What is CRE (Carbapenem-Resistant Enterobacteriaceae)?
CRE are Enterobacteriaceae bacteria that demonstrate resistance to carbapenem antibiotics (doripenem, imipenem, or meropenem), representing one of the most serious antimicrobial resistance threats in healthcare settings with high associated morbidity and mortality. 1
Definition and Classification
Carbapenem-resistant Enterobacteriaceae (CRE) are defined as Enterobacteriaceae that are resistant to doripenem, imipenem, or meropenem. 1 This definition encompasses both carbapenemase-producing organisms and those with other resistance mechanisms. 1
The term "carbapenemase-producing Enterobacteriaceae" (CPE) is more precise than CRE, as it specifically identifies organisms producing carbapenemase enzymes as the primary resistance mechanism, though other mechanisms like porin loss can also confer carbapenem resistance. 1, 2
Major Carbapenemase Enzyme Classes
CRE produce three main classes of carbapenemase enzymes based on the Ambler classification system: 1, 3
- Class A carbapenemases: KPC (Klebsiella pneumoniae carbapenemase) - most common in the United States, Colombia, Argentina, Greece, and Italy 1, 2
- Class B metallo-β-lactamases (MBLs): NDM, VIM, IMP - NDM-1 predominates in India, Pakistan, and Sri Lanka 1, 4, 2
- Class D carbapenemases: OXA-48-like enzymes - endemic in Turkey, Malta, Middle East, and North Africa 1, 2
Clinical Significance and Epidemiology
CRE infections are associated with high mortality rates, particularly among critically ill patients with prolonged hospitalization and those exposed to invasive devices such as ventilators or central venous catheters. 1 The World Health Organization identified CRE as a pathogen of critical threat in their global priority list of antibiotic-resistant bacteria. 1
In the United States, carbapenem-resistant Klebsiella pneumoniae (CRKP) is the most commonly encountered CRE species. 1 CDC data showed that 8% of all Klebsiella isolates were CRKP in 2007, compared to fewer than 1% in 2000. 1
Resistance Mechanisms
The three major mechanisms by which Enterobacteriaceae develop carbapenem resistance are: 2
- Enzyme production (most important): Carbapenemase enzymes that hydrolyze carbapenems 1, 2
- Efflux pumps: Active transport systems that expel antibiotics 2
- Porin mutations: Reduced membrane permeability 1, 2
The carbapenemase genes are typically carried on mobile genetic elements (plasmids and transposons), which dramatically increases the risk for rapid dissemination between bacterial species and across healthcare facilities. 1, 5
Treatment Implications
Rapid identification of the specific carbapenemase family (KPC, NDM, VIM, OXA-48-like) is crucial because each class confers different susceptibility profiles requiring distinct treatment strategies. 1
Metallo-β-lactamases (MBLs like NDM) are particularly concerning because they hydrolyze all β-lactam classes except monobactams (aztreonam), and classic serine β-lactamase inhibitors cannot inhibit them. 1, 4 For MBL-producing CRE, ceftazidime/avibactam plus aztreonam is preferred as first-line therapy. 4
For KPC-producing CRE, novel β-lactam agents such as ceftazidime/avibactam and meropenem/vaborbactam are recommended. 1
Infection Control Requirements
All acute care facilities must implement aggressive infection control strategies for CRE, including contact precautions for all patients with CRE and enhanced environmental cleaning. 1
In non-endemic areas, facilities should: 1
- Review microbiology records for the preceding 6-12 months to identify previously unrecognized CRE 1
- Perform point prevalence culture surveys in high-risk units if CRE are discovered 1, 4
- Conduct active surveillance cultures of patients with epidemiologic links to CRE cases 1, 4
Patients with history of CRE colonization or infection should have their medical records flagged for future admissions. 4