What is the recommended treatment for Escherichia coli (E. coli) bacteremia?

Treatment of E. coli Bacteremia

For E. coli bacteremia, an extended-spectrum penicillin (e.g., piperacillin/tazobactam) or an extended-spectrum cephalosporin (e.g., ceftriaxone, ceftazidime) together with an aminoglycoside is recommended for a minimum of 6 weeks of therapy, with the choice guided by antibiotic susceptibility of the isolate. 1

Initial Antibiotic Selection

First-line Options:

• Extended-spectrum penicillin:

  • Piperacillin/tazobactam 4.5g IV every 6 hours 1

• Extended-spectrum cephalosporin:

  • Ceftriaxone 1-2g IV once daily 1, 2
  • Ceftazidime 1-2g IV every 8-12 hours 1

• Add an aminoglycoside to either of the above:

  • Gentamicin (dosed according to weight and renal function) 1
  • Amikacin 20 mg/kg/day (in cases where gentamicin resistance is suspected) 1

Alternative Options (based on susceptibility):

• Carbapenems:

  • Meropenem 1g IV every 8 hours 1
  • Imipenem 500mg IV every 6-8 hours 1
  • Ertapenem 1g IV once daily 1

• Fluoroquinolones (if susceptible):

  • Ciprofloxacin 400mg IV every 12 hours 1, 3
  • Levofloxacin 750mg IV once daily 1

Treatment Duration and Monitoring

1. Duration of therapy:

   • Minimum of 6 weeks for E. coli bacteremia 1
   • For uncomplicated bacteremia (no endocarditis, no implanted prostheses, defervescence within 72h, no metastatic infection), a shorter course of 2 weeks may be considered 1

2. Follow-up blood cultures:

   • Obtain follow-up blood cultures 2-4 days after initial positive cultures to document clearance of bacteremia 1

3. Source identification and control:

   • Identify and eliminate the source of infection (e.g., urinary tract, intra-abdominal) 1
   • Drainage of abscesses or removal of infected devices if present 1

Special Considerations

For urinary source (most common source):

• E. coli is the cause of 75-95% of uncomplicated UTIs 4
• If bacteremia is from a urinary source, ensure adequate urinary tract evaluation and management 4, 5

For ESBL-producing E. coli:

• Carbapenems are the most reliable treatment 6
• Piperacillin/tazobactam, fluoroquinolones, and amikacin may be effective alternatives if susceptible 6
• Risk factors for ESBL-producing strains include recent hospitalization, severe underlying disease, prior exposure to urinary catheters, and nosocomial acquisition 7

For immunocompromised patients:

• Higher risk of relapse (subhazard ratio 4.67) 8
• Consider longer treatment duration and more aggressive source control 8

Step-down Therapy

Once the patient is clinically stable with negative follow-up blood cultures:

• Consider oral step-down therapy based on susceptibility results
• Beta-lactams appear to be a safe and effective step-down option compared to fluoroquinolones (clinical cure 94% vs 98%, not statistically different) 9

Pitfalls and Caveats

1. Delayed appropriate therapy: Ensure empiric therapy covers the most likely pathogens while awaiting culture results.

2. Inadequate source control: Failure to identify and address the primary source of infection can lead to persistent bacteremia.

3. Antimicrobial resistance: E. coli resistance rates are increasing:

   • Ciprofloxacin non-susceptibility: 18.4%
   • Third-generation cephalosporin non-susceptibility: 10.4%
   • Piperacillin-tazobactam non-susceptibility: 10.2%
   • Gentamicin non-susceptibility: 9.7%
   • Carbapenem non-susceptibility: 0.2% 5

4. Hospital-acquired strains: Hospital-onset E. coli bacteremia shows higher rates of antibiotic resistance compared to community-onset cases 5

5. Treatment failure with cephalosporins: Even when in vitro testing shows susceptibility, treatment with ceftazidime has failed in some cases of ESBL-producing E. coli 7

By following these evidence-based recommendations and considering patient-specific factors, clinicians can effectively manage E. coli bacteremia while minimizing the risk of treatment failure and relapse.