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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

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

  • 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

    • Empiric therapy depends both on the situation and the suspected organism

      • For febrile neutropenic patients receiving cancer chemotherapy, suspect sepsis due to S aureus, Pseudomonas, Klebsiella, E coli, and empirically administer ceftazidime, 2 g intravenously every 8 hours; or cefepime, 2 g intravenously every 8 hours

      • For sepsis due to pyelonephritis, suspect E coli, Klebsiella, Enterobacter, Pseudomonas and administer ceftriaxone, 1 g intravenously every 24 hours; or ciprofloxacin, 400 mg intravenously every 12 hours (500 mg orally); or levofloxacin, 500 mg once daily (intravenously or orally)

      • For septic thrombophlebitis(eg, IV tubing, IV shunts), suspect S aureus, gram-negative aerobic bacteria and administer vancomycin, 15 mg/kg intravenously every 12 hours plus ceftriaxone, 1 g intravenously every 24 hours

      • Drugs of choice for the most common gram-negative rods to cause sepsis include

        • Acinetobacter—imipenem, meropenem (alternatives: tigecycline, ertapenem, minocycline, doxycycline, aminoglycosides, colistin)

        • Bacteroides, gastrointestinal strains—metronidazole (alternatives: ticarcillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam, carbapenem)

        • Enterobacter—ertapenem, imipenem, meropenem, cefepime (alternatives: aminoglycoside, a fluoroquinolone, TMP-SMZ)

        • Escherichia coli—cefotaxime, ceftriaxone (alternatives: imipenem or meropenem, aminoglycosides, a fluoroquinolone, aztreonam, ticarcillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam)

        • Haemophilus—cefotaxime, ceftriaxone (alternative: aztreonam)

        • Klebsiella—cephalosporin (alternatives: TMP-SMZ, aminoglycoside, imipenem or meropenem, a fluoroquinolone, aztreonam, ticarcillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam)

        • Prevotella, oropharyngeal strains—clindamycin (alternative: metronidazole)

        • Proteus mirabilis—ampicillin (alternatives: An aminoglycoside, TMP-SMZ, a fluoroquinolone, a cephalosporin)

        • Proteus vulgaris and other species (Morganella, Providencia)—cefotaxime, ceftriaxone (alternatives: aminoglycoside, imipenem, TMP-SMZ, a fluoroquinolone)

        • Pseudomonas aeruginosa—piperacillin-tazobactam or ceftazidime or cefepime, or imipenem or meropenem or doripenem ± aminoglycoside (alternatives: ciprofloxacin (or levofloxacin) ± piperacillin-tazobactam; ciprofloxacin (or levofloxacin) ± ceftazidime; ciprofloxacin (or levofloxacin) ± cefepime; piperacillin-tazobactam + tobramycin; ceftazidime + tobramycin; cefepime + tobramycin; meropenem (imipenem, doripenem) + tobramycin)

        • Salmonella (bacteremia)—ceftriaxone (alternative: a fluoroquinolone)

        • Serratia—carbapenem (alternatives: TMP-SMZ, aminoglycosides, a fluoroquinolone, cefotaxime, ceftriaxone)

  • 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 ...

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