Current Pharmaceutical Design - Volume 14, Issue 19, 2008

Sepsis is a common and devastating syndrome that causes over 200,000 deaths per year in the United States, and the incidence of sepsis is increasing at an alarming rate. The manifestations of sepsis result from the complex interaction between microbe and host. Microbial invasion triggers a robust but tightly regulated host inflammatory response. However, when this response becomes amplified and dysregulated, Read More

Sepsis is a common and devastating syndrome that represents a significant healthcare burden worldwide. The average annual cost to care for patients with sepsis has been estimated to being $16.7 billion. Uniform definitions have been developed for the spectrum of sepsis syndrome, including the systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock. SIRS describes the clinical manif Read More

The host's inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial infla Read More

The inability of present therapies to mitigate the devastating effects of sepsis and multiple organ failure in the critically ill patient indicates that more knowledge of the pathophysiology of sepsis is needed if we are to develop better, more effective interventions. This review will examine the concept that a portion of the immune and organ dysfunctions encountered in the septic rodent/ patient is a reflection of not only the typ Read More

Intravascular and extravascular fibrin formation are characteristic findings in patients with sepsis, suggesting that the activation of coagulation and the inhibiton of fibrinolysis are important in the pathogenesis of sepsis. Activation of coagulation during sepsis is primarily driven by the tissue factor (TF) pathway, while inhibition of fibrinolysis is primarily due to increases in plasminogen activator inhibitor -1(PAI-1). Downregulation of t Read More

The often fatal sepsis syndrome is characterized by the systemic release of inflammatory mediators, which is regulated and counterbalanced by the coordinated expression of anti-inflammatory molecules. The magnitude of sepsis-induced tissue injury and subsequent risk of infectious complications is dictated by the balance between the expression of pro- and anti-inflammatory mediators. As our understanding of the p Read More

The role of the hypothalamic-pituitary adrenal axis in the host response to infection is crucial. The initial inflammatory response to sepsis activates the endogenous release of cortisol, which in turn modulates the synthesis and release of both pro- and antiinflammatory mediators to restrict inflammation in infected tissues. However, a number of factors, including vascular or ischemic damage, inflammation and apoptosis wit Read More

Hyperglycemia is a common feature of the critically ill in general and of patients with sepsis in particular. Even a moderate degree of hyperglycemia appears detrimental for the outcome of critically ill patients, since maintenance of normoglycemia (blood glucose levels ≤110 mg/dL) with intensive insulin therapy has shown to improve survival and reduce morbidity in prolonged critically ill patients in both surgic Read More

Sepsis and septic shock, are complex disorders that are a major cause of mortality in the intensive care unit. In spite of major advances in our understanding of the pathophysiology of sepsis, accurate prediction of susceptibility to sepsis, multi-organ dysfunction, and death, even in the setting of a seemingly similar burden of infection, continues to challenge critical care clinicians. Evidence from family-based studies and Read More

Over the past decade, trends in antimicrobial resistance, epidemiology, and drug development have occurred that affect both the empiric and definite selection of antimicrobials in the septic patient. The rapid spread of highly pathogenic community-associated methicillin resistant Staph aureus (MRSA) requires clinicians to consider the inclusion of empiric coverage for MRSA even in community- acquired sepsis. Moreover Read More