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| Carbapenem-resistant Enterobacteriaceae | |
|---|---|
| Name | Carbapenem-resistant Enterobacteriaceae |
| Classification | Bacteria |
| Domain | Bacteria |
| Phylum | Proteobacteria |
| Classis | Gammaproteobacteria |
| Ordo | Enterobacterales |
| Familia | Enterobacteriaceae |
Carbapenem-resistant Enterobacteriaceae are a group of Gram-negative bacteria within the family Enterobacteriaceae that have acquired resistance to carbapenem antibiotics. First described in clinical isolates in the late 20th century, these organisms have since been implicated in outbreaks and endemic transmission across hospitals and communities worldwide, prompting responses from bodies such as the World Health Organization, Centers for Disease Control and Prevention, and national public health agencies like Public Health England.
Carbapenem-resistant Enterobacteriaceae (CRE) are defined by phenotypic resistance or reduced susceptibility to carbapenems such as imipenem, meropenem, doripenem, and ertapenem, or by carriage of carbapenemase genes such as KPC, NDM, OXA-48, VIM, and IMP. Taxonomically they belong to genera including Escherichia, Klebsiella, Enterobacter, Serratia, and Proteus within the order Enterobacterales; clinically important species include Escherichia coli and Klebsiella pneumoniae. International classification and reporting have been influenced by organizations like the European Centre for Disease Prevention and Control and the Infectious Diseases Society of America.
Resistance arises via enzymatic degradation by carbapenemases (serine beta-lactamases such as KPC, class D oxacillinases like OXA-48, and metallo-beta-lactamases such as NDM, VIM, IMP), often encoded on mobile elements like plasmids and transposons that facilitate horizontal transfer among bacteria. Additional mechanisms include porin loss or modification and upregulation of efflux pumps, which act in concert with extended-spectrum beta-lactamases (ESBLs) or AmpC enzymes to produce high-level resistance. Molecular epidemiology studies by groups at institutions such as Johns Hopkins Hospital, University of Oxford, and the Pasteur Institute have detailed the genetic contexts and international spread of these determinants.
CRE have been reported on every continent, with marked regional variation: endemicity of KPC-producing strains in the United States, parts of Brazil, and Greece; rapid international dissemination of NDM producers linked to healthcare and travel from the Indian subcontinent; widespread OXA-48 circulation in Turkey, North Africa, and parts of Europe; and VIM or IMP occurrences in Spain and Japan. Outbreak investigations by teams from Columbia University, Karolinska Institute, and the Robert Koch Institute have documented nosocomial transmission in intensive care units, long-term care facilities, and during medical tourism. Surveillance networks such as the European Antimicrobial Resistance Surveillance Network and programs by the World Bank-supported initiatives have tracked trends over time.
Clinical presentations range from urinary tract infections and intra-abdominal infections to ventilator-associated pneumonia, bloodstream infections, and surgical site infections; severity correlates with host factors and site of infection. Risk factors identified in cohort and case-control studies include prior exposure to broad-spectrum antimicrobials (notably carbapenems and cephalosporins), prolonged hospitalization or ICU stay, invasive devices (central venous catheters, mechanical ventilation), recent surgery, organ transplantation, dialysis, and residence in long-term care facilities. Patient cohorts managed at centers like Mayo Clinic, Massachusetts General Hospital, and Cedars-Sinai Medical Center have informed risk stratification and outcome analyses.
Laboratory detection employs phenotypic screening (disk diffusion, automated susceptibility testing, modified Hodge test, carbapenem inactivation methods) and confirmatory molecular assays (PCR for blaKPC, blaNDM, blaOXA-48-like, blaVIM, blaIMP), as well as sequencing approaches (whole-genome sequencing) used by reference laboratories including the National Institutes of Health and national public health laboratories. Rapid diagnostics include immunochromatographic assays and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) adjunct methods, which have been implemented in settings such as Singapore General Hospital, Royal Melbourne Hospital, and regional reference centers.
Therapeutic options are limited and guided by susceptibility testing; agents used include polymyxins (colistin), tigecycline, fosfomycin, aminoglycosides, and newer beta-lactamase inhibitor combinations (ceftazidime–avibactam for KPC and some OXA-48, meropenem–vaborbactam for KPC, imipenem–relebactam) whose deployment has been informed by trials and approvals from regulatory agencies like the Food and Drug Administration and the European Medicines Agency. Combination therapy, optimized dosing, and pharmacokinetic/pharmacodynamic strategies are frequently employed, while emergent therapies such as bacteriophages and monoclonal antibodies are under investigation at institutions like Harvard Medical School and Imperial College London. Antimicrobial stewardship programs at hospitals including Stanford Health Care and Cleveland Clinic aim to reduce selective pressure through guideline-driven prescribing, prospective audit, and education.
Containment relies on standard and contact precautions, active surveillance cultures, patient cohorting, environmental cleaning, hand hygiene promotion, and antimicrobial stewardship. Multidisciplinary outbreak responses have involved infection prevention teams, hospital epidemiologists, and public health authorities such as CDC field teams and regional agencies coordinating measures including screening of contacts, temporary unit closures, and equipment decontamination. Policies from bodies like the Joint Commission and guidelines by the Society for Healthcare Epidemiology of America inform facility-level protocols.
CRE are categorized as urgent or critical antimicrobial resistance threats by organizations including the World Health Organization and Centers for Disease Control and Prevention, with substantial implications for morbidity, mortality, healthcare costs, and surgical outcomes. National and international surveillance efforts—such as mandatory reporting in some jurisdictions, genomic surveillance initiatives, and data sharing through platforms linked to the Global Health Security Agenda—seek to detect emergence, monitor trends, and guide policy. Responses encompass investment in novel therapeutics, diagnostic capacity, infection prevention infrastructure, and global collaboration among ministries of health, academic centers, and non-governmental organizations like the Bill & Melinda Gates Foundation.
Category:Antibiotic-resistant bacteria