Bacteremia & Sepsis, Gram-Negative

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

Diagnosis

• 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

Treatment

• 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 ...