What is the treatment for Enterobacter cloacae bacteremia, including cases with suspected or confirmed resistance?

Treatment of Enterobacter cloacae Bacteremia

For Enterobacter cloacae bacteremia, fourth-generation cephalosporins (cefepime) should be used if ESBL is absent, but carbapenems (meropenem or imipenem) are the drugs of choice for multidrug-resistant strains, ESBL-producers, or critically ill patients. 1

Key Resistance Considerations

Enterobacter cloacae has intrinsic resistance mechanisms that make treatment selection critical:

• First and second-generation cephalosporins are NOT effective against E. cloacae infections 1
• Third-generation cephalosporins are NOT recommended due to high likelihood of resistance, particularly with E. cloacae and E. aerogenes 1
• E. cloacae produces inducible AmpC β-lactamases, which confer resistance to many β-lactams 2

Treatment Algorithm by Resistance Pattern

Non-ESBL Producing E. cloacae

Cefepime (fourth-generation cephalosporin) is effective against AmpC-producing organisms when ESBL is absent 1

Critical caveat: Avoid cefepime if the isolate is cefepime-susceptible dose-dependent (SDD) with MIC 4-8 μg/ml, as this is associated with 71.4% mortality compared to 18.2% with carbapenem therapy 3

ESBL-Producing E. cloacae

Carbapenems are the drugs of choice:

• Meropenem and imipenem are preferred for critically ill patients and high bacterial loads 4, 5
• Carbapenem therapy for ESBL-producing E. cloacae bacteremia reduces breakthrough bacteremia (9.6% vs 58.0% with non-carbapenem β-lactams) 5
• Carbapenem therapy shows lower sepsis-related mortality (9.4% vs 29.5% with non-carbapenem β-lactams) 5

Carbapenem-Resistant E. cloacae

For carbapenem-resistant strains, treatment options include: 1

• Polymyxins (colistin)
• Tigecycline
• Fosfomycin
• Double carbapenem regimen (in specific situations)

Newer agents for carbapenem-resistant Enterobacterales (if E. cloacae produces KPC):

• Ceftazidime-avibactam 2.5 g IV q8h infused over 3 hours 1
• Meropenem-vaborbactam 4 g IV q8h infused over 3 hours 1
• Imipenem-cilastatin-relebactam 1.25 g IV q6h 1

Important limitation: These newer agents are primarily effective against KPC-producing organisms; vaborbactam and relebactam inhibit class A (KPC) and class C β-lactamases but NOT class B (MBL) or class D (OXA-48) β-lactamases 1

Combination Therapy Considerations

Combination therapy is NOT routinely recommended for carbapenem-resistant Enterobacterales infections based on current evidence 1

However, combination therapy may be considered in:

• Patients with severe illness or septic shock 1
• High-risk patients with pneumonia 2
• Polymyxin-based combinations for critically ill patients 1

Critical Clinical Pitfalls

Avoid piperacillin/tazobactam for E. cloacae bacteremia, as it has controversial efficacy even in stable patients and should not be first-line 1

Monitor for breakthrough bacteremia when using non-carbapenem β-lactams for ESBL-producing strains, as this occurs in 58% of cases 5

Do not use fluoroquinolones as first-line due to widespread resistance, though they may be considered for β-lactam allergies in mild infections (with metronidazole for anaerobic coverage) 1

Ensure adequate source control alongside antibiotic therapy, as this is critical for optimizing outcomes 1