Source: TEXAS A&M UNIVERSITY submitted to
MAXIMIZING VOLUNTARY COMPLIANCE IN ANTIMICROBIAL STEWARDSHIP PROGRAMS: A CRITICAL FACTOR FOR EFFECTIVE INTERVENTION
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1008081
Grant No.
2016-68003-24607
Project No.
TEX09632
Proposal No.
2015-07840
Multistate No.
(N/A)
Program Code
A4171
Project Start Date
Jan 15, 2016
Project End Date
Jan 14, 2023
Grant Year
2016
Project Director
Scott, H. M.
Recipient Organization
TEXAS A&M UNIVERSITY
750 AGRONOMY RD STE 2701
COLLEGE STATION,TX 77843-0001
Performing Department
Vet Pathobiology
Non Technical Summary
Antimicrobial drug resistance (AMR) has reached a critical level of importance; if unchecked, it will reverse decades of advances in human and animal health. The Centers for Disease Control and Prevention (CDC) estimates that AMR bacteria kill approximately 23,000 people in the U.S. each year and 2 million are clinically infected. As a result, AMR costs the U.S. economy approximately $70 billion annually. In addition to clear threats to public health, AMR poses immediate challenges to the security of our agricultural economy because AMR can also decrease the effectiveness and diminish the availability of antimicrobials useful against bacteria that cause significant food-animal disease. Vibrant and effective public and animal-health systems depend on approaches to prevent and cure infectious diseases. Solutions to AMR are of paramount importance to the U.S.Worldwide, many have called for a wholesale reduction in the use of antimicrobials, citing evidence that there is either overuse or misuse of these products. In multiple jurisdictions, regulatory approaches to reduce 'overuse' or 'misuse' proceed either on the basis of defining what is not considered judicious use, point to scientific data supporting a prohibition order for a specified product (sometimes, a change in new drug approval processes, or else invoke the use of the precautionary principle to protect the efficacy of a product in the absence of firm scientific evidence.In the United States, several recent Food and Drug Administration (FDA) documents of note, whose major purpose is to ensure the prudent approval and use of antimicrobials in veterinary medicine and animal agriculture, have been published (e.g., Guidance for Industry (GFI) #152, #159, #209, and #213; to a major extent, these consist of non-binding recommendations). In 2003, GFI #152 established the risk assessment framework under which new animal drug approvals would proceed. This process included guidance to drug sponsors that qualitatively categorized antimicrobials as to criticality, but also established aspects of hazard, release, exposure, and consequence assessment that were previously less well defined for microbial hazards. A simplified framework for examining the risk of release of resistant bacteria and their determinants from agricultural facilities as part of a broader quantitative risk assessment framework presents a compelling opportunity to aim to achieve 'zero' release of resistant bacteria (or determinants) above baseline or background risk levels. Since animal production can only take ownership of what is under its control this seems the logical place to start a discussion of what constitutes antimicrobial stewardship, and how this can be promoted into the future.Our overall long term goal is to identify, evaluate, and implement practical, effective and widely adoptable interventions for managing antimicrobial resistance (AMR) among enteric bacteria; in this project, our focus is on developing - through a systems-based stakeholder-centered process - science-based voluntary stewardship programs suited to animal production. In pursuit of this overall goal we focus our efforts - herein on beef and dairy cattle production systems - and directly address the following supporting objectives in this proposal: 1) recruit key stakeholders to qualitatively explore the essential components and systems framework to maximize voluntary compliance with highly effective antimicrobial stewardship programs, 2) conduct empirical field studies to provide key microbiological, production, economic, and social science decision support data, 3) perform qualitative and quantitative modeling needed to design, test, and improve essential decision support tools, and 4) engage key stakeholders to further develop, refine and communicate highly effective decision support tools to enhance their voluntary adoption and diffusion and to maximize antimicrobial stewardship.Both AMR and the likelihood of unintended consequences of uninformed, broad-sweeping attempts to control it pose a direct threat to the sustainability of U.S. agriculture. In our integrated standard grant project, we will design, evaluate and deliver efficacious and implementable interventions to mitigate AMR, based on voluntary stewardship principles and guidelines, facilitated by science-based decision tools and multiple and broad stakeholder input and support.
Animal Health Component
75%
Research Effort Categories
Basic
0%
Applied
100%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7123499117030%
7123399117030%
7123499301010%
7123399301010%
7123499308010%
7123399308010%
Knowledge Area
712 - Protect Food from Contamination by Pathogenic Microorganisms, Parasites, and Naturally Occurring Toxins;

Subject Of Investigation
3499 - Dairy cattle, general/other; 3399 - Beef cattle, general/other;

Field Of Science
3010 - Economics; 3080 - Sociology; 1170 - Epidemiology;
Goals / Objectives
Our overall long term goal is to identify, evaluate, and implement practical, effective and widely adoptable interventions for managing antimicrobial resistance (AMR) among enteric bacteria. In this project, our focus is on developing - through a systems-based stakeholder-centered process - science-based voluntary stewardship programs suited to animal production. In pursuit of this overall goal we first focus our efforts - herein on beef and dairy cattle production systems - and directly address the following supporting objectives in this proposal: 1) recruit key stakeholders to qualitatively explore the essential components and systems framework to maximize voluntary compliance with highly effective antimicrobial stewardship programs, 2) conduct empirical field studies to provide key microbiological, production, economic, and social science decision support data, 3) perform qualitative and quantitative modeling needed to design, test, and improve essential decision support tools, and 4) engage key stakeholders to further develop, refine and communicate highly effective decision support tools to enhance their voluntary adoption and diffusion and to maximize antimicrobial stewardship.
Project Methods
Overall:In Objective 1, our proactive engagement of a wide range of stakeholders through facilitated workshops will help to comprehensively map the wicked problem of AMR, to adapt the concept of stewardship from clinical to production medicine settings, to explore the nature of shared and conflicting values and their boundaries, and to understand in advance the likely consequences of setting bounds on the practices of stewardship in animal agriculture. We expect this approach to provide a model of exploration that will migrate readily to other agricultural (e.g., swine, poultry) and non-agricultural settings (e.g., community health). Importantly, in situations where there exists evidence that labeled slaughter withholding period requirements appear insufficient to optimally protect public health, we aim to provide science-based decision tools to facilitate voluntary compliance with stewardship guidelines. These will be built upon real-world field data; especially using sound animal field studies (beef and dairy), microbiological and sociological methods (Objective 2), sophisticated mathematical, economic, sociological and systems models (Objective 3), and operating within a framework of stewardship developed from the shared common values of all stakeholders in the agri-food continuum. Finally, our summative workshop (Objective 4) will complete this process through a final consultation with stakeholders. By identifying and taking 'ownership' of the release component inherent in quantitative risk assessments, and to aspire to release from the farm among animals sent to slaughter no more resistance elements than occur at baseline levels, producers and their consulting veterinarians have a specific, measureable, and achievable, timely and realistic (SMART) set of objectives to aim to achieve. This will result in much more widespread adoption and diffusion of novel decision-tool technology and its underlying principles, aided by the highly consultative process under which the stewardship concept, its metrics, resulting decision tools, and definitions of success were formed.Efforts:For Objective 1: We will produce qualitatively and quantitatively data-rich maps (i.e., visual representations) of the relationships among the actors of the monetary, political, and moral economies of the dairy and fed-beef production-consumption system. We will begin with an inclusive approach and then focus on those key relationships needed to develop and implement stewardship programs against AMR in cattle production systems. Because our approach to establishing a metric of stewardship depends on the concept of release assessment, and 'release from farm at above baseline levels' in particular, we do not aim to achieve 'zero' resistance but rather to foster and encourage targets that reflect an ethic of 'do no harm' to the patient; in this case, the 'patient' is the microbial ecology of cattle enteric flora among cattle heading to slaughter.For Objective 2: We will generate new data directly supportive of tools that producers and their consulting veterinarians can use to make near-slaughter decisions including: 1) an extended voluntary withholding period (both dairy and beef), 2) use of a 'terminal pen' where antibiotics have never been used (beef only), and 3) use of direct-fed microbials containing enterococci (beef only). We will directly measure both microbiological and production endpoints during these trials and combine them with concurrent and historical economic data of major influence on dairy and beef producer decision making such as: 1) price of beef, 2) price of feed, 3) yardage, shrink, and mortality risk. In addition, internet-based surveys of a narrow and broad sector of members of the dairy farm and beef feeding industries in the high plains regions of Texas and New Mexico will be presented with a variety of current and future scenarios. These will include data from past and present studies concerning probability of animals going to slaughter with elevated levels of resistance and using the 'Theory of Planned Behavior' questions measuring attitudes, beliefs, constraints, moral and social norms and trust will be used to better understand behavior.For Objective 3: Existing models will be expanded to include the following elements specific to the study of AR among commensal enteric bacteria. We will include two phenotypes of bacteria: Resistant and Sensitive, both E. coli and Enterococcus. Our model will predict the dynamic changes of sensitive and resistant bacteria in each habitat, with an end-stage estimate of the total and relative burden of antibiotic-resistant bacteria present in the feces of an animal at slaughter. The key difference here versus what we have done in the past is that we predict with probabilistic estimates of confidence whether or not a cow or steer has returned to 'baseline' level of resistance as this is the target for 'no release' from the farm. Multiple interventions can be assessed in any one or more of the 'patches', concurrently or consecutively throughout the production period. This allows us to investigate the relative effectiveness of a number of interventions that might be targeted at any or all of the water, environment, and host (or, groups of hosts) habitats and to prepare a decision tool readily accessible to dairy and beef producers.For Objective 4: The extension/outreach component of this project will be to maximize adoption and diffusion of voluntary compliance with antimicrobial stewardship as facilitated by the science based decision tools for beef and dairy production settings. The initial products will aid in decisions regarding days post-treatment for culling of adult dairy cows and on the feasibility and cost/benefit of using: 1) terminal pens, 2) direct fed microbials containing enterococci, and 3) a voluntary slaughter withholding period of varying lengths for tylosin used to prevent liver abscesses in feeder cattle. Several activities will be used to accomplish these goals. As this activity is tightly integrated with Obj. 1, through stakeholder engagement, we will further refine the systemic intervention (in this case, voluntary stewardship practices informed by science based decision tools) that are informed by a) reflection of quantified relationships of the economic and political-moral economies, b) their perceived acceptance and implementation potential, and c) their efficacy.Evaluation:The Institute for Measurement, Methodology, Analysis, and Policy (IMMAP) at Texas Tech University will design the evaluation plan and will collaborate with the project team to develop a schedule of data collection, analysis, and reporting for summative evaluation of research as well as outreach/extension efforts. Overarching evaluation questions to be addressed in the summative evaluation will be refined in an ongoing basis with the project team/stakeholders and will likely include: 1) was the overall process, synergy between research and outreach components, and collaboration between partners and stakeholders effective, 2) did the project fill knowledge gaps regarding the concept of stewardship, development of effective and user-friendly decision tools as practical solutions to improve mitigation strategies for antimicrobial resistance, and 3) were extension/outreach adoption and diffusion efforts successful and was there a change in knowledge, attitude, and behavior by producers, veterinarians, policy makers, and/or other stakeholders?

Progress 01/15/16 to 01/14/23

Outputs
Target Audience:Targeted audiences during this reporting period included the scientific community through presentations, posters, and peer reviewed publications. These occurred at national (e.g., CRWAD) and international levels. COVID restrictions on in-person meetings began to wane during this period from January 2022 through 2023. One scientist was prevented from traveling during this period due to a CVID infection prior to travel dates. This hamperedthe face-to-face delivery of output from the project; however, the PDs participated in virtual (e.g., via Zoom) and other engagement with target audiences. The extension/outreach components also continued through Dr. Juan Pineiro (dairy extension specialist) in the Texas panhandle with on-farm visits, development of K-12 antimicrobial stewardship classroom materials, and a series of videos created to reduce the need for antibiotics for post-partum metritis. This also included demonstrations to farm staff utilizing models for dysotcia management with a clear focus on reducing the need for treatment of clinical metritis. Ongoing surveys involving the outreach to the beef and dairy sectors (producers and veterinarians) focus on the values, beliefs and norms concerning stewardship in treatment, control and prevention of bacterial infectious diseases warranting antibiotictherapy. Theproducts of this project have been developed forstudents and farm workers. A PhD student from Brazil (via Cornell) has worked on the outreach components in the final year of the project, focused on developing online materials for assessing the project outcomes. The other major groups targeted were: dairy farmers and veterinarians, beef feedlot operators and veterinarians, staff of government agencies engaged in regulating and providing oversight to agriculture and food safety including antimicrobial use, food product companies (meat and dairy), pharmaceutical companies, and consumer and public health advocacy groups. Changes/Problems:Our final engagement with stakeholders is ongoing (continuing past period of grant) via a Qualtrics survey platform rather than engaging in face-to-face meetings. We have received the support of the beef and dairy sectors for this approach to reaching their members and for understanding their motivations for improving stewardship. Our final report on earlier broader stakeholder engagement has been warmly received. it is under review for journal publication but has been made available in its entirety at the following location:Toward System Change to Tackle Antimicrobial Resistance: Improving the Voluntary Stewardship of Antimicrobials in US Agriculture (worktribe.com)We would be very pleased to see it published in its current form at any USDA-NIFA website/document repository should the sponsor be interested in doing so. What opportunities for training and professional development has the project provided? Southwest Dairy Days in Scotland, TX. October 2022. Over 400 people participated in this educational field day with tours to 3 dairy farms using milking robots and tunnel ventilated barns. At each stop academics delivered presentations on how heat abatement technologies and precision technologies allow for increased cow's health and performance, and earlier identification of cows getting sick, prompt diagnosis and early treatment. Delivered four dairy farm personnel training programs on best calving management practices and Beef Quality Assurance trainings that aim to reduce the incidence of postpartum diseases, and injection site lesions and antimicrobial residues, respectively. Best calving management practices training program for dairy farm personnel (in Spanish). Mobeetie, TX. August 2022. Dairy farm personnel BQA Training, collaboration with Dr. Hairgrove. Clovis, NM. April 2022. Dairy farm personnel BQA Training, collaboration with Dr. Hairgrove. Hereford, TX. April 2022. Dairy farm personnel training, collaboration with Dr. Schuenemann. Friona, TX. April 2022. Transition Cow Management Program. Collaboration with Dr. Schuenemann from The Ohio State University. Delivered international certificate program focused on disease prevention of periparturient dairy cows to 50 dairy farm managers and consultants from Argentina, Costa Rica, Mexico and U.S. Four Points by Sheraton, Amarillo, Texas. August 2022. Field consultation and investigation at a dairy farm on the effect of a preventative strategy supplementing one or two calcium boluses at calving to decrease the incidence of metabolic (hypocalcemia) and infectious diseases. Muleshoe, Texas. USDETC 2022. Delivered presentations and hands-on practices to 32 students at dairy farms and labs regarding strategies to prevent diseases periparturient dairy cows. How have the results been disseminated to communities of interest?Extension personnel were engaged with beef and dairy industry partners in working towards practical stewardshipapproaches that are implementable on large-scale dairy farms. Dr. Juan Pineiro (dairy extension specialist) has created a multitude of YouTube videos available on the extension website (see other products) aimed at reducing the need for antibiotics in metritis therapy through prevention. Other reports have been generated and engagement with stakeholders in beef and dairy sectors continue past the grant deadline in exploring motivations to engage and improve in stewardship. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? During this period the final report was completed regarding stakeholder engagement in defining stewardship in beef and dairy cattle operations. Outreach and extension activities comprised most of the efforts in the final no-cost extension year of the project. Empirical field studies and other work were performed during earlier reporting periods. The final report has been published at the University of Hull repository (see products) and is currently under consideration for publication in an operations research journal and another venue. Ongoing efforts will continue after the grant has expired to better understand the values, beliefs and norms that help guide decision-making in beef and dairy cattle production. this is being performed via a Qualtrics online survey with the cooperation of southwest beef and dairy organizations and consulting veterinarians

Publications

  • Type: Other Status: Published Year Published: 2023 Citation: Midgley, G., Elkins, A., Loneragan, G.H., Babowicz, M., Dass, M., Grohn, Y.T., Jordan, E., Lhermie, G., Lunt, L., McIntosh, W.A., Pi�eiro, J.M., Sawyer, J., Scott, H.M. (2023) Toward System Change to Tackle Antimicrobial Resistance: Improving the Voluntary Stewardship of Antimicrobials in US Agriculture. University of Hull (UK) Repository https://hull-repository.worktribe.com/output/4276641
  • Type: Book Chapters Status: Accepted Year Published: 2022 Citation: 1. Pi�eiro, J.M. 2023. Antimicrobial Stewardship. Veterinary Science Preparatory Training for the Veterinary Assistant. Texas A&M AgriLife Extension Service, Texas A&M University System.


Progress 01/15/21 to 01/14/22

Outputs
Target Audience:Targeted audiences during this reporting period included the scientific community through presentations, posters, and peer-reviewed publications. These occurred at national (e.g., CRWAD) and international levels. COVID restrictions on in-person meetings greatly resstricted the face-to-face delivery of output from the project; however, the PDs participated in virtual (e.g., via Zoom) and other engagement with target audiences. The extension/outreach components also continued through Dr. Juan Pineiro (dairy extension specialist) in the Texas pandhandle with on-farm visits, development of K-12 antimicrobial stewardship classroom materials, and a series of videos created to reduce the need for antibiotics for post-partum metritis. These products are directed for additional non-scientific audiences, including students and farm workers. In adition to students and farm workers and manahers, the other major groups taregeted were: dairy farmers andveterinarians, beef feedlot operators and veterinarians, staff of government agencies engaged in regulating and providingoversight to agriculture and food safety including antimicrobial use, food productcompanies (meat and dairy), pharmaceutical companies, and consumer and public health advocacy groups. Changes/Problems:There have been no major changes to the approaches. However, if as ofApril 30, 2022it appears unlikely to be able to host in-person stewardship workshops with the four major stakeholder groups in fall of 2022 (due to projected/remaining COVID restrictions), we will rework our IRB approval submission to instead coordinate these online via Zoom while protecting the anonymity of respondents during the workshops and during audiotranscription. What opportunities for training and professional development has the project provided?Multiple PDs were involved with online conferences (national and international) directed towards veterinary professionals (e.g., International One Health Stewardship, CRWAD, Bangladesh, WHO Tricycle Project launch). Most of the in person opportunities booked for last year werecancelled; however, as of late 2021 several in-person options became available right before the surge in omicron cases slowed in-person engagement once again early in 2022. Direct engagement with producer groups (beef and dairy) continued on a smaller scale via extension services. How have the results been disseminated to communities of interest?Extension personnel were engaged with beef and dairy industry partners in working towards practical stewardship approaches that are implementable on large-scale dairy farms. Dr. Juan Pineiro (dairy extension specialist) has presented results of the dairy field study (see Taylor et al., PLoS One 2021) on best management and preventive medicine practices to reduce the use of antimicrobials. Data concerning macrolide effects and mitigation via in-feed probiotics have been published and share with interested communities (Murray et al, 2022). Results of additional analyses on dairy cattle fecal samples in response to two-dose treatment with ceftiofur crystalline-free acid have been presented to the scientific community. What do you plan to do during the next reporting period to accomplish the goals?The remaining tasks will be to: 1) complete the two sets (dairy farm workers and managers as audience; K-12 agricultural education on stewardship) extension materials for online distribution via the Texas A&M AgriLife Extension website, 2) complete analysis of the online survey data developed and modified from Stern (2000) VBM theoretical model with extensions to Ajzen's (1991) Theory of Planned Behavior(Qualtrics platform) and publish these results, 3) integrate these findings with the field trial and modeling/economics data to develop a series of stewardship scenarios for engagement with stakeholder groups, and 4) host these stakeholder meetings either in person (Amarillo, TX and Washington, DC) or else online (Zoom) with a modified IRB approval to close out this project by January 14, 2023.

Impacts
What was accomplished under these goals? We completed all of our objectives prior to this reporting period, except those that relate to analyzing the data from an online survey of four different stakeholder groups (briefly: dairy, beef, regulatory and consumer groups) and hosting a second and final face-to-face set of engagements with our four groups of stakeholders at the end of theproject. The events of the past two years (i.e., COVID-19) rendered itimpossible to complete all of our objectives by January 14, 2022leading to yet another a request to extend this in order to allow for thiscompletion. Are plan is to make a decision to go/not-go as of April 30, 2022 with an in-person set of workshops, or to revise our IRB approval to instead host these online via Zoom or similar.We have also begun some additional analyses of the samples taken from dairy cattle in deploying aditional metagenomic and qPCR approaches to quantifying resistance, both direct and co-selection. We have identified that co-selection of fluoroquinolone and macrolide resistance can occur among E. cioli harboring ESBL genes; however, this remains a qualitative observation and we see no evidence thus far of quantifiable impacts via qPCR. In summary, all of our field trial work is complete, our marketing and mathematical models and economic analyses arecomplete, as are the qualitative stakeholder engagements and the transcript analysis thereof. We have previously published multiplepeer-reviewed artciles, with 3-4 in the queue for the next year.

Publications

  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Taylor, E.A., Ossa-Trujillo, C., Vinasco, J., Jordan, E.R., Garc�a Buitrago, J.A., Hagevoort, R., Norman, K.N., Lawhon, S.D., Pi�eiro, J.M., Levent, G., Scott, H.M. (2021). Use of critically important antimicrobial classes early in life may adversely impact bacterial resistance profiles during adult years: potential co-selection for plasmid-borne fluoroquinolone and macrolide resistance via extended-spectrum beta-lactam use in dairy cattle. Letters in Applied Microbiology. 72(3):220-224. doi.org/ https://doi.org/10.1111/lam.13419
  • Type: Journal Articles Status: Published Year Published: 2022 Citation: Murray, S.A., Holbert, A.C., Norman, K.N., Lawhon, S.D., Sawyer, J.E., Scott, H.M. (2022) Effects of tylosin, a direct-fed microbial and feedlot pen environment on phenotypic resistance among enterococci isolated from beef cattle feces Antibiotics 2022, 11, 106. https:// doi.org/10.3390/antibiotics11010106
  • Type: Conference Papers and Presentations Status: Published Year Published: 2021 Citation: Ossa-Trujillo, C., Taylor, E., Pi�eiro, J., Lawhon, S., Norman, K., Hagevoort, R., Garcia Buitrago, J., Jordan, E., Sanwar, F., Scott, H.M. (2021) Effects of two-dose ceftiofur on quantities of third-generation cephalosporin, fluoroquinolone, and macrolide resistance genes in dairy cows. 102nd Conference of Research Workers in Animals Diseases, Chicago, IL, December 2021.


Progress 01/15/20 to 01/14/21

Outputs
Target Audience:Targeted audiences during this reporting period included the scientific community through presentations, posters, and peer- reviewed publications as well as via virtual presentations online. COVID-19 severely constrained the participation of investigators, staff and trainees in live and in-person engagement with stakeholders. Industry and regulatory stakeholders were engaged in multiple online forums and via presentations at national and international conferences and meetings aimed at veterinarians (practicing) and cattle producers. During the second and third quarter of 2020 almost all work-related activities were curtailed and so engagement was limited to publications. In the first and final quarters of 2020 and early 2021 prior to the annual renewal date there were newer engagements with national and international stakeholders.These occurred at national (e.g., FFAR, Pew Charitable Trusts) and international events (OIE on risk assessments, WHO Tricycle project). In addition, several PDs engaged in international efforts on the subject with foreign governments (e.g., Genome Canada). Changes/Problems:Because of the COVID-19 pandemic we were unable to conduct our final set of workshops and finalize our extension and outreach activities. The workshops were covered under an existing IRB that requires protections of participants' identities that could not readily be achieved in an online environment as currently approved. We sought a one-year NCE for additional time to allow the situation to resolve and permit in-person workshops and international travel for our overseas collaborator. If that cannot be achieved by summer 2021 (e.g., with vaccine) we will seek a new IRB approval for online workshops for late autumn 2021 and to develop approaches to allow anonymity in responses of participants. What opportunities for training and professional development has the project provided?Several PDs were involved with online conferences (national and international) directed towards veterinary proferssionals (e.g., International One Health Stewardship, CRWAD). Most of the in person opportunities booked for last year were cancelled and the uptick in online options took approximately 6 months to become fully operational. How have the results been disseminated to communities of interest?Extension personnel were engaged with beef and dairy industry partners in working towards practicalstewardship approaches that are implementable on large-scale dairy farms.Dr. Juan Pineiro (dairy extension specialist) has presented results of the dairy field study (see Taylor et al., PLoS One 2019) on best management and preventive medicine practices to reduce the use of antimicrobials. These include at the TAMU Department of Animal Science, Animal Science External Advisory Committee 2020 annual meeting, 2020 Mid-South Ruminant Nutrition Conference, 2020 U.S. Dairy Education & Training Consortium and at Texas Tech University (invited guest lecturer). What do you plan to do during the next reporting period to accomplish the goals?Because of the COVID-19 pandemic we have been unable to conduct our final set of workshops and our extension and outreach activities. The workshops are covered under anIRB approval that requires protections of participants' identities and that could not be achieved in an online environment as currently approved. We are aiming to fulfill this objectivbe in fall 2021 in order to permit in-person workshops and international travel for our overseas collaborator. Comnined with analysis of our online survey of stakeholders concerning stewardship in a values-beliefs-norms framework (Stern 2000) we will complete our objectives by January 15, 2022.

Impacts
What was accomplished under these goals? We have completed all of our objectives prior to this reporting period, except those that relate to administering an online survey and hosting a second and final face-to-face set of engagements with our four groups of stakeholders at the end of the project. These groups are: beef cattle producers and veterinarians, dairy cattle producers and veterinarians, public healthand consumer advocates, and regulator and industry oversight groups. The events of the past year (i.e., COVID-19) rendered it impossible to complete all of our objectives by January 14, 2021 leadingto a request to extend this in order to allow for this completion. In brief, all of our field trial work is complete, our marketing and mathematical models and economic analyses are complete, as are the qualitative stakeholder engagements and the transcript analysis thereof. We have many peer-reviewed publications, still other manuscripts are under review, and multiple others are in preparation for submission in the next several months. These analyses and their supporting reported data are crucial for linking together the approach to modeling the antimicrobial resistance endpoints expected through changes in stewardship. In our final set of stakeholderworkshops, extension personnel will engage stakeholders with our real-world resistance data in determining how stakeholders value treatment and culling decisions.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Ogunrinu, O.J.*, Norman, K.N., Vinasco, J., Levent, G., Lawhon, S.D., Fajt, V.R., Volkova, V.V., Gaire, T., Poole, T.L., Genovese, K.J., Wittum, T.E., Scott, H.M.** (2020). Can the use of older-generation beta-lactam antibiotics in livestock production over-select for beta-lactamases of greatest consequence for human medicine? An in vitro experimental model. PLoS One 15(11): e0242195. 10.1371/journal.pone.0242195
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Murray, S.A., Amachawadi, R.G., Norman, K.N., Lawhon, S.D., Nagaraja, T.G., Drouillard, J.S., Scott, H.M.** (2021) Effects of zinc and menthol-based diets on co-selection of antibiotic resistance among E. coli and Enterococcus spp. in beef cattle. Animals. 11, 259. 10.3390/ani11020259.
  • Type: Journal Articles Status: Published Year Published: 2021 Citation: Taylor, E.A.*, Ossa?Trujillo, C., Vinasco, J., Jordan, E.R., Garc�a Buitrago, J.A., Hagevoort, R., Norman, K.N., Lawhon, S.D., Pi�eiro, J.M., Levent, G., Scott, H.M.** (2021). Use of critically important antimicrobial classes early in life may adversely impact bacterial resistance profiles during adult years: potential co?selection for plasmid?borne fluoroquinolone and macrolide resistance via extended?spectrum beta?lactam use in dairy cattle. Letters in Applied Microbiology. 72(3):220-224. doi.org/ https://doi.org/10.1111/lam.13419.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Lhermie, G., Sauvage, P., Tauer, L. W., Chiu, L. V., Kanyiamattam, K., Ferchiou, A., Raboisson, D. Scott, H.M., Grohn, Y. T. (2020). Economic effects of policy options restricting antimicrobial use for high risk cattle placed in U.S. feedlots. PLoS One. 15(9), e0239135-e0239135.
  • Type: Theses/Dissertations Status: Published Year Published: 2020 Citation: Lunt, Lucas (2020) DRIVERS AND BARRIERS OF VOLUNTARY MARKETING STEWARDSHIP PROGRAM ADOPTION WITHIN A BUSINESS ECOSYSTEM (PhD Dissertation, Texas Tech University.
  • Type: Theses/Dissertations Status: Published Year Published: 2020 Citation: Murray, S.A. (2020) Effects of antibiotic alternatives on antimicrobial resistance among fecal bacteria in beef cattle (PhD Dissertation, Texas A&M University
  • Type: Theses/Dissertations Status: Published Year Published: 2019 Citation: Taylor, EA (2019) Critically important and of highest priority: the evolving story of cephalosporin use and antimicrobial resistance in U.S. dairy cattle (PhD Dissertation, Texas A&M University)


Progress 01/15/19 to 01/14/20

Outputs
Target Audience:Targeted audiences during this reporting period included the scientific community through presentations, posters, and peer-reviewed publications. These occurred at national (e.g., CRWAD, FFAR, Pew Charitable Trusts) and international events (OIE, WHO, FAO, AGISAR). In addition, several PDs engaged in international efforts on the subject with foreign governments (e.g., Canada, Uruguay, Colombia, The Netherlands). Six major categories of stakeholders were engaged through direct communications including facilitated discussions in 2019 concerning systems thinking, social psychology and marketing with industry partners concerning barriers to adoption of alternatives to antibiotics. The major groups were: dairy farmers and veterinarians, beef feedlot operators and veterinarians, staff of government agencies engaged in regulating and providing oversight to agriculture and food safety including antimicrobial use, food products companies (meat and dairy), pharmaceutical companies, and consumer and public health advocacy groups. Changes/Problems:Explorations of the qualitative data (transcripts) captured during stakeholder meetings with beef, dairy, public health/consumer advocates, and regulators have led to the development of a new marketing framework, systems thinking approaches and the development of an online quantitative survey. Plans to pretest these approaches through a second set of stakeholder workshops in person have been placed on hold due to the COVID-19 outbreak and the transition to virtual ZOOM meetings in ongoing efforts to reegage our original stakeholder groups in a diferent format. The remaining objectives that required earlier completion of field studies and modeling have been completed; thereafter, administering an online survey concerning alternative approaches to antimicrobial stewardship, populating the modeling dashboard with scenarios and data from the online survey and field studies, and finalizing our engagement with stakeholders in a series of closing Zoom-based virtual meetings. Our analysis of the stakeholder workshop transcripts and relating those insights to observed data from field studies (ours, and the published literature) have taken considerably more time than initially expected. To address slower-than-expected progress on the online survey development, we hired a DrPH level research associate in April 2018 to work towards completing these tasks. Since July 2019, one of our hires went on an extended leave until the end of this reporting period, which has slowed progress, especially of integrating the modeling. Our expected timelines for completing the remaining tasks are: online economic and social/systems science survey and analysis (August 2020), dashboard development (October 2020), and series of closing virtual Zoom stakeholder workshops (held through fall months of 2020). Final reporting to NIFA will occur in the last month of January 2021. What opportunities for training and professional development has the project provided?The project has conintued to provide unique opportunities for training undergraduate and graduate students, post-docs, as well as early stage research scientists. Since last report, four PhD students have transitioned to candidacy, one graduated and the remaining three are scheduled to defend in late spring of 2020. Post-doc and research scientists are developing their post-graduate skills and managing a variety of components of the project, including acting as the major organizer of stakeholder engagements and reconstructing the framework for stewardship in policy documents. There have been a number of synergistic developments including by the post-doc and PhD student at Cornell with students at Texas A&M University (see Cazer et al, 2020). Undergraduate students have participated in data analysis and completing of field and laboratory work. Many are excellent candidates for professional school (DVM) or graduate school. How have the results been disseminated to communities of interest?Dr. Juan Pineiro (dairy extension specialist) has presented results of the dairy field study (see Taylor et al., PLoS One 2019) on best management and preventive medicine practices to reduce the use of antimicrobials. These include at the TAMU Department of Animal Science, Animal Science External Advisory Committee annual meeting, 2019 Mid-South Ruminant Nutrition Conference, 2019 U.S. Dairy Education & Training Consortium and Texas Tech University (invited guest lecturer). Dr. H. Morgan Scott presented at the annual Dairy Cattle Welfare Symposium, Orlando, FL May 2019 on the results of Taylor et al, 2019. This is the largest gathering of veterinarians, dairy farmers, and herdsmen in the U.S. on the subject of dairy cattle welfare practices including the use of antibiotics. Dr. Scott has continued to engage on this topic with the stakeholder cattle feeding indusrty on this and other approaches using tylosin as well as approaches to using rapid diagnostics to imnprove stewardship of antimicrobials. What do you plan to do during the next reporting period to accomplish the goals?This will be the final year, which will bring the total number of years funded to five. The funds allocated to Texas A&M Agri-Life Research have been completely expended on the field trials, microbiology, and research support (Objectives 1 and 2). The two remaining objectievs to complete are 3) (integrated modeling) and 4) final stakeholder engagement on stweardship framework. The funds allocated to extension (Texas Agri-Life Extension) will be used for compelting and analyzing online surveys, implementing the dashboard approach to communicating with veterinarians, producers, and stakeholders, and also reserved for coordinating the closing stakeholder workshops via Zoom or in person if COVID-19 restrictions allow. The funds remaining for Cornell, Texas Tech and Hull universities are allocated to completing Objective 3 (modeling stewardship aspects of AMR, social/systems and economics) and participating in Objective 4.

Impacts
What was accomplished under these goals? We have made great progress towards completing most of our objectives. In brief, all of our field trial work is complete, as are the qualitative stakeholder engagements and the transcript analysis thereof. In addition to conference presentations and proceedings, along with extension presentations to key stakeholders, we have multiple peer-reviewed publications published, other manuscripts are under review, and still others are in preparation for submission in the next several months. These analyses and their supporting reported data are crucial for linking together the approach to modeling the antimicrobial resistance endpoints (both social, economics, and biological) expected through changes in stewardship. Implemented in a dashboard format, extension personnel can thus engage the stakeholders with real-world resistance data in making treatment and culling decisions for beef ad dairy cattle, along with those additional supporting social and systems science data that are being captured in an online survey. It was not possible to complete all of the tasks by the earlier projected end of the project (January 14, 2020). A final year no-cost extension was requested to complete Objectives 3 and implement Objective 4.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Lhermie, G., Verteramo, Chiu L., Kaniyamattam, K., Tauer, L.W., Scott, H.M., Gr�hn,Y.T.: Antimicrobial Policies in United States Beef Production: Choosing the Right Instruments to Reduce Antimicrobial Use and Resistance Under Structural and Market Constraints. Front Vet Sci. 2019; 6:245. doi: 10.3389/fvets.2019.00245.
  • Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Lunt, Lucas, Mayukh Dass, and Guy Loneragan, (2020) Antecedents and Barriers of Stewardship Program Adoption Within a Business Ecosystem, Under review - Journal of Marketing
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Lunt, Lucas, Mayukh Dass, Piyush Kumar, and Guy Loneragan, Voluntary Stewardship of Service Interventions. Frontiers in Services Conference, July 20, 2019, Singapore
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Taylor, E.A., Jordan, E.R., Garcia, J.A., Hagevoort, G.A., Norman, K.N., Lawhon, S.D., Pi�eiro, J.M., Scott, H.M. (2019) Effects of two-dose ceftiofur treatment for metritis on the temporal dynamics of antimicrobial resistance among fecal Escherichia coli in Holstein-Friesian dairy cows. PloS One 14 (7), e0220068
  • Type: Journal Articles Status: Submitted Year Published: 2020 Citation: Lunt, Lucas, Mayukh Dass, and Piyush Kumar, An Empirical Test of an Ecosystem-based Model of Stewardship Program Adoption, Submitted - Journal of the Academy of Marketing Science
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Cazer, C., Eldermire, E., Lhermie, G. Murray, S.A., Scott, H.M., Grohn, Y.T., (2020) The effect of tylosin on antimicrobial resistance in beef cattle enteric bacteria: a systematic review and meta-analysis. Preventive Veterinary Medicine. https://doi.org/10.1016/j.prevetmed.2020.104934.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Murray, S.A., Holbert, A.C., Norman, K.N., Lawhon, S.D., Sawyer, J.E., Scott, H.M.* (2019) Macrolide?susceptible probiotic Enterococcus faecium ST296 exhibits faecal?environmental?oral microbial community cycling among beef cattle in feedlots. Letters in Applied Microbiology. doi:10.1111/lam.13269.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Scott, H.M.*, Acuff, G., Bergeron, G., Bourassa, M.W, Simjee, S., Singer, R.S. (2019) Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture. Annals of the New York Academy of Sciences. 1441:3-7. doi: 10.1111/nyas.14058.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Scott, H.M.*, Acuff, G., Bergeron, G., Bourassa, M.W, Gill, J., Graham, D.W., Kahn, L.H., Morley, P.S., Salois, M.J., Simjee, S., Singer, R.S., Smith, T.C., Storrs, C., Wittum, T.E. (2019) Antimicrobial resistance in a One Health context: exploring complexities, seeking solutions, and communicating risks. Annals of the New York Academy of Sciences. 1441:8-16. doi: 10.1111/nyas.14057
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: S�gaard J�rgensen, P. Folke, C., Henriksson, P.J.G., Malmros, K., Troell, M., Zorzet, A., Aktipis, A., Brown, Z., Carri�re, Y., Downes, S., Dunn, R.R., Epstein, G., Gr�hn, Y.T., Tikaramsa Gujar, G., Hawthorne, D., Jasovsky, ., Klein, E., Y, Klein, F., Lhermie, G., Mota-Sanchez, D., Omoto, C., Schl�ter, M., Scott, H.M., Wernli, D., Carroll, S.P.: Co-evolutionary governance of antibiotic and pesticide resistance. Trends in Ecology and Evolution. June 2020. https://doi.org/10.1016/j.tree.2020.01.011
  • Type: Journal Articles Status: Submitted Year Published: 2020 Citation: Guillaume Lhermie, Pierre Sauvage, Leslie Verteramo Chiu, Didier Raboisson, Harvey Morgan Scott, Loren William Tauer, Yrjo Tapio Grohn. Economic effects of regulating antimicrobial use in U.S. feedlot.
  • Type: Journal Articles Status: Submitted Year Published: 2020 Citation: S�gaard J�rgensen, P., Klein, F., Wernli, D., Jasovsky, D., Aktipis, A., Dunn, R.,R. Gr�hn, Y.T, Lhermie, G., Scott, H.M., Klein, E. Y.: Ambitious action can reverse national increases in antibiotic resistance.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Guillaume Lhermie, Leslie Verteramo Chiu, Karun Kaniyamattam, Loren William Tauer, Yrjo Tapio Gr�hn. Antimicrobial policies in beef production: choosing the right instruments to reduce antimicrobial resistance under structural and market constraints. International Society for Economics and Social Science of animal health, Atlanta, USA. December 2019
  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Stapleton G, Cazer C, & Gr�hn Y. Tylosin phosphate physiologically-based pharmacokinetic model assesses antimicrobial pressure on enteric bacteria. Conference of Research Workers in Animal Diseases. Chicago, IL, November 2-5, 2019. (Poster Presentation).


Progress 01/15/18 to 01/14/19

Outputs
Target Audience:Targeted audiences during this reporting period included the scientific community through presentations, posters, and peer-reviewed publications. These occurred at national (e.g., CRWAD, ASM) and international events (e.g.,Chamonix, France, ISVEE 15 in Thailand, Singapore). In addition, several PDs engaged in international efforts on the subject with foreign governments (e.g., Uruguay, Colombia, Netherlands) and also engaged with international agencies such as OIE, WHO and FAO. Four major categories of stakeholders were engaged through direct communications including facilitated workshops in 2017 -2018 concerning systems thinking, social psychology and marketing. The four major groups were: dairy farmers and veterinarians, beef feedlot operators and veterinarians, staff of government agencies engaged in regulating and providing oversight to agriculture and food safety including antimicrobial use, and concumer and public health advocacy groups. in this latter case upwards of 50 individuals were deeply engaged in providing stakeholder inputs to concepts of stewardship in exploring boundaries of values and commond ground as well as behavioral motivators and opportunities to market products based on sound stewardship principles. Changes/Problems:The second set of complementary stakeholder workshops were held in Washington DC to ensure a sufficiently large and diverse set of viewpoints on consumer, public health, and government agency participants. This occurred in August 2018 rather than in 2017. Audio problems during recording of these two sessions made automated transcription difficult so the painstaking process of audited transcription by the research team on top of a commercial service has slowed the analysis. As a result, the timeline in which the online quantitative survey is to be developed, approved by the IRB, administered by the researchers and analysed is delayed and will necessitate an additional no-cost extension to the project to bring these data into the social systems dynamic models and ensure a completed project engagement with stakeholders during a final workshop to be held in early to mid- 2020. The field trials in dairy and beef cattle were generally completed without issues; however, compliance and enrollment rate issues with one dairy farm necessitated enrolling 1/3 more dairy cows in the remaining three more compliant farms once it became clear one dairy farm would be unable to complete the project. All field data collections are completed, and microbiological assays and metagenomic assays are almost all completed. Some additional endpoints (e.g., Salmonella) were added based on early findings. What opportunities for training and professional development has the project provided?The project has provided considerable opportunities for training to undergraduate and graduate students, post-docs, as well as early stage research scientists. This has extended to including skills not only in field trial coordination and conduct, and laboratory skills, but also in organizing and conducting stakeholder workshops in regional and national centers. Undergraduate student workers (4) have learned valuable skills in laboratory workflow and assays and analysis and reporting. Graduate student dissertations (3) are being written and scheduled for defense and publication in August and December of 2019. Post-doc and research scientists are developing their post-graduate skills and managing a variety of components of the project, including acting as the major organizer of stakeholder engagements and reconstructing the framework for stewardship in policy documents. How have the results been disseminated to communities of interest?Results have been distributed through formal research forums such as national and international research symposia, by participating in national and international workshops and focus groups, and directly through engagement with producers including to the cattle feeders' association and dairymen's organizations and through dialogue with public health and consumer groups. The two field trials are now yielding peer-reviewed publications as are the systems modeling efforts. These, along with the results of quantitative surveys in the near future will provide a rich basis for further engagement with the four major stakeholder groups to find common ground on the concept of stewardship in cattle production. What do you plan to do during the next reporting period to accomplish the goals?There remain several tasks that will build directly upon the empirical data gleaned from the two field trials and microbiological outcomes, as well as the four stakeholder workshops. First, systems dynamics models are being constructed for both the beef and dairy sectors between Cornell and Texas A&M scientists to facilitate a dashboard interface with farmer and veterinary decision makers concerning the use of varying voluntary slaughter withholding times and fixed durations of tylosin and use of probiotic Enterococcus faecium versus continuous feeding for dairy and beef cattle, respectively. These models will be completed and publicshed in the coming year along with large industry scale models incorporating social factors and behaviors as they relate to antibiotic use. In addition, an online survey will be administered, results analysd, and a final workshop planned, the latter of which are likely to extend into an additional grant fiscal year.

Impacts
What was accomplished under these goals? The reporting year included many major milestones and accomplishments. The two empirical field trials in dairy and beef were completed. Microbiological assays and metagenomic-based assays are nearly completed, and early results from culture-based assays are either under preparation or else submitted and under review. A systematic review/meta-analysis and a position/policy paper are also under review, both in peer-reviewed open access journals of repute. The last two stakeholder workshops were held in Washington, DC in August of 2018 engaging with federal agencies and regulators as well as consumer and public health stakeholders. These sessions were recorded, transcribed, and subjected to content and narrative analyses which are now formulating the basis of online quantitative surveys to be administered to the same set of stakeholders in coming months. The systems dynamics models are now well underway and aligned well with recent calls from the FDA for identifying ways to set duration of preventive regimens of antibiotics such as for tylosin for liver abscesses. Ecomomic analyses have yielded fruitful outputs and are being presented to stakeholders for marketing opportunities. These are aligned with recent 'pre-competitive' efforts to have USDA-verified One Health labeling that includes stewardship of antibiotics along with animal welfare, environment concerns (but does not emphasize 'never-ever' use). Few discussants in any of the workshops suggested that sick animals should not be treated with antibiotics, which runs counter to some consumer preferences. Alternative approaches that focus on 'stewardship' principles with process verified systems and enterprise level analysis of antibiotics use practices offer much hope and our efforts in this area will emphasize marketing of stewardship principles consistent with a One Health approach.

Publications

  • Type: Journal Articles Status: Under Review Year Published: 2018 Citation: Taylor, E. A., Jordan, E. R., Garcia, J. A., Hagevoort, G. R., Norman, K. N., Lawhon, S. D., Pi�eiro, J. M., & Scott, H. M., (In Review). Effects of a two-dose ceftiofur treatment on temporal dynamics of antimicrobial resistance among fecal Escherichia coli in Holstein-Friesian dairy cows. PLoS One.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: " Lunt, L., Dass, M., Kumar, P., & Loneragan, G. "Increasing Adoption of Voluntary Service Interventions," Frontiers in Service Conference, Singapore.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: " Elkins, A. D., McDonald, G. W., Midgley, G. R., Gorman, D. M., Kreuger, L. K., Osgood, N. D., Scott, H. M., & Lawley, M. A. (2018, September 13th). Epistemological Considerations of Modelers as Active Participants in Stakeholder Engagement  Examples from a Drunk Driving Prevention Project and an Antimicrobial Resistance Project. 60th Annual Conference of the Operational Research Society, Lancaster, UK, September 2018.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: " Elkins, A.D. (2018, September 14). Systems modelling in public health: Why the researcher's perspective really matters. Research seminar presented at The University of Hull's Business School in the Centre for Systems Studies, Hull, UK. Abstract doi:10.13140/RG.2.2.20748.77443
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: " Cazer, C.L., Ducrot, L., Volkova, V.V., Gr�hn, Y.T.: Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse. Frontiers in microbiology, 2017, 8:1753. DOI: 10.3389/fmicb.2017.01753
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Taylor, E. A., Jordan, E. R., Garcia, J. A., Hagevoort, G. R., Norman, K. N., Lawhon, S. D., Scott, H. M (2018, November). Effects of a two-dose ceftiofur treatment for metritis on levels of antimicrobial resistance among fecal Escherichia coli in Holstein-Friesian dairy cows at the time of slaughter-eligibility. Oral presentation at the 15th International Symposium of Veterinary Epidemiology and Economics, Chiang Mai, Thailand.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Impact of Direct-Fed Microbials and environment on Enterococcus spp resistance in feeder cattle Sarah A. Murray1, Ashlyn C. Holbert2, Keri N. Norman2, Sara D. Lawhon1, Javier Vinasco1, Roberta A. Pugh1, Jason E. Sawyer3, Harvey M. Scott1 International Symposium on Enterococcus, Chamonix, France April 2018
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: Impact of Direct-Fed Microbials and environment on Enterococcus spp resistance in feeder cattle Sarah A. Murray1, Ashlyn C. Holbert2, Keri N. Norman2, Sara D. Lawhon1, Javier Vinasco1, Roberta A. Pugh1, Jason E. Sawyer3, Harvey M. Scott1 International Society for Veterinary Epidemiology and Economics, Chiang Mai, Thailand, November 2018
  • Type: Journal Articles Status: Under Review Year Published: 2019 Citation: " Casey Cazer, Guillaume Lhermie, Erin Eldermire, Sarah Murray, H. Morgan Scott, Gr�hn, Y.T.: The effect of tylosin on antimicrobial resistance in beef cattle enteric bacteria. BMC Veterinary Science
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: " Casey Cazer, Guillaume Lhermie, Erin Eldermire, Sarah Murray, H. Morgan Scott, Gr�hn, Y.T.: The effect of tylosin on antimicrobial resistance in beef cattle enteric bacteria International Society for Veterinary Epidemiology and Economics Conference, Chiang Mai, Thailand, November 2018
  • Type: Conference Papers and Presentations Status: Published Year Published: 2018 Citation: " Stapleton, S. Cazer CL, and Gr�hn, Y.T.: Tylosin phosphate physiologically-based pharmacokinetic model assesses antimicrobial pressure on enteric bacteria. Conference of Research Workers in Animal Diseases. Chicago, IL, December 2018. (Poster Presentation).
  • Type: Journal Articles Status: Under Review Year Published: 2019 Citation: " Guillaume Lhermie, Leslie Verteramo, Karun Kaniyamattam, Loren William Tauer, Morgan Scott, Yrjo Tapio Gr�hn :Antimicrobial policies in beef production: choosing the right instruments to reduce antimicrobial use and resistance under structural and market constraints. Under Review (February 2019 Frontiers in Veterinary Science.)


Progress 01/15/17 to 01/14/18

Outputs
Target Audience:Targeted audiences reached during this reporting period included engagements with industry stakeholders including multiple direct meetings with cattle feeder organizations (Texas Cattle Feeder Association at their headquarters on 3 occasions), Texas Association of Dairymen in Amarillo (1 occasion), multiple direct farm visits (monthly over a one year period during 2017 to three large dairies), National Pork Board, and discussions with public health and regional and national consumer groups (Pew Trusts, Keep Antibiotics Working, Natural Resources Conservation Board). Federal agencies engaged included FDA-CVM, CDC, USDA-ARS/NIFA/APHIS, and NSF (SESYNC project on social dimensions of the environment). International groups such as OIE, WHO, FAO, EFSA, ECDC, EMA, Dutch Veterinary Medicines Agency were included.International government agencies and groups such as Interamerican Agency for Research in Agriculture (IICA), the Uruguayan government, the European Union (EFFORT project), and fellow scientists. Changes/Problems:The third stakeholder meeting with public health/consumer groups was delayed to allow for its undertaking in a more centralized location (Washington, DC versus Amarillo, TX) to save on travel costs for a broader representation of participants and to increase availability of same. One of the dairy herds withdrew due to unforeseen circumstances relating to macro trends in the dairy sector. As a result, sample sizes were boosted in the other dairy farms to allow for sufficient statistical power while accounting for changes in clustering (3 versus 4 aggregates). Much of the molecular work is driven by the findings (e.g., sequence types of dominant strains of E. coli and Enterococcus, for resistance genes, it was unknown as to which ESBL/AmpC beta-lactamase genes existed on each farm until the study began). As a result, some adjustments have been made to the genotypic approaches. The core microbiological characterization of the bacterial populations have not changed from the proposal. Sufficient statistical power for comparisons is retained. What opportunities for training and professional development has the project provided?Trainees have presented at national conferences of note (e.g., CRWAD) and have engaged with beef, dairy and public health stakeholders. Trainees are becoming experienced in biosafety, human subjects research and animal use protocols and complioance. Assigned graudate students and post-docs have travelled to research sites (all dairy and beef) and engaged in discussion with producers for practical and experiential learning. How have the results been disseminated to communities of interest?Distribution of resulsts have been through formal research dissemination (i.e., articles, conferences) and directly through engagement with producers including to the cattle feeders' association and dairymen's organizations and through dialogue with public health and consumer groups as mentioned elsewhere. Much of the early components of this project have been consultative (listening sessions) as opposed to merely being dissemination of research findings; instead, our research requires our engagement with these groups to better understanding the doundaries and identities of shared values and how they manifest in antibiotic use practices. What do you plan to do during the next reporting period to accomplish the goals?Our field studies (beef and dairy) have either been completed or are near to completion. Micrbiological assays are well underway and early reports are being published which will continue through the next reporting period. Our thrid stakeholder engagement will take place in Washington, DC in 2018 and the quantitative survey will soon follow. Results of the qualitative analyses will be submitted for publication along with microbiological results.

Impacts
What was accomplished under these goals? McGregor feedlot cattle trial Factors were tylosin/no tylosin, probiotic, and change of pen environment (existing versus brand new pens). The first replicate contained 90 cattle, starting on February 21, 2017 samples were collected every four weeks for 3 months on day -14, day 0, day 28, day 56, day 84, then weekly on day 91, day 98, day 105, and day 112. Cattle were separated on day 84 with the first half through the chute put into the new pens. Tylosin was also withdrawn at day 84, but steers from the probiotic groups were kept on the probiotic. After sample collection on day 112 cattle were sent to slaughter, livers were evaluated for abscesses. Two steers were lost by the end of the trial, the first after day 98 and the second after day 112. Fecal samples were preserved in 50% glycerol and non-glycerol. Similarly, the second replicate contained 96 cattle, starting on June 27, 2017 samples were collected as above. For the first replicate, day 0, day 84 and day 112, 0.5 g fecal samples from glycerol preservation were suspended in 4.5 ml PBS, plated on plain m-Enterococcus agar, along with agar supplemented with tetracycline and erythromycin at CLSI breakpoints. Two isolates were picked from plain and erythromycin agar and speciated using MALDI-TOF. MICs on E. faecium and E. hirae isolates from plain and erythromycin agar were obtained using Sensititre. Select E. faecium isolates were sequenced on the MiSeq platform, along with E. faecium isolates obtained from the probiotic. Prevalence of macrolide resistance peaked at day 84 then dropped after tylosin withdrawal.MDR isolate prevalence increased from day 0 to day 84, associated with expansion of isolates resistant to 6 and 7 classes of antibiotics and a decrease of pan-susceptible isolates.By day 112, isolates resistant to 6 and 7 classes of antibiotics were eliminated; however, the pan-susceptible isolates remained in the minority.Log10 CFU on plain m-Enterococcus significantly decreased by day 84 in the tylosin and combined tylosin/probiotic groups.Log10 CFU on m-Enterococcus with erythromycin increased significantly (P < 0.05) by day 84 in the tylosin group, while a smaller increase was observed in the combined tylosin/probiotic group. Log 10 CFU on m-Enterococcus with erythromycin did not change significantly (P > 0.05) in the control and probiotic only group, with less change observed in the probiotic group.The most abundant sequence types were ST296 and ST240, though there was a variety of r-phenotypic and r-genotypic differences among these sequence types. Isolates for which a sequence type could not be identified also tended to cluster together.ST296 and ST240 each had a distinct node, with differing clades.The E. faecium component of the commercial DFM (probiotic) was comprised of a pan-susceptible ST296 strain; of interest, we readily identified its presence in the feces of cattle. Less frequent sequence types only occurred in groups of one or two were spread among the three clades. We also sampled the pen environments to compare and contrast the findings from the rectal fecal samples to the pen itself (manure pack).The effect of an antibiotic-free environment versus one with antibiotics previously used (new versus old pen, respectively) appeared to affect the log10 CFU counts more than the administration of tylosin or DFM. The group that received tylosin, even when moved to a new pen, showed increased numbers of antibiotic resistant bacteria in the environment on day 119. These data suggest that environmental modifications may be effective methods for combatting antibiotic resistance in cattle feedyards. 3rd generation cephalosporin use for metritis in dairy farms and resistance decay In April of 2017, a pair-matched cohort study was launched on four dairy farms across western Texas and eastern New Mexico, two in each state, to evaluate the effects of a two dose ceftiofur crystalline-free acid (CCFA) treatment on levels of antimicrobial resistance among enteric bacteria in Holstein-Friesian dairy cattle. Cases were cows that were diagnosed with metritis via veterinary/dairy protocol and were given a two dose CCFA treatment. Control cows were healthy cows of a similar calving date, age, and lactation number, but having not received CCFA treatment. Prior to the start of the spring trial, environmental samples from feed, water, and various pens were collected. These samples, much like their cattle sample counterparts, were stored in 50 milliliter Falcon tubes, both with and without 50 percent glycerol, and stored at -80 degrees Celsius prior to being shipped to and processed in College Station, Texas. For the spring trial, 15 pairs of cattle were to be enrolled across each of the four dairies. Fecal samples were collected from study cattle on study days 0, 6, 16, 28, and 56. Sampling day 0 served as a baseline sample, as it was taken prior to the administering of CCFA. Dairy A had 148 of 150 samples collected. Of the 160 samples to be collected on Dairy B, which added an extra pair, 147 were collected. Dairy C collected 147 of 150 samples. Dairy D, which only enrolled eight pairs, collected only 34 of the expected 80 samples from those pairs. Unfortunately, due to unforeseen circumstances Dairy D withdrew from the study. Sample sizes were boosted on the remaining three farms to retain study power. Samples were spiral plated onto MacConkey agar (BD Difco™, NJ) and MacConkey agar with Ceftriaxone (Sigma-Aldrich, MO) added at 4 µg/mL. After an enrichment period with MacConkey broth (BD Difco™, NJ) containing 2 µg/mL of ceftriaxone, samples were spiral plated on CHROMAgar Extended-Spectrum Beta-Lactamase (ESBL) (CHROMAgar™, Paris, France). Isolates from the ESBL plates were streaked to blood agar, indole tested, and tested via MALDI-TOF (Bruker, MA) to verify they were E. coli before being put onto CryoBeads (Hardy Diagnostics™, CA) for storage at -80 degrees Celsius. Those with more than one isolate had two isolates preserved for an approximate number of 294 isolates saved. Isolates from 117 samples have been run on Gram negative Sensititre plates (Thermo Scientific Inc., MA) and 21 of them were run on ESBL specific plates. This same processing procedure was followed for environmental samples of the spring and fall trials. The fall trial began in September of 2017 and is set to come to a close in April of 2018. Due Dairy Dwithdrawal, the number of cattle pairs was increased from 15 to 25 for the fall trials. Overall, 78 pairs of cattle were enrolled during the fall trial. Of the 270 samples to be collected from Dairy A, 254 were collected with eight scheduled to be collected in the middle of April. Dairy B had 252 of 260 samples collected. With regards to Dairy C, all 250 samples were collected. Those samples, too, will undergo the microbiological processes performed on the spring trial samples. In the systems sector of the project, including engaging of stakeholders, two workshops were held in 2017 with another planned in 2018. The entire research team gathered in Amarillo, TX to meet and to engage with representative sectors of the beef cattle feeding sector and the local dairy sector to discuss the framework for antibiotic stewardship. Meeting notes were transcribed via flip charts and recorded and anonymized. Analyses are underway with the social scientists and systems thinkers exploring these dimesnaions and comparing/contrasting these to those generated form public health/consumer sectors. These will form the basis of the quantiative web-based surveys to be compleetd in the next reporting period and informed by the results of the field studies mentioned above..

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Cazer, C.L., Ducrot, L., Volkova, V.V., Gr�hn Y.T.: Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse. Frontiers. 2017 Sep 20;8:1753. doi: 10.3389/fmicb.2017.01753. eCollection 2017.
  • Type: Journal Articles Status: Submitted Year Published: 2018 Citation: Cazer, C.L., Volkova, V.V., Gr�hn Y.T.: Expanding Behavior Pattern Sensitivity Analysis with Model Selection and Survival Analysis. BMC Veterinary Research.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Cazer, L. C., Gr�hn, Y.T.: Applying Behavior Pattern Sensitivity Analysis to a System Dynamics Model of Resistant Enteric Bacteria in Beef Steers Fed Chlortetracycline. The Biological & Biomedical Sciences Symposium, Cornell, Ithaca, NY, Aug 18, 2017.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2017 Citation: Cazer, L. C., Volkova, V. V., Gr�hn, Y.T.: Behavior pattern sensitivity analysis identifies interventions to reduce enteric antimicrobial resistance in beef steers fed chlortetracycline. CRWAD. Chicago, December 3-5, 2017.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Poole TL, Callaway TR, Norman KN, Scott HM, Loneragan GH, Ison SA, Beier RC, Harhay DM, Norby B, Nisbet DJ. Transferability of antimicrobial resistance from multidrug-resistant Escherichia coli isolated from cattle in the USA to E coli and Salmonella Newport recipients. J Glob Antimicrob Resist. 2017 Dec;11:123-132. PubMed PMID: 28801276.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Ohta N, Norman KN, Norby B, Lawhon SD, Vinasco J, den Bakker H, Loneragan GH, Scott HM. Population dynamics of enteric Salmonella in response to antimicrobial use in beef feedlot cattle. Sci Rep. 2017 Oct 30;7(1):14310. PubMed PMID: 29085049; PubMed Central PMCID: PMC5662634.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: 27. Collignon, P. C., Conly, J. M., Andremont, A., McEwen, S.A., Aidara-Kane, A., Agerso, Y., Ninh, T.D., Donado-Godoy, P., Fedorka-Cray, P., Fernandez, H., Galas, M. Irwin, R., Karp, B., Matar, G., McDermott, P., McEwen, S., Mitema, E., Reid-Smith, R., Scott, H. M., Singh, R., Smith DeWaal, C., Stelling, S., Toleman, M., Watanabe, H., Woo, G-J. (2017) World Health Organization ranking of antimicrobials according to their importance in human medicine: a critical step for developing risk management strategies to control antimicrobial resistance from food animal production. Clinical Infectious Diseases. 63,1087-1093.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: 26. Cummings, K.J., Rodriguez?Rivera, L.D., Norman, K.N., Ohta, N., Scott, H.M. (2017) Identification of a plasmid?mediated quinolone resistance gene in Salmonella isolates from Texas dairy farm environmental samples. Zoonoses and Public Health. 64, 305-307.


Progress 01/15/16 to 01/14/17

Outputs
Target Audience:Targeted audiences reached during this reporting period include: 1) stakeholders including beef and dairy cattle producer groups such as the Texas Cattle Feeders Association (TCFA), Texas Association of Dairymen (TAD), National Cattlemen's Beef Association (NCBA), Beef Industry Food Safety Council (BIFSCO), 2) consumer and public health groups such as the World Health Organization, Keep Antibiotics Working, American Veterinary Medical Association, Pew Charitable Trusts, 3) National and international government agencies and groups such as USDA, FDA, CDC, the Interamerican Agency for Research in Agriculture (IICA), the Uruguayan government, the European Union (EFFORT project), Food and Agriculture Organization of the United Nations (FAO), NSF (SESYNC project on social dimensions of the environment), and scientists through conferences such as ASM, CRWAD and others. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Trainees have been asked to present at national conferences of note (e.g., CRWAD and BIFSCO). In addition, through online training, all participants have become well versed in human and animal subjects research compliance and biosafety guidelines. Assigned graudate students and post-docs have travelled to research sites (all dairy and beef) and have trained the staff on animal handling, treatments, and sample collection approaches as well as preparing and administering on site training to owners, staff (dairy and beef) and private veterinary practitioners. How have the results been disseminated to communities of interest?Dissemination of results has thus far been limited to staekolders from beef and dairy sectors relating to communication of approaches and updates on research progress, These include dairy (Texas Association of Dairymen), beef (Texas Cattle Feeders Association, BIFSCO), national (USDA, FDA, CDC) and international agencies (FAO, PAHO-WHO, IICA). These have been through regular WebEx teleconferences, meetings, platform presentations and other approaches. What do you plan to do during the next reporting period to accomplish the goals?The field trials are underway and should be completed (sample collections) by end of December of 2017; microbiological assays will also be ongoing and continue into subsequent years. The workshops will have been completed, transcribed, and analysis and reporting underway. Economics and systems dynamic modeling will continue throughout the next period.

Impacts
What was accomplished under these goals? Under the multiple objectives of this grant, we have made progress towards completion of Objectives 1 and 2, specifically, during this reporting year. Under the objective of engaging key stakeholders in workshops to work towards defining stewardship in agricultural settings, we have booked the venue in Amarillo, TX for a late Spring date and have the dairy and beef producer organizations contacting their membership to build the workshop participant list. We have all investigators and trainees certified per IRB at the 5 institutions to participate in the workshops. The consumer and public health stakeholders will be engaged later and separately in a similar exercise (summer 2017) usuing a parallel process. Regarding Objective 2, both dairy and feedlot projects are underway with a first replicate of cattle assigned to the older pens at the McGregor feedlot and with animals now on trial treatments (direct fed microbials of Enterococcus origin; conformed to contain no resistance genes per WGS) and tylosin. Change to new environment (new feedlot pens) will occur late in feeding period. A second replicate will start in August 2017. The dairy study is underway with environmental baseline samples taken and four cooperating dairy herds in new Mexico and Texas enrolled. Modeling of systems dynamics and economics are also underway at Cornell and Texas tech, respectively. A systematic review concerning tylosin is being performed jointly by trainees at Cornell and Texas A&M and a PhD student at Texas Tech is exploring features of the beef value chain that relate to antimicrobial stewardship. Presentations arising from the project thus far have been delivered at national and international forums covering broader issues of stewardship of antimicrobials in production agriculture as well as other empirical data concerning enteric bacterial population responses to antimicrobial treatments.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: G. Levent1, A. Schlochtermeier, S.E. Ives, K.N. Norman, S.D. Lawhon, G.H. Loneragan, R.C. Anderson, H.M. Scott. Prevalence, quantity and antibiotic resistance of Salmonella enterica in response to antibiotic use early in the cattle feeding period. 2016. Conference of Research Workers in Animal Diseases, Chicago, Illinois. 1Department of Veterinary Pathobiology, Texas A&M University, College Station, TX; 2Department of Agricultural Sciences, West Texas A&M University, Canyon, TX; 3Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX; 4Agricultural Research Service, United States Department of Agriculture, College Station, TX
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Naomi Ohta, Keri N. Norman, Henk den Bakker, Guy H. Loneragan, Sara D. Lawhon, Harvey M. Scott. Whole-genome sequencing of Salmonella derived from cattle treated with antibiotics. 2016. Conference of Research Workers in Animal Diseases, Chicago, Illinois.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Loneragan, GH. Antimicrobial Stewardship in Livestock: Principles and Practice. The Hague, The Netherlands, September 26-28, 2016 4th International Conference on Responsible Use of Antibiotics in Animals
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Loneragan, GH. Australia y Nueva Zelanda, pai?ses orientados a la exportacio?n del hemisferio Sur. Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Loneragan, GH. Escenarios Nacionales y Globales. Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Loneragan, GH. Los sistemas de vigilancia de la resistencia antimicrobiana en Europa, Australia y Nueva Zelanda. Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Scott, HM. Comparison and contrast of timelines and case studies:European Union versus United States (&and Canada). Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Scot, HM. Interventions in the food chain to reduce multi-drug resistance: Farm-level and commodity sector-level studies. Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Scott, HM. Surveillance systems for antimicrobial resistance: General approach to integrated surveillance via WHO guidelines. Resistencia antimicrobiana en las cadenas productivas, 1� y 2 de diciembre, 2016, Montevideo, Uruguay.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Scott, HM. Antimicrobials in animal health and food production:Parables of scientific paradox and public policy. Presented at the COLMIC, Medellin, Colombia. September 28, 2016
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: Scot, HM. Antimicrobials in animal health and production:Parables of scientific paradox and public policy. Presented at the Food and Agriculture Organization of the United Nations (FAO), Rome, Italy. March 30, 2016 12:00