title: Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).
abstract: The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.
authors.affiliation: a Department of Epidemiology , The Johns Hopkins Bloomberg School of Public Health , Baltimore , MD , USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Goodman
authors.affiliation: b Department of Pathology, Division of Medical Microbiology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Simner
authors.affiliation: a Department of Epidemiology , The Johns Hopkins Bloomberg School of Public Health , Baltimore , MD , USA.|c Department of Pediatrics, Division of Pediatric Infectious Diseases , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Tamma
authors.affiliation: a Department of Epidemiology , The Johns Hopkins Bloomberg School of Public Health , Baltimore , MD , USA.|c Department of Pediatrics, Division of Pediatric Infectious Diseases , Johns Hopkins University School of Medicine , Baltimore , MD , USA.|d Department of Hospital Epidemiology and Infection Control , The Johns Hopkins Hospital , Baltimore , MD , USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Milstone
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015780:Carbapenems / Q000627:therapeutic use*; D003140:Communicable Disease Control / Q000379:methods; D003428:Cross Infection / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission; D062665:Epidemiological Monitoring; D015870:Gene Expression; D022761:Gene Transfer, Horizontal; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Antibiotic stewardship (AS); antimicrobial drug resistance; carbapenem-resistant Enterobacteriaceae (CRE); carbapenemase; carbapenemase-producing Enterobacteriaceae (CPE); hospital epidemiology; transmission