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For further information, see CMDT Part 33-16: Gram-Negative Bacteremia & Sepsis

Key Features

  • Most common sites for gram-negative bacteremia

    • Genitourinary system

    • Hepatobiliary tract

    • Gastrointestinal tract

    • Lungs

  • Less common sources include

    • Intravenous lines

    • Infusion fluids

    • Surgical wounds

    • Drains

    • Pressure injuries

  • Mortality rates

    • 40–60% in patients with potentially fatal underlying conditions in the short term, such as

      • Neutropenia

      • Immunoparesis

    • 15–20% in patients with serious underlying diseases likely to be fatal in 5 years, such as

      • Solid tumors

      • Cirrhosis

      • Aplastic anemia

    • ≤ 5% in patients with no underlying diseases

Clinical Findings

  • Fevers and chills, often with abrupt onset

  • However, some patients are hypothermic (temperature ≤ 36.4 °C) at presentation

  • Hyperventilation with respiratory alkalosis and changes in mental status are important early manifestations

  • Hypotension and shock are unfavorable prognostic signs


  • Neutropenia or neutrophilia, often with increased numbers of immature forms of polymorphonuclear leukocytes

  • Thrombocytopenia occurs in 50% of patients, laboratory evidence of coagulation abnormalities in 10%, and overt disseminated intravascular coagulation in 2–3%

  • If possible, three sets of blood cultures from separate sites should be obtained in rapid succession before starting antimicrobial therapy


  • Antibiotics

    • In general, bactericidal antibiotics should be used and given intravenously to ensure therapeutic serum levels

    • Penetration of antibiotics into the site of primary infection is critical for successful therapy

    • Sepsis caused by gram-positive organisms cannot be differentiated on clinical grounds from that due to gram-negative bacteria. Therefore, initial therapy should include antibiotics active against both types of organisms

    • Table 30–4 provides a guide for empiric therapy

  • Remove predisposing factors

    • Decrease or stop immunosuppressive medications

    • Give granulocyte colony-stimulating factor (filgrastim; G-CSF) to the neutropenic patient with positive blood cultures

  • Identify source of bacteremia and remove it (central venous catheter) or drain it (abscess)

  • Supportive measures include

    • Maintaining blood pressure with vasopressor medications

    • Managing disseminated intravascular coagulation with

      • Antimicrobials for underlying infection

      • Platelet transfusions and fresh frozen plasma for significant bleeding

      • Cryoprecipitate for bleeding and fibrinogen levels < 80–100 mg/dL

      • Low-dose heparin infusion for refractory bleeding

Table 30–4.Medication of choice for suspected or documented microbial pathogens (listed in alphabetical order, within classes).

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