CRE

CRE
Name	Carbapenem-resistant Enterobacteriaceae
Classification	Bacteria, Enterobacterales
Notable species	Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae
Resistance mechanisms	Carbapenemases, porin loss, efflux pumps
First reported	1990s
Clinical manifestations	Sepsis, urinary tract infection, pneumonia, intra-abdominal infection
Treatment	Polymyxins, tigecycline, ceftazidime/avibactam, combination therapy
Prevention	Antimicrobial stewardship, contact precautions, surveillance

CRE

Introduction

Carbapenem-resistant Enterobacteriaceae are a group of Enterobacterales notable for resistance to carbapenem antibiotics and associated with high morbidity and mortality. First recognized in the 1990s, these organisms have been implicated in outbreaks in hospitals such as Johns Hopkins Hospital and countries including United States, India, Greece, Italy, and Israel. Major public health agencies like the Centers for Disease Control and Prevention and the World Health Organization have prioritized surveillance and containment efforts. Clinical impact spans intensive care units in tertiary centers such as Mayo Clinic and long-term care facilities like Veterans Health Administration hospitals.

Terminology and Classification

Terminology distinguishes Enterobacterales by genus and resistance phenotype; key taxa include Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, Serratia marcescens, and Proteus mirabilis. Resistance classification often references molecular families: Ambler class A carbapenemases exemplified by Klebsiella pneumoniae carbapenemase (KPC), class B metallo-β-lactamases like New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), and class D oxacillinases such as OXA-48. Clinical laboratories follow guidelines from organizations such as the Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing to categorize isolates.

Epidemiology and Risk Factors

Epidemiology studies report endemic transmission in regions including South Asia, Southern Europe, and parts of North America, with healthcare-associated outbreaks in facilities like acute care hospitals and long-term acute care hospitals. Patient-level risk factors include prior admission to tertiary centers such as University Hospital Cleveland Medical Center, exposure to broad-spectrum agents like carbapenems prescribed per Infectious Diseases Society of America guidance, invasive devices used in intensive care units, and comorbidities managed at institutions like Massachusetts General Hospital. Interfacility patient transfers between centers such as rehabilitation hospitals and skilled nursing facilities facilitate spread.

Pathogenesis and Mechanisms of Resistance

Resistance arises via production of carbapenem-hydrolyzing enzymes encoded on mobile elements such as plasmids circulating among species including Klebsiella pneumoniae and Escherichia coli. Genes such as blaKPC, blaNDM, blaVIM, and blaOXA-48 are often associated with transposons and integrons observed in genomic studies at centers like Broad Institute and Wellcome Sanger Institute. Additional mechanisms include porin mutations described in isolates from tertiary care hospitals and upregulation of efflux systems characterized in research from Harvard Medical School. Horizontal gene transfer events between pathogens in healthcare settings mirror findings from outbreak investigations at Mount Sinai Hospital.

Clinical Presentation and Diagnosis

Clinical syndromes mirror those caused by Enterobacterales: bloodstream infection presenting with sepsis managed following Surviving Sepsis Campaign protocols; complicated urinary tract infection seen in patients at urogenic bladder clinics; ventilator-associated pneumonia encountered in intensive care units; and intra-abdominal infection after procedures performed at centers such as Cleveland Clinic. Diagnosis relies on culture and susceptibility testing per Clinical and Laboratory Standards Institute standards, phenotypic screens like modified Hodge test and Carba NP developed in academic laboratories, and molecular assays targeting bla genes deployed in public health labs such as Public Health England laboratories.

Treatment and Management

Therapeutic options are limited and often guided by susceptibility profiles generated in laboratories affiliated with institutions like Stanford Health Care. Agents used include polymyxins (colistin), tetracycline derivatives such as tigecycline, and novel β-lactam/β-lactamase inhibitor combinations like ceftazidime/avibactam and meropenem/vaborbactam when active against specific enzymes (eg, KPC). Combination regimens and dosing strategies are informed by randomized trials and observational studies from networks including Antimicrobial Resistance Research Network and clinical guidelines from the Infectious Diseases Society of America. Management of bacteremia and device-associated infection requires source control as outlined by surgical teams at centers like Cleveland Clinic and infectious diseases consultants at Johns Hopkins Hospital.

Prevention and Infection Control

Prevention emphasizes antimicrobial stewardship programs modeled on initiatives from World Health Organization and Centers for Disease Control and Prevention, contact precautions implemented per policy at hospitals such as Mayo Clinic, active surveillance cultures conducted in outbreak settings like Tel Aviv Medical Center, and environmental cleaning protocols employing guidance from Association for Professionals in Infection Control and Epidemiology. Interfacility communication during patient transfers, cohorting strategies used in outbreaks at University College London Hospitals, and vaccination programs for preventable comorbid infections advocated by American Hospital Association contribute to control. Public health responses involve reporting to agencies including Centers for Disease Control and Prevention and coordination with regional health authorities.

Category:Antimicrobial resistance