Carbapenemase-Producing Organisms (CPOs)

Background

Carbapenemase-producing organisms (CPO) are an epidemiologically important group of multidrug-resistant pathogens classified by the Centers for Disease Control and Prevention (CDC) as an urgent threat to public health.¹ Since the detection of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae in the United States in 1996, CPO have spread throughout the country and include many organism-carbapenemase combinations.^2,3 Infections caused by CPO are difficult to treat and associated with high mortality.⁴ CPO commonly contain mobile genetic elements, such as plasmids, that can facilitate transmission of resistance genes within and between bacterial species and in turn, facilitate transmission between patients. Early detection and implementation of infection prevention and control strategies are necessary to prevent further spread of CPO.

Laboratory Criteria

Confirmatory laboratory evidence:

• Positive phenotypic test^* result for carbapenemase production in a specimen, OR
• Positive molecular test^** result detecting a carbapenemase gene^*** (with or without organism identification), OR
• Detection of carbapenemase gene^*** by next generation sequencing (NGS)^‡

* Phenotypic testing methods include but are not limited to: metallo-β-lactamase test, modified Hodge test, Carba NP, carbapenem inactivation method (CIM), modified carbapenem inactivation method (mCIM), EDTA-modified carbapenem inactivation method (eCIM), or immunochromatography tests (ICT).

** Molecular tests for carbapenemase genes include but are not limited to: Cepheid Xpert Carba-R, Nanosphere VERIGENE, Streck ARM-D, validated laboratory-developed NAAT.

*** Carbapenemase genes include: bla_KPC, bla_NDM, bla_VIM, bla_IMP, bla_OXA-48, but other carbapenemase genes include but are not limited to: bla_SIM, bla_GIM, bla_SPM, other bla_OXA, etc.

‡ It is not necessary to report organisms with known chromosomal carbapenemase genes, including but not limited to SME+ Serratia marcescens, unless they have additional non-chromosomal carbapenemase genes.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

Criteria to Distinguish a New Case from an Existing Case

• A specific organism/carbapenemase combination in a person should be counted as a separate case from other organism/carbapenemase combinations in the same person (e.g., KPC+ K. pneumoniae vs. NDM+ E. coli). A specific organism/carbapenemase combination can include a carbapenemase gene(s) without an organism detected (e.g., NDM+ no organism vs. NDM+ E. coli).
• A person classified as a clinical case should not be counted as a screening case thereafter for the same organism/carbapenemase combination (e.g., patient with known NDM+ E. coli infection who later has NDM+ E. coli colonization should not be counted as a separate case).
• A person classified as a screening case can be later counted as a clinical case with the same organism/carbapenemase combination (e.g., patient with NDM+ E. coli peri-rectal screening swab who later develops NDM+ E. coli blood stream infection would be counted twice, once in each category). This is the only way that the same organism/carbapenemase combination can be counted twice for the same person.
• A case with a known carbapenemase but unknown organism should only be counted once for that carbapenemase (e.g., an NDM+ screening case is later screened at a different facility and tests NDM+ positive and no organism is identified again).

Case Classification

Confirmed

Any specimen that meets the confirmatory laboratory evidence.

Case Classification Comments

The following provides guidance for health departments to use for the further classification of CPO cases. Each CPO report should be stratified by whether the specimen was clinical (i.e., collected for the purpose of diagnosing or treating disease in the course of normal care) versus screening (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 specimens from clinical specimens based on microbiology records, screening cases should generally be limited to CPO identified in rectal, peri-rectal, axilla, groin, or stool specimens. Specimens from such sites can be assumed to be for screening unless specifically noted otherwise. Laboratories may also note screening specimens from other sites (e.g., wound, tracheostomy or central line sites). Laboratories do not need to change their practice; public health wants to identify all CPO whether they come from screening or clinical specimens.

Each report should also specify carbapenemase gene(s) when known (e.g., bla_KPC, bla_NDM, bla_OXA-48, bla_VIM, bla_IMP, etc.), listing all genes within the same specimen (e.g., NDM+ OXA-48+ E. coli).

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