Carbapenem-resistant Enterobacteriaceae (CRE) and other Carbapenem-Resistant Organisms

Cause: Carbapenem-resistant Enterobacterales (CRE) and other carbapenem-resistant organisms (CRO) are a significant public health concern and contribute to the growing problem of antibiotic resistance. The Enterobacterales constitute a large order of Gram-negative bacilli, many of which are normal inhabitants of the intestinal tract in humans, other mammals, and birds. Enterobacterales most commonly encountered in healthcare settings include the genera, Citrobacter, Enterobacter, Escherichia, Klebsiella, Morganella, Proteus, Providencia, and Serratia. Other frequently encountered carbapenem-resistant Gram-negative organisms (not in the order, Enterobacterales) include Acinetobacter and Pseudomonas. They are common inhabitants of soil and water and may colonize human skin (both), intestines (Pseudomonas), and other body sites.

Carbapenem antibiotics (doripenem, ertapenem, imipenem, and meropenem) are broad spectrum (active against many different groups of bacteria) and usually reserved for severe life-threatening infections. Certain Gram-negative bacilli, including the Enterobacterales, Pseudomonas, and Acinetobacter, have developed carbapenem resistance which limits options for treating infections due to these organisms. The mechanism of resistance can be varied; most concerning are carbapenemases, enzymes produced by bacteria that directly inactivate carbapenems. Carbapenemase genes transmitted on plasmids are primarily responsible for the worldwide spread of CP-CRE.

Illness and treatment: Healthy people usually do not get infections due to CR-organisms (CRO). These bacteria can colonize body sites and cause no symptoms. CRO infections occur most commonly in patients who are weakened due to illness or surgery, have invasive medical devices (e.g., ventilators, bladder catheters, or intravenous catheters), or have received multiple antibiotics. Few antibiotics are effective against CRO. Infectious Disease consultation should be considered for guidance on treating infections. Decolonization should not be attempted except in extremely rare situation.

Sources: The most common sources for colonization or infection with CRO are from health care worker's hands and other contaminated objects in the healthcare environment.

Additional Risks: The outcomes from infections due to resistant bacteria are generally worse than from infections due to antibiotic sensitive bacteria. For CRE, the mortality rate associated with blood stream infections has been reported to be 50%.

Prevention: The best way to prevent colonization and infections with CRO is through strict infection control precautions in healthcare settings including hand washing; placing patients infected with CRE on "contact precautions" (private room, caring for patient with gloves and gown); minimizing the use of invasive devices such as central venous lines, urinary catheters and ventilators; and using antibiotics only when necessary and for the minimum time.

Recent Washington trends: In Washington, CRE and other CRO are routinely detected by commercial laboratories. Since systematic reporting began in 2012, approximately 10% of CRO are found, on testing at PHL, to produce a carbapenemase but the proportion of carbapenemases varies by genus: approximately 30% for Acinetobacter, 15% for Enterobacterales, and 3% of Pseudomonas. As of 2021, DOH has received reports of 7 types of plasmid-associated carbapenemases: KPC, NDM, VIM, IMP, OXA-48, OXA-23, and OXA-24/40.

Purpose of Reporting and Surveillance

  • To increase awareness of carbapenem-resistant Enterobacterales (CRE) and other carbapenem-resistant organisms (CRO) by public health and healthcare professionals.
  • To promote appropriate infection control interventions to prevent transmission of CRE and other CRO within and between healthcare facilities, and between healthcare facilities and the community.
  • To rapidly identify carbapenemase-producing CRE (CP-CRE) and other carbapenemase-producing-organisms (CPO) and prevent or eliminate sources or sites of ongoing transmission within Washington.
  • To better characterize the epidemiology of these infections in Washington to guide response.

Required Reporting - mandated as of January 1, 2022*

Laboratories

Lab report to the local health jurisdiction (LHJ) and isolate submission to PHL required (2 business days) for E. coli, Klebsiella spp., and Enterobacter spp.

Reporting and submission of other CRO isolates, including other CR-genera in the order, Enterobacterales, CR-Pseudomonas spp., and CR-Acinetobacter spp., is strongly encouraged but not required.

*CRE and CRO documented to be carbapenemase-positive is reportable as a Highly Antibiotic Resistant Organism (HARO) in the Washington Disease Reporting System.

Healthcare facilities, providers and laboratories

Notifiable to the local health jurisdiction (LHJ) within 3 business days for E. coli, Klebsiella spp., and Enterobacter spp.

Positive for known carbapenemase resistance gene (including but not limited to KPC, NDM, VIM, IMP, or OXA-48) demonstrated by nucleic acid detection (NAT or NAAT) or whole genome sequencing;

Positive on a phenotypic test for carbapenemase production including but not limited to Metallo-B-lactamase test, modified Hodge test (MHT) (for E. coli and Klebsiella species only), CarbaNP, Carbapenem Inactivation Method (CIM) or modified CIM (mCIM);

Resistant to any carbapenem including but not limited to doripenem, ertapenem, imipenem or meropenem (minimum inhibitory concentrations of ≥ 4 mcg/ml for meropenem, imipenem, and doripenem or ≥ 2 mcg/ml for ertapenem).

Local health jurisdictions

Notifiable to Washington State Department of Health (DOH) Office of Communicable Disease Epidemiology (CDE) within 7 days of case investigation completion or summary information required within 21 days for E. coli, Klebsiella spp., and Enterobacter spp.

Positive for known carbapenemase resistance gene (including but not limited to KPC, NDM, VIM, IMP, or OXA-48) demonstrated by nucleic acid detection (NAT or NAAT) or whole genome sequencing;

Positive on a phenotypic test for carbapenemase production including but not limited toy Metallo-B-lactamase test, modified Hodge test (MHT) (for E. coli and Klebsiella spp. only), CarbaNP, Carbapenem Inactivation Method (CIM), or modified CIM (mCIM).

Positive for known carbapenemase resistance gene (including but not limited to KPC, NDM, VIM, IMP, or OXA-48) demonstrated by nucleic acid detection (NAT or NAAT) or whole genome sequencing; Positive on a phenotypic test for carbapenemase production including but not limited to Metallo-B-lactamase test, modified Hodge test (MHT) (for E. coli and Klebsiella species only), CarbaNP, Carbapenem Inactivation Method (CIM) or modified CIM (mCIM); Resistant to any carbapenem including but not limited to doripenem, ertapenem, imipenem or meropenem (minimum inhibitory concentrations of ≥ 4 mcg/ml for meropenem, imipenem, and doripenem or ≥ 2 mcg/ml for ertapenem). Isolates should be accompanied by a Public Health Laboratories (PHL) Antibiotic Resistance Lab Network (ARLN) Requisition Form and clinical lab antimicrobial susceptibility test result. See ARLN Test Menu and Specimen Collection and Submission Instructions for details on isolate submission.