Rapid risk assessment - Carbapenem-resistant Enterobacterales – third update

Since the last update of ECDC’s rapid risk assessment on carbapenem-resistant Enterobacterales (CRE) was published in 2019, there have been various signs that the epidemiological situation in the EU/EEA is continuing to deteriorate. These signs include (a) an increase in the incidence of carbapenem-resistant K. pneumoniae bloodstream infections in 23 EU Member States due to continued transmission of high-risk lineages of carbapenem-resistant K. pneumoniae in hospitals; (b) convergence of virulence and resistance in K. pneumoniae, including healthcare-associated spread of hypervirulent K. pneumoniae ST23 carrying carbapenemase genes; (c) newly emerging Enterobacterales species carrying carbapenemase genes; (d) plasmid-mediated spread of carbapenemase genes causing outbreaks within hospitals and across healthcare networks, and (e) increasing detection of isolates (including isolated cases and clusters) of high-risk lineages of E. coli carrying carbapenemase genes with a risk of spread in the community.

Risk assessment

Based on the deteriorating epidemiological situation, the probability of further spread of CRE in the EU/EEA is high. CRE bloodstream infections are associated with a high level of attributable mortality, primarily due to delays in administration of effective antimicrobial therapy, and the limited number of alternative and easily available treatment options, despite the existence of newly approved antimicrobials. Consistent application of infection prevention and control (IPC) measures and antimicrobial stewardship can reduce the spread of CRE, but their implementation in many hospitals is sub-optimal and has been insufficient to achieve sustained control of high-risk lineages of carbapenem-resistant K. pneumoniae and other Enterobacterales. If spread of CRE continues at the current rate, the impact is expected to be high. If strong, consistent EU/EEA-wide national control efforts are implemented to slow down the spread of CRE, the impact will be moderate. When considered together, probability and impact result in a high-to-very-high risk of further spread of CRE in the EU/EEA.

Recommendations

Enhanced efforts are required to control and reduce harm related to the spread of CRE in the EU/EEA, as follows:

• Strengthen national coordination of control measures between hospitals and regions and support to hospitals in the implementation of control measures. If not already in existence, a dedicated multidisciplinary national management team should be set up at the appropriate national level.
• Develop a CRE management plan (as part of the National Action Plan on antimicrobial resistance, an action plan on multidrug-resistant organisms (MDROs), or as a stand-alone document) outlining actions and budget, with regular public reporting on progress. Clear targets should be established with defined timelines.
• Implement enhanced IPC measures in hospitals to interrupt transmission of carbapenem-resistant K. pneumoniae and other CRE. This also includes pre-emptive isolation and screening for asymptomatic CRE carriage on hospital admission for patients who have been hospitalised in a country or hospital with a known or suspected high prevalence of CRE in the preceding 12 months. Detailed IPC measures are outlined in the Recommendations section.
• Apply antimicrobial stewardship to decrease selection pressure and preserve the effectiveness of the carbapenems and the newly approved antimicrobials. This includes national treatment guidelines for CRE infections and audits of their implementation.
• Strengthen genomic surveillance, including whole-genome sequencing in near real time, accompanied by systematic metadata to guide IPC measures by identifying sources of CRE outbreaks and delineating transmission chains. Genomic surveillance is also required for E. coli carrying carbapenemase genes for early identification of community-associated spread.
• Provide adequate laboratory capacity for rapid detection and characterisation of CRE, including phenotypic antimicrobial susceptibility testing and identification of carbapenemase genes to enable targeted use of newly approved antimicrobials.
• Strengthen innovation and access to antimicrobials indicated against CRE infections.

Infections with MDROs, including CRE, result in a substantial human and economic burden for EU/EEA countries. Nevertheless, according to a study from the Organisation for Economic Co-operation and Development, investment in implementing a mixed policy package, including improving IPC and antimicrobial stewardship, would be not only cost-effective, but would also result in savings for EU/EEA countries.