Towards One Health surveillance of antibiotic resistance: characterisation and mapping of existing programmes in humans, animals, food and the environment in France, 2021.

BackgroundInternational organisations are calling for One Health approaches to tackle antimicrobial resistance. In France, getting an overview of the current surveillance system and its level of integration is difficult due to the diversity of surveillance programmes.AimThis study aimed to map and describe all French surveillance programmes for antibiotic resistance (ABR), antibiotic use (ABU) and antibiotic residues, in humans, animals, food and the environment, in 2021. Another objective was to identify integration points, gaps and overlaps in the system.MethodsWe reviewed the literature for surveillance programmes and their descriptions. To further characterise programmes found, semi-directed interviews were conducted with their coordinators.ResultsIn total 48 programmes in the human (n = 35), animal (n = 12), food (n = 3) and/or the environment (n = 1) sectors were identified; 35 programmes focused on ABR, 14 on ABU and two on antibiotic residues. Two programmes were cross-sectoral. Among the 35 ABR programmes, 23 collected bacterial isolates. Bacteria most targeted were Escherichia coli (n = 17 programmes), Klebsiella pneumoniae (n = 13), and Staphylococcus aureus (n = 12). Extended-spectrum beta-lactamase-producing E. coli was monitored by most ABR programmes (15 of 35) in humans, animals and food, and is a good candidate for integrated analyses. ABU indicators were highly variable. Areas poorly covered were the environmental sector, overseas territories, antibiotic-resistant-bacterial colonisation in humans and ABU in companion animals.ConclusionThe French surveillance system appears extensive but has gaps and is highly fragmented. We believe our mapping will interest policymakers and surveillance stakeholders. Our methodology may inspire other countries considering One Health surveillance of ABR.

Risk Ranking of Antimicrobial-Resistant Hazards Found in Meat in Switzerland.

Human exposure to bacteria resistant to antimicrobials and transfer of related genes is a complex issue and occurs, among other pathways, via meat consumption. In a context of limited resources, the prioritization of risk management activities is essential. Since the antimicrobial resistance (AMR) situation differs substantially between countries, prioritization should be country specific. The objective of this study was to develop a systematic and transparent framework to rank combinations of bacteria species resistant to selected antimicrobial classes found in meat, based on the risk they represent for public health in Switzerland. A risk assessment model from slaughter to consumption was developed following the Codex Alimentarius guidelines for risk analysis of foodborne AMR. Using data from the Swiss AMR monitoring program, 208 combinations of animal species/bacteria/antimicrobial classes were identified as relevant hazards. Exposure assessment and hazard characterization scores were developed and combined using multicriteria decision analysis. The effect of changing weights of scores was explored with sensitivity analysis. Attributing equal weights to each score, poultry-associated combinations represented the highest risk. In particular, contamination with extended-spectrum ß-lactamase/plasmidic AmpC-producing Escherichia coli in poultry meat ranked high for both exposure and hazard characterization. Tetracycline- or macrolide-resistant Enterococcus spp., as well as fluoroquinolone- or macrolide-resistant Campylobacter jejuni, ranked among combinations with the highest risk. This study provides a basis for prioritizing future activities to mitigate the risk associated with foodborne AMR in Switzerland. A user-friendly version of the model was provided to risk managers; it can easily be adjusted to the constantly evolving knowledge on AMR.

Assigning defined daily doses animal: a European multi-country experience for antimicrobial products authorized for usage in pigs.

OBJECTIVES: To establish a consensus defined daily dose animal (DDDA) for each active substance (AS) and administration route for porcine veterinary antimicrobial products authorized in four European countries, thus allowing cross-country quantification and comparison of antimicrobial usage data. METHODS: All veterinary antimicrobial products authorized for porcine use in Belgium, France, Germany and Sweden were listed for each administration route. First, separate DDDAs for each product were defined based on the recommended dosing for the main indication. Second, a consensus DDDA was established by taking the mean of the DDDAs for each product within a certain category of AS plus administration route. RESULTS: One-hundred-and-fifty-nine, 240, 281 and 50 antimicrobial products were licensed in Belgium, France, Germany and Sweden, respectively, in February 2013. Large variations were observed for dosage and treatment duration recommendations between products and between countries for the same ASs. Only 6.8% of feed/water and 29.4% of parenteral AS groups had the same recommended dosage in the four countries. CONCLUSIONS: This study presents a consensus DDDA list for use in the quantification and comparison of antimicrobial consumption. Four major recommendations have been formulated: (i) urgent need for harmonization of authorization and recommended summary of product characteristics (SPC) dosages; (ii) expand the developed preliminary DDDA list to include all authorized veterinary medicinal products in all EU member states and for all (food-producing) animal species; (iii) improved accessibility of country-specific SPC data would be preferable; and (iv) statement of the 'long-acting' duration of a product in the SPC.

Moving towards One Health surveillance of antibiotic resistance in France: a semi-quantitative evaluation of the level of collaboration within the national surveillance system.

Objectives: Collaboration between surveillance programmes is the keystone of One Health surveillance and international organizations call for integrated surveillance systems to manage antibiotic resistance (ABR). In France, the ABR surveillance system covers human, animal, food and the environment sectors, but appears to be fragmented, questioning its level of integration. This study aimed to evaluate collaboration within this system and to formulate recommendations towards more integration. Methods: ECoSur, a semi-quantitative tool, was used to evaluate collaboration between surveillance programmes. A total of 31 attributes were evaluated using information from the literature and 52 interviews with surveillance actors from all four sectors. Evaluation results were visualized via three output figures displaying aspects related to governance and functionality of collaboration. Results were validated by an expert committee. Results: Overall, the French collaborative strategy for ABR surveillance was well formalized and relevant to its objectives. However, a cross-sectoral coordination body was lacking to help with its practical implementation. The environmental sector was largely uncovered, but its integration appeared necessary to meet the strategy objectives. Data sharing and joint data analyses between programmes were insufficient, mainly due to limited resources and data interoperability issues. Collaboration was operational for internal and external communication of the results. Twelve recommendations were suggested to decision makers to foster collaboration within the French surveillance system and feed future strategies against ABR. Conclusions: This first evaluation of collaboration within the French ABR surveillance system produced concrete recommendations to move towards One Health integrated surveillance. Both the approach and the findings could be of interest to other countries.

Implementation of One Health surveillance systems: Opportunities and challenges - lessons learned from the OH-EpiCap application.

As the complexity of health systems has increased over time, there is an urgent need for developing multi-sectoral and multi-disciplinary collaborations within the domain of One Health (OH). Despite the efforts to promote collaboration in health surveillance and overcome professional silos, implementing OH surveillance systems in practice remains challenging for multiple reasons. In this study, we describe the lessons learned from the evaluation of OH surveillance using OH-EpiCap (an online evaluation tool for One Health epidemiological surveillance capacities and capabilities), the challenges identified with the implementation of OH surveillance, and the main barriers that contribute to its sub-optimal functioning, as well as possible solutions to address them. We conducted eleven case studies targeting the multi-sectoral surveillance systems for antimicrobial resistance in Portugal and France, Salmonella in France, Germany, and the Netherlands, Listeria in The Netherlands, Finland and Norway, Campylobacter in Norway and Sweden, and psittacosis in Denmark. These evaluations facilitated the identification of common strengths and weaknesses, focusing on the organization and functioning of existing collaborations and their impacts on the surveillance system. Lack of operational and shared leadership, adherence to FAIR data principles, sharing of techniques, and harmonized indicators led to poor organization and sub-optimal functioning of OH surveillance systems. In the majority of studied systems, the effectiveness, operational costs, behavioral changes, and population health outcomes brought by the OH surveillance over traditional surveillance (i.e. compartmentalized into sectors) have not been evaluated. To this end, the establishment of a formal governance body with representatives from each sector could assist in overcoming long-standing barriers. Moreover, demonstrating the impacts of OH-ness of surveillance may facilitate the implementation of OH surveillance systems.

Application of loop analysis for the qualitative assessment of surveillance and control in veterinary epidemiology.

BACKGROUND: Systems for animal disease mitigation involve both surveillance activities and interventions to control the disease. They are complex organizations that are described by partial or imprecise data, making it difficult to evaluate them or make decisions to improve them. A mathematical method, called loop analysis, can be used to model qualitatively the structure and the behavior of dynamic systems; it relies on the study of the sign of the interactions between the components of the system. This method, currently widely used by ecologists, has to our knowledge never been applied in the context of animal disease mitigation systems. The objective of the study was to assess whether loop analysis could be applied to this new context. We first developed a generic model that restricted the applicability of the method to event-based surveillance systems of endemic diseases, excluding the emergence and eradication phases. Then we chose the mitigation system of highly pathogenic avian influenza (HPAI) H5N1 in Cambodia as an example of such system to study the application of loop analysis to a real disease mitigation system. RESULTS: Breaking down the generic model, we constructed a 6-variables model to represent the HPAI H5N1 mitigation system in Cambodia. This construction work improved our understanding of this system, highlighting the link between surveillance and control which is unclear in traditional representations of this system. Then we analyzed the effect of the perturbations to this HPAI H5N1 mitigation system that we interpreted in terms of investment in a given compartment. This study suggested that increasing intervention at a local level can optimize the system's efficiency. Indeed, this perturbation both decreases surveillance and intervention costs and reduces the disease's occurrence. CONCLUSION: Loop analysis can be applied to disease mitigation systems. Its main strength is that it is easy to design, focusing on the signs of the interactions. It is a simple and flexible tool that could be used as a precursor to large-scale quantitative studies, to support reflection about disease mitigation systems structure and functioning.

How to move towards One Health surveillance? A qualitative study exploring the factors influencing collaborations between antimicrobial resistance surveillance programmes in France.

Introduction: Antimicrobial resistance (AMR) is a major public health issue, against which international organisations and governmental bodies call for integration between surveillance programmes involved in human, animal, and environmental sectors. Collaborations are the primary feature of integration and deserve to be supported. However, little is known about the factors that can foster collaborations between surveillance programmes. This study aimed to provide a better understanding of the factors for setting-up collaborations between AMR surveillance programmes in France. Methods: We performed a qualitative study based on 36 semi-structured interviews with programmes' coordinators and 15 with key-informant experts involved in AMR surveillance. Results: The implementation of collaboration between sectors was multifactorial: we identified 42 factors grouped into six categories (i.e., characteristics of the overall AMR surveillance system, features of the collaborating programme, profile of the actors involved, characteristics of the collaboration itself, broader context, and AMR research activities). Collaborations were mainly fostered by good interpersonal relationship between actors, their interest in transdisciplinary approaches and the benefits of collaboration on the programmes involved. Limited resources and the complexity of the AMR surveillance system hindered collaboration. Paradoxically, coordinators generally did not perceive collaborations as a resource-pooling tool since they generally set them up only after consolidating their own programme. Discussion: Since most factors identified were not specific to AMR, these results can be useful for other collaborative surveillance system. Ultimately, they provide a better understanding of stakeholders' motivations and influences driving collaboration, and can help researchers and risk managers promoting a One Health approach against public health threats.

OH-EpiCap: a semi-quantitative tool for the evaluation of One Health epidemiological surveillance capacities and capabilities.

Although international health agencies encourage the development of One Health (OH) surveillance, many systems remain mostly compartmentalized, with limited collaborations among sectors and disciplines. In the framework of the OH European Joint Programme "MATRIX" project, a generic evaluation tool called OH-EpiCap has been developed to enable individual institutes/governments to characterize, assess and monitor their own OH epidemiological surveillance capacities and capabilities. The tool is organized around three dimensions: organization, operational activities, and impact of the OH surveillance system; each dimension is then divided into four targets, each including four indicators. A semi-quantitative questionnaire enables the scoring of each indicator, with four levels according to the degree of satisfaction in the studied OH surveillance system. The evaluation is conducted by a panel of surveillance representatives (during a half-day workshop or with a back-and-forth process to reach a consensus). An R Shiny-based web application facilitates implementation of the evaluation and visualization of the results, and includes a benchmarking option. The tool was piloted on several foodborne hazards (i.e., Salmonella, Campylobacter, Listeria), emerging threats (e.g., antimicrobial resistance) and other zoonotic hazards (psittacosis) in multiple European countries in 2022. These case studies showed that the OH-EpiCap tool supports the tracing of strengths and weaknesses in epidemiological capacities and the identification of concrete and direct actions to improve collaborative activities at all steps of surveillance. It appears complementary to the existing EU-LabCap tool, designed to assess the capacity and capability of European microbiology laboratories. In addition, it provides opportunity to reinforce trust between surveillance stakeholders from across the system and to build a good foundation for a professional network for further collaboration.

Capturing systematically users' experience of evaluation tools for integrated AMU and AMR surveillance.

Tackling antimicrobial resistance (AMR) is a goal for many countries. Integrated surveillance of antimicrobial use (AMU) and resistance is a prerequisite for effective risk mitigation. Regular evaluation of any surveillance is needed to ensure its effectiveness and efficiency. The question is how to evaluate specifically integrated surveillance for AMU and AMR. In an international network called CoEvalAMR, we have developed guidelines for selection of the most appropriate tools for such an evaluation. Moreover, we have assessed different evaluation tools as examples using a country case format and a methodology with a focus on the user's experience. This paper describes the updated methodology, which consists of a brief introduction to the case and to the tool separately. Moreover, there are 12 functional aspects and nine content themes which should be scored using a 4-tiered scale. Additionally, four Strengths, Weaknesses, Opportunities, Threats (SWOT) questions should be addressed. Results are illustrated using radar diagrams. An example of application of the updated methodology is given using the ECoSur evaluation tool. No tool can cover all evaluation aspects comprehensively in a user-friendly manner, so the choice of tool must be based upon the specific evaluation purpose. Moreover, adequate resources, time and training are needed to obtain useful outputs from the evaluation. Our updated methodology can be used by tool users to share their experience with available tools, and hereby assist other users in identifying the most suited tool for their evaluation purpose. Additionally, tool developers can get valuable information for further improvements of their tool.

Users' perception of the OH-EpiCap evaluation tool based on its application to nine national antimicrobial resistance surveillance systems.

Introduction: Antimicrobial resistance (AMR) is a One Health (OH) challenge. To achieve or maintain an effective and efficient AMR surveillance system, it is crucial to evaluate its performance in meeting the proposed objectives, while complying with resource restrictions. The OH-EpiCap tool was created to evaluate the degree of compliance of hazard surveillance activities with essential OH concepts across the following dimensions: organization, operational activities, and impact of the surveillance system. We present feedback on the application of the OH-EpiCap tool from a user's perspective, based on the use of the tool to evaluate nine national AMR surveillance systems, each with different contexts and objectives. Methods: The OH-EpiCap was assessed using the updated CoEvalAMR methodology. This methodology allows the evaluation of the content themes and functional aspects of the tool and captures the user's subjective experiences via a strengths, weaknesses, opportunities, and threats (SWOT) approach. Results and Discussion: The results of the evaluation of the OH-EpiCap are presented and discussed. The OH-EpiCap is an easy-to-use tool, which can facilitate a fast macro-overview of the application of the OH concept to AMR surveillance. When used by specialists in the matter, an evaluation using OH-EpiCap can serve as a basis for the discussion of possible adaptations of AMR surveillance activities or targeting areas that may be further investigated using other evaluation tools.

Pilot testing the EARS-Vet surveillance network for antibiotic resistance in bacterial pathogens from animals in the EU/EEA.

Introduction: As part of the EU Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections, an initiative has been launched to build the European AMR Surveillance network in veterinary medicine (EARS-Vet). So far, activities included mapping national systems for AMR surveillance in animal bacterial pathogens, and defining the EARS-Vet objectives, scope, and standards. Drawing on these milestones, this study aimed to pilot test EARS-Vet surveillance, namely to (i) assess available data, (ii) perform cross-country analyses, and (iii) identify potential challenges and develop recommendations to improve future data collection and analysis. Methods: Eleven partners from nine EU/EEA countries participated and shared available data for the period 2016-2020, representing a total of 140,110 bacterial isolates and 1,302,389 entries (isolate-antibiotic agent combinations). Results: Collected data were highly diverse and fragmented. Using a standardized approach and interpretation with epidemiological cut-offs, we were able to jointly analyze AMR trends of 53 combinations of animal host-bacteria-antibiotic categories of interest to EARS-Vet. This work demonstrated substantial variations of resistance levels, both among and within countries (e.g., between animal host species). Discussion: Key issues at this stage include the lack of harmonization of antimicrobial susceptibility testing methods used in European surveillance systems and veterinary diagnostic laboratories, the absence of interpretation criteria for many bacteria-antibiotic combinations of interest, and the lack of data from a lot of EU/EEA countries where little or even surveillance currently exists. Still, this pilot study provides a proof-of-concept of what EARS-Vet can achieve. Results form an important basis to shape future systematic data collection and analysis.

EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach.

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.

Evaluation of the French surveillance system for epidemiological surveillance of antimicrobial resistance in the community and nursing homes.

Background: Antimicrobial resistance (AMR) has been widely recognized as a major public health issue, which can be addressed through effective AMR surveillance systems. In 2018, a national surveillance programme for AMR in the community and nursing homes called Mission PRIMO was established in France. It builds on an existing network called MedQual-Ville that had been monitoring AMR mainly in the west of France community since 2003. Objectives and Methods: To evaluate the MedQual-Ville surveillance activities and to formulate practical recommendations for improvement, using a semi-quantitative evaluation framework called OASIS. Results: The evaluation showed that MedQual-Ville is overall a well-performing surveillance system. Its major strengths rely on excellent coordination and internal communication with clinical laboratories that participate on a voluntary basis. Surveillance objectives and procedures are clear to all participants. Hence, the quality and reliability of the data being produced is very high. At this stage, the major area for improvement is representativeness, with poor coverage achieved in several densely populated areas. Besides, the utility and impact of surveillance data could be improved by strengthening communication towards end-users, especially local prescribers. Conclusions: There is currently no European programme or guidance for AMR surveillance in the community and nursing homes. Our results partly fill this gap, by evaluating how surveillance is being performed in France and providing recommendations that could be applicable to other countries with similar health systems. This work also highlighted the relevance of OASIS for evaluation of surveillance systems in the human sector.

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.

A farm-to-fork quantitative risk assessment model for Salmonella Heidelberg resistant to third-generation cephalosporins in broiler chickens in Canada.

Salmonella Heidelberg resistant to ceftiofur (a third-generation cephalosporin antimicrobial agent) in broiler chicken products pose a risk to public health in Canada. The objective of this study was to assess the extent of that risk and to evaluate the effect of intervention measures along the agri-food chain. A stochastic farm-to-fork quantitative microbial risk assessment model was developed following the Codex Alimentarius Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance. Different scenarios were analyzed to assess the individual relative effects of 18 possible interventions in comparison to a baseline scenario. The baseline scenario represented the first year of on-farm antimicrobial use surveillance in the Canadian broiler industry and the year before an industry-imposed ban on the preventive use of antimicrobials of very high importance to human health (2013), where 31.3% of broiler flocks consisted of birds to which ceftiofur was administered. The baseline scenario predicted an average probability of illness of 1.1 per 100,000 servings (SE: 0.064 per 100,000), corresponding to an average of 22,000 human infections (SE: 1900) with ceftiofur-resistant S. Heidelberg per year, which is likely an overestimation. This risk was reduced by 90% or 20% when two separate scenarios designed to capture the effect of withdrawing preventive ceftiofur use from poultry production were simulated using different approaches; data used for the former scenario were confounded by other potential concomitant control measures (e.g. Salmonella vaccination programme), so the true effect likely lies somewhere between the two estimates. A theoretical 'worst case' scenario where all flocks had birds exposed to ceftiofur increased the risk by 107%. A 50% reduction in the probability of human prior exposure to antimicrobials, which has a selective and competitive effect for Salmonella spp. following ingestion of contaminated products, reduced the risk by 65%. Other promising measures that could be considered for further risk management included improved cleaning and disinfection between broiler flocks on farm (risk reduction by 26%), exclusive use of air chilling (risk reduction by 34%), and the improvement of meat storage and preparation conditions, e.g., no temperature abuse at retail (risk reduction by 88%). These findings showed the importance of a structured approach to assessing and potentially implementing effective interventions to reduce the risk associated with ceftiofur-resistant S. Heidelberg at different steps along the agri-food chain. Major data gaps included information on concentrations of resistant bacteria, cross contamination at processing and how ceftiofur-resistant S. Heidelberg behave in comparison with susceptible ones, e.g., in terms of growth and survival ability, as well as pathogenicity and virulence.

Effectiveness of alternative measures to reduce antimicrobial usage in pig production in four European countries.

BACKGROUND: The reduction of antimicrobial usage (AMU) is in the focus in modern pig production. The objective of this study was to assess the effectiveness of alternatives to reduce AMU at herd level. In a prospective study, 68 farrow-to-finish pig herds located in Belgium, France, Germany and Sweden were recruited on a voluntary basis to implement tailor-made intervention plans to reduce their AMU. Alternative measures included improvement of biosecurity (n = 29 herds), vaccination (n = 30), changes of feeding schemes or drinking water quality (n = 45), improved pig health and welfare care (n = 21) as well as changes in stable climate and zootechnical measures (n = 14). Herds were followed for 1 year after implementation of measures. Annual antimicrobial expenditures or treatment records, as well as disease incidence scores were collected and compared to those of the year before intervention. AMU was measured as the treatment incidence and calculated by age category, antimicrobial class and administration route. RESULTS: Compliance with the intervention plans was high (median 93%). AMU was significantly reduced following the implementation of alternative measures: in the median herd of the four countries, pigs were treated before intervention 25% of their expected lifespan (200 days from birth to slaughter) and after intervention 16%. AMU of suckling and weaned pigs were significantly reduced by 37 and 54%, respectively. The usage of polymyxins and tetracyclines was significantly reduced by 69 and 49%, respectively. AMU via feed and water, as well as parenteral AMU were significantly reduced by 46 and 36%, respectively. Herds with a higher AMU level before intervention achieved a bigger reduction. The majority of disease incidence were similar before and after intervention, with a few exceptions of disorders related to the gastro-intestinal tract in suckling pigs (decreased) and in breeding pigs (increased). CONCLUSION: Following tailor-made implementation of alternative measures, a substantial reduction of AMU in pig production was achievable without jeopardizing animal health. The AMU reduction in the youngest age categories (suckling and weaned pigs) and the reduction of group treatments via feed and water was in line with the recent European Guidelines on the prudent use of antimicrobials in veterinary medicine.

A within-flock model of Salmonella Heidelberg transmission in broiler chickens.

As part of the development of a quantitative microbial risk assessment (QMRA) model of third-generation cephalosporins (3GC)-resistant Salmonella Heidelberg, a compartmental (SEIR) model for S. Heidelberg transmission within a typical Canadian commercial broiler chicken flock was developed. The model was constructed to estimate the within-flock prevalence and the bacterial concentration in the barn environment at pre-harvest, and to assess the effect of selected control measures. The baseline scenario predicted an average within-flock prevalence of 23.5 % (95 % tolerance interval: 15.7-31.4) and an average bacterial concentration of 3.579 (0-4.294) log CFU/g of feces in the barn environment at pre-harvest (on the day the flock is sent to slaughter). Because vertical introduction of S. Heidelberg into the barn was already uncommon in the baseline scenario, vaccination of broiler parent flocks appeared to have a negligible effect, while vaccination of broiler chicken flocks substantially reduced the bacterial concentration at pre-harvest. Cleaning and disinfection between batches markedly reduced the within-flock prevalence at pre-harvest, but the effect on bacterial concentration was limited outside of the beginning of the production period. Extending downtime between batches by 7 days had little effect on within-flock prevalence or bacterial concentration of S. Heidelberg when compared to the baseline scenario. This study provides a basis to describe S. Heidelberg dynamics within a broiler chicken flock and to predict the within-flock prevalence and bacterial concentration at pre-harvest, and includes a description of the limitations and data gaps. The results of these analyses and associated uncertainties are critical information for populating QMRA models of the downstream impacts on public health from on-farm and other food-chain practices. Specifically, the study findings will be integrated into a broader farm-to-fork QMRA model to support the risk-based control of S. Heidelberg resistant to 3GC in broiler chicken in Canada.

Developing Canadian Defined Daily Doses for Animals: A Metric to Quantify Antimicrobial Use.

Antimicrobial use surveillance data need to be analyzed and reported in a standardized and harmonized way. In veterinary medicine, one approach is to use defined daily doses (DDD) for animals. DDD for animals are technical standards used in various measures or metrics that quantify antimicrobial use. The European Medicines Agency published principles for assigning DDDvet values based on information on dosing obtained from nine European countries. For measuring antimicrobial use in livestock within Canada, DDDs for animals reflective of Canadian veterinary antimicrobial use (DDDvetCAs) were needed. Our objectives were (1) to describe the development of DDDvetCA standards for pigs and poultry (broiler chickens and turkeys) for authorized and compounded antimicrobial active ingredients used in Canada, including those used extra-label; and (2) to compare the DDDvetCAs with EMA's DDDvets, where possible. Species-specific DDDvetCAs were assigned based on the average of unique antimicrobial daily doses obtained from product information, stratified by route of administration and age indication (where applicable). The feed, water and bolus DDDvetCAs were compared to oral DDDvets, and injectable DDDvetCAs to parenteral DDDvets, that matched by antimicrobial active ingredient. Seventy-five DDDvetCAs were assigned for pigs; 51 for poultry. Seventeen injectable DDDvetCAs could be compared to 14 EMA's parenteral DDDvets and 53 feed, water, and bolus DDDvetCAs could be compared to 40 oral DDDvets. Feed and water DDDvetCAs were generally lower than EMA's oral DDDvets, although differences in methodology between Canada and Europe make comparisons challenging. The assignment of DDDvetCAs was a resource intensive and iterative process. EMA's published principles for assigning DDDvets were an invaluable source of information. The use of DDDvetCAs will reflect exposure of Canadian animals to antimicrobials, be useful for evaluating associations between use and resistance within Canada and provide information for risk assessment and stewardship policies. However, when reporting antimicrobial use data internationally, using the same DDD standards as other reporting countries will facilitate between country comparisons, although differences in which antimicrobial active ingredients are licensed between countries may create challenges. Future steps include assigning DDDvetCAs for other food animal species, such as cattle, veal, and farmed fish.

How Input Parameters and Calculation Rules Influence On-Farm Antimicrobial Use Indicators in Animals.

A variety of indicators of antimicrobial use are available in veterinary medicine, their choice should depend on the study objective as none has been recognized as the most appropriate metric. Calculation of indicators of antimicrobial use is based on a number of parameters (e.g., treatment dose or weight at treatment) that can be informed using theoretical (also called "standard") or actual (also called "used") values. Although few studies compare the application of several indicators to the same antimicrobial data, the obtained results lead to apparent discrepancies or contradictions. This study aimed to investigate antimicrobial use at the weaning stage in French pig farms and, more specifically, the impact the sources of information regarding doses, body weight at treatment and treatment length, had on the indicators results. A cross-sectional survey was conducted, and data collected from 70 farms made it possible to calculate four indicators at the weaning stage using different input values. The indicator values did not show significant differences when calculated based on the theoretical dose and length of treatment (as recommended by the summary of product characteristics) or when calculated based on the dose used and treatment length as applied by the farmer. However, all of the indicators showed significant differences when calculated using the standard theoretical weight (15 kg) or actual weight (P < 0.05). It appears that if data collection plans cannot be harmonized, clarification of indicator calculations in the literature is needed to allow comparisons between studies.

Integrating Whole-Genome Sequencing Data Into Quantitative Risk Assessment of Foodborne Antimicrobial Resistance: A Review of Opportunities and Challenges.

Whole-genome sequencing (WGS) will soon replace traditional phenotypic methods for routine testing of foodborne antimicrobial resistance (AMR). WGS is expected to improve AMR surveillance by providing a greater understanding of the transmission of resistant bacteria and AMR genes throughout the food chain, and therefore support risk assessment activities. At this stage, it is unclear how WGS data can be integrated into quantitative microbial risk assessment (QMRA) models and whether their integration will impact final risk estimates or the assessment of risk mitigation measures. This review explores opportunities and challenges of integrating WGS data into QMRA models that follow the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR. We describe how WGS offers an opportunity to enhance the next-generation of foodborne AMR QMRA modeling. Instead of considering all hazard strains as equally likely to cause disease, WGS data can improve hazard identification by focusing on those strains of highest public health relevance. WGS results can be used to stratify hazards into strains with similar genetic profiles that are expected to behave similarly, e.g., in terms of growth, survival, virulence or response to antimicrobial treatment. The QMRA input distributions can be tailored to each strain accordingly, making it possible to capture the variability in the strains of interest while decreasing the uncertainty in the model. WGS also allows for a more meaningful approach to explore genetic similarity among bacterial populations found at successive stages of the food chain, improving the estimation of the probability and magnitude of exposure to AMR hazards at point of consumption. WGS therefore has the potential to substantially improve the utility of foodborne AMR QMRA models. However, some degree of uncertainty remains in relation to the thresholds of genetic similarity to be used, as well as the degree of correlation between genotypic and phenotypic profiles. The latter could be improved using a functional approach based on prediction of microbial behavior from a combination of 'omics' techniques (e.g., transcriptomics, proteomics and metabolomics). We strongly recommend that methodologies to incorporate WGS data in risk assessment be included in any future revision of the Codex Alimentarius Guidelines for Risk Analysis of Foodborne AMR.