Improving the detection of integrative conjugative elements in bovine nasopharyngeal swabs using multiplex recombinase polymerase amplification.

Bovine respiratory disease (BRD) is an important health and economic burden to the cattle industry worldwide. Three bacterial pathogens frequently associated with BRD (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) can possess integrative and conjugative elements (ICEs), a diverse group of mobile genetic elements that acquire antimicrobial resistance (AMR) genes (ARGs) and decrease the therapeutic efficacy of antimicrobial drugs. We developed a duplex recombinase polymerase amplification (RPA) assay to detect up to two variants of ICEs in these Pasteurellaceae. Whole genome sequence analysis of M. haemolytica, P. multocida, and H. somni isolates harbouring ICEs revealed the presence of tnpA or ebrB next to tet(H), a conserved ARG that is frequently detected in ICEs within BRD-associated bacteria. This real-time multiplex RPA assay targeted both ICE variants simultaneously, denoted as tetH_tnpA and tetH_ebrB, with a limit of detection (LOD) of 29 (95% CI [23, 46]) and 38 genome copies (95% CI [30, 59]), respectively. DNA was extracted from 100 deep nasopharyngeal swabs collected from feedlot cattle on arrival. Samples were tested for ICEs using a real-time multiplex RPA assay, and for M. haemolytica, P. multocida, H. somni, and Mycoplasma bovis using both culture methods and RPA. The assay provided sensitive and accurate identification of ICEs in extracted DNA, providing a useful molecular tool for timely detection of potential risk factors associated with the development of antimicrobial-resistant BRD in feedlot cattle.

Variation in Pen-Level Prevalence of BRD Bacterial Pathogens and Antimicrobial Resistance Following Feedlot Arrival in Beef Calves.

Antimicrobials are crucial for treating bovine respiratory disease (BRD) in beef feedlots. Evidence is needed to support antimicrobial use (AMU) decisions, particularly in the early part of the feeding period when BRD risk is highest. The study objective was to describe changes in prevalence and antimicrobial susceptibility of BRD bacterial pathogens at feedlot processing (1 day on feed (1DOF)), 12 days later (13DOF), and for a subset at 36DOF following metaphylactic antimicrobial treatment. Mixed-origin steer calves (n = 1599) from Western Canada were managed as 16 pens of 100 calves, receiving either tulathromycin (n = 1199) or oxytetracycline (n = 400) at arrival. Deep nasopharyngeal swabs collected at all time points underwent culture and antimicrobial susceptibility testing (AST). Variability in the pen-level prevalence of bacteria and antimicrobial susceptibility profiles were observed over time, between years, and metaphylaxis options. Susceptibility to most antimicrobials was high, but resistance increased from 1DOF to 13DOF, especially for tetracyclines and macrolides. Simulation results suggested that sampling 20 to 30 calves per pen of 200 reflected the relative pen-level prevalence of the culture and AST outcomes of interest. Pen-level assessment of antimicrobial resistance early in the feeding period can inform the evaluation of AMU protocols and surveillance efforts and support antimicrobial stewardship in animal agriculture.

Laboratory tools for the direct detection of bacterial respiratory infections and antimicrobial resistance: a scoping review.

Rapid laboratory tests are urgently required to inform antimicrobial use in food animals. Our objective was to synthesize knowledge on the direct application of long-read metagenomic sequencing to respiratory samples to detect bacterial pathogens and antimicrobial resistance genes (ARGs) compared to PCR, loop-mediated isothermal amplification, and recombinase polymerase amplification. Our scoping review protocol followed the Joanna Briggs Institute and PRISMA Scoping Review reporting guidelines. Included studies reported on the direct application of these methods to respiratory samples from animals or humans to detect bacterial pathogens ±ARGs and included turnaround time (TAT) and analytical sensitivity. We excluded studies not reporting these or that were focused exclusively on bioinformatics. We identified 5,636 unique articles from 5 databases. Two-reviewer screening excluded 3,964, 788, and 784 articles at 3 levels, leaving 100 articles (19 animal and 81 human), of which only 7 studied long-read sequencing (only 1 in animals). Thirty-two studies investigated ARGs (only one in animals). Reported TATs ranged from minutes to 2 d; steps did not always include sample collection to results, and analytical sensitivity varied by study. Our review reveals a knowledge gap in research for the direct detection of bacterial respiratory pathogens and ARGs in animals using long-read metagenomic sequencing. There is an opportunity to harness the rapid development in this space to detect multiple pathogens and ARGs on a single sequencing run. Long-read metagenomic sequencing tools show potential to address the urgent need for research into rapid tests to support antimicrobial stewardship in food animal production.

Perceptions of antimicrobial stewardship: identifying drivers and barriers across various professions in Canada utilizing a one health approach.

Introduction: As antimicrobial resistance (AMR) represents a substantial threat to the efficacy of available antimicrobial options, it is important to understand how to implement effective and practical mitigation efforts, including antimicrobial stewardship (AMS), across human, animal, and environmental sectors. Methods: A mixed-methods questionnaire was distributed virtually to attendees of the virtual One Health Antimicrobial Stewardship Conference (March 10-12, 2021) and their professional networks. Respondents (n = 81) were largely from the veterinary (75%) or human (19%) health sectors. Qualitative data were analyzed in NVivo using template analysis whereas quantitative data were analyzed in STATA using Kruskall-Wallis tests. The questionnaire asked respondents about their perceptions of AMS, as well as the perceived barriers and drivers of AMS efforts. Results: Perceptions of what AMS meant to the respondents personally and their profession as a whole were grouped into 3 main themes: 1) AMS strategies or considerations in antimicrobial prescribing and use; 2) responsibility to maintain health and preserve antimicrobial effectiveness; and 3) reducing antimicrobial use (AMU) as a goal of AMS efforts. Identified AMS barriers had 3 main themes: 1) lack of various prescribing and AMU support mechanisms; 2) shift in prescriber attitudes to drive change; and 3) stronger economic considerations to support shifting prescribing practices. Drivers of AMS had the following themes: 1) leadership to guide change; 2) education to support optimizing AMU; and 3) research to identify best practices and opportunities for action. Across all questions, 2 cross-cutting themes emerged: 1) a One Health understanding of AMS; and 2) blame placed on others for a lack of AMS success. Conclusion: Overall, sector-specific, but particularly cross-sectoral AMS drivers and barriers were identified, highlighting the importance of a One Health approach in AMR research and mitigation.

A scoping review of factors associated with antimicrobial-resistant Campylobacter species infections in humans.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

Factors associated with antimicrobial resistant enterococci in Canadian beef cattle: A scoping review.

Introduction: Antimicrobial resistance (AMR) is a global health concern, occurring when bacteria evolve to render antimicrobials no longer effective. Antimicrobials have important roles in beef production; however, the potential to introduce AMR to people through beef products is a concern. This scoping review identifies factors associated with changes in the prevalence of antimicrobial-resistant Enterococcus spp. applicable to the Canadian farm-to-fork beef continuum. Methods: Five databases (MEDLINE, BIOSIS, Web of Science, Embase, and CAB Abstracts) were searched for articles published from January 1984 to March 2022, using a priori inclusion criteria. Peer-reviewed articles were included if they met all the following criteria: written in English, applicable to the Canadian beef production context, primary research, in vivo research, describing an intervention or exposure, and specific to Enterococcus spp. Results: Out of 804 screened articles, 26 were selected for inclusion. The included articles discussed 37 factors potentially associated with AMR in enterococci, with multiple articles discussing at least two of the same factors. Factors discussed included antimicrobial administration (n = 16), raised without antimicrobials (n = 6), metal supplementation (n = 4), probiotics supplementation (n = 3), pen environment (n = 2), essential oil supplementation (n = 1), grass feeding (n = 1), therapeutic versus subtherapeutic antimicrobial use (n = 1), feeding wet distiller grains with solubles (n = 1), nutritional supplementation (n = 1) and processing plant type (n = 1). Results were included irrespective of their quality of evidence. Discussion: Comparability issues arising throughout the review process were related to data aggregation, hierarchical structures, study design, and inconsistent data reporting. Findings from articles were often temporally specific in that resistance was associated with AMR outcomes at sampling times closer to exposure compared to studies that sampled at longer intervals after exposure. Resistance was often nuanced to unique gene and phenotypic resistance patterns that varied with species of enterococci. Intrinsic resistance and interpretation of minimum inhibitory concentration varied greatly among enterococcal species, highlighting the importance of caution when comparing articles and generalizing findings. Systematic Review Registration: [http://hdl.handle.net/1880/113592].

Naturalized Escherichia coli in Wastewater and the Co-evolution of Bacterial Resistance to Water Treatment and Antibiotics.

Antibiotic resistance represents one of the most pressing concerns facing public health today. While the current antibiotic resistance crisis has been driven primarily by the anthropogenic overuse of antibiotics in human and animal health, recent efforts have revealed several important environmental dimensions underlying this public health issue. Antibiotic resistant (AR) microbes, AR genes, and antibiotics have all been found widespread in natural environments, reflecting the ancient origins of this phenomenon. In addition, modern societal advancements in sanitation engineering (i.e., sewage treatment) have also contributed to the dissemination of resistance, and concerningly, may also be promoting the evolution of resistance to water treatment. This is reflected in the recent characterization of naturalized wastewater strains of Escherichia coli-strains that appear to be adapted to live in wastewater (and meat packing plants). These strains carry a plethora of stress-resistance genes against common treatment processes, such as chlorination, heat, UV light, and advanced oxidation, mechanisms which potentially facilitate their survival during sewage treatment. These strains also carry an abundance of common antibiotic resistance genes, and evidence suggests that resistance to some antibiotics is linked to resistance to treatment (e.g., tetracycline resistance and chlorine resistance). As such, these naturalized E. coli populations may be co-evolving resistance against both antibiotics and water treatment. Recently, extraintestinal pathogenic strains of E. coli (ExPEC) have also been shown to exhibit phenotypic resistance to water treatment, seemingly associated with the presence of various shared genetic elements with naturalized wastewater E. coli. Consequently, some pathogenic microbes may also be evolving resistance to the two most important public health interventions for controlling infectious disease in modern society-antibiotic therapy and water treatment.

Evaluating the potential of third generation metagenomic sequencing for the detection of BRD pathogens and genetic determinants of antimicrobial resistance in chronically ill feedlot cattle.

BACKGROUND: Bovine respiratory disease (BRD) is an important cause of morbidity and mortality and is responsible for most of the injectable antimicrobial use in the feedlot industry. Traditional bacterial culture can be used to diagnose BRD by confirming the presence of causative pathogens and to support antimicrobial selection. However, given that bacterial culture takes up to a week and early intervention is critical for treatment success, culture has limited utility for informing rapid therapeutic decision-making. In contrast, metagenomic sequencing has the potential to quickly resolve all nucleic acid in a sample, including pathogen biomarkers and antimicrobial resistance genes. In particular, third-generation Oxford Nanopore Technology sequencing platforms provide long reads and access to raw sequencing data in real-time as it is produced, thereby reducing the time from sample collection to diagnostic answer. The purpose of this study was to compare the performance of nanopore metagenomic sequencing to traditional culture and sensitivity methods as applied to nasopharyngeal samples from segregated groups of chronically ill feedlot cattle, previously treated with antimicrobials for nonresponsive pneumonia or lameness. RESULTS: BRD pathogens were isolated from most samples and a variety of different resistance profiles were observed across isolates. The sequencing data indicated the samples were dominated by Moraxella bovoculi, Mannheimia haemolytica, Mycoplasma dispar, and Pasteurella multocida, and included a wide range of antimicrobial resistance genes (ARGs), encoding resistance for up to seven classes of antimicrobials. Genes conferring resistance to beta-lactams were the most commonly detected, while the tetH gene was detected in the most samples overall. Metagenomic sequencing detected the BRD pathogens of interest more often than did culture, but there was limited concordance between phenotypic resistance to antimicrobials and the presence of relevant ARGs. CONCLUSIONS: Metagenomic sequencing can reduce the time from sampling to results, detect pathogens missed by bacterial culture, and identify genetically encoded determinants of resistance. Increasing sequencing coverage of target organisms will be an essential component of improving the reliability of this technology, such that it can be better used for the surveillance of pathogens of interest, genetic determinants of resistance, and to inform diagnostic decisions.

One Health, One Hive: A scoping review of honey bees, climate change, pollutants, and antimicrobial resistance.

Anthropogenic climate change and increasing antimicrobial resistance (AMR) together threaten the last 50 years of public health gains. Honey bees are a model One Health organism to investigate interactions between climate change and AMR. The objective of this scoping review was to examine the range, extent, and nature of published literature on the relationship between AMR and honey bees in the context of climate change and environmental pollutants. The review followed systematic search methods and reporting guidelines. A protocol was developed a priori in consultation with a research librarian. Resulting Boolean search strings were used to search Embase® via Ovid®, MEDLINE®, Scopus®, AGRICOLA™ and Web of Science™ databases. Two independent reviewers conducted two-stage screening on retrieved articles. To be included, the article had to examine honey bees, AMR, and either climate change or environmental pollution. Data, in accordance with Joanna Briggs Institute guidelines, were extracted from relevant articles and descriptively synthesized in tables, figures, and narrative form. A total of 22 articles met the inclusion criteria, with half of all articles being published in the last five years (n = 11/22). These articles predominantly investigated hive immunocompetence and multi-drug resistance transporter downregulation (n = 11/22), susceptibility to pests (n = 16/22), especially American foulbrood (n = 9/22), and hive product augmentation (n = 3/22). This review identified key themes and gaps in the literature, including the need for future interdisciplinary research to explore the link between AMR and environmental change evidence streams in honey bees. We identified three potential linkages between pollutive and climatic factors and risk of AMR. These interconnections reaffirm the necessity of a One Health framework to tackle global threats and investigate complex issues that extend beyond honey bee research into the public health sector. It is integral that we view these "wicked" problems through an interdisciplinary lens to explore long-term strategies for change.

Integrated surveillance of antimicrobial resistance and antimicrobial use: Evaluation of the status in Canada (2014-2019).

OBJECTIVE: Integrated surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) across One Health sectors is critically important for effective, evidence-based policy, stewardship, and control of AMR. Our objective was to evaluate progress towards achieving comprehensive, integrated AMR/AMU surveillance in Canada. MATERIALS AND METHODS: Based on an environmental scan, interviews of subject matter experts, and reports from the 2014 National Collaborating Centre for Infectious Diseases and the 2016 Canadian Council of Chief Veterinary Officers, we identified 8 core surveillance requirements and their specific components; the latter were assessed using a 2-way classification matrix, with 7 common elements ranked according to development stage. RESULTS: Components that mapped to requirements of a comprehensive, fully integrated AMR/AMU surveillance system were mostly in the lowest stages of development (Exploration or Program Adoption). However, both the establishment of the Canadian AMR Surveillance System integrated reporting and expansion of existing components under the Canadian Nosocomial Infection Surveillance Program and the Canadian Integrated Program for AMR Surveillance are improvements. Regardless, obvious gaps in Canadian AMR/AMU surveillance prevent this from being a comprehensive and integrated One Health program. CONCLUSION: Action is needed in 3 crucial areas: i) development of a complete, integrated AMR/AMU surveillance program, based on current success; ii) changes in Federal/Provincial/Territorial policies to require standardized AMR/AMU reporting; and iii) more resources for AMR/AMU surveillance (dedicated persons, funding, and enabling structures and policy). There is an urgent need for prioritization by Federal/Provincial/Territorial governments to address governance, leadership, and funding to create surveillance systems that inform stewardship and policy.

OBJECTIF: La surveillance intégrée de la résistance aux antimicrobiens (RAM) et de l'utilisation des antimicrobiens (UAM) dans les secteurs Une seule santé est d'une importance cruciale pour une politique, une gestion et une maitrise efficaces et fondées sur des preuves de la résistance aux antimicrobiens. Notre objectif était d'évaluer les progrès vers la réalisation d'une surveillance complète et intégrée de la RAM/UAM au Canada. MÉTHODES: Sur la base d'une analyse de l'environnement, d'entrevues d'experts en la matière et de rapports du Centre de collaboration nationale des maladies infectieuses de 2014 et du Conseil canadien des chefs vétérinaires de 2016, nous avons identifié huit exigences de surveillance de base et leurs composantes spécifiques ; ces derniers ont été évalués à l'aide d'une matrice de classification à deux voies, avec sept éléments communs classés selon le stade de développement. RÉSULTATS: Les composants correspondant aux exigences d'un système de surveillance de la RAM/UAM complet et entièrement intégré en étaient pour la plupart aux stades les plus bas de développement (Exploration ou Adoption de programme). Cependant, l'établissement du Système canadien de surveillance de la RAM et l'expansion des éléments existants dans le cadre du Programme canadien de surveillance des infections nosocomiales et du Programme intégré canadien de surveillance de la RAM constituent des améliorations. Quoi qu'il en soit, des lacunes évidentes dans la surveillance canadienne de la RAM/UAM l'empêchent d'être un programme Une seule santé complet et intégré. CONCLUSION: Des actions sont nécessaires dans trois domaines cruciaux : 1) le développement d'un programme de surveillance complet et intégré de la RAM/AMU, basé sur le succès actuel; 2) des changements aux politiques fédéralesprovinciales-territoriales pour exiger des rapports normalisés sur la RAM/UAM; et 3) davantage de ressources pour la surveillance de la RAM/UAM (personnes dédiées, financement, structures et politiques habilitantes). Il est urgent que les gouvernements fédéral-provincial-territorial établissent des priorités pour aborder la gouvernance, le leadership et le financement afin de créer des systèmes de surveillance qui éclairent la gouvernance et les politiques.(Traduit par Dr Serge Messier).

Integrated surveillance of antimicrobial resistance and antimicrobial use: Evaluation of the status in Canada (2014-2019).

OBJECTIVE: Integrated surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) across One Health sectors is critically important for effective, evidence-based policy, stewardship, and control of AMR. Our objective was to evaluate progress towards achieving comprehensive, integrated AMR/AMU surveillance in Canada. MATERIALS AND METHODS: Based on an environmental scan, interviews of subject matter experts, and reports from the 2014 National Collaborating Centre for Infectious Diseases and the 2016 Canadian Council of Chief Veterinary Officers, we identified 8 core surveillance requirements and their specific components; the latter were assessed using a 2-way classification matrix, with 7 common elements ranked according to development stage. RESULTS: Components that mapped to requirements of a comprehensive, fully integrated AMR/AMU surveillance system were mostly in the lowest stages of development (Exploration or Program Adoption). However, both the establishment of the Canadian AMR Surveillance System integrated reporting and expansion of existing components under the Canadian Nosocomial Infection Surveillance Program and the Canadian Integrated Program for AMR Surveillance are improvements. Regardless, obvious gaps in Canadian AMR/AMU surveillance prevent this from being a comprehensive and integrated One Health program. CONCLUSION: Action is needed in 3 crucial areas: i) development of a complete, integrated AMR/AMU surveillance program, based on current success; ii) changes in Federal/Provincial/Territorial policies to require standardized AMR/AMU reporting; and iii) more resources for AMR/AMU surveillance (dedicated persons, funding, and enabling structures and policy). There is an urgent need for prioritization by Federal/Provincial/Territorial governments to address governance, leadership, and funding to create surveillance systems that inform stewardship and policy.

RéSUMé: OBJECTIF: La surveillance intégrée de la résistance aux antimicrobiens (RAM) et de l'utilisation des antimicrobiens (UAM) dans les secteurs Une seule santé est d'une importance cruciale pour une politique, une gestion et une maitrise efficaces et fondées sur des preuves de la résistance aux antimicrobiens. Notre objectif était d'évaluer les progrès vers la réalisation d'une surveillance complète et intégrée de la RAM/UAM au Canada. MéTHODES: Sur la base d'une analyse de l'environnement, d'entrevues d'experts en la matière et de rapports du Centre de collaboration nationale des maladies infectieuses de 2014 et du Conseil canadien des chefs vétérinaires de 2016, nous avons identifié huit exigences de surveillance de base et leurs composantes spécifiques; ces derniers ont été évalués à l'aide d'une matrice de classification à deux voies, avec sept éléments communs classés selon le stade de développement. RéSULTATS: Les composants correspondant aux exigences d'un système de surveillance de la RAM/UAM complet et entièrement intégré en étaient pour la plupart aux stades les plus bas de développement (Exploration ou Adoption de programme). Cependant, l'établissement du Système canadien de surveillance de la RAM et l'expansion des éléments existants dans le cadre du Programme canadien de surveillance des infections nosocomiales et du Programme intégré canadien de surveillance de la RAM constituent des améliorations. Quoi qu'il en soit, des lacunes évidentes dans la surveillance canadienne de la RAM/UAM l'empêchent d'être un programme Une seule santé complet et intégré. CONCLUSION: Des actions sont nécessaires dans trois domaines cruciaux : 1) le développement d'un programme de surveillance complet et intégré de la RAM/AMU, basé sur le succès actuel; 2) des changements aux politiques fédérales/provinciales/territoriales pour exiger des rapports normalisés sur la RAM/UAM; et 3) davantage de ressources pour la surveillance de la RAM/UAM (personnes dédiées, financement, structures et politiques habilitantes). Il est urgent que les gouvernements fédéral/provincial/territorial établissent des priorités pour aborder la gouvernance, le leadership et le financement afin de créer des systèmes de surveillance qui éclairent la gouvernance et les politiques.

Knowledge Gaps in the Understanding of Antimicrobial Resistance in Canada.

Current limitations in the understanding and control of antimicrobial resistance (AMR) in Canada are described through a comprehensive review focusing on: (1) treatment optimization; (2) surveillance of antimicrobial use and AMR; and (3) prevention of transmission of AMR. Without addressing gaps in identified areas, sustained progress in AMR mitigation is unlikely. Expert opinions and perspectives contributed to prioritizing identified gaps. Using Canada as an example, this review emphasizes the importance and necessity of a One Health approach for understanding and mitigating AMR. Specifically, antimicrobial use in human, animal, crop, and environmental sectors cannot be regarded as independent; therefore, a One Health approach is needed in AMR research and understanding, current surveillance efforts, and policy. Discussions regarding addressing described knowledge gaps are separated into four categories: (1) further research; (2) increased capacity/resources; (3) increased prescriber/end-user knowledge; and (4) policy development/enforcement. This review highlights the research and increased capacity and resources to generate new knowledge and implement recommendations needed to address all identified gaps, including economic, social, and environmental considerations. More prescriber/end-user knowledge and policy development/enforcement are needed, but must be informed by realistic recommendations, with input from all relevant stakeholders. For most knowledge gaps, important next steps are uncertain. In conclusion, identified knowledge gaps underlined the need for AMR policy decisions to be considered in a One Health framework, while highlighting critical needs to achieve realistic and meaningful progress.

One Health Evaluation of Antimicrobial Use and Resistance Surveillance: A Novel Tool for Evaluating Integrated, One Health Antimicrobial Resistance and Antimicrobial Use Surveillance Programs.

We describe the development, application and utility of our novel, One Health Evaluation of Antimicrobial Use and Resistance Surveillance (OHE-AMURS) tool that we created to evaluate progress toward integrated, One Health surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) as a complex system in Canada. We conducted a qualitative inquiry into the current state of policy and programs for integrated AMR/AMU surveillance using explicit and tacit knowledge. To assess the "messy" state of public health surveillance program development, we synthesized recommendations from previous reports by the National Collaborating Centre for Infectious Diseases and the Canadian Council of Chief Veterinary Officers; conducted an environmental scan to find all federal, provincial, and territorial AMR/AMU surveillance programs in Canada; and conducted semi-structured interviews with Canadian subject matter experts. To integrate evidence from these different sources we adapted two published tools to create a new evaluation matrix, deriving 36 components of the ideal integrated AMR/AMU surveillance system. Our two-way matrix tool allowed us to examine seven common, foundational elements of sustainable programs for each component, and assign a stage of development/sustainability ranking for each component according to the matrix definitions. Our adaptable novel tool allowed for granular and repeatable assessment of the many components of a complex surveillance system. The assessment proved robust and exacting to ensure transparency in our methods and results. The matrix allows flexible assignment of program components based on program principles, and stages can be adapted to evaluate any aspect of an AMR/AMU surveillance or other multi-faceted, multi-jurisdictional system. Future refinement should include an assessment of the scope of surveillance components.

Antimicrobial Use Surveillance Indicators for Finfish Aquaculture Production: A Review.

Quantification and tracking of antimicrobial use (AMU) are key factors for the development of responsible antimicrobial stewardship programs and comparison between countries. Global finfish aquaculture growth and increased AMU creates the potential for exchange of antimicrobial resistance between aquatic and terrestrial environments, making AMU surveillance imperative for this industry. The objective of this review is to collate current literature on AMU surveillance indicators and their application to commercial finfish aquaculture production. A systematic search strategy was applied to five databases: Medline, Embase, Agricola, CAB abstracts, and Biosis. To be included, studies must report on at least one AMU surveillance indicator for use in animals. There is no single, standardized indicator suitable to report finfish aquaculture AMU. The type and availability of finfish aquaculture data presents unique considerations for AMU reporting. Ultimately, the indicator used should be fit-for-purpose to satisfy the objective of the surveillance program, motivation for comparison and provide useful information to the industry stakeholders. Finfish aquaculture total annual slaughter weight allows estimation of biomass for the population correction unit (PCU) to report annual total mg of active antimicrobial ingredient per PCU. These data are commonly reported by finfish aquaculture-producing countries, allowing for international comparisons. However, this precludes the ability to compare to terrestrial livestock where the PCU is based on animal numbers and an average treatment weight, which are not available for finfish aquaculture. The mg per adjusted PCU indicator provides an interesting alternative that incorporates the length of the marine grow-out phase for finfish, but is subject to the same limitations. The number of defined daily doses animal per animal-days-at-risk is useful but also limited by a lack of a defined average treatment weight. The concept of average treatment weight remains challenging for the industry as it does not accurately reflect the timing of actual AMU to fish in the system. The term "average biomass" is more reflective of the intent of AMU surveillance indicators. Defining an average treatment weight, or average biomass, will require industry engagement, which is crucial if AMU reporting is to be deemed credible and provide value back to the finfish aquaculture industry.

An Internet survey of risk factors for injury in North American dogs competing in flyball.

A survey was used to investigate injuries in dogs competing in flyball. Complete surveys were obtained from 272 respondents with 589 dogs. In the past year, 23.3% of dogs were injured, with 34.1% injured during their career to date. Common injury sites were paws/digits, back, shoulder, and iliopsoas muscle/groin. Injury in previous years, modified by weight:height ratio, was a significant risk factor for injury. Dogs > 2 y of age had increased risk of injury, as did dogs with best times < 4.0 s. Canadian dogs had increased risk of injury (30.7% injured) compared to United States dogs (20.1% injured). This relationship was modified by participation in other sports, which generally reduced risk of injury in Canadian dogs. Further investigation of risk factors should include differences in training and competition between the United States and Canada, as well as injury prevention strategies.

Un sondage Internet sur les facteurs de risque de blessure chez les chiens nord-américains participant au flyball. Un sondage a été utilisé pour enquêter sur les blessures chez les chiens participant au flyball. Des enquêtes complètes ont été obtenues auprès de 272 répondants avec 589 chiens. Au cours de la dernière année, 23,3 % des chiens ont été blessés, et 34,1 % au cours de leur carrière à ce jour. Les sites de blessure les plus courants étaient les pattes/doigts, le dos, l'épaule et l'aine/muscle psoas iliaque. Les blessures des années précédentes, modifiées par le rapport poids/taille, étaient un facteur de risque important de blessures. Les chiens de plus de 2 ans présentaient un risque accru de blessures, tout comme les chiens avec les meilleurs temps < 4,0 s. Les chiens canadiens présentaient un risque accru de blessures (30,7 % de blessés) par rapport aux chiens américains (20,1 % de blessés). Cette relation était modifiée par la participation à d'autres sports, ce qui réduisait généralement le risque de blessure chez les chiens canadiens. Une enquête plus approfondie sur les facteurs de risque devrait inclure les différences d'entraînement et de compétition entre les États-Unis et le Canada, ainsi que des stratégies de prévention des blessures.(Traduit par Dr Serge Messier).

Feedlot Cattle Antimicrobial Use Surveillance Network: A Canadian Journey.

Antimicrobial drugs are important tools for maintaining human and animal health. Globally, antimicrobial use (AMU) in food-producing animals is under increasing scrutiny due to its potential to promote antimicrobial resistance (AMR). Historically, comprehensive Canadian data related to the types of antimicrobial drugs used, extent of use, common indicators of use and the demographics of the cattle populations receiving antimicrobial drugs have been limited, in part due to segmentation in the cattle industry and fragmentation of the drug distribution system. Appropriate AMU estimates are required to understand AMU practices, to interpret AMR levels and patterns, to meaningfully assess associated public health risks, and to inform stewardship activities. The Canadian beef cattle industry has a long history of collaboration in AMU and AMR research. Prior research projects identified both opportunities and challenges in the collection of AMU data. Cornerstone projects provided insight into the complexity of collecting AMU data in Canada's feedlot sector. This paper will discuss how the lessons learned from past work have contributed to the formation of a Canadian fed-cattle antimicrobial surveillance program that was initiated in 2019. This important surveillance program will allow feedlot cattle AMU to improve management decisions and support AMU best practices in the evolving Canadian AMR landscape.

Antimicrobial Resistance of Human Campylobacter Species Infections in Saskatchewan, Canada (1999-2006): A Historical Provincial Collection of All Reported Cases.

To describe a historical baseline of antimicrobial resistance (AMR) profiles for human clinical Campylobacter species isolates obtained by laboratory surveillance in the province of Saskatchewan from 1999 to 2006; to determine if there were differences in resistance between Campylobacter jejuni and Campylobacter coli; and to determine if there were changes in the annual resistance levels in the two species. One thousand three hundred seventy-eight Campylobacter isolates were subjected to antimicrobial susceptibility testing using the E-test method. Annual resistance levels in C. jejuni and C. coli were compared using logistic regression models. One thousand two hundred (87.1%) isolates were C. jejuni and 129 (9.4%) were C. coli. Resistance in C. jejuni isolates included ciprofloxacin (CIP: 9.4%), erythromycin (ERY: 0.5%), and tetracycline (33.3%). CIP resistance in C. jejuni was higher in 1999 (15.5%, odds ratio [OR] = 3.96, p = 0.01), 2000 (12.7%, OR = 3.10, p = 0.01), 2005 (10.2%, OR = 2.47, p = 0.05), and 2006 (13.0%, OR = 3.22, p = 0.01) compared with 2004 (4.4%). C. coli had significantly higher CIP resistance (15.5%, OR = 1.78, p = 0.03), ERY resistance (13.2%, OR = 60.12, p < 0.01), multidrug resistance (2.3%, OR = 36.29, p < 0.01), and CIP-ERY resistance (3.1%, OR = 50.23, p < 0.01) compared with C. jejuni. This represents the first and most current report of AMR of the collective human Campylobacter isolates from a province in Canada and provides a baseline against which current and future resistance patterns can be compared. Fluoroquinolone resistance in C. jejuni isolates fluctuated from 1999 to 2006, including an increased prevalence in 2005-2006, while macrolide/lincosamide resistance remained very low. Human clinical C. jejuni isolates from Saskatchewan demonstrated resistance to multiple antimicrobials but had significantly less fluoroquinolone and macrolide resistance than C. coli isolates.

Antimicrobial Use on 36 Beef Feedlots in Western Canada: 2008-2012.

The accurate quantification of antimicrobial use (AMU) in production animals is critical for monitoring trends in exposure to antimicrobial drugs (AMD) over time and examining potential associations with antimicrobial resistance in bacteria. In this study, a census sample of cattle was used to quantify individually-dosed and in-feed AMU as both numbers of animal daily doses (nADD) and total grams of AMD (gAMD) used in cattle placed in 36 western Canadian feedlots between 1-November, 2008 and 31-October, 2012; representing about 21.5% of fed cattle in Canada during that time period. Of the ~2.6 million cattle placed during the 48-month period, 45% were calves, 63% were male, 62% arrived in the fall or winter, and 39% were assessed as high risk for developing bovine respiratory disease (BRD). The proportion of cattle categorized as high risk (HR) for developing BRD was consistent over the 4 years of placement cohorts. Both medically important AMU and ionophore use were summarized but presented separately. A decrease in AMU was observed over the study period, both as nADD and total gAMD, which was primarily driven by a decline in the in-feed administration of tetracyclines. Most in-feed AMU was directed toward prevention and control of liver abscesses. The majority of individually dosed AMU was administered as metaphylaxis to address BRD risks, with category III AMD (medium importance to human medicine as categorized by Health Canada Veterinary Drugs Directorate) used most frequently. Not surprisingly, risk level for developing BRD influenced parenteral AMD exposures, with 95% of cattle categorized as being HR for developing BRD receiving individually dosed AMD compared to 59% of cattle categorized as being low risk (LR) for developing BRD. Cattle categorized as HR for developing BRD were more likely to receive macrolides for BRD metaphylaxis compared to cattle categorized as LR for developing BRD, and cattle categorized as LR for developing BRD were more likely to receive tetracycline for the same purpose. In summary, these data provide an unprecedented representation of AMU in fed cattle in western Canada and direction for future monitoring of AMU in fed cattle.

Calculation of Antimicrobial Use Indicators in Beef Feedlots-Effects of Choice of Metric and Standardized Values.

The potential for antimicrobial use (AMU) to lead to the development of antimicrobial resistant bacteria is an increasingly important priority in human and veterinary medicine. Accurate AMU quantification is essential to assessing the risk of antimicrobial resistance due to AMU. The quantification of AMU in production animals can be difficult, and feedlot beef cattle present a number of unique challenges. This paper presents selected parenteral data from western Canadian beef feedlots to illustrate variations in interpretation of AMU that can arise from the use of different metrics and standards. Specific examples presented compare the number of animal daily doses calculated from a given amount of antimicrobial drug (AMD) using actual and estimated weights of cattle at exposure, dose-based to weight-based indicators representing the same amount of antimicrobial, dose-based AMU indicators using different estimated durations of effect (DOE), and AMU indicators calculated using different standard weights of cattle at exposure. Changing these factors when calculating AMU indicators can have notable influences on the results obtained. Transparency about the methods used to calculate AMU indicators is critical to ensure that comparisons of use among different populations is meaningful and accurate.