S M Opal1, J Cohen. 1. Brown University School of Medicine, Povidence, RI, USA. Steven_Opal@brown.edu
Abstract
OBJECTIVE: To review the basic differences between gram-positive and gram-negative sepsis and to assess the effect of these differences on current and future therapeutic strategies for sepsis. DESIGN: Literature review of the past 30 yrs of laboratory and clinical reports that analyze the microbial aspects of sepsis and the immunologic response to systemic infection. RESULTS: The increasing prevalence of sepsis from gram-positive bacterial pathogens necessitates reevaluation of many of the basic assumptions about the molecular pathogenesis of septic shock. It has been assumed that the initiation of the systemic inflammatory response with activation of the proinflammatory cytokine networks and other mediators results in a similar pathophysiologic process, regardless of the causative microbic pathogen. Yet, there is increasing experimental evidence that fundamental differences exist in the host response to gram-positive bacterial pathogens compared with the host response to gram-negative organisms. Systemic immune activation during sepsis may promote the clearance of the microbic pathogen; however, generalized inflammation also contributes to the pathogenesis of septic shock. The balance between these beneficial and deleterious effects may differ between gram-positive and gram-negative pathogens. CONCLUSIONS: Results of antimediator therapies in clinical trials in septic shock are inconclusive but suggest that the response may differ, depending on the type of microbic pathogen. The immune-mediated pathophysiologic mechanisms that underlie gram-positive sepsis and the potential interactions between the infecting microorganism and efficacy of anticytokine therapies require further investigation. Treatment strategies that explain the causative organism may be necessary for optimal use of immunoadjuvants in the future.
OBJECTIVE: To review the basic differences between gram-positive and gram-negative sepsis and to assess the effect of these differences on current and future therapeutic strategies for sepsis. DESIGN: Literature review of the past 30 yrs of laboratory and clinical reports that analyze the microbial aspects of sepsis and the immunologic response to systemic infection. RESULTS: The increasing prevalence of sepsis from gram-positive bacterial pathogens necessitates reevaluation of many of the basic assumptions about the molecular pathogenesis of septic shock. It has been assumed that the initiation of the systemic inflammatory response with activation of the proinflammatory cytokine networks and other mediators results in a similar pathophysiologic process, regardless of the causative microbic pathogen. Yet, there is increasing experimental evidence that fundamental differences exist in the host response to gram-positive bacterial pathogens compared with the host response to gram-negative organisms. Systemic immune activation during sepsis may promote the clearance of the microbic pathogen; however, generalized inflammation also contributes to the pathogenesis of septic shock. The balance between these beneficial and deleterious effects may differ between gram-positive and gram-negative pathogens. CONCLUSIONS: Results of antimediator therapies in clinical trials in septic shock are inconclusive but suggest that the response may differ, depending on the type of microbic pathogen. The immune-mediated pathophysiologic mechanisms that underlie gram-positive sepsis and the potential interactions between the infecting microorganism and efficacy of anticytokine therapies require further investigation. Treatment strategies that explain the causative organism may be necessary for optimal use of immunoadjuvants in the future.