What antibiotic coverage is recommended for Enterobacteriaceae infections?

Antibiotic Coverage for Enterobacteriaceae Infections

For Enterobacteriaceae infections, third-generation cephalosporins (cefotaxime or ceftriaxone) are the first-line treatment, with carbapenems reserved for ESBL-producing strains. 1

First-Line Treatment Options

Non-ESBL-producing Enterobacteriaceae

• Third-generation cephalosporins:
  • Ceftriaxone: 2g IV every 12-24 hours
  • Cefotaxime: 2g IV every 6-8 hours
  • Duration: 7-14 days depending on infection site and severity 1

ESBL-producing Enterobacteriaceae

• Carbapenems (preferred option):
  • Meropenem: 2g IV every 8 hours
  • Imipenem-cilastatin: 500mg-1g IV every 6-8 hours
  • Ertapenem: 1g IV daily (for non-Pseudomonas infections)
  • Duration: 10-14 days depending on infection site 1

Site-Specific Considerations

Intra-abdominal Infections

• Non-ESBL strains: Ceftriaxone or cefotaxime plus metronidazole
• ESBL-producing strains: Carbapenem (meropenem, imipenem, or ertapenem)
• Duration: 5-14 days 1

Meningitis

• Enterobacteriaceae isolated from CSF: Continue 2g ceftriaxone IV 12-hourly or 2g cefotaxime IV 6-hourly
• If ESBL suspected: Meropenem 2g IV every 8 hours
• Duration: 21 days 1

Urinary Tract Infections

• Uncomplicated UTIs with ESBL-producers: Fosfomycin 3g single dose (if susceptible)
• Complicated UTIs: Carbapenems or ceftazidime-avibactam
• Duration: 7-14 days 1, 2

Carbapenem-Resistant Enterobacteriaceae (CRE)

For CRE infections, newer antimicrobial options include:

1. Ceftazidime-avibactam: 2.5g (2g ceftazidime + 0.5g avibactam) IV every 8 hours 2

   • First choice for KPC-producing Enterobacteriaceae
   • Duration: 7-14 days depending on infection site

2. Meropenem-vaborbactam: For CRE infections not responsive to other therapies 3

3. Combination therapy may be considered for severe CRE infections:

   • Polymyxins (colistin) + carbapenem
   • Tigecycline + carbapenem (for non-urinary infections)
   • Aminoglycoside + carbapenem 4, 5

Important Considerations

• Carbapenem-sparing strategies should be employed in settings with high incidence of carbapenem-resistant K. pneumoniae 1

• Piperacillin-tazobactam may be considered for mild-moderate infections with susceptible strains, but is controversial for ESBL-producing organisms 1

• Fluoroquinolones (ciprofloxacin, levofloxacin) are no longer appropriate as first-line treatment in many regions due to high resistance rates 1

• Dosage adjustments are necessary for patients with renal impairment 2

Pitfalls to Avoid

1. Indiscriminate carbapenem use can promote resistance development; reserve for confirmed ESBL-producers or severe infections 6

2. Delayed effective therapy increases mortality, especially with resistant strains; obtain cultures before starting antibiotics but don't delay treatment 5

3. Inadequate source control can lead to treatment failure regardless of appropriate antibiotic selection

4. Monotherapy for CRE infections may be inadequate; combination therapy is often preferred for severe CRE infections 4, 5

5. Failure to adjust therapy based on culture and susceptibility results can lead to treatment failure or unnecessary broad-spectrum coverage

Remember that local antimicrobial resistance patterns should guide empiric therapy choices, and therapy should be narrowed based on culture and susceptibility results.