• Clin. Infect. Dis. · Jul 2003

    Randomized Controlled Trial Multicenter Study Clinical Trial

    Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated).

    • Steven M Opal, Gary E Garber, Steven P LaRosa, Dennis G Maki, Ross C Freebairn, Gary T Kinasewitz, Jean-Francois Dhainaut, S Betty Yan, Mark D Williams, Delores E Graham, David R Nelson, Howard Levy, and Gordon R Bernard.
    • Brown University School of Medicine, Providence, RI, USA. Steven_Opal@brown.edu
    • Clin. Infect. Dis. 2003 Jul 1;37(1):50-8.

    AbstractClinical 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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