Key Clinical Updates in Gram-Negative Bacteremia & Sepsis
Directed therapy for gram-negative bacteremia may be treated with as few as 7 days of antibiotic therapy.
Gram-negative bacteremia can originate in a number of sites, the most common being the genitourinary system, hepatobiliary tract, gastrointestinal tract, and lungs. Less common sources include intravenous lines, infusion fluids, surgical wounds, drains, and pressure injuries.
Patients with potentially fatal underlying conditions in the short term such as neutropenia or immunoparesis have a mortality rate of 40–60%; those with serious underlying diseases likely to be fatal in 5 years, such as solid tumors, cirrhosis, and aplastic anemia, die in 15–20% of cases; and individuals with no underlying diseases have a mortality rate of 5% or less.
Most patients have fevers and chills, often with abrupt onset. However, 15% of patients are hypothermic (temperature 36.4°C or less) at presentation, and 5% never develop a temperature above 37.5°C. Hyperventilation with respiratory alkalosis and changes in mental status are important early manifestations. Hypotension and shock, which occur in 20–50% of patients, are unfavorable prognostic signs.
Neutropenia or neutrophilia, often with increased numbers of immature forms of polymorphonuclear leukocytes, is the most common laboratory abnormality in septic patients. Thrombocytopenia occurs in 50% of patients, laboratory evidence of coagulation abnormalities in 10%, and overt disseminated intravascular coagulation in 2–3%. Both clinical manifestations and the laboratory abnormalities are nonspecific and insensitive, which accounts for the relatively low rate of blood culture positivity (approximately 20–40%). If possible, three blood cultures from separate sites should be obtained in rapid succession before starting antimicrobial therapy. The chance of recovering the organism in at least one of the three blood cultures is greater than 95%. The false-negative rate for a single culture of 5–10 mL of blood is 30%. This may be reduced to 5–10% (albeit with a slight false-positive rate due to isolation of contaminants) if a single volume of 30 mL is inoculated into several blood culture bottles. Blood cultures may be falsely negative; when a patient with presumed septic shock, negative blood cultures, and inadequate explanation for the clinical course responds to antimicrobial agents, therapy should be continued for 10–14 days.
Several factors are important in the management of patients with sepsis.
A. Removal of Predisposing Factors
This usually means decreasing or stopping immunosuppressive medications and, in certain circumstances, giving granulocyte colony-stimulating factor (filgrastim; G-CSF) to the neutropenic patient.
B. Identifying the Source of Bacteremia
By simply finding the source of bacteremia and removing it (central venous catheter) or draining it (abscess), a fatal disease becomes easily treatable.