Gram-negative sepsis: a dilemma of modern medicine

Abstract

Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone. Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high. To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis. In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation. These events often occur even when appropriate antimicrobial therapy has been instituted. An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects. These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis.

TLR4 Signaling Is Coupled to SRC Family Kinase Activation, Tyrosine Phosphorylation of Zonula Adherens Proteins, and Opening of the Paracellular Pathway in Human Lung Microvascular Endothelia

“…Despite the development of new antibiotics, mortality from Gram-negative sepsis remains unacceptably high (2). Life-threatening Gram-negative sepsis can be complicated by systemic vascular collapse, disseminated intravascular coagulation, and vascular leak syndromes, including the acute respiratory distress syndrome (3,4).…”

Detection of Bacteria in Phagocyte‐Smears from Septicemia‐Suspected Blood by In Situ Hybridization Using Biotinylated Probes

“…Because Bacteremia is associated with high mortality, septicemia has always been an emergency condition treated by the blind administration of broad-spectrum antibiotics (1,2). As a result, the percentage of bacteria detected is low in blood cultures and blood smears submitted to the clinical microbiology laboratory using conventional processing and histology (16,18,21,29).…”

Involvement of IRAK-M in Peptidoglycan-induced Tolerance in Macrophages

“…It is an adaptive host response that may represent an essential regulatory mechanism during Gram-negative bacterial infection, but it may also promote subsequent infection in survivors of septic shock (5)(6)(7)(8)(9)(10)(11). Monocytes from septic patients have a reduced capacity to release TNF-␣, IL-1␤, IL-6, IL-10, and IL-12 (12)(13)(14).…”