the incidence of new failures of the respiratory, coagulation, liver, and kidney systems. The concentration decreased in ICU over 7 days in patients with negative blood cultures, and in those with positive blood cultures and appropriate antibiotic therapy; it increased with inappropriate antibiotic therapy (p = 0.0009). Baseline presepsin was independently associated with, and correctly reclassified, the risk of ICU and 90-day mortality. Increasing concentrations of presepsin from day 1 to day 2 predicted higher ICU and 90-day mortality (adjusted p < 0.0001 and 0.01, respectively). Albumin had no effect on presepsin concentration.

Conclusions

Presepsin is an early predictor of host response and mortality in septic patients. Changes in concentrations over time seem to reflect the appropriateness of antibiotic therapy.

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Acknowledgments

The authors thank Giuseppe Cappelletti and Alessandro Castelli (GEPA Srl, Bollate, Italy) for valuable help with the presepsin assay.

Conflicts of interest

SM, PC, RL, and LG received limited research support from Mitsubishi Chemical Europe GmbH, the manufacturer of the presepsin assay. RT is an employee at Mitsubishi Chemical Europe GmbH; he had no access to raw data and did not influence the analyses or drafting of the manuscript. The present work was partially presented at EuroMedLab (Milan, May 2013) and at the Annual Meeting of the American Association for Clinical Chemistry (Chicago, July 2014).

Funding

The ALBIOS trial was funded by grants from the Italian Medicines Agency (AIFA, grant FARM6JS3R5, 2006) and the Italian Ministry of Health (Ricerca Finalizzata 2011–2012, grant RF-2011-02348358). Reagents for measuring presepsin were kindly provided by Mitsubishi Chemical Europe GmbH.

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Authors and Affiliations

  1. Department of Cardiovascular Research, IRCCS–Istituto di Ricerche Farmacologiche “Mario Negri”, Via Privata Giuseppe La Masa 19, 20156, Milan, Italy

    Serge Masson, Roberto Bernasconi & Roberto Latini

  2. Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

    Pietro Caironi & Luciano Gattinoni

  3. Dipartimento di Anestesia, Rianimazione, ed Emergenza Urgenza, Fondazione IRCCS Ca’ Granda–Ospedale Maggiore Policlinico, Milan, Italy

    Pietro Caironi & Luciano Gattinoni

  4. Fondazione Mario Negri Sud, Santa Maria Imbaro, Italy

    Caterina Fanizza, Marilena Romero & Gianni Tognoni

  5. Mitsubishi Chemical Europe GmbH, Duesseldorf, Germany

    Ralf Thomae

  6. Azienda Ospedaliera San Paolo, Milan, Italy

    Andrea Noto

  7. Ospedale del Mugello, Borgo San Lorenzo, Italy

    Roberto Oggioni

  8. Ospedale Civile S. Giovanni di Dio, Orbetello Scalo, Italy

    Giovanni Stefano Pasetti

Authors
  1. Serge Masson
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  2. Pietro Caironi
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  3. Caterina Fanizza
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  4. Ralf Thomae
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  5. Roberto Bernasconi
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  6. Andrea Noto
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  7. Roberto Oggioni
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  8. Giovanni Stefano Pasetti
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  9. Marilena Romero
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  10. Gianni Tognoni
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  11. Roberto Latini
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  12. Luciano Gattinoni
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Corresponding author

Correspondence to Serge Masson.

Additional information

On behalf of the ALBIOS Study Investigators.

A complete list of centers and investigators participating in the ALBIOS substudy on biomarkers was published elsewhere (Masson et al. 2014, Crit Care 18:R6).

S. Masson and P. Caironi contributed equally to the present work.

Take-home message: Presepsin, a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity, is an early and accurate predictor of host response and mortality in patients with severe sepsis enrolled in the multicenter ALBIOS trial. Changes in its concentration over time may reflect appropriateness of the antibiotic therapy applied.

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Masson, S., Caironi, P., Fanizza, C. et al. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial. Intensive Care Med 41, 12–20 (2015). https://doi.org/10.1007/s00134-014-3514-2

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  • DOI: https://doi.org/10.1007/s00134-014-3514-2

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