Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated).
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.
Opal
Steven M
SM
Brown University School of Medicine, Providence, RI, USA. Steven_Opal@brown.edu
Garber
Gary E
GE
LaRosa
Steven P
SP
Maki
Dennis G
DG
Freebairn
Ross C
RC
Kinasewitz
Gary T
GT
Dhainaut
Jean-Francois
JF
Yan
S Betty
SB
Williams
Mark D
MD
Graham
Delores E
DE
Nelson
David R
DR
Levy
Howard
H
Bernard
Gordon R
GR
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
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015415:Biomarkers; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated