What is the recommended treatment for AmpC (Ampicillin C)-producing Enterobacter cloacae infections?

Treatment of AmpC-Producing Enterobacter cloacae Infections

For infections caused by AmpC-producing Enterobacter cloacae, carbapenems (particularly meropenem) are the first-line treatment option due to their stability against AmpC β-lactamases and associated lower rates of microbiological failure. 1, 2

First-Line Treatment Options

Carbapenems

• Meropenem: 1g IV every 8 hours (first choice)

  • Provides reliable efficacy against AmpC producers 1
  • Associated with lower microbiological failure rates (0% vs 13% with piperacillin-tazobactam) 1
  • Achieves good epithelial lining fluid concentrations (63% penetration ratio) 3
  • Dose adjustment required for renal impairment

• Imipenem-cilastatin or Doripenem: Alternative carbapenems if meropenem unavailable 3

Second-Line Treatment Options

Cefepime

• 1-2g IV every 8-12 hours
• Reasonable alternative for less severe infections, particularly when:
  • Source control is adequate 4, 5
  • Patient is clinically stable 5
  • No renal impairment 5
• Cefepime is stable against AmpC hydrolysis despite being a cephalosporin 6
• Recent evidence shows comparable outcomes to carbapenems for bloodstream infections 5

Novel β-lactam/β-lactamase inhibitor combinations

For infections with co-resistance mechanisms:

• Ceftazidime-avibactam: For KPC or OXA-48 co-producing strains 3
• Meropenem-vaborbactam: For KPC co-producing strains 3
• Imipenem-relebactam: Alternative for KPC co-producing strains 3

Treatment Considerations

Infection Site

• Bloodstream infections: Carbapenems preferred, especially with high-risk features 1
• Pneumonia: Meropenem may be preferred due to better lung penetration 3
• Urinary tract infections: Consider site-specific pharmacokinetics

Severity Assessment

• Severe infections/critically ill patients: Carbapenems strongly recommended 3
• Mild to moderate infections: Cefepime may be considered if the isolate tests susceptible 4, 5

Duration of Therapy

• Bloodstream infections: 7-14 days depending on source control and clinical response
• Complicated intra-abdominal infections: 5-14 days 7
• Pneumonia: 7-14 days

Pitfalls and Caveats

1. Inducible resistance: AmpC β-lactamases can be induced during therapy with certain β-lactams, leading to treatment failure. Carbapenems remain stable against this mechanism 6

2. Co-resistance mechanisms: Test for co-production of ESBLs or carbapenemases, which would necessitate different treatment approaches 2

3. Piperacillin-tazobactam limitations: Higher microbiological failure rates (13%) compared to meropenem (0%) in AmpC-producing Enterobacterales bloodstream infections 1

4. Antimicrobial stewardship: While carbapenems are most reliable, consider carbapenem-sparing options (cefepime) for less severe infections to reduce selection pressure for carbapenem resistance 6

5. Source control: Surgical or interventional drainage of abscesses or removal of infected devices is critical and may allow for use of less broad-spectrum agents 4

Monitoring

• Assess clinical response within 48-72 hours of initiating therapy
• Monitor for development of resistance during therapy
• Adjust therapy based on susceptibility testing results
• Monitor renal function for appropriate dosing adjustments

In conclusion, while several options exist for treating AmpC-producing Enterobacter cloacae infections, carbapenems remain the most reliable first-line therapy, particularly for severe infections or when adequate source control cannot be achieved. Cefepime represents a reasonable carbapenem-sparing alternative for less severe infections in clinically stable patients.