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 approximately 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. Use of medically important AMU and ionophore use was also summarized but was not combined with medically important AMU. 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 AMDs (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 AMDs 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.

Bovine respiratory disease (BRD) is the most important illness of feedlot cattle. Disease management targets the associated bacterial pathogens, Mannheimia haemolytica, Mycoplasma bovis, Pasteurella multocida, Histophilus somni, and Trueperella pyogenes. We conducted a cross-sectional study to measure the frequencies of antimicrobial-resistant BRD pathogens using a collaborative network of veterinarians, industry, government, and a diagnostic laboratory. Seven private veterinary practices in southern Alberta collected samples from both living and dead BRD-affected animals at commercial feedlots. Susceptibility testing of 745 isolates showed that 100% of the M. haemolytica, M. bovis, P. multocida, and T. pyogenes isolates and 66.7% of the H. somni isolates were resistant to at least one antimicrobial class. Resistance to macrolide antimicrobials (90.2% of all isolates) was notable for their importance to beef production and human medicine. Multidrug resistance (MDR) was high in all target pathogens with 47.2% of the isolates resistant to four or five antimicrobial classes and 24.0% resistance to six to nine classes. We compared the MDR profiles of isolates from two feedlots serviced by different veterinary practices. Differences in the average number of resistant classes were found for M. haemolytica (p < 0.001) and P. multocida (p = 0.002). Compared to previous studies, this study suggests an increasing trend of resistance in BRD pathogens against the antimicrobials used to manage the disease in Alberta. For the veterinary clinician, the results emphasize the importance of ongoing susceptibility testing of BRD pathogens to inform treatment protocols. Surveillance studies that collect additional epidemiological information and manage sampling bias will be necessary to develop strategies to limit the spread of resistance.

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.

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.

We previously demonstrated the existence of naturalized strains of E. coli in wastewater and herein perform an in-depth comparative whole genome analysis of these strains (n = 17). Fourteen of the Canadian E. coli strains, isolated from geographically separated wastewater treatment plants, were virtually identical at the core genome and were ≥96% similar at the whole genome level, suggesting clonal-relatedness among these isolates. Remarkably, these strains were shown to be extremely similar to the genome of an E. coli isolated from wastewater in Switzerland, suggesting a global distribution of these strains. The genomes of three other Canadian wastewater strains were more diverse but very similar to the genomes of E. coli isolates collected from U.S. wastewater samples. Based on maximum likelihood phylogenetic analysis, wastewater strains from Canada, the U.S. and Switzerland formed a clade separate from other known enteric phylogroups (i.e., A, B1, B2, D, E) and the cryptic clades. All Canadian, Swiss and U.S. wastewater strains possessed a common SNP biomarker pattern across their genomes, and a sub-population (i.e., 14 Canadian and 1 Swiss strain) also possessed a previously identified wastewater-specific marker known as uspC-IS30-flhDC element. Biochemical heat mapping of 518 categories of genes recapitulated phylogeny, with wastewater strains phenotypically clustering separately from enteric and cryptic clades. Wastewater strains were enriched for stress-response genes (i.e., nutrient acquisition/deprivation, DNA repair, oxidative stress, and UV resistance) - elements reflective of their environmental survival challenges. Wastewater strains were shown to carry a plethora of known antibiotic resistance (AR) genes, the patterns of which were remarkably similar among all Canadian, U.S. and Swiss wastewater strains. Virulence gene composition was also similar among all the wastewater strains, with an abundant representation of virulence genes commonly associated with urinary pathogenic E. coli (UPEC) as well as enterohemorrhagic (EHEC) E. coli. The remarkable degree of similarity between all wastewater strains from Canada, Switzerland and the U.S. suggests the evolution and global-dissemination of water treatment-resistant clone of E. coli. These finding, along with others, raise some important concerns about the potential for emergence of E. coli pathotypes resistant to water-treatment.

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 byMoraxella bovoculi, Mannheimia haemolytica, Mycoplasma dispar,andPasteurella 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 thetetHgene 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.