title: 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.
authors.affiliation: Brown University School of Medicine, Providence, RI, USA. Steven_Opal@brown.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Gary E
authors.initials: GE
authors.lastname: Garber
authors.forename: Steven P
authors.initials: SP
authors.lastname: LaRosa
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Maki
authors.forename: Ross C
authors.initials: RC
authors.lastname: Freebairn
authors.forename: Gary T
authors.initials: GT
authors.lastname: Kinasewitz
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Dhainaut
authors.forename: S Betty
authors.initials: SB
authors.lastname: Yan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Williams
authors.forename: Delores E
authors.initials: DE
authors.lastname: Graham
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.forename: Howard
authors.initials: H
authors.lastname: Levy
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
mesh_terms: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001419:Bacteria / Q000145:classification; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects; D004311:Double-Blind Method; D005658:Fungi / Q000145:classification; D006801:Humans; D007249:Inflammation / Q000209:etiology; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015415:Biomarkers; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated