What is the treatment for carbapenem-resistant Escherichia coli (E. coli) in blood and endotracheal tube (ET) infections?

Treatment for Carbapenem-Resistant Escherichia coli in Blood and Endotracheal Tube Infections

For carbapenem-resistant Escherichia coli infections in blood and endotracheal tube, ceftazidime-avibactam is the preferred first-line treatment, with combination therapy recommended for severe infections to improve survival outcomes. 1

First-Line Treatment Options

Bloodstream Infections

• Ceftazidime-avibactam 2.5 g IV q8h is the preferred first-line treatment for carbapenem-resistant E. coli bloodstream infections 1
• Meropenem-vaborbactam 4 g IV q8h is an alternative option if available 1
• Imipenem-cilastatin-relebactam 1.25 g IV q6h can be considered if the first two options are unavailable 1
• Treatment duration should be 7-14 days, individualized based on clinical response 1

Respiratory Tract Infections (Endotracheal Tube)

• Ceftazidime-avibactam 2.5 g IV q8h remains the preferred treatment for respiratory infections 1, 2
• For optimal administration, prolonged infusion (3 hours) of ceftazidime-avibactam and appropriate renal adjustment are associated with improved 30-day survival 1
• Consider adding aerosolized polymyxin (colistin) to intravenous therapy for respiratory tract infections with poor response to initial treatment 1

Combination Therapy Considerations

For severe infections (sepsis/septic shock), combination therapy is recommended:

• Polymyxin-based combinations:

  • Colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA (1.5 CrCl + 30) IV q12h + Tigecycline 100 mg IV loading dose, then 50 mg IV q12h 1
  • Alternatively, colistin + high-dose extended-infusion meropenem (1 g IV q8h by extended infusion over 3 hours) even when MICs are higher (≤16 mg/L) 1

• For metallo-β-lactamase-producing CRE:

  • Ceftazidime-avibactam combined with aztreonam is suggested as a preferential choice 1
  • This combination has shown lower 30-day mortality (19.2% vs 44%) and lower clinical treatment failure compared to other active antimicrobial agents 1

Special Considerations

Antimicrobial Susceptibility Testing

• Always perform susceptibility testing to guide therapy, especially for determining MICs to carbapenems 1
• For carbapenem-containing regimens, high-dose extended-infusion meropenem should be considered when MICs are ≤8 mg/L 1
• Determine the carbapenemase type (KPC, NDM, OXA-48, etc.) whenever possible to guide optimal therapy 1

Double Carbapenem Therapy

• Double carbapenem therapy (typically ertapenem plus another carbapenem) may be considered for highly resistant strains when other options are limited 1
• The rationale is based on ertapenem's higher affinity for carbapenemases, potentially allowing the second carbapenem to exert antibacterial activity 1
• Evidence is limited, but some observational studies suggest improved survival in patients with invasive KPC infections 1

Monitoring and Follow-up

• Follow-up cultures are recommended in case of treatment failure to detect resistance development 1
• Optimal antibiotic dosing schemes should be used, with attention to adverse effects, especially with polymyxins and aminoglycosides 1
• Source control should always be a priority to optimize outcomes and shorten antibiotic treatment durations 1

Emerging Options

• Newer agents like plazomicin, eravacycline, and cefiderocol may be considered based on susceptibility testing when available 3, 4
• For pan-resistant strains, select antibiotics with the least resistance based on MICs relative to breakpoints, with emphasis on optimal source control 1

The treatment of carbapenem-resistant E. coli infections remains challenging, but the introduction of newer β-lactam/β-lactamase inhibitor combinations has significantly improved outcomes. Combination therapy is often necessary for severe infections to maximize treatment success and reduce mortality 3, 5.