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.

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.

Prevalence, Risk Factors, and Antimicrobial Resistance Profile of Respiratory Pathogens Isolated From Suckling Beef Calves to Reprocessing at the Feedlot: A Longitudinal Study.

Here, we investigated the prevalence and risk factors for the presence of Histophilus somni, Mannheimia haemolytica, Mycoplasma bovis, and Pasteurella multocida in the respiratory tract of calves from the spring processing to the reprocessing at feedlots. Additionally, we characterized, phenotypically and genotypically, the antimicrobial resistance (AMR) profile of the four species. Calves from 22 cow-calf operations were enrolled in the study (n = 30 calves per operation) and sampled by deep nasopharyngeal swabs at three time points: spring processing, weaning, or induction into feedlots, and at reprocessing at the feedlot. Isolates were tested for susceptibility using the minimum inhibitory concentration (MIC) test against commonly administered antimicrobials. Additionally, a subset of isolates underwent whole-genome sequencing to infer presence of AMR genes and resistance determinants. Among studied pathogens, P. multocida was the most prevalent species, regardless of time point, followed by M. haemolytica, M. bovis, and H. somni. For M. bovis, a sharp increase in prevalence was detected at the reprocessing sampling, whereas for P. multocida, an increase in prevalence was observed at the weaning/induction sampling. Comingling and co-location of feedlots were not associated with prevalence of any respiratory pathogen. In terms of AMR, resistance against macrolides was prevalent in M. bovis, with most isolates resistant against tildipirosin, tilmicosin, and tylosin. In general, there was limited evidence to support an increase in resistance rates of respiratory bacteria from the spring processing to reprocessing at feedlots, with the exception of florfenicol resistance in M. bovis, which increased at reprocessing. Metaphylactic administration of tetracyclines at feedlot induction was not associated with the MIC of tetracyclines in any respiratory bacteria. Conversely, there were clear associations between the parenteral use of macrolides as metaphylaxis at the feedlot induction, and increased MIC against macrolides in P. multocida, M. haemolytica, and H. somni. Overall, the AMR phenotypes were corroborated by presence of AMR genes. We hypothesize that the administration of macrolides such as tulathromycin at feedlot induction contributes to historical changes in macrolides MIC data of respiratory bacteria of beef cattle.

Multidrug Resistance in Pasteurellaceae Associated With Bovine Respiratory Disease Mortalities in North America From 2011 to 2016.

Multidrug-resistant (MDR; resistance to ≥3 antimicrobial classes) members of the Pasteurellaceae family may compromise the efficacy of therapies used to prevent and treat bovine respiratory disease (BRD) in feedlot cattle. This study examined the prevalence of multidrug resistance in strains of Mannheimia haemolytica and Pasteurella multocida collected from BRD cattle mortalities in North America. Isolates of M. haemolytica (n = 147) and P. multocida (n = 70) spanning 69 Alberta feedlots from 2011 to 2016 and two United States feedlots from 2011 to 2012 were examined for antimicrobial resistance (AMR) in association with integrative and conjugative elements (ICEs). Overall, resistance was high in both bacterial species with an increase in the prevalence of MDR isolates between 2011 and 2016. Resistance to >7 antimicrobial drugs occurred in 31% of M. haemolytica and 83% of P. multocida isolates. Resistance to sulfadimethoxine, trimethoprim/sulfamethoxazole, neomycin, clindamycin oxytetracycline, spectinomycin, tylosin, tilmicosin, and tulathromycin was most common. Although >80% of strains harbored three or more ICE-associated genes, only 12% of M. haemolytica and 77% of P. multocida contained all six, reflecting the diversity of ICEs. There was evidence of clonal spread as P. multocida and M. haemolytica isolates with the same pulsed-field gel electrophoresis profile from the United States in 2011 were isolated in Alberta in 2015-2016. This work highlights that MDR strains of Pasteurellaceae containing ICEs are widespread and may be contributing to BRD therapy failure in feedlot cattle. Given the antimicrobial resistance gene profiles identified, these MDR isolates may be selected for by the use of macrolides, tetracyclines, and/or in-feed supplements containing heavy metals.

Corrigendum: Multidrug Resistance in Pasteurellaceae Associated With Bovine Respiratory Disease Mortalities in North America From 2011 to 2016.

[This corrects the article DOI: 10.3389/fmicb.2020.606438.].

Antimicrobial Susceptibility of Bacteria That Cause Bovine Respiratory Disease Complex in Alberta, Canada.

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.

Genetics of alcohol consumption in Drosophila melanogaster.

Individual variation in alcohol consumption in human populations is determined by genetic, environmental, social and cultural factors. In contrast to humans, genetic contributions to complex behavioral phenotypes can be readily dissected in Drosophila, where both the genetic background and environment can be controlled and behaviors quantified through simple high-throughput assays. Here, we measured voluntary consumption of ethanol in ∼3000 individuals of each sex from an advanced intercross population derived from 37 lines of the Drosophila melanogaster Genetic Reference Panel. Extreme quantitative trait loci mapping identified 385 differentially segregating allelic variants located in or near 291 genes at P < 10-8 . The effects of single nucleotide polymorphisms associated with voluntary ethanol consumption are sex-specific, as found for other alcohol-related phenotypes. To assess causality, we used RNA interference knockdown or P{MiET1} mutants and their corresponding controls and functionally validated 86% of candidate genes in at least one sex. We constructed a genetic network comprised of 23 genes along with a separate trio and a pair of connected genes. Gene ontology analyses showed enrichment of developmental genes, including development of the nervous system. Furthermore, a network of human orthologs showed enrichment for signal transduction processes, protein metabolism and developmental processes, including nervous system development. Our results show that the genetic architecture that underlies variation in voluntary ethanol consumption is sexually dimorphic and partially overlaps with genetic factors that control variation in feeding behavior and alcohol sensitivity. This integrative genetic architecture is rooted in evolutionarily conserved features that can be extrapolated to human genetic interaction networks.

Information needs, sources, and decision-making by hatching egg and broiler chicken producers: A qualitative study in Alberta, Canada.

Understanding the sources and use of information from hatching egg and broiler chicken producers, their constraints, and unmet information needs can help define future research agendas. This report presents the results from a qualitative study using interviews of 11 hatching egg producers and 12 broiler producers in Alberta, Canada. Patterns were reported and described using thematic analysis. Producers recognized that there were numerous sources of information available to them for managing disease in their flocks. Complex disease issues such as early mortality were discussed, but many producers did not believe they had any influence over the outcomes and did not see a benefit from additional information to improve outcomes. Producers described their experience, trust in the information source, and the usefulness of the information for decision-making as necessary for information uptake.

Besoins et sources d'information et prise de décisions par les producteurs d'œufs d'incubation et de poulets à griller : une étude qualitative en Alberta, au Canada. La compréhension des sources et de l'utilisation de l'information par les producteurs d'œufs d'incubation et de poulets à griller ainsi que des contraintes et des besoins d'information non comblés pourrait aider à définir les programmes de recherche futurs. Ce document présente les résultats provenant d'une étude qualitative se basant sur des entrevues réalisées auprès de 11 producteurs d'œufs d'incubation et de 12 producteurs de poulets à griller en Alberta, au Canada. Nous avons utilisé une analyse thématique pour signaler et décrire les tendances. Les producteurs ont reconnu qu'il y avait plusieurs sources d'information qui étaient mises à leur disposition pour la gestion des maladies dans leurs troupeaux. Des problèmes de maladie complexes, comme une mortalité précoce, ont été discutés, mais beaucoup de producteurs ne croyaient pas qu'ils exerçaient une influence sur les résultats et ils n'envisageaient pas d'avantages provenant de renseignements additionnels afin d'améliorer les résultats. Ils ont décrit que l'expérience, la confiance envers la source d'information et l'utilité de l'information pour la prise de décisions étaient nécessaires pour l'assimilation de renseignements.(Traduit par Isabelle Vallières).

Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior.

The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild-derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]-element insertion mutants in Sema-5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their coisogenic wild-type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, showing extensive nonadditive genetic variation. We performed genome-wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the nonadditive genetic variance. Candidate genes could be placed in interaction networks. Several candidate modifiers are associated with neural development. Analyses of mutants of candidate epistatic partners with neur (merry-go-round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema-5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared with coisogenic controls. Thus, integrating genome-wide analyses of natural variants with mutations at defined genomic locations in a common coisogenic background can unmask specific epistatic modifiers of behavioral phenotypes.

Spatial-temporal clustering of companion animal enteric syndrome: detection and investigation through the use of electronic medical records from participating private practices.

There is interest in the potential of companion animal surveillance to provide data to improve pet health and to provide early warning of environmental hazards to people. We implemented a companion animal surveillance system in Calgary, Alberta and the surrounding communities. Informatics technologies automatically extracted electronic medical records from participating veterinary practices and identified cases of enteric syndrome in the warehoused records. The data were analysed using time-series analyses and a retrospective space-time permutation scan statistic. We identified a seasonal pattern of reports of occurrences of enteric syndromes in companion animals and four statistically significant clusters of enteric syndrome cases. The cases within each cluster were examined and information about the animals involved (species, age, sex), their vaccination history, possible exposure or risk behaviour history, information about disease severity, and the aetiological diagnosis was collected. We then assessed whether the cases within the cluster were unusual and if they represented an animal or public health threat. There was often insufficient information recorded in the medical record to characterize the clusters by aetiology or exposures. Space-time analysis of companion animal enteric syndrome cases found evidence of clustering. Collection of more epidemiologically relevant data would enhance the utility of practice-based companion animal surveillance.

Using informatics and the electronic medical record to describe antimicrobial use in the clinical management of diarrhea cases at 12 companion animal practices.

Antimicrobial drugs may be used to treat diarrheal illness in companion animals. It is important to monitor antimicrobial use to better understand trends and patterns in antimicrobial resistance. There is no monitoring of antimicrobial use in companion animals in Canada. To explore how the use of electronic medical records could contribute to the ongoing, systematic collection of antimicrobial use data in companion animals, anonymized electronic medical records were extracted from 12 participating companion animal practices and warehoused at the University of Calgary. We used the pre-diagnostic, clinical features of diarrhea as the case definition in this study. Using text-mining technologies, cases of diarrhea were described by each of the following variables: diagnostic laboratory tests performed, the etiological diagnosis and antimicrobial therapies. The ability of the text miner to accurately describe the cases for each of the variables was evaluated. It could not reliably classify cases in terms of diagnostic tests or etiological diagnosis; a manual review of a random sample of 500 diarrhea cases determined that 88/500 (17.6%) of the target cases underwent diagnostic testing of which 36/88 (40.9%) had an etiological diagnosis. Text mining, compared to a human reviewer, could accurately identify cases that had been treated with antimicrobials with high sensitivity (92%, 95% confidence interval, 88.1%-95.4%) and specificity (85%, 95% confidence interval, 80.2%-89.1%). Overall, 7400/15,928 (46.5%) of pets presenting with diarrhea were treated with antimicrobials. Some temporal trends and patterns of the antimicrobial use are described. The results from this study suggest that informatics and the electronic medical records could be useful for monitoring trends in antimicrobial use.

Blindness and cataract surgical services in Atsinanana region, Madagascar.

PURPOSE: To assess the prevalence and causes of avoidable blindness in Atsinanana Region, Madagascar, with the Rapid Assessment of Avoidable Blindness (RAAB) survey. We analyzed the hospital records to supplement the findings for public health care planning. MATERIALS AND METHODS: Only villages within a two-hour walk from a road, about half of the population of Atsinanana was included. Seventy-two villages were selected by population-proportional-to-size sampling. In each village, compact segment sampling was used to select 50 people over age 50 for eye examination using standard RAAB methods. Records at the two hospitals providing cataract surgery in the region were analyzed for information on patients who underwent cataract surgery in 2010. Cataract incidence rate and target cataract surgery rate (CSR) was modeled from age-specific prevalence of cataract. RESULTS: The participation rate was 87% and the sample prevalence of blindness was 1.96%. Cataract was responsible for 64% and 85.7% of blindness and severe visual impairment, respectively. Visual impairment was due to cataract (69.4%) and refractive error (14.1%). There was a strong positive correlation between cataract surgical rate by district and the proportion of people living within 2 hours of a road. There were marked differences in the profiles of the cataract patients at the two facilities. The estimated incidence of cataract at the 6/18 level was 2.4 eyes per 100 people over age 50 per year. CONCLUSIONS: Although the survey included only people with reasonable access, the main cause of visual impairment was still cataract. The incidence of cataract is such that it ought to be possible to eliminate it as a cause of visual impairment, but changes in service delivery at hospitals and strategies to improve access will be necessary for this change.

Mining free-text medical records for companion animal enteric syndrome surveillance.

Large amounts of animal health care data are present in veterinary electronic medical records (EMR) and they present an opportunity for companion animal disease surveillance. Veterinary patient records are largely in free-text without clinical coding or fixed vocabulary. Text-mining, a computer and information technology application, is needed to identify cases of interest and to add structure to the otherwise unstructured data. In this study EMR's were extracted from veterinary management programs of 12 participating veterinary practices and stored in a data warehouse. Using commercially available text-mining software (WordStat™), we developed a categorization dictionary that could be used to automatically classify and extract enteric syndrome cases from the warehoused electronic medical records. The diagnostic accuracy of the text-miner for retrieving cases of enteric syndrome was measured against human reviewers who independently categorized a random sample of 2500 cases as enteric syndrome positive or negative. Compared to the reviewers, the text-miner retrieved cases with enteric signs with a sensitivity of 87.6% (95%CI, 80.4-92.9%) and a specificity of 99.3% (95%CI, 98.9-99.6%). Automatic and accurate detection of enteric syndrome cases provides an opportunity for community surveillance of enteric pathogens in companion animals.

The application of medical informatics to the veterinary management programs at companion animal practices in Alberta, Canada: a case study.

Companion animals closely share their domestic environment with people and have the potential to, act as sources of zoonotic diseases. They also have the potential to be sentinels of infectious and noninfectious, diseases. With the exception of rabies, there has been minimal ongoing surveillance of, companion animals in Canada. We developed customized data extraction software, the University of, Calgary Data Extraction Program (UCDEP), to automatically extract and warehouse the electronic, medical records (EMR) from participating private veterinary practices to make them available for, disease surveillance and knowledge creation for evidence-based practice. It was not possible to build, generic data extraction software; the UCDEP required customization to meet the specific software, capabilities of the veterinary practices. The UCDEP, tailored to the participating veterinary practices', management software, was capable of extracting data from the EMR with greater than 99%, completeness and accuracy. The experiences of the people developing and using the UCDEP and the, quality of the extracted data were evaluated. The electronic medical record data stored in the data, warehouse may be a valuable resource for surveillance and evidence-based medical research.

Strategies for collaboration in the interdisciplinary field of emerging zoonotic diseases.

The integration of the veterinary, medical and environmental sciences necessary to predict, prevent or respond to emerging zoonotic diseases requires effective collaboration and exchange of knowledge across these disciplines. There has been no research into how to connect and integrate these professions in the pursuit of a common task. We conducted a literature search looking at the experiences and wisdom resulting from collaborations built in health partnerships, health research knowledge transfer and exchange, business knowledge management and systems design engineering to identify key attributes of successful interdisciplinary (ID) collaboration. This was followed by a workshop with 16 experts experienced in ID collaboration including physicians, veterinarians and biologists from private practice, academia and government agencies. The workshop participants shared their perspectives on the facilitators and barriers to ID collaboration. Our results found that the elements that can support or impede ID collaboration can be categorized as follows: the characteristics of the people, the degree to which the task is a shared goal, the policies, practices and resources of the workplace, how information technology is used and the evaluation of the results. Above all, personal relationships built on trust and respect are needed to best assemble the disciplinary strength of the professions. The challenge of meeting collaborators outside the boundaries of one's discipline or jurisdiction may be met by an independent third party, an ID knowledge broker. The broker would know where the knowledge could be found, would facilitate introductions and would help to build effective ID teams.

The effects of arachidonic acid on the endocrine and osmoregulatory response of tilapia (Oreochromis mossambicus) acclimated to seawater and subjected to confinement stress.

In previous studies in freshwater tilapia (Oreochromis mossambicus), dietary supplementation with arachidonic acid (ArA; 20:4n - 6) had considerable, opposing effects on the main ion-transporting enzyme Na(+)/K(+)-ATPase in gills and kidneys and changed the release of osmoregulatory hormones, such as cortisol. The present study was performed to assess the influence of dietary ArA on (1) the osmoregulatory capacity of tilapia acclimated to seawater (SW) (34‰) and (2) the osmoregulatory imbalance associated with acute stress. The increased ambient salinity was associated with significant alterations in the tissue fatty acid composition, particularly the n - 6 polyunsaturated fatty acids (PUFAs). Tissue levels of ArA were further increased as a result of dietary supplementation, whereas docosahexaenoic acid (DHA, 22:6n - 3) and eicosapentaenoic acid (EPA, 20:5n - 3) decreased in gills and kidneys. Basal plasma cortisol as well as lactate levels were elevated in the ArA-supplemented SW-acclimated tilapia compared with the control group. The 5 min of confinement (transient stress) increased plasma cortisol, glucose, and lactate levels with significantly higher levels in ArA-supplemented tilapia. Confinement was also associated with significantly elevated plasma osmolality, sodium, chloride, and potassium levels. ArA-supplemented tilapia showed markedly lower ionic disturbances after confinement, suggesting that dietary ArA can attenuate the hydromineral imbalance associated with acute stress. These results emphasize the involvement of ArA and/or its metabolites in the endocrine and osmoregulatory processes and the response to confinement stress.

Functional dissection of Odorant binding protein genes in Drosophila melanogaster.

Most organisms rely on olfaction for survival and reproduction. The olfactory system of Drosophila melanogaster is one of the best characterized chemosensory systems and serves as a prototype for understanding insect olfaction. Olfaction in Drosophila is mediated by multigene families of odorant receptors and odorant binding proteins (OBPs). Although molecular response profiles of odorant receptors have been well documented, the contributions of OBPs to olfactory behavior remain largely unknown. Here, we used RNAi-mediated suppression of Obp gene expression and measurements of behavioral responses to 16 ecologically relevant odorants to systematically dissect the functions of 17 OBPs. We quantified the effectiveness of RNAi-mediated suppression by quantitative real-time polymerase chain reaction and used a proteomic liquid chromatography and tandem mass spectrometry procedure to show target-specific suppression of OBPs expressed in the antennae. Flies in which expression of a specific OBP is suppressed often show altered behavioral responses to more than one, but not all, odorants, in a sex-dependent manner. Similarly, responses to a specific odorant are frequently affected by suppression of expression of multiple, but not all, OBPs. These results show that OBPs are essential for mediating olfactory behavioral responses and suggest that OBP-dependent odorant recognition is combinatorial.