Endothelial glycocalyx injury in bacterial bloodstream infection: biological determinants and association with host response aberrations.

INTRODUCTION

Damage to the endothelial glycocalyx plays a key role in the pathogenesis of sepsis. Syndecan-1 is a widely used biomarker of glycocalyx degradation. The objectives of this study were (1) to determine whether the pathogen type is correlated with differences in glycocalyx disruption in critically ill patients with bacterial bloodstream infection (BSI) and (2) to assess the association of plasma syndecan-1 levels with host response changes implicated in the pathogenesis of sepsis.

METHODS

We measured 24 plasma biomarkers reflective of key pathophysiological domains and whole-blood transcriptomes in intensive care unit (ICU) patients with bacterial BSI. Plasma syndecan-1 was used as biomarker of glycocalyx degradation.

RESULTS

In 188 ICU patients, the most common pathogens were Escherichia coli (n =38), Streptococcus spp. (n =34), Enterococcus spp. (n =25), and Staphylococcus aureus (n =23). Higher syndecan-1 was independently associated with increased 30-day mortality. Disease severity explained most syndecan-1 variance (19.2%), whereas pathogen category (6.7%) and infection site (2.2%) contributed little. High syndecan-1 was associated with host response changes, particularly those related to endothelial dysfunction, followed by inflammation and coagulation. Restricted cubic spline regression, mapping biomarker variation across the range of syndecan-1 levels, suggested that some host response anomalies were most pronounced at relatively high degree of glycocalyx degradation (impairment of endothelial barrier function, signs of consumptive coagulopathy), whereas others showed stronger associations at lower syndecan-1 levels (endothelial cell activation and injury). Analysis of the blood transcriptome in a subgroup of patients (n =142) revealed enhanced expression of hemostasis-related pathways, notably platelet degranulation, in patients with elevated syndecan-1 levels.

DISCUSSION: In ICU patients with BSI, glycocalyx disruption as measured by plasma syndecan-1 is associated with poor clinical outcomes and a variety of host response aberrations. Glycocalyx disruption in BSI appears to relate more strongly to disease severity than to the causative pathogen category.