Technical Information CRE | CREATE | THERE IS (2023)

For public health, laboratories, health centers and doctors.

Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant organisms that can cause serious infections and require public health interventions to prevent spread. Aimed at medical, laboratory, and public health professionals, the following information provides answers to frequently asked questions about CRE, including types of CRE, identification and epidemiology, and prevention strategies.

Types of CRE

How does the CDC define CRE?

Enterobacteriaceae that are resistant to at least one of the carbapenem antibiotics (ertapenem, meropenem, doripenem, or imipenem) or produce a carbapenemase (an enzyme that can make them resistant to carbapenem antibiotics) are referred to as CREs.

Einige Enterobacteriaceae (z. B.Proteus spp., Morganella spp., Providencia spp..) have intrinsically high Minimum Inhibitory Concentrations (MICs) for imipenem and therefore the results for meropenem, doripenem and ertapenem for these organisms should be used to determine whether these organisms meet the CLP definition.

How does Enterobacterales become resistant to carbapenems?

Many different mechanisms can lead to carbapenem resistance in Enterobacterales.

Carbapenemase-producing CREs produce enzymes called carbapenemases that inactivate carbapenems and other beta-lactam antibiotics, including penicillins and cephalosporins. The presence of a carbapenemase is usually sufficient to induce resistance to carbapenems. Many carbapenemase genes are located on mobile genetic elements that can be passed from one bacterium to another, spreading resistance. A carbapenemase thatKlebsiella pneumoniaeCarbapenemase (KPC), was first identified in 2001 in the United States. Since then, KPC-producing bacteria have spread across the country. In addition to KPC, there are several other carbapenemases associated with mobile genetic elements, including

• Neu-Delhi Metallo-Beta-Lactamase (NDM)
• Verona Integrron-Encoded Metallo-Beta-Lactamase (VIM)
• Imipenemasa (IMP)
• Oxacilinasa-48 (OXA-48)

Although non-KPC carbapenemases have historically been linked to health exposures outside of the United States, they have been identified in many states across the country and in patients who have not received medical care abroad.

CRE can also become resistant to carbapenems through a combination of chromosomal mutations and acquired mechanisms of non-carbapenemase (eg, lactamase) resistance. CREs lacking carbapenemase are referred to as non-carbapenemase producing CREs.

Some enterobacteria, such asmorganella morganii,Schutztypes andprovidencespecies, always have high minimum inhibitory concentrations (MIC) for carbapenem, but imipenem has also been found to contain carbapenemase genes.

What is the difference between CRE and CP-CRE?

CREs are enteric bacteria resistant to carbapenem antibiotics. This is a phenotypic definition (ie based on the organism's antibiotic susceptibility pattern). There are many different mechanisms (ie genotypes) that can lead to carbapenem resistance. CREs that produce carbapenemases, enzymes that break down carbapenems and related antimicrobial agents and render them ineffective, are called carbapenemase-producing CREs (CP-CREs). CP-CREs ​​are therefore a subset of all CREs.

How common are carbapenemases?

In the United States, CREs are commonly associated with healthcare settings, and approximately 30% of CREs contain a carbapenemase. These carbapenemase genes are often located on mobile genetic elements that are easily shared between bacteria, leading to the rapid spread of resistance.

How common are metallobetalactamase genes such as NDM and VIM in CRE in the United States?

NDM, VIM, and IMP are identified less frequently in CRE than in KPC in the US. Since the AR Lab Network began testing in 2017, only about 10% of identified carbapenemases have been metallo-β-lactamases (MBLs). Preventing the spread of these carbapenemases is critical because they are resistant to some newer antibiotics that are effective against KPC-producing CRE.

The 2018 Sanford Guidelines for Antimicrobial Therapy recommend ceftazidime-avibactam + aztreonam combination therapy for the treatment of severe infections caused by MBL-producing CRE. Talk to your HAI coordinator about testing MBL-producing CRE isolates against this combination therapy via the AR Lab Network.

Identification of CRE and carbapenemases

Why is the carbapenemase test important?

Testing for the carbapenemase mechanism is important for the prevention of CRE because it identifies CP-CREs ​​for which a public health response is recommended and allows healthcare facilities and public health departments to better target various interventions to patients. different types of CRE. For more information on specific CRE measures for healthcare facilities, seeCDC CRE Toolkit PDF-Symbol [PDF – 1 Seite].

How can a laboratory determine if a CRE is a producer of carbapenemases?

Clinical laboratories can perform phenotypic assays for carbapenemase production (eg, CarbaNP, mCIM, and mCIM with eCIM) or molecular assays for the presence of a carbapenemase gene (CLSI, M100, S29).

Carbapenemase testing is available through the AR Lab Network. This assay includes phenotypic testing for carbapenemase activity and molecular identification of the five carbapenemases most commonly identified in CRE: KPC, NDM, VIM, OXA-48 type, and IMP.

Note that carbapenem susceptibility results must be reported as established along with the appropriate interpretation. Results from tests that detect carbapenemase production should not be used to alter the interpretation of a carbapenemase susceptibility result. The result of a carbapenemase test should be reported to infection control, a case report should be sent to the National Disease Notifiable Surveillance System (NNDSS), and those requesting or requesting epidemiological information should be notified (e.g., state or local public health agencies). of the program). ).

CRE Epidemiology and Prevention

How are CREs transmitted?

In healthcare, CREs are transmitted from person to person, often through the hands of healthcare workers or through contaminated medical equipment. Additionally, sink and toilet drains are increasingly recognized as an environmental reservoir and source of CRE transmission. Preventing the transmission of CRE requires careful hand hygiene, the appropriate use of transmission-based precautions (i.e. the use of contact precautions or enhanced barrier measures, depending on the environment and organism), protection of the environment through cleanliness, and compliance with Hygiene Practices for Sinks and Toilets.

Which patients are most at risk of acquiring CRE?

The major risk factors for acquiring CRE in the United States include exposure to medical care and exposure to antibiotics. Risk factors associated with health care include the need for assistance with most activities of daily living, such as walking. B. toileting and bathing, exposure to an intensive care unit, and mechanical ventilation. Several antibiotics have been associated with the occurrence of CRE, including carbapenems, cephalosporins, fluoroquinolones, and vancomycin.

Exposure to antibiotics can change the community of bacteria that live in a person's body (microbiome). This might make it easier for someone without a CRE to acquire. For patients with CRE that colonize their digestive tract, taking antibiotics can increase the amount of CRE in the body and the chance of developing an infection or spreading CRE to other patients. Several antibiotics have been associated with the occurrence of CRE, including carbapenems, cephalosporins, fluoroquinolones, and vancomycin.

What infections cause CREs?

CRE can cause infections in almost any part of the body, including urinary tract infections, bloodstream infections, ventilator-associated pneumonia, and intra-abdominal abscesses.

What is the difference between colonization and infection by CRE?

Infection occurs when a pathogen such as CRE invades a site in the body and causes signs and symptoms of disease. Colonization means that the organism is in or on the body but does not cause any symptoms or disease. People colonized with CRE can develop CRE infections and transmit CRE to other patients; Therefore, SRC prevention practices include colonized and infected individuals.

CRE most commonly colonizes the digestive tract. Screening of specific individuals at high risk for CRE colonization is a CDC-recommended intervention that may help prevent the spread of CRE-CP. These high-risk individuals include patients or residents who share some of the same risk factors as a newly identified CP-CRE-colonized individual (eg, hospitalized in the same unit) and patients who have been hospitalized outside of the United States in the past became 6 months. . . AR Lab Network offers free colonization testing.

What are the recommendations to prevent the spread of CP-CRE?

Most of the increase in carbapenem resistance in Enterobacterales in the United States and worldwide has been attributed to the spread of carbapenemase genes. These genes can be transferred between bacteria, increasing the spread of carbapenem resistance. Therefore, CP-CREs ​​are the target of intensive prevention efforts. The CDC recommends a coordinated public health response to identify even single cases of unusual carbapenemase, with an assessment of infection control practices and an assessment of possible transmission through colonization screening.

Because CP-CREs ​​are transmitted by contact, careful adherence to basic infection control practices prevents human-to-human transmission. This includes:

• Use of contact precautions for CRE-infected or colonized individuals in the ICU
• Improved barrier measures for CRE-infected or colonized individuals in post-acute care
• Compliance with hand hygiene and environmentally friendly cleaning and disinfection

For more information on installation-level prevention strategies, see the CRE Toolkit and Facility Information on CRE.

What are the recommendations for preventing the spread of CREs that do not produce carbapenemases?

CREs that do not produce carbapenemases generally remain resistant to multiple antibiotics (i.e., multidrug-resistant organisms) and likely justify the use of specific infection control measures (e.g., contact precautions in intensive care units) in healthcare settings to limit transmission. More aggressive interventions, such as B. colonization screening in contacts, but are generally reserved for CP-CRE, which have a greater potential for spread.