Clinical experience with drotrecogin alfa in treating gram-positive and -negative pathogens in patients with severe sepsis.
BACKGROUND
Newer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study.


METHODS
We treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections.


RESULTS
In contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived.


CONCLUSIONS
Those patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.
Cone
Lawrence A
LA
Department of Medicine, Eisenhower Medical Center, P#308, 39000 Bob Hope Drive, Rancho Mirage, CA 92270, USA. laconemedico@aol.com
Stone
Richard A
RA
Jesser
Kenneth
K
Nelson
Richard
R
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated