Clinical experience with drotrecogin alfa in treating gram-positive and -negative pathogens in patients with severe...

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.

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.

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.

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.