What is CRE?
CRE stands for Carbapenem-resistant Enterobacterales—bacteria from the Enterobacterales family that are resistant to at least one carbapenem antibiotic (such as meropenem, imipenem, or ertapenem). These organisms represent a critical global public health threat due to limited treatment options and high mortality rates 1, 2.
Key Definitions and Mechanisms
CRE encompasses two distinct resistance mechanisms:
Carbapenemase-producing Enterobacterales (CP-CRE): Bacteria that produce carbapenemase enzymes that actively destroy carbapenem antibiotics. These are particularly concerning because they are highly transmissible and more likely to cause healthcare-associated outbreaks 3.
Non-carbapenemase-producing CRE: Bacteria resistant to carbapenems through other mechanisms (e.g., porin loss, efflux pumps) without producing carbapenemase enzymes 4.
The proportion of CP-CRE among all CRE has been steadily increasing—from 61.9% in 2020 to 78.3% in 2024 in surveillance data 3. This trend is clinically significant because CP-CRE strains are more transmissible and require different treatment approaches.
Common Carbapenemase Types
The most frequently encountered carbapenemase families include 1, 4:
- KPC (Klebsiella pneumoniae carbapenemase): The predominant type, accounting for 76.6% of carbapenemase genotypes 3
- NDM (New Delhi metallo-β-lactamase): A metallo-β-lactamase requiring different treatment strategies
- OXA-48-like enzymes: Increasing from 4.3% in 2020 to 8.3% in 2024 3
- IMP and VIM: Less common metallo-β-lactamases
Most Common Species
The predominant CRE species are 3:
- Klebsiella pneumoniae (69.3%)
- Escherichia coli (29.3%)
- Enterobacter cloacae complex (22.2%)
Clinical Significance
CRE infections carry mortality rates often exceeding 40-70% in critically ill patients 5. The World Health Organization designated CRE as a critical-priority pathogen in 2017, placing it among the top threats requiring urgent development of new antibiotics 2, 6.
Important Clinical Pitfall
The term "CRE" is imprecise and can lead to confusion 7. It may include organisms with inherent resistance (like Proteus species naturally resistant to imipenem), porin-deficient strains resistant only to ertapenem, or OXA-48 producers that remain "susceptible" at breakpoint. For optimal treatment selection, identifying the specific carbapenemase type is essential, as different carbapenemases have vastly different treatment implications—particularly regarding newer β-lactam/β-lactamase inhibitor combinations 1, 7.
Epidemiological Trends
CRE cases have been steadily increasing since mandatory surveillance began. Reports show a 155.5% increase from 2018 to 2022 in some regions 8. Notably, reports from long-term care hospitals increased from 8.2% in 2020 to 21.1% in 2024, likely reflecting population aging and facility-related factors 3.