Systemic Host Responses in Severe Sepsis Analyzed by Causative Microorganism and Treatment Effects of Drotrecogin Alfa (Activated)

Abstract

Clinical trials with novel therapeutic agents for severe sepsis have suggested that patients might respond differently depending on causative microorganism. Data from a large, placebo-controlled trial of recombinant human drotrecogin alfa (activated) (DrotAA) were analyzed by type of causative microorganism for treatment-associated differences in mortality, coagulopathy, and inflammatory response. Compared with placebo, mortality rates associated with DrotAA were consistently reduced for each microorganism group (gram-positive bacteria, gram-negative bacteria, mixed bacteria, fungi, other, and unknown microbial etiology), with a stratified relative risk (RR) of 0.80 (95% confidence interval [CI], 0.69-0.94). The greatest reduction in the mortality rate was for Streptococcus pneumoniae infection (RR, 0.56; 95% CI, 0.35-0.88). Levels of coagulation and inflammation biomarkers varied with different pathogens at study entry. Results demonstrate that DrotAA, administered as an adjunct to standard anti-infective therapy, can improve the rate of survival for patients who develop severe sepsis regardless of causative microorganism.