What is the recommended empirical antibiotic therapy for infections caused by Enterobacterales?

Empirical Antibiotic Therapy for Enterobacterales Infections

For empirical treatment of infections caused by Enterobacterales, carbapenems (imipenem-cilastatin, meropenem, or doripenem), piperacillin-tazobactam, or cefepime with metronidazole are recommended as first-line options, with selection based on infection severity, local resistance patterns, and patient risk factors for multidrug-resistant organisms. 1

Treatment Selection Based on Infection Severity and Setting

Community-Acquired Infections

• Mild to Moderate Severity:

  • First choice: Amoxicillin-clavulanic acid 1
  • Alternative options:
    • Cefotaxime or ceftriaxone plus metronidazole 1
    • Ciprofloxacin plus metronidazole (caution due to increasing resistance) 1

• Severe Infections:

  • First choice: Cefotaxime or ceftriaxone plus metronidazole 1
  • Alternative options:
    • Piperacillin-tazobactam 1
    • Meropenem (reserve for severe cases) 1

Healthcare-Associated Infections

• Any Severity with Risk of Resistant Organisms:
  • First choice: Carbapenems (imipenem-cilastatin, meropenem, doripenem) 1
  • Alternative options:
    • Piperacillin-tazobactam (if local ESBL rates <20%) 1
    • Cefepime plus metronidazole (if local ESBL rates <20%) 1
    • Add vancomycin if MRSA risk factors present 1

Special Considerations Based on Resistance Patterns

ESBL-Producing Enterobacterales

• Preferred treatment: Carbapenems (imipenem-cilastatin, meropenem, doripenem) 1
• Alternatives when carbapenems should be spared:
  • Piperacillin-tazobactam (for ESBL-E. coli with MIC ≤16 mg/L in non-severe infections) 2
  • Ceftazidime-avibactam (for severe infections) 3

Carbapenem-Resistant Enterobacterales (CRE)

• Preferred options:
  • Ceftazidime-avibactam (for KPC producers) 3
  • Meropenem-vaborbactam (for KPC producers) 3
  • Imipenem-cilastatin-relebactam 3
  • Consider combination therapy in severe infections 3

Pitfalls and Important Considerations

1. Fluoroquinolone resistance: Due to increasing resistance of E. coli to fluoroquinolones, review local susceptibility patterns before using ciprofloxacin or levofloxacin empirically 1

2. Enterococcal coverage:

   • Not required for community-acquired infections 1
   • Recommended for healthcare-associated infections, particularly:
     • Postoperative infections
     • Previous cephalosporin exposure
     • Immunocompromised patients
     • Patients with valvular heart disease or prosthetic intravascular materials 1, 4

3. Antibiotic stewardship considerations:

   • Tailor therapy once culture and susceptibility results are available 1
   • Avoid unnecessary broad-spectrum antibiotics for mild-to-moderate community-acquired infections 1
   • Consider rapid diagnostic tests to improve time to appropriate therapy in severe infections 1

4. Risk factors for multidrug-resistant Enterobacterales:

   • Recent hospitalization
   • Previous antibiotic exposure (especially cephalosporins and fluoroquinolones)
   • Healthcare-associated infection
   • Local high prevalence of ESBL-producing organisms
   • Immunosuppression 1, 5

5. Drugs to avoid:

   • Ampicillin-sulbactam (high rates of resistance among community-acquired E. coli) 1
   • Cefotetan and clindamycin (increasing resistance in B. fragilis group) 1
   • Aminoglycosides as monotherapy (less effective and more toxic than alternatives) 1

Treatment Algorithm

1. Assess infection severity and setting:

   • Community-acquired vs. healthcare-associated
   • Mild-moderate vs. severe infection

2. Evaluate risk factors for resistant organisms:

   • Prior antibiotic exposure
   • Healthcare contact
   • Local resistance patterns
   • Immunocompromised status

3. Select empiric therapy based on assessment:

   • Low risk for resistance: Narrower-spectrum options (amoxicillin-clavulanic acid)
   • High risk for resistance: Broader-spectrum options (carbapenems, piperacillin-tazobactam)

4. Obtain cultures before starting antibiotics when possible

5. Re-evaluate and de-escalate therapy when culture results become available

Remember that local antibiogram data should guide empiric therapy decisions, as resistance patterns vary significantly between institutions and geographic regions.