Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE)
2018 Case Definition

Background

Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae (CP-CRE) is defined as E. coli, Klebsiella spp., or Enterobacter spp. where the isolate is:

• • Positive for carbapenemase production by a phenotypic method

-OR-

• Positive for a known carbapenemase resistance mechanism by a recognized test (see below for included carbapenemases)

CP-CRE are an emerging and epidemiologically important threat. Since the first detection of CP-CRE in the United States (1), CP-CRE have spread rapidly, with cases reported in all 50 states (2). Infections with CP-CRE are difficult to treat and associated with high mortality rates (3). Carbapenem antibiotics are often used as the last line of treatment for infections caused by highly resistant bacteria, including those in the Enterobacteriaceae family. Increased antimicrobial resistance limits treatment options (4). CP-CRE contain mobile resistance elements that facilitate transmission of resistance to other Gram negative bacilli (5). Early detection and aggressive implementation of infection prevention and control strategies are necessary to prevent further spread of CP-CRE, especially novel CP-CRE. These strategies require an understanding of the prevalence or incidence of CP-CRE.

Laboratory Criteria For Diagnosis

Laboratory evidence of carbapenemase production in an isolate by a phenotypic method or positive for a known carbapenemase resistance mechanism by specific testing methods, such as:

• Phenotypic methods for carbapenemase production:
  • Carba NP positive
  • Metallo-β-lactamase testing (e.g., E-test) positive
  • Modified Carbapenem Inactivation Method (mCIM) positive or indeterminate
  • Carbapenem Inactivation Method (CIM) positive
  • Modified Hodge Test (MHT) positive
  • Positive for phenotypic carbapenemase production (e.g., mCIM, CIM, CarbaNP) but negative by polymerase chain reaction (PCR) (e.g., Xpert Carba-R) for all known resistance mechanisms (e.g. Klebsiella pneumoniae Carbapenemase [KPC], New Delhi metallo-β-lactamase [NDM], oxacillinase-48 [OXA-48], Verona integron-encoded metallo-β-lactamase [VIM], imipenemase [IMP])
• Molecular methods for resistance mechanism:
  • PCR positive (for KPC, NDM, OXA-48, IMP, or VIM)
  • Xpert Carba-R positive (for KPC, NDM, OXA-48, VIM, IMP)
  • PCR or Xpert Carba-R positive for novel carbapenemase

Criteria to Distinguish a New Case from an Existing Case

• Different organisms/species/carbapenemases are counted as separate events from other organisms/species/carbapenemases.
• There is at least a 12 month interval from previous notification event for clinical cases.
• A person with a clinical case should not be counted as a screening/surveillance case thereafter (e.g., patient with known infection who later has colonization of GI tract is not counted as more than one case).
• A person with a screening case can be later categorized as a clinical case (e.g., patient with positive peri-rectal screening swab who later develops blood stream infection would be counted in both categories).

Confirmed

E. coli, Klebsiella spp., or Enterobacter spp. from any isolate that is:

• • Positive for known carbapenemase resistance mechanism (e.g., KPC, NDM, VIM, IMP, OXA-48) demonstrated by a recognized test (e.g., PCR, Xpert Carba-R);

-OR-

• Positive on a phenotypic test for carbapenemase production (e.g., metallo-β-lactamase test, modified Hodge test, Carba NP, Carbapenem Inactivation Method [CIM], or modified CIM).

Case Classification Comments

1. Cases involving isolates that are phenotypically positive for carbapenemase production (e.g., mCIM), but negative for KPC, NDM, OXA-48, VIM, and IMP should be counted as confirmed CP-CRE. Isolates should be submitted to the regional laboratories of the ARLN for further characterization (potential novel carbapenemase).
2. A positive Modified Hodge Test (MHT) can be used to confirm CP-CRE for Klebsiella spp and E. coli but not Enterobacter spp. An isolate that tests positive on MHT but negative PCR for KPC, NDM, OXA-48, VIM and IMP should have additional characterization performed with another phenotypic test for carbapenemase such as mCIM.
3. If isolate is indeterminate on mCIM and negative by PCR for KPC, NDM, OXA-48, VIM and IMP, isolate should be tested using CarbaNP (at state public health laboratory or regional ARLN lab).
4. CP-CRE should be stratified by the 3 subtypes (genera): Klebsiella spp, Enterobacter spp and E.coli. Each subtype/ genus should be stratified by whether the cultures were clinical (i.e., collected for the purpose of diagnosing or treating disease in the course of normal care) versus for screening/surveillance (i.e., collected for the detection of colonization and not for the purpose of diagnosing or treating disease). Because it can be difficult to differentiate screening cultures from clinical cultures based on microbiology records, screening tests should generally be limited to rectal, peri-rectal or stool cultures. Cultures from such sites can be assumed to be for screening unless specifically noted otherwise. Laboratory may also note screening culture for other sites (e.g., wounds, tracheostomy or central line sites). Laboratories do not need to change their practice; public health wants to identify all CP-CRE whether they come from screening or clinical cultures.