Antimicrobial resistance is an important public health problem worldwide. Diseases caused by bacteria, parasites, viruses and fungi that are resistant to antibiotics and other drugs are already responsible for around 700.000 deaths every year. Experts predict that by 2050 more people will die from these superbugs than from cancer.

Among the resistant bacteria, carbapenemase-producing (CP) bacteria - mainly the carbapenemase-producing Enterobacteriaceae species (CPE) and Acinetobacter (CPA) - are classified as the most important ones on the World Health Organization's (WHO) priority list, as carbapenem is one of the most powerful antibiotics in use. Carbapenems are broad-spectrum agents that are very effective in treating a wide variety of infections, such as complicated urinary tract infections, certain meningitis or even pneumonia.

The major mechanism for carbapenem resistance in enterobacteriaceae is the production of enzymes of the class carbapenemases. Carbapenemases are β–lactamase enzymes with the ability to hydrolyse most β-lactam-antibiotics, including carbapenems. Carbapenemases are classified into Ambler class A, B and D. Among them, the most broadly spread carbapenemases are KPC, VIM, IMP, NDM and OXA-48. Frequently, carbapenemase-producing enterobacteriaceae are multidrug-resistant because they also harbour genes encoding for resistance against other antibiotic classes, such as fluoroquinolones and aminoglycosides.

Carbapenemase-producing bacteria have so far been isolated almost exclusively from human cases, mainly non-zoonotic Klebsiella pneumoniae and carbapenemase-resistant Acinetobacter baumannii are common in hospital-acquired infections. Carbapenem-resistant enterobacterial infections are difficult to treat and can cause death in about half of the infected patients. Carbapenemase genes have also been found in other enterobacteria, e.g. E. coli, Salmonella, Pseudomonas.

The European Antimicrobial Resistance Genes Surveillance Network (EURGen-Net), established by the European Centre for Disease Prevention and Control (ECDC), last assessed the epidemiological situation of CPE in Europe in 2018, involving 37 countries. The prevalence of CPE in a given country was assessed on a seven-point scale (0, 1, 2a, 2b, 3, 4, 5), where 0 means no case has been reported and 5 means endemic situation. Hungary has been at level 4 since 2013, i.e. in the inter-regional spread phase. In Greece, Italy, Turkey and Malta the situation is endemic.

The worldwide human-to-human spread of CPE and CRA means that the risk of transfer of bacteria and/or resistance genes to pets and production animals increases accordingly – potentially leading to extensive animal reservoirs of carbapenemase producing bacteria. Transmission of bacteria from humans to animals has been documented in the case of the livestock-associated MRSA CC398, where the bacteria originated from a human strain of MSSA (Methicillin-Sensitive S. aureus) CC398.

The scientific opinion from EFSAs BIOHAZ panel (2013) emphasised the importance to prevent carbapenemase producing strains becoming widespread in livestock.

Since the use of carbapenems has never been licensed for food-producing animals in any country worldwide, their residues in foods of animal origin are not actually allowed.

There have been relatively few reports of carbapenemase-producing bacteria and/or enzymes in food-producing animals or foods. Some of the reported cases:

• VIM-1 producing Escherichia coli and Salmonella Infantis from pigs and poultry in Germany
• OXA-23-producing Acinetobacter spp. from cattle and horses in France and Belgium
• NDM-producing Acinetobacter spp. from pigs and poultry in China
• CPE’s were reported in broiler meat from Egypt
• In Canada, carbapenemase producing bacteria such as Pseudomonas fluorescens, Pseudomonas putida, Stenotrophomonas maltophila, Myroides odoratimimus and Stenotrophomonas spp. have been reported from seafood, clams and squid from South Korea and China

In a 2019 paper in addition to the above mentioned examples, other cases and the occurrence of carbapenemase-producing bacteria in the environment and in wildlife are presented. In wildlife, a few cases have been identified so far, e.g. in Germany bla_NDM-1 Salmonella Corvallis was identified in black kites, in France VIM-1-producing E. coli was found in yellow-legged gulls, and in Africa carbapenemase-producing bacteria were identified in wild boars.

They have also tested for the presence of carbapenemase-producing bacteria in hospital sewage water, wastewater treatment plants, lakes and rivers. From wastewater, resistant bacteria can enter the environment, for example into soil and then into plants and wildlife, causing serious problems for public and animal health and the ecosystems.

Several studies agree that antibiotic resistance plasmids and other transferable elements are circulating among livestock and wild animals worldwide and across vertebrate species barriers. In addition to environmental and wildlife transmission, the treatment of farm animals with β-lactam antimicrobials such as cephalosporins also increases the risk of carbapenemase-producing bacteria appearing in livestock.

Although the overall prevalence of CP microorganisms in food-producing animals and wildlife appears to be low, CP bacteria transmission from food-producing animals to their derived products (e.g. meat and dairy products) could be a threat to consumers, thus promoting mobile carbapenemase gene pools in human enteric flora and supporting transmission of resistant determinants between commensal and pathogenic microorganisms with unknown, but potentially severe consequences for human health.

What has been done in the EU:

Commission Implementing Decision 2013/652/EU on the monitoring and reporting of antimicrobial resistance in zoonotic bacteria and commensal bacteria, which ordered the monitoring of CPE from 2014.

The ECDC has published guidance on the management of CPE infections in human healthcare and has produced a rapid risk assessment, which is regularly updated. Most Member States have also produced their own or revised guidance and monitoring strategies, which are also available on the ECDC website.

Further recommendations:

The role of livestock, wildlife, terrestrial and aquatic environments in the persistence and spread of carbapenemase-producing bacteria has not been adequately investigated. Further research is needed on the following topics as well:

• testing for the presence of carbapenemase-producing bacteria in food producing animals, in particular pigs, cattle and poultry
• the link between the prevalence of carbapenemase-producing bacteria and the use of antimicrobials on farms, in particular the use of third and fourth generation cephalosporins, should be better investigated
• test for co-resistance to cephalosporins and carbapenems by genomic sequencing of isolates
• encouraging comparative genomic analysis of CP isolates from humans, animals and the environment, and thus exploring different transmission pathways.