Treatment of Enterobacter cloacae Complex Infections
Carbapenems are the recommended first-line treatment for Enterobacter cloacae complex infections, with meropenem, imipenem-cilastatin, or doripenem being the preferred agents due to their high efficacy and low resistance rates. 1
First-line Treatment Options
- Carbapenems: Meropenem (1g IV q8h), imipenem-cilastatin (1g IV q8h), or doripenem (500mg IV q8h) are the preferred first-line agents for serious Enterobacter cloacae complex infections due to their broad spectrum of activity and low resistance rates 1
- Cefepime: Can be considered as a carbapenem-sparing option (2g IV q8h) for susceptible isolates, particularly for bloodstream infections when ESBL prevalence is low 2
- Ceftazidime-avibactam: 2.5g IV q8h (infused over 3 hours) is recommended for carbapenem-resistant Enterobacter cloacae complex (CREC) infections 1, 3
Treatment Based on Infection Site
Intra-abdominal Infections
- For complicated intra-abdominal infections (cIAI), use carbapenems (meropenem, imipenem-cilastatin, doripenem) or ceftazidime-avibactam plus metronidazole 1
- Alternative options include piperacillin-tazobactam (4.5g IV q6h), though this may be less effective against AmpC-producing strains 1
- For carbapenem-resistant strains, consider tigecycline (100mg loading dose, then 50mg IV q12h) or eravacycline (1mg/kg IV q12h) 1
Urinary Tract Infections
- For complicated UTIs, carbapenems or ceftazidime-avibactam are recommended first-line options 3
- For carbapenem-resistant strains, consider aminoglycosides (e.g., amikacin, plazomicin) or fosfomycin if susceptible 1
Bloodstream Infections
- Carbapenems show the highest clinical cure rates (92.3%) for Enterobacter cloacae complex bloodstream infections 2
- Cefepime can be an effective alternative with reported success rates of 88.9% 2
- For carbapenem-resistant bloodstream infections, consider meropenem-vaborbactam (4g IV q8h) or ceftazidime-avibactam (2.5g IV q8h) 1, 4
Special Considerations
Carbapenem-Resistant Enterobacter cloacae Complex (CREC)
- For CREC infections, newer agents are preferred: 1, 4
- Ceftazidime-avibactam (2.5g IV q8h)
- Meropenem-vaborbactam (4g IV q8h)
- Imipenem-cilastatin-relebactam (1.25g IV q6h)
- For highly resistant strains, polymyxin-based combination therapy may be necessary 1
Risk Factors for CREC
- Prior carbapenem exposure 5
- Chronic pulmonary disease 5
- Mechanical ventilation 5
- Steroid therapy 5
- Prolonged hospitalization 6
Duration of Therapy
- Complicated intra-abdominal infections: 5-14 days 1
- Complicated UTIs: 7-14 days 1
- Bloodstream infections: 14 days (uncomplicated) to 4-6 weeks (complicated) 2
Monitoring and Follow-up
- Monitor clinical response within 48-72 hours of initiating therapy 2
- For bloodstream infections, follow-up blood cultures are recommended to ensure clearance, especially when using non-carbapenem beta-lactams (which have higher breakthrough bacteremia rates of 58% vs 9.6% with carbapenems) 7
- Regular monitoring of renal function is essential, particularly when using aminoglycosides or polymyxins 1
Common Pitfalls and Caveats
- Enterobacter species can rapidly develop resistance to third-generation cephalosporins during therapy due to AmpC beta-lactamase induction or derepression 1, 2
- Mortality is significantly higher for infections with derepressed AmpC producers compared to inducible AmpC producers (29.4% vs 3.8%) 2
- Avoid third-generation cephalosporins (ceftriaxone, cefotaxime) due to high risk of treatment failure and resistance development 1, 7
- Piperacillin-tazobactam may have suboptimal efficacy against AmpC-producing strains 2
The treatment of Enterobacter cloacae complex infections requires careful consideration of local resistance patterns, site of infection, and patient-specific factors. Carbapenems remain the most reliable option for serious infections, while newer agents like ceftazidime-avibactam provide valuable alternatives for resistant strains.