Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

Initial Assessment and Treatment

The American College of Microbiology recommends determining the carbapenemase type (KPC, NDM, OXA-48, etc.) to guide optimal therapy for patients with CRE infections 2
Ceftazidime-avibactam 2.5 g IV every 8 hours infused over 3 hours is the preferred first-line treatment for CRE infections, particularly for KPC and OXA-48 producers, with a treatment duration of 7-14 days for bloodstream infections 1, 2, 3
For Metallo-β-Lactamase producers, Ceftazidime-avibactam 2.5 g IV every 8 hours PLUS aztreonam is the preferential choice, with significantly lower 30-day mortality (19.2% vs 44%) compared to other active antimicrobial agents 2, 3

The Infectious Diseases Society of America recommends Ceftazidime-avibactam 2.5 g IV every 8 hours, Meropenem-vaborbactam 4 g IV every 8 hours, or Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours as first-line treatment options for CRE infections 1, 2, 3
Meropenem-vaborbactam may be preferred for pneumonia due to better lung penetration 3

Polymyxin-based combination therapy is recommended for severe CRE infections with sepsis or septic shock, as it reduces mortality compared to monotherapy (35.7% vs 55.5%) 1, 4, 3
Aminoglycoside-containing combination therapy showed 417 fewer clinical treatment failures per 1000 patients compared to combinations without aminoglycosides 5

High-dose extended-infusion meropenem may be considered when MICs are ≤8 mg/L 2
Double carbapenem therapy may be considered for highly resistant strains when other options are limited, with observational studies suggesting improved survival in patients with invasive KPC infections 2

Never use tigecycline monotherapy for CRE bloodstream infections, as it has poor plasma concentrations and performs poorly in bacteremic patients 6, 4, 3
Avoid tigecycline for meningitis due to poor CSF penetration 4
Do not use ceftazidime-avibactam monotherapy for MBL producers, as avibactam lacks activity against Class B enzymes 3

Perform therapeutic drug monitoring (TDM) for polymyxins, aminoglycosides, and carbapenems when available 4
Follow-up cultures are recommended in case of treatment failure to detect resistance development 2
Monitor for nephrotoxicity with polymyxins and aminoglycosides 5, 4