FAQs about Choosing and Implementing a CRE Definition

Introduction

	CDC Vital Signs. Learn vital information about stopping C. difficile infections. Read CDC Vital SignsCarbapenem resistance among Enterobacteriaceae is complex; unlike methicillin resistance among Staphylococcus aureus which, for the most part, represents one resistance mechanism in one species of bacteria, Enterobacteriaceae include more than 70 different genera and many different mechanisms can lead to carbapenem resistance. All carbapenem-resistant Enterobacteriaceae (CRE), regardless of the mechanism underlying the carbapenem resistance, are likely multidrug-resistant organisms for which interventions might be required in healthcare settings to prevent transmission. However, carbapenemase-producing CRE (CP-CRE) are currently believed to be primarily responsible for the increasing spread of CRE in the United States and have therefore been targeted for aggressive prevention. A reliable way to differentiate CP-CRE from non-CP-CRE might help guide such targeting by identifying the organisms of greatest epidemiologic interest. Because mechanism testing is not recommended for guiding therapeutic decisions, this testing is not routinely performed in many U.S. clinical laboratories, so phenotypic definitions, based on the bacteria’s antibiotic susceptibility pattern, are the primary way clinical laboratories and infection prevention teams attempt to identify CP-CRE; although no phenotypic definition will perform perfectly in distinguishing between CP-CRE and non-CP-CRE.

The previous CDC CRE definition (nonsusceptible to imipenem, meropenem, or doripenem, AND resistant to all third generation cephalosporins tested) was designed to be more specific for CP-CRE; however, it has proven to be complicated, difficult to implement, and has been found to miss some CP-CRE. In January 2015, The Centers for Disease Control and Prevention (CDC) modified its surveillance definition for CRE to the current definition (resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate possess a carbapenemase). The following document provides answers to frequently asked questions from healthcare facilities and laboratories about choosing and implementing a CRE definition.

CRE are Enterobacteriaceae that are nonsusceptible to carbapenem antibiotics. This is a phenotypic definition (i.e., based on the antibiotic susceptibility pattern of the organism) and it includes bacteria that are not susceptible to carbapenems via more than one type of mechanism. In general, these carbapenem resistance mechanisms include:

  • The production of carbapenemases (called CP-CRE), enzymes that break down carbapenems and related antimicrobials making them ineffective. This includes enzymes like Klebsiella pneumoniae carbapenemase (KPC)
  • The combination of mechanisms other than carbapenemase production (called non-CP-CRE), most commonly the production of beta-lactamases (e.g., AmpC) in combination with alterations in the bacteria’s cell membrane (e.g., porin mutations).

Therefore, CP-CRE are a subset of all CRE. CP-CRE have been targeted for prevention because much of the recent increase in CRE in the United States appears to have been driven by the spread of CP-CRE strains and experience from both the United States and from other parts of the world suggests that these organisms have the ability to spread rapidly and can cause infections that are associated with high mortality rates. U.S. phenotypic CRE definitions have attempted to target CP-CRE for both surveillance and prevention; however, no phenotypic CRE definition is perfect and some non-CP-CRE can also meet these definitions. At this time, mechanism testing that might readily differentiate CP-CRE from non-CP-CRE is not widely used and phenotypic definitions are the only available option for many facilities to target CRE prevention efforts.

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