Guidance on the Selection of Appropriate Indicators for Quantification of Antimicrobial Usage in Humans and Animals

An increasing variety of indicators of antimicrobial usage has become available in human and veterinary medicine, with no consensus on the most appropriate indicators to be used. The objective of this review is therefore to provide guidance on the selection of indicators, intended for those aiming to quantify antimicrobial usage based on sales, deliveries or reimbursement data. Depending on the study objective, different requirements apply to antimicrobial usage quantification in terms of resolution, comprehensiveness, stability over time, ability to assess exposure and comparability. If the aim is to monitor antimicrobial usage trends, it is crucial to use a robust quantification system that allows stability over time in terms of required data and provided output; to compare usage between different species or countries, comparability must be ensured between the different populations. If data are used for benchmarking, the system comprehensiveness is particularly crucial, while data collected to study the association between usage and resistance should express the exposure level and duration as a measurement of the exerted selection pressure. Antimicrobial usage is generally described as the number of technical units consumed normalized by the population at risk of being treated in a defined period. The technical units vary from number of packages to number of individuals treated daily by adding different levels of complexity such as daily dose or weight at treatment. These technical units are then related to a description of the population at risk, based either on biomass or number of individuals. Conventions and assumptions are needed for all of these calculation steps. However, there is a clear lack of standardization, resulting in poor transparency and comparability. By combining study requirements with available approaches to quantify antimicrobial usage, we provide suggestions on the most appropriate indicators and data sources to be used for a given study objective

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

Water hardness is a critical factor that affects oxytetracycline dissolution by chelation with cations. These interactions may lead to impaired dosing and consequently decrease absorption. Moreover, feed present in gastrointestinal tract may interact with antibiotic and alter pharmacokinetic parameters. In the present study, dissolution profiles of an oxytetracycline veterinary formulation were assessed in purified, soft and hard water. Furthermore, oxytetracycline absolute bioavailability, after oral administration of the drug dissolved in soft or hard water, was evaluated in fed and fasted piglets. A maximum dissolution of 86% and 80% was obtained in soft and hard water, respectively, while in purified water dissolution was complete. Results from in vivo study reconfirmed oxytetracycline´s very low oral bioavailability. The greatest values were attained when antibiotic was dissolved in soft water and in fasted animals. Statistically significant lower absolute bioavailability was achieved when hard water was used and/or animals were fed. Moreover, Cmax attained in all treatments was lower than MIC90 of most important swine pathogens. For these reasons, the oral use of OTC formulations, that have demonstrated low oral bioavailability, should be avoided to treat systemic diseases in pigs.Fil: Decundo, Julieta María. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencia Veterinarias. Departamento de Fisiopatología. Laboratorio de Toxicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Dieguez, Susana Nelly. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencia Veterinarias. Departamento de Fisiopatología. Laboratorio de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Martínez, Guadalupe. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Romanelli, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología; ArgentinaFil: Fernández Paggi, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología; ArgentinaFil: Pérez, Denisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología; ArgentinaFil: Amanto, Fabian A.. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Producción Animal; ArgentinaFil: Soraci, Alejandro Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencia Veterinarias. Departamento de Fisiopatología. Laboratorio de Toxicología; Argentin

Monitoring of Farm-Level Antimicrobial Use to Guide Stewardship: Overview of Existing Systems and Analysis of Key Components and Processes

peer-reviewedThe acknowledgment of antimicrobial resistance (AMR) as a major health challenge in humans, animals and plants, has led to increased efforts to reduce antimicrobial use (AMU). To better understand factors influencing AMR and implement and evaluate stewardship measures for reducing AMU, it is important to have sufficiently detailed information on the quantity of AMU, preferably at the level of the user (farmer, veterinarian) and/or prescriber or provider (veterinarian, feed mill). Recently, several countries have established or are developing systems for monitoring AMU in animals. The aim of this publication is to provide an overview of known systems for monitoring AMU at farm-level, with a descriptive analysis of their key components and processes. As of March 2020, 38 active farm-level AMU monitoring systems from 16 countries were identified. These systems differ in many ways, including which data are collected, the type of analyses conducted and their respective output. At the same time, they share key components (data collection, analysis, benchmarking, and reporting), resulting in similar challenges to be faced with similar decisions to be made. Suggestions are provided with respect to the different components and important aspects of various data types and methods are discussed. This overview should provide support for establishing or working with such a system and could lead to a better implementation of stewardship actions and a more uniform communication about and understanding of AMU data at farm-level. Harmonization of methods and processes could lead to an improved comparability of outcomes and less confusion when interpreting results across systems. However, it is important to note that the development of systems also depends on specific local needs, resources and aims

Les filières « porcs élevés sans antibiotiques » en France : caractéristiques, atouts, limites et perspectives Projet européen ROADMAP

International audienceThe European project ROADMAP promotes transitions for prudent and responsible antimicrobial use in livestock farming. Besides animal and veterinary sciences, it uses social sciences and economics to analyse the structure of food and drug supply chains, as well as the practices, knowledge and behaviours of stakeholders involved in managing the health of farmed animals. This article presents results of the assessment carried out in this project in 2020, based on interviews with (i) 10 veterinarians or quality managers from five producer organizations (PO), a processor and a retailer, and then (ii) 18 pig farmers, half of them in an antibiotic (AB)-free scheme. It clarifies the practices and behaviours of breeders in animal-health management and use of antibiotics, as well as the ABfree private schemes. Methods for calculating the quantities of antibiotics used at the farm level, when it is done, vary among POs, which does not allow conclusions to be drawn about differences in use between AB-free and conventional farms belonging to different POs. The AB-free lines developed by the pig sector over the past 10 years meet societal expectations and secure outlets.They represent approximately 15% of French pig production. The main motivation of breeders to enter a scheme is economic: they perceive a bonus, which varies according to the constraints and their degree of supply from their PO. Unlike a GMO-free claim, the AB-free claim is not subject to any legal definition, leading to very diverse specifications and labelling. Simplifying them could lead to segmentation into four sectors: standard ‘Le Porc Français-Qualité et Traçabilité (entry level of harmonized claims), under product conformity certification (CCP, upper levels), Label Rouge, and organic. With a single CCP, each breeder could deliver to several slaughterhouses, which would help improve the power balance.Les filières « porcs élevés sans antibiotiques » en France : caractéristiques, atouts, limites et perspectives Le projet européen ROADMAP vise à accompagner les transitions vers une utilisation prudente et responsable des antibiotiques en élevage. Il mobilise les sciences sociales et l'économie au côté des sciences animales et vétérinaires. Cet article présente les résultats du diagnostic réalisé dans ce cadre en 2020, à partir d'entretiens auprès (i) de 10 vétérinaires ou responsables qualité de cinq organisations de producteurs (OP), d'un transformateur et d'un distributeur, puis (ii) de 18 éleveurs dont la moitié en filière sans antibiotiques (SA). Il éclaire sur les pratiques et comportements des éleveurs en santé animale et usage d'antibiotiques, et sur le fonctionnement des filières SA : historique, partenaires, motivations, rémunération, volumes et contrôles. Les modes de calcul des quantités d'antibiotiques utilisées en élevage, lorsqu'il existe, sont hétérogènes entre OP ce qui ne permet pas de conclure sur des différences de niveaux d'usage entre élevages SA et hors SA adhérents à des OP différentes. Les filières SA développées par les acteurs de la filière depuis 10 ans répondent à des attentes sociétales et sécurisent les débouchés. Elles représentent environ 15% de la production française. La première motivation des éleveurs pour y entrer est économique : ils perçoivent une plus-value, variable selon les contraintes et leur degré d'approvisionnement auprès de leur OP. Contrairement au critère sans OGM, l'allégation SA ne fait l'objet d'aucune définition légale, conduisant à des cahiers des charges et étiquetages très divers. Leur simplification pourrait conduire à une segmentation en quatre filières : standard « Le Porc Français-Qualité et Traçabilité » (niveau d'entrée d'allégations harmonisées), sous certification de conformité des produits (CCP) (exigences supérieures), Label Rouge, BIO. Avec une seule CCP, chaque éleveur pourrait livrer plusieurs abattoirs ce qui contribuerait à un meilleur équilibre dans le rapport de force entre la production et l'aval de la filière. "Antibiotic-free" pig supply schemes in France: characteristics, advantages, limits and prospects The European project ROADMAP promotes transitions for prudent and responsible antimicrobial use in livestock farming. Besides animal and veterinary sciences, it uses social sciences and economics to analyse the structure of food and drug supply chains, as well as the practices, knowledge and behaviours of stakeholders involved in managing the health of farmed animals. This article presents results of the assessment carried out in this project in 2020, based on interviews with (i) 10 veterinarians or quality managers from five producer organizations (PO), a processor and a retailer, and then (ii) 18 pig farmers, half of them in an antibiotic (AB)-free scheme. It clarifies the practices and behaviours of breeders in animal-health management and use of antibiotics, as well as the ABfree private schemes. Methods for calculating the quantities of antibiotics used at the farm level, when it is done, vary among POs, which does not allow conclusions to be drawn about differences in use between AB-free and conventional farms belonging to different POs. The AB-free lines developed by the pig sector over the past 10 years meet societal expectations and secure outlets. They represent approximately 15% of French pig production. The main motivation of breeders to enter a scheme is economic: they perceive a bonus, which varies according to the constraints and their degree of supply from their PO. Unlike a GMO-free claim, the AB-free claim is not subject to any legal definition, leading to very diverse specifications and labelling. Simplifying them could lead to segmentation into four sectors: standard 'Le Porc Français-Qualité et Traçabilité (entry level of harmonized claims), under product conformity certification (CCP, upper levels), Label Rouge, and organic. With a single CCP, each breeder could deliver to several slaughterhouses, which would help improve the power balance

What Matters in Piglets’ Exposure to Antibiotics Administered through Drinking Water?

A number of drugs are given in drinking water in piglet farming, although this way of administering drugs leads to significant and uncontrolled variability in exposures. Three main explanations for this variability have been described in the literature: (1) the drinking behavior of animals, (2) the drug concentration in water, and (3) the inter-individual variability in the pharmacokinetic (PK) parameters. This article assesses the relative importance of these three sources of exposure variability for doxycycline and amoxicillin using pharmacokinetic simulations and by observing watering behavior, and analyzes the consequences of this exposure variability. The water consumption behavior was by far the most important factor as it led to a variation in exposures of up to a factor of 7 between piglets. The second most influential factor was the drug concentration in the drinking water with variations ranging from −43.3% to +48.7% at the beginning and the end of the pipeline. Finally, the between-individual variation in PK parameters depends on the drug, but had a low impact on exposure variability. In the most variable case (doxycycline), the mean ratio between the 10% less exposed and the 10% most exposed piglets varied from 3.7 without PK parameters variability to 6 with PK variability. For both drugs, this study also showed that only a small percentage of the piglets (36%) could be considered as well exposed in case of infection by Actinobacillus pleuropneumoniae or Pasteurella multocida. There may be some existing technical ways to reduce this important variability. However, their cost and ease of implementation merit examination

Field evaluation of piglet vaccination with a Mycoplasma hyopneumoniae bacterin as compared to a ready-to-use product including porcine circovirus 2 and M. hyopneumoniae in a conventional French farrow-to-finish farm

Abstract Background A controlled randomized trial was performed on a well-managed conventional French 180-sow farm. The trial compared the growth performances of piglets vaccinated at weaning (single shot) either with a commercial monovalent Mycoplasma hyopneumoniae bacterin vaccine or with a commercial bivalent vaccine (Porcilis® PCV M Hyo) against M. hyopneumoniae and porcine circovirus 2 (PCV2). The farm’s porcine reproductive and respiratory syndrome status was stable, and most diseases (enzootic pneumonia, atrophic rhinitis, post-weaning multisystemic wasting syndrome) were controlled by routine vaccination. Results During the post-weaning phase, the growth performances of the piglets vaccinated with the bivalent vaccine were not significantly different from those vaccinated with the monovalent vaccine. However, during the fattening phase the group vaccinated with the bivalent vaccine had a significantly improved ADG (+34 g/d, p = 0. 047), resulting in a 5-day earlier shipment to slaughter. The group also had a shorter and lower PCV2 load in serum during the fattening period, and an improved lung lesions score. In both groups, three pigs died during the peak PCV2 viraemia (16–23 weeks of age). Immunohistochemistry of the lymph nodes showed that in the group vaccinated with the bivalent vaccine, none of these pigs had PCV2-like lesions, while 2 out of the 3 from the other group did. Results suggest that the added PCV2 valence in the vaccination protocol helps countering the negative impact of subclinical PCV2 infection on growth. The calculated return on investment of the added PCV2 vaccine valence was €1.7 extra revenue per slaughtered pig (€ 39 additional revenue per sow and per year), despite the fact that the cost of the bivalent vaccine was higher than the monovalent M. hyopneumoniae vaccine. Conclusion In this healthy conventional sow farm, the combined M. hyopneumoniae and PCV2 vaccination was efficacious, convenient to administer and profitable

Antimicrobial usage evolution between 2010, 2013 and 2013 in a group of French pig farms

Introduction: Monitoring antimicrobial usage in pig farms is a key element of a reduction plan. The objective ofthis study was to analyse the antimicrobial usage evolution in the same farms between 2010-2013-2016 and to identify the factors of variations.Material & Methods: The study monitored antimicrobial usage in 2016 in 33 farrow-to-finish farms in the West of France. The antimicrobial usage had ever been registered twice for 23 of them in 2010 and 2013 and once for 10 of them in 2013. It was quantified by the number of Course Doses per produced pig per year (nCD/pig). Farmers were asked about the factors that could explain the evolution between 2013-2016.Results: On average, antimicrobial usage significantly decreased over six years (-38%). However, a highvariability of individual evolutions was observed: among the 23 farms with three annual data, 43% decreased their use between 2010-2013 (-3 nCD/pig on average) but had a stable use between 2013-2016 (-0,2 nCD/pig). 26% decreased their use between 2010-2013 (-4 nCD/pig on average) and also between 2013-2016 (-2 nCD/pig). 9% increased then decreased their use during the two periods (+4 then -7 nCD/pig). One farm had the opposite trajectory (-9 then +2 nCD/pig) and another always increased its use (+2 then +5 nCD/pig). Among the 33 farms with data in 2013-2016, 36% decreased their use (-2 nCD/pig on average), 39% had a stable use and 24% increased their use (+3 nCD/pig).Increases were explained by occurrence of sanitary problems (mainly urogenital, digestive and respiratory problems on sows, piglets and fatteners respectively). Decreases were explained by vaccination, stop of preventive treatments and improvement of herd management.Discussion & Conclusion: This study highlights the variability of individual trajectories in antimicrobial usage, due to sanitary issues. It usefully complements the monitoring of average evolution at the country leve

Learning Processes and Trajectories for the Reduction of Antibiotic Use in Pig Farming: A Qualitative Approach

Since 2011, French public policy has been encouraging a reduction in the use of antibiotics in animal farming. The aim of this article is to look at how some farms have already managed to lower their consumption of antibiotics, and to highlight the levers of change in farming health practices. Our research uses a qualitative study based on 21 semi-structured interviews with farmers and veterinarians in the French pig-farming sector. We use the notion of “trajectory of change” to examine, over time, the intersection of the technical, economic, social and organisational determinants which affect the reduced use of antibiotics. The “learning process” concept makes it possible to take account of the way in which the actors assimilate, appropriate and implement new health practices. We have identified three interdependent levels of learning: technical learning, cognitive learning and organisational learning