Gram-negative sepsis

Sepsis is a life-threatening systemic condition that may develop in patients with serious infections. Sepsis is defined by major systemic manifestations of infection (tachypnea, tachycardia, and fever or hypothermia) and is often associated with major organ dysfunction remote to the site of infection. Although sepsis may be produced by a variety of microorganisms, most cases are due to bacterial infections. The majority of bacterial infections resulting in sepsis are due to gram-negative organisms. Both the incidence and mortality associated with gram-negative sepsis are increasing. The infection sites are likely to be associated with gram-negative sepsis include the genitourinary, gastrointestinal, and respiratory tracts. Patients at risk for gram-negative sepsis are essentially those at risk for serious gram-negative infection and include immunocompromised and hospitalized patients. The initiator of gram-negative sepsis is endotoxin, the lipopolysaccharide (LPS) component of the gram-negative bacterial cell wall. Endotoxin stimulates the release of cellular mediators of inflammation that may result in life-threatening systemic abnormalities. Patients with gram-negative sepsis are usually febrile (or hypothermic), tachycardic, and tachypneic. Hypotension may or may not be present. Systemic manifestations of sepsis include: hypotension, metabolic acidosis, altered mental status, liver dysfunction, renal insufficiency, clotting abnormalities, and lung dysfunction. The cardiovascular dysfunction is due to a combination of myocardial depression and dilated arterioles. The differential diagnosis of sepsis includes not only gram-negative infection but also gram-positive and fungal sepsis as well as non-infectious causes such as pancreatitis or burns. A clinical diagnosis of gram-negative sepsis is made in patients with known or suspected gram-negative infection who have severe systemic manifestations of infection. Definitive diagnosis of the causative organism is best made by blood cultures, which are positive in 30 to 40% of patients with a prospective clinical diagnosis of gram-negative sepsis. Therapy of gram-negative sepsis includes antibiotics, surgical intervention as indicated, and supportive therapy. Due to the continued high mortality rate, innovative therapy for gram-negative sepsis is needed. Immunotherapy seems to hold great promise. Multicenter clinical trials using monoclonal antibody against endotoxin indicate that this therapy is effective in decreasing mortality in subgroups of patients with gram-negative sepsis. Other multicenter clinical trials will test the potential efficacy of monoclonal antibody against tumor necrosis factor as well as lipid X and pentoxifylline.