Review and Analysis of National Monitoring Systems for Antimicrobial Resistance in Animal Bacterial Pathogens in Europe: A Basis for the Development of the European Antimicrobial Resistance Surveillance Network in Veterinary Medicine (EARS-Vet).

The monitoring of antimicrobial resistance (AMR) in bacterial pathogens of animals is not currently coordinated at European level. To fill this gap, experts of the European Union Joint Action on Antimicrobial Resistance and Healthcare Associated Infections (EU-JAMRAI) recommended building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet). In this study, we (i) identified national monitoring systems for AMR in bacterial pathogens of animals (both companion and food-producing) among 27 countries affiliated to EU-JAMRAI, (ii) described their structures and operations, and (iii) analyzed their respective strengths, weaknesses, opportunities and threats (SWOT). Twelve countries reported having at least one national monitoring system in place, representing an opportunity to launch EARS-Vet, but highlighting important gaps in AMR data generation in Europe. In total, 15 national monitoring systems from 11 countries were described and analyzed. They displayed diverse structures and operations, but most of them shared common weaknesses (e.g., data management and representativeness) and common threats (e.g., economic vulnerability and data access), which could be addressed collectively under EARS-Vet. This work generated useful information to countries planning to build or improve their system, by learning from others' experience. It also enabled to advance on a pragmatic harmonization strategy: EARS-Vet shall follow the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards, collect quantitative data and interpret AMR data using epidemiological cut-off values.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: kept fish species.

In this Opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to the health of certain kept fish species have been assessed. Atlantic salmon (Salmo salar), carp (Cyprinus spp.), rainbow trout (Oncorhynchus mykiss), sea bream (Sparus aurata) and tilapia (Oreochromis spp.), selected as representative of the most important fish species and production systems that are commercially reared in fresh and saltwater farms, were the focus of this assessment. The assessment was performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate Opinion. The global state of play of antimicrobial resistance in Aeromonas hydrophila, Aeromonas salmonicida, Flavobacterium psychrophilum and Flavobacterium columnare is provided. Among these bacteria, none was identified as being among the most relevant antimicrobial-resistant bacteria in the assessed kept fish species in the EU due to the very limited scientific evidence available.

Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): a bottom-up and One Health approach.

BACKGROUND: Building the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach. OBJECTIVES: To define the combinations of animal species/production types/age categories/bacterial species/specimens/antimicrobials to be monitored in EARS-Vet. METHODS: The EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the ECDC and the European Food Safety Authority (EFSA). RESULTS: EARS-Vet plans to monitor AMR in six animal species [cattle, swine, chickens (broilers and laying hens), turkeys, cats and dogs], for 11 bacterial species (Escherichia coli, Klebsiella pneumoniae, Mannheimia haemolytica, Pasteurella multocida, Actinobacillus pleuropneumoniae, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus hyicus, Streptococcus uberis, Streptococcus dysgalactiae and Streptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Molecular data detecting the presence of ESBLs, AmpC cephalosporinases and methicillin resistance shall be collected too. CONCLUSIONS: A preliminary EARS-Vet scope was defined, with the potential to fill important AMR monitoring gaps in the animal sector in Europe. It should be reviewed and expanded as the epidemiology of AMR changes, more countries participate and national monitoring capacities improve.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: cattle.

In this opinion, the antimicrobial resistant bacteria responsible for transmissible diseases that constitute a threat to the health of cattle have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Escherichia coli (non-VTEC), Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus uberis, Streptococcus dysgalactiae, Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Moraxella bovis, Fusobacterium necrophorum and Trueperella pyogenes is provided. Among those bacteria, EFSA identified E. coli and S. aureus with ≥ 66% certainty as being the most relevant antimicrobial resistant bacteria in cattle in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: sheep and goats.

In this opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to the health of sheep and goats have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Staphylococcus aureus, Escherichia coli (non-VTEC), Pseudomonas aeruginosa, Dichelobacter nodosus, Moraxella ovis, Mannheimia haemolytica, Pasteurella multocida, Mycoplasma ovipneumoniae, Mycoplasma agalactiae, Trueperella pyogenes, Streptococcus uberis, Bibersteinia trehalosi, Campylobacter fetus, Mycoplasma mycoides subsp. capri, Mycoplasma capricolum subsp. capricolum, Fusobacterium necrophorum is provided. Among those bacteria, EFSA identified E. coli with ≥ 66% certainty as being the most relevant antimicrobial-resistant bacteria in sheep and goat in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: Dogs and cats.

In this opinion the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to dog and cat health have been assessed. The assessment has been performed following a methodology based on information collected via an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play of antimicrobial resistant Staphylococcus pseudintermedius, Staphylococcus aureus, Staphylococcus schleiferi, Escherichia coli, Proteus mirabilis, Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa, Clostridium perfringens, Clostridioides difficile, Enterococcus faecalis and Enterococcus faecium has been provided. Among those bacteria, EFSA identified S. pseudintermedius, E. coli and P. aeruginosa with > 90% certainty as the most relevant antimicrobial resistant bacteria in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Ad hoc method for the assessment of animal diseases caused by bacteria resistant to antimicrobials.

The European Commission requested EFSA assess antimicrobial-resistant bacteria responsible for animal transmissible diseases, with a view to listing such pathogens for European Union action. This Scientific Opinion addresses the ad hoc method developed: (i) to give a global state of play as regards resistant animal pathogens that cause transmissible animal diseases, (ii) to identify the most relevant bacteria in the EU and (iii) to summarise their actual or potential animal health impact, and to perform their assessment for being listed and categorised according to the criteria of Articles 7, 5, 9 and 8 within the Animal Health Law (AHL) framework. An extensive literature review is carried out to give the global state of play of selected resistant bacteria that constitute a threat to animal health (i). An expert judgement procedure, based on the outcome of the literature review, is applied to identify which among those bacteria subjected to the literature review are the 'most relevant' in the European Union (ii). Their animal health impact in the European Union and their assessment for being listed and categorised according to the AHL framework will follow the 'ad hoc method for the assessment on listing and categorisation of animal diseases within the framework of the Animal Health Law' that EFSA has developed in the past (iii). The assessment of (i) and (ii) is addressed in distinct scientific opinions that are published separately by animal species of interest (dogs and cats, horses, pigs, poultry, cattle, small ruminants, rabbits and aquatic animal species). The assessment of (iii) is addressed in distinct scientific opinions and published separately by the animal pathogen.

Comparison of Phenotypical Antimicrobial Resistance between Clinical and Non-Clinical E. coli Isolates from Broilers, Turkeys and Calves in Four European Countries.

Livestock data on antimicrobial resistance (AMR) are commonly collected from bacterial populations of clinical and non-clinical isolates. In contrast to data on non-clinical isolates from livestock, data on clinical isolates are not harmonized in Europe. The Normalized Resistance Interpretation (NRI) method was applied to overcome the lack of harmonization of laboratory methods and interpretation rules between monitoring systems. Statistical analyses were performed to identify associations between the isolate type (clinical vs. non-clinical) and resistance to four antimicrobials (ampicillin, tetracycline, gentamicin, and nalidixic acid) per animal category in Germany and France. Additional statistical analyses comparing clinical and non-clinical isolates were performed with the available data on the same antimicrobial panel and animal categories from the UK and Norway. Higher resistance prevalence was found in clinical isolates compared to non-clinical isolates from calves to all antimicrobials included in Germany and France. It was also found for gentamicin in broilers from France. In contrast, in broilers and turkeys from Germany and France and in broilers from the UK, a higher resistance level to ampicillin and tetracycline in non-clinical isolates was encountered. This was also found in resistance to gentamicin in isolates from turkeys in Germany. Resistance differed within countries and across years, which was partially in line with differences in antimicrobial use patterns. Differences in AMR between clinical and non-clinical isolates of Escherichia coli are associated with animal category (broiler, calf, and turkey) and specific antimicrobials. The NRI method allowed comparing results of non-harmonized AMR systems and might be useful until international harmonization is achieved.

Building the European Antimicrobial Resistance Surveillance network in veterinary medicine (EARS-Vet).

Antimicrobial resistance (AMR) should be tackled through a One Health approach, as stated in the World Health Organization Global Action Plan on AMR. We describe the landscape of AMR surveillance in the European Union/European Economic Area (EU/EEA) and underline a gap regarding veterinary medicine. Current AMR surveillance efforts are of limited help to veterinary practitioners and policymakers seeking to improve antimicrobial stewardship in animal health. We propose to establish the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) to report on the AMR situation, follow AMR trends and detect emerging AMR in selected bacterial pathogens of animals. This information could be useful to advise policymakers, explore efficacy of interventions, support antimicrobial stewardship initiatives, (re-)evaluate marketing authorisations of antimicrobials, generate epidemiological cut-off values, assess risk of zoonotic AMR transmission and evaluate the burden of AMR in animal health. EARS-Vet could be integrated with other AMR monitoring systems in the animal and medical sectors to ensure a One Health approach. Herein, we present a strategy to establish EARS-Vet as a network of national surveillance systems and highlight challenges of data harmonisation and bias. Strong political commitment at national and EU/EEA levels is required for the success of EARS-Vet.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: rabbits.

In this opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to the health of farmed rabbits have been assessed. The assessment has been performed following a methodology based on information collected through an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play on antimicrobial resistance in clinical isolates of Pasteurella multocida, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bordetella bronchiseptica, Clostridium difficile, Clostridium perfringens and Clostridium spiroforme is provided. Among these bacteria, none were identified as being the most relevant antimicrobial-resistant bacteria in rabbits in the EU due to the very limited scientific evidence available.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: Horses.

In this opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to the health of horses have been assessed. The assessment has been performed following a methodology composed of information collected via an extensive literature review and expert judgement. Details on the methodology used for this assessment are explained in a separate opinion. A global state of play of antimicrobial-resistant Actinobacillus equuli, Dermatophilus congolensis, Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, Pasteurella spp., Pseudomonas aeruginosa, Rhodococcus equi, Staphylococcus aureus and Streptococcus dysgalactiae subsp. dysgalactiae/equisimilis and Streptococcus equi subsp. equi and subsp. zooepidemicus has been provided. Among those bacteria, EFSA identified E. coli, Staphylococcus aureus and R. equi with more than 66% certainty as the most relevant antimicrobial-resistant bacteria in the EU, given their importance as causative agents of clinical disease in horses and the significant levels of resistance to clinically relevant antimicrobials. The animal health impact of these 'most relevant' bacteria as well as their eligibility of being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: Swine.

In this opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to the health of pigs have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play of antimicrobial resistant Escherichia coli, Streptococcus suis, Actinobacillus pleuropneumoniae, Pasteurella multocida, Glaeserella parasuis, Bordetella bronchiseptica, Staphylococcus aureus, Staphylococcus hyicus, Brachyspira hyodysenteriae, Trueperella pyogenes, Erysipelothrix rhusiopathiae, Streptococcus dysgalactiae, Mycoplasma hyosynoviae, Mycoplasma hyorhinis, Mycoplasma hyopneumoniae and Brachyspira pilosicoli has been provided. Among those bacteria, EFSA identified E. coli and B. hyodysenteriae with > 66% certainty as being the most relevant antimicrobial resistant bacteria in the EU based on the available evidence. The animal health impact of these most relevant bacteria, as well as their eligibility for being listed and categorised within the animal health law framework will be assessed in separate scientific opinions.

Assessment of animal diseases caused by bacteria resistant to antimicrobials: Poultry.

In this opinion, the antimicrobial-resistant bacteria responsible for transmissible diseases that constitute a threat to poultry health have been assessed. The assessment has been performed following a methodology based on information collected by an extensive literature review and expert judgement. Details of the methodology used for this assessment are explained in a separate opinion. A global state of play is provided for: Avibacterium (Haemophilus) paragallinarum, Bordetella avium, Clostridium perfringens, Enterococcus faecalis and Enterococcus cecorum, Erysipelothrix rhusiopathiae, Escherichia coli, Gallibacterium spp., Mycoplasma synoviae, Ornithobacterium rhinotracheale, Pasteurella multocida, Riemerella anatipestifer and Staphylococcus aureus. Among those bacteria, EFSA identified Escherichia coli, Enterococcus faecalis and Enterococcus cecorum with ≥ 66% certainty as being the most relevant antimicrobial resistant bacteria in the EU based on the available evidence. The animal health impact of these most relevant bacteria, and their eligibility for being listed and categorised within the Animal Health Law Framework, will be assessed in separate scientific opinions.

White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

BACKGROUND: The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions to link the surveillance of antimicrobial usage (AMU) and antimicrobial resistance (AMR) with antimicrobial stewardship (AMS) activities in four different settings. This White Paper focuses on the veterinary setting and embraces the One Health approach. METHODS: A review of the literature was carried out addressing research questions in three areas: AMS leadership and accountability; AMU surveillance and AMS; and AMR surveillance and AMS. Consensus on target actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine and public health, from 18 countries. RESULTS/DISCUSSION: Forty-six target actions were developed and qualified as essential or desirable. Essential actions included the setup of AMS teams in all veterinary settings, building government-supported AMS programmes and following specific requirements on the production, collection and communication of AMU and AMR data. Activities of AMS teams should be tailored to the local situation and capacities, and be linked to local or national surveillance systems and infection control programmes. Several research priorities were also identified, such as the need to develop more clinical breakpoints in veterinary medicine. CONCLUSIONS: This White Paper offers a practical tool to veterinary practitioners and policy makers to improve AMS in the One Health approach, thanks to surveillance data generated in the veterinary setting. This work may also be useful to medical doctors wishing to better understand the specificities of the veterinary setting and facilitate cross-sectoral collaborations.