What is the recommended treatment for Enterobacter cloacae infections?

Treatment of Enterobacter cloacae Infections

For Enterobacter cloacae infections, ceftazidime-avibactam should be considered the first-line treatment option, particularly for complicated infections, as it has demonstrated clinical efficacy against this pathogen with a cure rate of 84.6% in clinical trials. 1

Treatment Algorithm Based on Infection Type and Severity

First-line Options:

1. Complicated Intra-abdominal Infections (cIAI)

   • Ceftazidime-avibactam (2.5g IV q8h) plus metronidazole (500mg IV q8h) 1
   • Clinical cure rate for E. cloacae: 84.6% in clinical trials 1
   • Duration: 5-14 days based on clinical response

2. Complicated Urinary Tract Infections (cUTI)

   • Ceftazidime-avibactam (2.5g IV q8h) 2, 1
   • Meropenem-vaborbactam (4g IV q8h) 2
   • Duration: 7-14 days

3. Hospital-acquired/Ventilator-associated Pneumonia

   • Ceftazidime-avibactam (2.5g IV q8h) 1
   • Duration: 7-14 days

Alternative Options (Based on Susceptibility):

1. Carbapenems

   • Imipenem-cilastatin, meropenem, or doripenem 2
   • Note: Resistance concerns exist, especially with carbapenem-hydrolyzing β-lactamase-producing strains 3

2. For Carbapenem-Resistant E. cloacae

   • If KPC-producing: Ceftazidime-avibactam or meropenem-vaborbactam 2
   • If OXA-48-producing: Ceftazidime-avibactam 2
   • If MBL-producing: Ceftazidime-avibactam plus aztreonam 2

3. Other Options

   • Cefepime with metronidazole (for mixed infections) 2
   • Imipenem-cilastatin-relebactam 2
   • Tigecycline (for intra-abdominal infections) 2

Special Considerations

Carbapenem-Resistant E. cloacae

Carbapenem resistance in E. cloacae is increasingly common and requires special attention:

• For KPC-producing strains: Ceftazidime-avibactam or meropenem-vaborbactam are strongly recommended 2
• For severe infections with MIC ≤8 mg/L for carbapenems: Consider combination therapy with a carbapenem plus colistin, high-dose tigecycline, or an aminoglycoside 4
• For strains with MIC >8 mg/L for carbapenems: Combination regimens involving colistin, high-dose tigecycline, aminoglycosides, and/or fosfomycin 4

Bloodstream Infections

For E. cloacae bacteremia, particularly ESBL-producing strains:

• Carbapenems have shown better outcomes compared to non-carbapenem β-lactams 5
• Lower breakthrough bacteremia rates with carbapenem therapy (9.6% vs 58.0% with non-carbapenem β-lactams) 5

Endocarditis

E. cloacae endocarditis is rare but serious:

• Combination therapy including aminoglycosides, cephalosporins, or carbapenems is typically used 6
• Surgical intervention may be necessary, especially for prosthetic valve endocarditis

Treatment Duration

• Uncomplicated infections: 7-10 days
• Complicated infections: 10-14 days
• Bloodstream infections: 14 days (minimum)
• Endocarditis: 4-6 weeks

Monitoring and Follow-up

• Obtain cultures before initiating antibiotics
• Monitor clinical response within 48-72 hours
• Consider follow-up blood cultures for bloodstream infections to ensure clearance
• Adjust therapy based on susceptibility testing results

Common Pitfalls to Avoid

1. Inducible resistance: E. cloacae can develop resistance during therapy with certain β-lactams due to inducible AmpC β-lactamases
2. Empiric monotherapy with 3rd generation cephalosporins: High risk of treatment failure due to inducible resistance
3. Delayed source control: Inadequate drainage of abscesses or removal of infected devices can lead to treatment failure regardless of appropriate antimicrobial therapy
4. Underdosing: Consider extended infusions for β-lactams against isolates with elevated MICs

The treatment of E. cloacae infections requires careful consideration of local resistance patterns and the specific infection site. Ceftazidime-avibactam has emerged as a preferred option for many E. cloacae infections, especially those with resistance concerns, but therapy should be guided by susceptibility testing whenever possible.