In the United States, septicemia is the 13th leading cause of death, and accounts for $5 - 10 billion health care dollars spent annually. Patients at risk of developing sepsis frequently present initially to the Emergency Department (ED), with a 'preseptic' syndrome, known as 'systemic inflammatory response syndrome' (SIRS). Prompt recognition, evaluation and initiation of therapy in this group of patients is an area of intensive investigation, since early therapeutic intervention with well established modalities (intravenous fluids and antibiotics) has been shown to be associated with improved outcomes. Furthermore, advances in understanding of the pathophysiology of bacteremia has opened the door for the development of additional therapeutics (e.g. antiendotoxin antibodies) for interrupting the cascade of events associated with full blown sepsis. Establishing an early diagnosis of septicemia remains challenging however. Not all patients with SIRS (fever, tachycardia, tachypnea, and elevated white blood cell count) have a bacterial infection. SIRS can also occur in patients with severe trauma, pancreatitis, and burns without infections. Additionally, demonstration that an infection is the inciting stimulus for SIRS is complicated by the fact that culture reports are usually not available for 24-48 hours, and blood cultures are positive in only about 60% of cases of sepsis. A sensitive and specific clinical diagnostic test for earlier detection of infection would allow physicians to make the diagnosis of septicemia more rapidly, and identify patients who would benefit from specific therapy. Previous efforts toward the development of an assay for early detection of bacteremia have focused on gram-negative infections, as these bacteria are responsible for the majority of cases of sepsis in the United States. The only test currently available assay, the Limulus amebocte lysate test (LAL) is an indirect semiquantitative assay, which has variable sensitivity and specificity and is thus utilized only for industry and research purposes. Recent investigations from the sponsor of this protocol (LINK technology) have demonstrated that a ligand binding assay (LBA) exceeds the sensitivity and specificity of the LAL for the detection of endotoxin in plasma, and may therefore provide the first clinically useful test for early identification of patients with gram negative septicemia. LINK's endotoxin test is based on the core discovery that endotoxin binds to an A1 adenosine receptor. A sensitive and specific clinical diagnostic that quantitates the level of endotoxin in blood has a broad range of clinical uses including: (a) early diagnosis of gram negative septicemia allowing for antibiotic specific therapy; (b) early prediction of impending organ dysfunction; and (c) monitoring of the effectiveness of antibiotics or other therapeutic agents targeted at eradicating the infection and treating the complications associated with gram negative bacteremia. We hypothesize that the detection of endotoxin in human blood by a LBA is an early, sensitive, and specific predictor of organ dysfunction associated with gram negative septicemia. The following specific objectives for this pilot study are: 1) to establish the relationship between the LBA and organ dysfunction; 2) to estimate the correlation of diagnostic errors between the LBA and blood culture; and 3) to identify potential confounders.
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