What is the recommended treatment for infections caused by the Enterobacter cloacae complex?

Treatment of Infections Caused by Enterobacter cloacae Complex

For infections caused by Enterobacter cloacae complex, ceftazidime/avibactam or meropenem/vaborbactam should be the first-line treatment options when carbapenem resistance is present, with the choice depending on the specific resistance mechanism. 1

Treatment Algorithm Based on Resistance Pattern

For KPC-producing Enterobacter cloacae complex:

• First-line options:

  • Ceftazidime/avibactam 2.5g IV q8h infused over 2-3 hours 1, 2
  • Meropenem/vaborbactam 4g IV q8h infused over 3 hours 1

• Alternative options:

  • Imipenem/relebactam or cefiderocol (when first-line agents are not available) 1
  • For pneumonia specifically, meropenem/vaborbactam may be preferred due to better epithelial lining fluid penetration 1

For OXA-48-like producing Enterobacter cloacae complex:

• First-line option:
  • Ceftazidime/avibactam 2.5g IV q8h 1

For MBL-producing (NDM, VIM, IMP) Enterobacter cloacae complex:

• First-line option:
  • Ceftazidime/avibactam plus aztreonam 1
• Alternative option:
  • Cefiderocol 1

For ESBL-producing Enterobacter cloacae (without carbapenemase):

• First-line options:
  • Carbapenems (meropenem or imipenem) 3, 4
  • Cefepime (if susceptible) 5, 3

Important Clinical Considerations

• Rapid testing to identify specific carbapenemase type is crucial for guiding appropriate therapy 1

• Local epidemiology and resistance patterns should be considered when selecting therapy 1

• Site of infection may influence drug selection:

  • For pneumonia, meropenem/vaborbactam may be preferred due to better lung penetration 1
  • For complicated intra-abdominal infections, ceftazidime/avibactam should be combined with metronidazole 2

• Resistance development:

  • Monitor for emergence of ceftazidime/avibactam resistance in KPC-producing isolates (0-12.8%) 1
  • KPC variants with D179Y mutations may develop resistance to ceftazidime/avibactam but remain susceptible to meropenem/vaborbactam 1

Dosing Considerations

• Ceftazidime/avibactam: 2.5g (ceftazidime 2g + avibactam 0.5g) IV q8h over 2 hours 2
• Meropenem/vaborbactam: 4g IV q8h over 3 hours 1
• Imipenem/cilastatin/relebactam: 1.25g IV q6h 1, 6
• Extended or continuous infusions may optimize pharmacokinetic/pharmacodynamic targets, especially for difficult-to-treat infections like osteomyelitis 6
• Dose adjustment required for renal impairment 2

Treatment Outcomes and Mortality

• Carbapenem therapy for ESBL-producing E. cloacae bacteremia is associated with lower breakthrough bacteremia rates compared to non-carbapenem β-lactams (9.6% vs 58.0%) 4
• In the TANGO II study, meropenem/vaborbactam monotherapy for CRE infections showed higher clinical cure rates and decreased mortality compared to best available therapy 1
• Ceftazidime/avibactam has demonstrated favorable outcomes in observational studies of KPC-producing Enterobacteriaceae infections 1

Pitfalls to Avoid

• Do not use first and second-generation cephalosporins against Enterobacter infections due to intrinsic resistance 1
• Avoid third-generation cephalosporins due to high likelihood of resistance development during therapy, particularly for E. cloacae 1
• Do not rely on tigecycline monotherapy for bloodstream infections due to low serum concentrations 1
• Avoid delaying appropriate therapy as time to active antibiotic therapy influences outcomes in critically ill patients with bloodstream infections 1