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 (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 can be transmitted on plasmids. This "horizontal inheritance" is primarily responsible for the worldwide spread of carbapenemase producing organisms (CPO).

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 have long term hospitalizations, invasive medical devices (e.g., ventilators, bladder catheters, or intravenous catheters), or have international healthcare. 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 situations.

Sources: In the US, 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 implementation of appropriate infection control precautions in healthcare settings including hand washing; placing patients infected with CRE on transmission based precautions; minimizing the use of invasive devices; 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, but CP-CRE and other CPO are less common. Before systematic reporting began in 2012, 8 CP-CRE had been identified in Washington.

As of end of 2023, KPC is the most common carbapenemase in Enterobacterales in the United States; in Washington, NDM are slightly more numerous than KPC. DOH has received reports of 10 different carbapenemases in CRE, Acinetobacter, and Pseudomonas: KPC, NDM, VIM, IMP and OXA-48-like, OXA-23-like, OXA 24/40-like, OXA-235-like, OXA-58-like and IMI/NMC. The DOH MDRO Dashboard provides a summary of CRO and CPO surveillance in Washington since 2012. Inpatient healthcare remains the most likely reported source of acquisition for carbapenemases.

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.

Legal Reporting Requirements

Health care providers and health care facilities: notifiable to local health jurisdiction (LHJ) within 3 business days.
- Per WAC 246-101-101, CRE isolates limited to those due to Enterobacter species, E. coli and Klebsiella species.
- Per WAC 246-101-015, by Secretary of Health request of provisional reporting for CPOs, all carbapenem resistant (CR) isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumanii, suspected and confirmed carbapenemase producing isolates, and all confirmed CPO cases. See Appendix I, Table 2 for confirmatory carbapenemase tests.
Laboratories: notifiable to local health jurisdiction within 2 business days; submission required – isolate or, if no isolate, submit specimen associated with positive result, within 2 business days.
- Per WAC 246-101-201, Enterobacter species, E. coli, and Klebsiella species,
  - Positive for known carbapenemase resistance gene (including but not limited to KPC, NDM, VIM, IMP, or OXA-48-like) 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, CarbaNP, Carbapenem Inactivation Method (CIM) or modified CIM (mCIM); See Appendix I, Table 2 for confirmatory carbapenemase tests.
  - Resistant to any carbapenem including but not limited to ertapenem, imipenem or meropenem (minimum inhibitory concentrations of ≥ 4 mcg/ml for meropenem, and imipenem, or ≥ 2 mcg/ml for ertapenem).
- Per WAC 246-101-015, by Secretary of Health request of provisional reporting for CPOs,
  - Carbapenem resistant isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii for which the species is not intrinsically resistant. See Appendix I, Table 1 for antimicrobial susceptibility criteria.
  - Isolates with preliminary or confirmed positive carbapenemase. See Appendix I, Table 2 for confirmatory carbapenemase tests.

See ARLN Test Menu and Specimen Collection and Submission Instructions for details on isolate submission.

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.
- Per WAC 246-101-505 and WAC 246-101-015,
  - Confirmed carbapenemase producing organism cases. See Appendix I, Table 2 for confirmatory carbapenemase tests.