• Serge Masson, Pietro Caironi, Caterina Fanizza, Ralf Thomae, Roberto Bernasconi, Andrea Noto, Roberto Oggioni, Giovanni Stefano Pasetti, Marilena Romero, Gianni Tognoni, Roberto Latini, and Luciano Gattinoni.
• Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via Privata Giuseppe La Masa 19, 20156, Milan, Italy, serge.masson@marionegri.it.
• Intensive Care Med. 2015 Jan 1; 41 (1): 12-20.

PurposePresepsin 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.MethodsPlasma 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.ResultsPresepsin 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.ConclusionsPresepsin 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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