What is the source and appropriate antibiotic (abx) treatment for Enterobacter cloacae complex infections?

Treatment of Enterobacter cloacae Complex Infections

For Enterobacter cloacae complex infections, carbapenems are the first-line treatment option, with ceftazidime-avibactam as an alternative for carbapenem-resistant strains. 1

Source of Infection

Enterobacter cloacae complex is commonly found in:

• Healthcare-associated settings:

  • Urinary tract infections (particularly catheter-associated)
  • Intra-abdominal infections
  • Surgical site infections
  • Pneumonia (especially ventilator-associated)
  • Bloodstream infections

• Community settings (less common):

  • Gastrointestinal tract (natural reservoir)
  • Soil and water environments

Antibiotic Treatment Algorithm

First-line Treatment:

• Carbapenems: Meropenem (1g IV every 8 hours) or Imipenem/cilastatin (1g IV every 8 hours) 1, 2
  • For severe infections, consider high-dose extended-infusion meropenem (2g IV q8h as 3-hour infusion) 2

For Carbapenem-Resistant E. cloacae:

1. KPC-producing strains:

   • Ceftazidime-avibactam (2.5g IV every 8 hours) 1, 3
   • Alternative: Meropenem-vaborbactam 1

2. OXA-48-producing strains:

   • Ceftazidime-avibactam (2.5g IV every 8 hours) 1

3. MBL-producing strains:

   • Ceftazidime-avibactam plus aztreonam 1
   • Alternative: Cefiderocol 1

For Specific Infection Sites:

• Complicated intra-abdominal infections: Add metronidazole (500mg IV every 8 hours) to any of the above regimens 1, 3
• Urinary tract infections: Carbapenems or ceftazidime-avibactam as monotherapy 1, 3
• Pneumonia: Consider meropenem-vaborbactam due to better pulmonary penetration 1

Treatment Duration

• Bloodstream infections: 10-14 days 2
• Complicated UTI: 7-14 days 2, 3
• Intra-abdominal infections: 5-14 days 2, 3
• Pneumonia: 7-14 days 2

Clinical Evidence and Rationale

Carbapenems are strongly recommended as first-line therapy for E. cloacae complex infections due to the high prevalence of AmpC β-lactamases and potential for ESBL production in these organisms. Studies have shown significantly better outcomes with carbapenem therapy compared to non-carbapenem alternatives:

• A study of ESBL-producing E. cloacae bloodstream infections showed that patients treated with carbapenems had lower sepsis-related mortality (9.4% vs 29.5%) compared to those treated with non-carbapenem β-lactams 4
• Another study demonstrated that clinical failure at 96 hours was significantly lower in patients receiving carbapenems (25%) compared to non-carbapenem antibiotics (77.8%) 5

Traditional third-generation cephalosporins should be avoided due to the high risk of treatment failure, even if initially reported as susceptible, due to inducible AmpC β-lactamases 6.

For carbapenem-resistant strains, ceftazidime-avibactam has shown promising results, particularly for KPC and OXA-48-producing strains 1. The FDA has specifically approved ceftazidime-avibactam for infections caused by E. cloacae in complicated intra-abdominal infections, complicated UTIs, and hospital-acquired/ventilator-associated pneumonia 3.

Important Considerations and Pitfalls

1. Avoid third-generation cephalosporins: E. cloacae can rapidly develop resistance during treatment with third-generation cephalosporins due to inducible AmpC β-lactamases 6

2. Consider local resistance patterns: Treatment should be guided by local susceptibility data and individual patient risk factors for resistant organisms 2

3. Antimicrobial stewardship: Reserve newer agents like ceftazidime-avibactam for confirmed resistant infections to prevent further resistance development 2

4. Source control: Surgical drainage of abscesses, removal of infected devices, and other source control measures are essential components of treatment 1

5. Monitoring for resistance: For patients on prolonged therapy, consider repeat cultures to monitor for development of resistance 2

By following this evidence-based approach to the treatment of E. cloacae complex infections, clinicians can optimize outcomes while practicing appropriate antimicrobial stewardship.