2012 CRE Toolkit - Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE)

Background

The emergence and dissemination of carbapenem resistance among Enterobacteriaceae in the United States represent a serious threat to public health. These organisms are associated with high mortality rates and have the potential to spread widely. Decreasing the impact of these organisms will require a coordinated effort involving all stakeholders including healthcare facilities and providers, public health, and industry. This document expands on the 2009 Centers for Disease Control and Prevention (CDC) and Healthcare Infection Control Practices Advisory Committee (HICPAC) recommendations and will continue to evolve as new information becomes available.

Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE) - 2012 CRE Toolkit

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The approach to controlling transmission of these organisms in healthcare facilities includes the following:

Recognizing these organisms as epidemiologically important
Understanding the prevalence in their region
Identifying colonized and infected patients when present in the facility
Implementing regional and facility–based interventions designed to stop the transmission of these organisms

Carbapenem-resistant Enterobacteriaceae (CRE) appear to have been uncommon in the United States before 1992. However, carbapenemase-producing Enterobacteriaceae, most commonly producing Klebsiella pneumoniaecarbapenemase (KPC), have disseminated widely throughout the United States since being first reported in 2001. Despite the spread of KPC-producing Enterobacteriaceae, the current U.S. distribution of CRE appears to be heterogeneous; these organisms are commonly isolated from patients in some parts of the United States, but they are not regularly found in patients from other regions. Even in areas where CRE are found they may be more common in some healthcare settings, such as long-term acute care, than they are in others.

In addition to KPC-producing Enterobacteriaceae, several different metallo-β-lactamase-producing strains have been identified in the United States since 2009. These include the New Delhi metallo-β-lactamase (NDM), Verona integronencoded metallo-β-lactamase (VIM), and the imipenemase (IMP) metallo-β-lactamase. These enzymes are more common in other areas of the world and in the United States have generally been found among patients who received medical care in countries where these organisms are known to be present.

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Definitions

CDC has developed the following interim surveillance definition for CRE. CRE are defined as Enterobacteriaceae that are:

CRE are epidemiologically important for several reasons:

CRE have been associated with high mortality rates (up to 50% in some studies).
In addition to β-lactam/carbapenem resistance, CRE often carry genes that confer high levels of resistance to many other antimicrobials, often leaving very limited therapeutic options. “Pan-resistant” KPC-producing strains have been reported.
CRE have spread throughout many parts of the United States and have the potential to spread more widely.

Nonsusceptible to one of the following carbapenems: doripenem, meropenem, or imipenem AND
Resistant to all of the following third-generation cephalosporins that were tested: ceftriaxone, cefotaxime, and ceftazidime.
(Note: All three of these antimicrobials are recommended as part of the primary or secondary susceptibility panels for Enterobacteriaceae)
Klebsiella species and Escherichia coli that meet the CRE definition are a priority for detection and containment in all settings; however, other Enterobacteriaceae (e.g.,Enterobacter species) might also be important in some regions.
For bacteria that have intrinsic imipenem nonsusceptibility (i.e., Morganella morganii, Proteus spp.,Providencia spp.), requiring nonsusceptibility to carbapenems other than imipenem as part of the definition might increase specificity.
This CRE surveillance definition is based upon the current (M100-S22 2012) Clinical and Laboratory Standards Institute (CLSI) interpretative criteria (breakpoints) for carbapenem susceptibility among Enterobacteriaceae (Appendix A); if the older CLSI breakpoints (pre-dating M100-S20 U) are being used to determine carbapenem susceptibility, consideration should be given to including ertapenem in the CRE definition to increase sensitivity.

Definitions for CRE are complicated by a number of factors including the diversity of the genera. Another important challenge to developing a standardized definition of CRE is a recent (mid-2010) change in the Clinical and Laboratory Standards Institute (CLSI) interpretative criteria (breakpoints) for determining susceptibility to carbapenems among Enterobacteriaceae. These new recommendations lowered the breakpoints and removed the requirement for testing for carbapenemase (e.g., modified Hodge Test) to determine susceptibility. These breakpoints were further modified in January 2012 (M100-S22).

Changes in the breakpoints are shown in Appendix A. Although the use of the current CLSI breakpoints offers laboratories a simpler and more straightforward approach to identifying CRE, adoption may be delayed by the fact that the U.S. Food and Drug Administration has not yet approved all of these breakpoints and some automated susceptibility panels currently do not include dilutions low enough to allow for application of the lower breakpoints.

Since most carbapenem resistance mediated by carbapenemases in the United States is found among Klebsiella spp. and E. coli, individual facilities or public health authorities might choose to apply the CRE surveillance definition only to these specific Enterobacteriaceae.

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