Considerations in the therapy of septic shock.

In summary, gram-negative sepsis is unique among infectious illnesses in that it is a disorder that recruits endogenous physiologic processes to mediate tissue injury. This host damage frequently occurs in the absence of microbial invasion of affected organs. The resultant hypotension, coagulation defects, and organ dysfunction may be associated with serious morbidity or may contribute to mortality. Ultimately, however, mortality in patients with septic shock depends on the nature of the infectious process and the severity of the underlying illnesses. Unfortunately, attempts to aggressively treat septic patients with a formidable array of antimicrobial and pharmaceutical agents have not remarkably reduced mortality. Nor does it seem likely that future elucidation of the inflammatory mechanisms of sepsis will lead to the generation of therapeutic agents that will significantly improve survival. On the other hand, prophylactic or therapeutic modalities that deter colonization or invasion by pathogenetic organisms or that alter the ability of pathogens to evoke adverse host responses may be more likely to impact on the incidence and morbidity of gram-negative bacillary infections. Until modifications in the initial interactions of gram-negative pathogens with human hosts can be realized, the mortality of gram-negative sepsis is likely to remain high.