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

Opal, Steven M.; Garber, Gary E.; LaRosa, Steven P.; Maki, Dennis G.; Freebairn, Ross C.; Kinasewitz, Gary T.; Dhainaut, Jean-Francois; Yan, S. Betty; Williams, Mark D.; Graham, Delores E.; Nelson, David R.; Levy, Howard; Bernard, Gordon R.
July 2003
Clinical Infectious Diseases;7/1/2003, Vol. 37 Issue 1, p50
Academic Journal
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.


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