Biomarkers of Thrombosis, Fibrinolysis, and Inflammation in Patients with Severe Sepsis due to Community-Acquired Pneumonia with and without Streptococcus pneumoniae

Background: Severe Streptococcus pneumoniae (S. pneum) pneumonia has historically been associated with an acute presentation and increased mortality. Using data from patients with community-acquired pneumonia (CAP) and severe sepsis, we investigated: (1) the baseline patient characteristics and biomarkers of thrombosis, fibrinolysis, and inflammation in patients with CAP due to S. pneum infection (S. pneum CAP) or CAP due to infection with other or unidentified organisms (non-S. pneum CAP); (2) the behavior of these biomarkers over time and during treatment with drotrecogin alfa (activated) (DrotAA, recombinant activated protein C). Patients and Methods: Data from the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation on Severe Sepsis) trial were retrospectively analyzed by treatment (DrotAA or placebo) in patients with CAP. Results: Patients with S. pneum CAP (n = 157) tended to be younger and had fewer comorbid conditions than patients with non-S. pneum CAP (n = 445). Overall disease severity (median APACHE II scores) was not significantly different between the two groups at baseline. However, there were significant baseline differences in protein C and markers of coagulation, fibrinolysis, and inflammation. Although thrombosis markers were not different at baseline, D-dimer levels significantly increased from baseline to day 4 in placebo-treated patients with S. pneum compared to those with non-S. pneum. DrotAA treatment was associated with statistically significant improvements in protein C and markers of thrombosis in patients with S. pneum. In addition, the proportion of patients with severe protein C deficiency (