Bacteremia & Sepsis, Gram-Negative

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

• 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

• 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 catheter) or drain it (abscess)

• Supportive measures include maintaining blood pressure with vasopressor medications and 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, and low-dose heparin infusion for refractory bleeding

• Corticosteroids

  • Based on available data, cosyntropin stimulation testing is not recommended in patients with septic shock

  • Stress-dose hydrocortisone may benefit patients with severe septic shock (systolic blood pressure < 90 mm Hg for more than 1 hour despite adequate fluid resuscitation and vasopressor administration)

  • However, such corticosteroid administration is unlikely to benefit those with less severe septic shock