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.

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.

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.

Trends in antimicrobial resistance among Escherichia coli from defined infections in humans and animals.

OBJECTIVES: To characterize and compare resistance trends in clinical Escherichia coli isolates from humans, food-producing animals (poultry, cattle and swine) and pets (dogs and cats). METHODS: Antibiogram results collected between January 2014 and December 2017 by MedQual [the French surveillance network for antimicrobial resistance (AMR) in bacteria isolated from the community] and RESAPATH (the French surveillance network for AMR in bacteria from diseased animals) were analysed, focusing on resistance to antibiotics of common interest to human and veterinary medicine. Resistance dynamics were investigated using generalized additive models. RESULTS: In total, 743 637 antibiograms from humans, 48 170 from food-producing animals and 7750 from pets were analysed. For each antibiotic investigated, the resistance proportions of isolates collected from humans were of the same order of magnitude as those from food-producing animals or pets. However, resistance trends in humans differed from those observed in pets and food-producing animals over the period studied. For example, resistance to third-generation cephalosporins and fluoroquinolones was almost always below 10% for both humans and animals. However, in contrast to the notable decreases in resistance observed in both food-producing animals and pets, resistance in humans decreased only slightly. CONCLUSIONS: Despite several potential biases in the data, the resistance trends remain meaningful. The strength of the parallel is based on similar data collection in humans and animals and on a similar statistical methodology. Resistance dynamics seemed specific to each species, reflecting different antibiotic-use practices. These results advocate applying the efforts already being made to reduce antibiotic use to all sectors and all species, both in human and veterinary medicine.

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.

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.

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.

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.

Assessment of the specificity of a gamma-interferon test performed with specific antigens to detect bovine tuberculosis, after non-negative results to intradermal tuberculin testing.

In cattle herds in France, cervical skin tests (STs) using simple intradermal tuberculin (SIT) are performed to detect bovine tuberculosis (bTB). When positive results are found on ST screening, the herd is considered to be 'under suspicion' and confined, raising economic issues. The suspicion can be lifted by carrying out a single intradermal cervical comparative test (SICCT) at least six weeks later. The authors conducted an experimental study in France between 2013 and 2015 to assess the accuracy of the gamma-interferon test (IFN-γ), used in series after a non-negative result to ST screening, and to study the possibility of replacing the SICCT performed six weeks later by an IFN performed within a few days. Data were collected concerning 40 infected and 1825 bTB-free animals from herds with non-negative results to ST screening. This study showed that the IFN-γ test based on specific antigens and performed within a few days of a non-negative result to the ST has higher sensitivity than the SICCT performed six weeks later and equal specificity. The IFN test is more convenient to perform; however, it is more expensive. The IFN-γ test based on MIX antigens may be a useful alternative to the SICCT, to shorten the confinement period of suspect herds without underdetecting bTB.

Antimicrobial resistance of Pasteurella multocida isolated from diseased food-producing animals and pets.

Surveillance of Pasteurella multocida resistance in food-producing animals is essential to guide the first-line treatment of respiratory diseases and to limit economic losses. Since Pasteurella are the most common bacteria isolated from dog and cat bites, this surveillance is also needed to guide treatment in humans in case of bites. The aim of this study was to characterize the phenotypic resistance of P. multocida strains isolated from respiratory infections in animals, including both food-producing animals and pets. Data collected between 2012 and 2017 by the French national surveillance network for antimicrobial resistance referred to as RESAPATH were analyzed. The proportions of resistance to antimicrobials of relevance in veterinary and human medicines were estimated for each animal species. For cattle, resistance trends over the period were investigated using non-linear analysis applied to time-series. In total, 5356 P. multocida isolates were analyzed. Proportions of resistance of P. multocida were almost all below 20% over the period, and, more precisely, all resistance proportions were below 10% for rabbits, sheep and dogs. The highest resistance proportions to enrofloxacin were identified for cattle (4.5%) and dogs (5.2%). Despite its frequent use in livestock, resistance to florfenicol was less than 1% in P. multocida strains, regardless of the animal species considered. Time series analyses revealed continuous increases in resistance to tetracycline, tilmicosin, flumequine and fluoroquinolones in P. multocida strains isolated from cattle. These trends contrast with the decrease in use of antibiotics in cattle in France and with the decrease in resistance observed in E. coli isolated from diseased cattle.

Co-resistance to Amoxicillin and Tetracycline as an Indicator of Multidrug Resistance in Escherichia coli Isolates From Animals.

OBJECTIVES: To examine the relevance of co-resistance to amoxicillin and tetracycline as an indicator of multidrug resistance (MDR) in animal health. METHODS: Escherichia coli isolates collected between 2012 and 2016 by the French surveillance network for antimicrobial resistance in diseased animals (RESAPATH) were analyzed. The proportions of MDR isolates and the proportions of isolates presenting co-resistance to amoxicillin and tetracycline were calculated for seven animal species (cattle, horse, dog, swine, poultry, duck, and turkey). The degree of agreement between these two proportions was estimated by calculating the kappa value. RESULTS: In total, 55,904 isolates were analyzed. MDR proportions were variable among animal species, ranging from 21.9% [20.2; 23.7] in horses to 56.0% [55.4; 56.7] in cattle. A similar situation was observed for proportions of isolates with co-resistance to amoxicillin and tetracycline, with the highest value for cattle 65.0% [64.3; 65.6]. This co-resistance was also most often associated with resistance to other antibiotics, regardless of the animal species considered. Comparative analysis showed substantial agreement between MDR and this co-resistance, with a kappa value of 0.75, all animal species considered. CONCLUSION: Given the widespread use of penicillins and tetracyclines in animal health, co-resistance to amoxicillin and tetracycline could be an efficient indicator of MDR in E. coli isolates. Based on a specific resistance profile and not an arbitrary number of resistances compared with MDR, this potential indicator is also precise, convenient and suitable for routine use.

Why do veterinarians ask for antimicrobial susceptibility testing? A qualitative study exploring determinants and evaluating the impact of antibiotic reduction policy.

For public health reasons, increasing attention has focused on more rational use of antimicrobials in farm animals. Guidance concerning the prescription of antibiotics and antimicrobial susceptibility testing (antibiograms in this case) are beneficial tools to help control the development of antimicrobial resistance. Nevertheless, even though there are already several qualitative studies analysing the determinants of antimicrobial prescription and use in veterinary medicine, little is known about decision-making concerning the use of antibiograms. The aim of this study was to provide a better understanding of veterinarians' motivations and role-players' influence concerning the choice of whether to ask for an antibiogram in the bovine, porcine, poultry and equine sectors in France. We concurrently evaluated the impact of a new French decree (2016) requiring an antibiogram before certain critically important antimicrobial agents can be used in veterinary medicine. Semi-structured interviews with veterinarians were conducted in France. Thematic analysis was used to analyse transcripts. In all, we surveyed 66 veterinarians. Use of antibiograms in veterinary medicine was multifactorial - 46 factors grouped into 11 categories were identified - and differed between animal sectors: use was almost systematic in poultry, frequent in pigs and rare in both the bovine and equine sectors. The decree has not increased the use of antibiograms but has induced a change in prescriptions due to field constraints and the time needed to obtain the results of antibiograms. Respondents see the decree as an aid in promoting responsible and rational use of antibiotics, fostering the use of alternatives. Our findings provide the basis of veterinarians' position regarding antibiogram use and antimicrobial resistance, pointing out levers to facilitate the use of antibiograms in veterinary medicine (for example communication on the benefits of this test and external financial support). Furthermore, the evaluation of the impact of the decree aimed at reducing the use of critically important antibiotic highlights key factors for a successful change in regulations, such as advance planning, precise and adapted communication, and demonstration of the measure's legitimacy. These results will be useful in guiding representative veterinary bodies and regulatory authorities during their decision-making, communication, and policy and regulation choices to combat antimicrobial resistance.

Comparative epidemiology of E. coli resistance to third-generation cephalosporins in diseased food-producing animals.

Categorized by WHO as critically important antibiotics, third-generation cephalosporins (3GCs) are one of the latest therapeutic alternatives to fight severe infectious diseases in humans. Some antibiotics belonging to this class are prescribed to treat food-producing animals in specific pathological contexts. Preserving the effectiveness of 3GCs requires characterization and careful monitoring of 3GCs resistance and the identification and implementation of measures that can limit this antimicrobial resistance (AMR). Here, we characterized the 3GCs resistance in Escherichia coli isolated from diseased animals. Using data collected from broilers, hens, calves, piglets, sows, turkeys and ducks between 2006 and 2016 by the French surveillance network of AMR in pathogenic bacteria of animal origin (called RESAPATH), we investigated the dynamics of resistance to 3GCs. Our non-linear analysis applied to time series showed that the evolution of E. coli resistance to 3GCs is specific to each animal category. From 2006 to 2010, resistance to 3GCs increased for most animal categories. We observed peaks of high-level of resistance for hens (21.5% in 2010) and broilers (26.7% in 2011), whereas trends stayed below 10% for the other animal categories throughout the study period. Resistance later decreased and, since 2014, 3GCs resistance has dropped below 10% for all animal categories. The parallel between trends and measures to limit AMR over the period shed lights on the impact of practices changes, public policies (EcoAntibio Plan) and sector-led initiatives (moratorium in swine sector). Finally, they highlight the usefulness and importance of AMR surveillance networks in animal health, such as RESAPATH.