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One Health Antimicrobial Stewardship Conference - Alberta 2021 Report
One Health Antimicrobial Stewardship Conference - Alberta 2021 Report

This report is commissioned by the ABVMA and produced in partnership with the National Collaborating Centre for Infectious Diseases.

Acknowledgements

Authors:
Amreen Babujee, BSc, MPH, Former Project Management Lead & Research Analyst, HEAT-AMR, School of Public Health | University of Alberta; AMR – One Health Consortium

Kathy Naum, Manager of Communications and Professional Enhancement. Alberta Veterinary Medical Association

Jocelyn Forseille, DVM, Assistant Registrar. Alberta Veterinary Medical Association

Phil Buote, DVM, Complaints Director and Deputy Registrar, Alberta Veterinary Medical Association

Darrell Dalton, DVM, Registrar, Alberta Veterinary Medical Association

Simon Otto, BSc, DVM, PhD, Lead – HEAT-AMR and Lead – Healthy Environments, Centre for Health Communities, School of Public Health | University of Alberta; AMR – One Health Consortium

The ABVMA would like to recognize Alberta Agriculture and Forestry for the funding support required to host the One Health Antimicrobial Stewardship Conference summarized within these proceedings.

The ABVMA would further like to thank all attendees, speakers, committee members and others for their involvement and participation.

The ABVMA thanks NCCID for partnering in the production of the final conference report.

Contents

Introduction

Antimicrobial resistance (AMR) requires a multisector, One Health approach to combat this global threat to humans, animals and the environmental. A key aspect of this response is antimicrobial stewardship (AMS).  

The One Health Antimicrobial Stewardship Conference, held virtually March 10-12, 2021, brought together over 400 experts across sectors in animal health, human health and environmental science, as well as undergraduate and graduate students. The conference aimed to serve as a platform to share leading practices in antimicrobial stewardship and provide evidence-informed information for participants across One Health sectors. 

The objectives of the conference were to: 

  • provide a forum for communication about antimicrobial stewardship across the animal, human and environmental sectors in western Canada,
  • identify opportunities for One Health collaboration in stewardship activities across sectors,
  • improve One Health understanding of the antimicrobial resistance challenges facing animal, human and environmental health,
  • improve awareness of the implications of recent resistance and stewardship research and policy on front line practice, and
  • inform antimicrobial stewardship practices by the human, animal and environmental sectors using evidence-based knowledge. 

This conference was hosted by the Alberta Veterinary Medical Association (ABVMA) with funding support from Alberta Agriculture and Forestry. The 2021 event followed the 2016 ABVMA One Health Antimicrobial Workshop and the Western Canadian One Health Antimicrobial Stewardship Conference held in Regina, Saskatchewan in January 2019. The conference schedule was developed by the Program Planning Committee, consisting of representatives from various organizations, including ABVMA, Alberta Agriculture and Forestry, University of Alberta, University of Calgary, AMR – One Health Consortium, Alberta Health Services, College of Physicians & Surgeons of Alberta, and Saskatchewan Agriculture.

A key aspect of this conference was to promote antimicrobial stewardship through a One Health lens. The One Health concept promotes a multisector approach that includes collaboration between animal health, public health and environmental health to achieve better health outcomes. The presentations and panel discussions highlighted the many One Health initiatives and research at local and national levels.

The conference agenda centred on three major themes relevant to antimicrobial stewardship practices: The Big Picture (current initiatives), Challenges to the Current Status Quo and Moving Forward. These themes covered a wide range of presentations by speakers from various backgrounds and expertise. 

Conference registration was complimentary and was open to: 

  • human and veterinary health practitioners,
  • diagnostic laboratory professionals in the animal, human and environmental sectors,
  • agriculture industry, service providers and commodity associations,
  • organizations that advocate for human patients,
  • antimicrobial stewardship policy decision makers (e.g., government and professional associations),
  • water and environment regulators,
  • environmental assessment businesses and staff, and
  • academia (faculty and trainees such as postdoctoral fellows, graduate and undergraduate students).

This diverse audience provided effective discussions resulting from high-quality presentations. 

Presentations were given by leading experts and trainees across the different sectors of One Health. Panel discussions with presenters were focused on themes of The Big Picture and Moving Forward. As each day of this three-day conference featured a different theme, attendees were exposed to different styles of presentation, leading to an engaging conference. 

This report summarizes the key concepts of each presentation and discussion panel. It was written and prepared under the direction of the One Health Antimicrobial Stewardship Conference Program Planning Committee with support from the National Collaborating Centre for Infectious Diseases.

Conference Program Planning Committee

The One Health Antimicrobial Stewardship Conference Program Planning Committee included:

ABVMA
Dr. Phil Buote
Dr. Darrell Dalton
Dr. Jocelyn Forseille
Kathy Naum

Alberta Agriculture and Forestry
Dr. Keith Lehman

Alberta Health
Dean Blue
Tricia Morris

College of Physicians and Surgeons of Alberta (CPSA)
Karen Smilski

Government of Saskatchewan
Dr. Wendy Wilkins

University of Alberta
Dr. Simon Otto (Conference Chair)
Dr. Nick Ashbolt
Dr. Lynora Saxinger

University of Calgary
Dr. Michele Anholt
Dr. Herman Barkema
Dr. Sylvia Checkley
Samantha Larose

Agenda

Day 1: March 10, 2021

Antimicrobial Stewardship - The Big Picture

TIMETOPICSPEAKER
8-8:05 a.m.Introduction and Opening RemarksDr. Simon Otto, University of Alberta
8:10-8:30 a.m.Welcome from the Government of Alberta
8:30-9 a.m.Keynote - Challenging Assumptions for Antimicrobial Stewardship for Human and Animal HealthDr. Morgan Scott, Texas A & M University
9-9:30 a.m.Council of Canadian Academies (CCA) Report on AMR in Canada: Socioeconomic Case for StewardshipDr. David Patrick, BC Centre
for Disease Control
9:30-10 a.m.Alberta’s AMR StrategyDr. Keith Lehman, Alberta
Agriculture & Forestry
10-10:15 a.m.Pan-Canadian AMR Action PlanDr. Howard Njoo, Public Health Agency of Canada
10:15-10:30 a.m.Break
10:30-11 a.m.Stewardship: the Big Picture - The Environmental Dimension of Antibiotic Resistance and its MobilizationDr. Chris Yost, University of Regina
11 a.m.-12 p.m.Questions & Panel DiscussionAll presenters.
Moderated by: Dr. Simon Otto
12-1 p.m.Trainee Presentations
1 p.m.Wrap-upDr. Simon Otto, University of Alberta
Day 2: March 11, 2021

Antimicrobial Stewardship Challenges

TIMETOPICSPEAKER
8-8:05 a.m.Introduction & Recap from Day 1Dr. Simon Otto, University of Alberta
8:05-8:15 a.m.Welcome from the Government of Alberta
8:15-10 a.m.Rapid fire: Stewardship Challenges from Specific Sectors – Challenging the Status Quo
1. Removing Barriers to Antimicrobial Stewardship in Companion Animal Medicine (8:15-8:30 a.m.)
2. Dairy Selective Dry Cow Tx (8:30-8:45 a.m.)
3. Opportunities and Barriers for Stewardship in the Swine Industry (8:45-9 a.m.)
4. Responsible Antibiotic Use: Chicken Farmers of Canada’s Strategy (9-9:15 a.m.)
5. Equine Practice (9:15-9:30 a.m.)
6. Opportunities and Barriers for Antimicrobial Stewardship in the Aquaculture Industry (9:30- 9:45 a.m.)
7. Beef Industry for BRD and Liver Abscess Management (9:45-10 a.m.)
1. Dr. Emily Feyes, Ohio State University, College of Veterinary Medicine
2. Dr. Kayley McCubbin, University of Calgary, Faculty of Veterinary Medicine
3. Dr. Egan Brockhoff, Prairie Swine Health Services
4. Steve Leech, Chicken Farmers of Canada
5. Dr. Gillian Haanen, Moore Equine
6. Dr. Patrick Whittaker, Grieg Seafood
7. Dr. Guillaume Lhermie, University of Calgary, Faculty of Veterinary Medicine
10-10:15 a.m.Break
10:15 a.m.-12 p.m.Rapid fire: Stewardship Challenges from Specific Sectors – Challenging the Status Quo (continued)
1. Diagnostic and Treatment, UTI Stewardship (10:15-10:30 a.m.)
2. Long Term Care UTI Stewardship (10:30-10:45 a.m.)
3. Human Hospital Stewardship (10:45-11 a.m.)
4. Primary Care (11-11:15 a.m.)
5. CPSA Antimicrobial Utilization (11:15-11:30 a.m.)
6. Do Bugs Need Drugs (11:30-11:45 a.m.)
7. Human Pharmacy (11:45 a.m.-12 p.m.)
1. Darren Pasay, Alberta Health Services, Pharmacy Services
2. Dr. Patrick Quail, Alberta Health Services
3. Dr. Miranda So, University of Toronto
4. Dr. Kevin Shwartz, Public Health Ontario
5. Fizza Gilani, College of Physicians and Surgeons of Alberta
6. Simon Habegger, Alberta Health Services
7. Margaret Gray, Alberta Health Services, Pharmacy Services
12-1 p.m.Trainee Presentations
1 p.m.Wrap-upDr. Simon Otto, University of Alberta
Day 3: March 12, 2021

The Vision for Antimicrobial Stewardship: How Do We Move Forward?

TIMETOPICSPEAKER
8-8:05 a.m.Introduction & Recap from Day 2Dr. Simon Otto, University of Alberta
8:05-8:15 a.m.Welcome from the Government of Alberta
8:15-9:15 a.m.Social Science - How Do We Influence People to Change?
1. Social Science - How do we influence people in livestock production to change? Systems and individual barriers and enablers (8:15-8:45 a.m.)
2. Individual barriers (8:45-9:15 a.m.)
1. Dr. Ellen Goddard, University of Alberta
2. Dr. Cora-Mihaela Constantinescu, University of Calgary
9:15-10:15 a.m.What is the Vision for Antimicrobial Stewardship?
1. International perspective on stewardship in Animal Health (9:15-9:45 a.m.)
2. Pharmaceutical industry (9:45-10:15 a.m.)
1. Dr. Sarah Thompson, Canadian Food Inspection Agency
2. Dr. Robert Tremblay, Boehringer Ingelheim
10:15-10:30 a.m.Break
10:30-11:30 a.m.What is the Vision for Antimicrobial Stewardship? (continued)
1. Environment (10:30-11 a.m.)
2. Human Stewardship (11-11:30 a.m.)
1. Dr. Meghan Frost-Davis, Johns Hopkins
2. Dr. Lynora Saxinger, Alberta Health Services
11:30 a.m.-12:30 p.m.Panel Discussion - What is the Vision for Antimicrobial Stewardship?All presenters.
Moderated by: Dr. Herman Barkema
12:30 p.m.Conference Closing RemarksDr. Simon Otto, University of Alberta

Demographics

Over 400 people attended the conference from all over the world:
OHASC 2021 Report attendee demographic map

Attendee Backgrounds

  • Veterinarians 110
  • Trainee Presenters 48
  • RVTs 17
  • Industry, Academia, Government & Students 210

Trainees Presenters

  • Undergraduate Students - 7
  • MSc Students - 21
  • PhD Students - 22
  • Post-doctoral Fellows - 11

The attendees came from diverse backgrounds, including 110 veterinarians, 48 trainee presenters, 17 registered veterinary technologists and 210 that were a combination of industry, academia, government and students. From the trainees, there were seven undergraduate students, 21 MSc students, 22 PhD students and 11 postdoctoral fellows. Overall, 74 abstracts were submitted to the conference with 10 trainees selected for presentations.

Opening Remarks

Government of Alberta 

The following government officials provided opening remarks:

  • Day 1: MLA Jackie Lovely for Honourable Devin Dreeshen, Minister of Agriculture and Forestry
  • Day 2: Honourable Jason Nixon, Minister of Environment and Parks
  • Day 3: Honourable Doug Schweitzer, Minister of Jobs, Economy and Innovation

The diversity of these speakers demonstrates the importance of a One Health approach.  

Thank you to the Government of Alberta for their support through funding and committee representatives.

Presentation Summaries

Day 1:
Antimicrobial Stewardship - The Big Picture

Keynote

Challenging Assumptions for Antimicrobial Stewardship for Human and Animal Health

Conceptualizing Antimicrobial Stewardship

Defining “stewardship” in the context of antimicrobials can be challenging on a global scale. In literature indexed on PubMed and published between 1990 and 2020, AMS has been poorly defined or described, making it difficult to reach a consensus on what AMS truly means. Therefore, focusing on the goal of stewardship might provide a solution.

“In stewardship, it is important to focus on the bacteria and not only the antimicrobials. A lot of the programs in stewardship and the measurements are about the antimicrobials. The goal of stewardship is to manage populations of bacteria and conserve the susceptibility of that population to treat with antimicrobials when needed.”

To further illustrate this, Dr. Scott used the following example: when treating a patient, human or animal, with antimicrobials, susceptible bacteria get eradicated, which creates space for resistant bacteria to colonize the individual instead. This resistant strain can then spread to others in a hospital ward or animal pen, further expanding the number of resistant bacteria. If this occurs in food animals, the risk of resistant bacteria in the food supply chain for humans increases.

Conflicting Moral Imperatives, Ethics, Values, Beliefs and Norms

Concerns from the public and others outside of animal health over antimicrobial use practices in agriculture make it important to understand the values of these different stakeholder groups to develop meaningful solutions. “We need to find ways to assist others and ourselves in changing our behaviour to be consistent with our values, beliefs and norms.”

Different sets of values can dictate antimicrobial use (AMU) and the level of stewardship. For example, one set of values could give preference to human medicine over animal medicine and agricultural use while another set of values could give importance to using antimicrobials for prevention of disease in animals. The way to foster stewardship and bring stakeholder groups together is to focus on common values to ensure stewardship program success, such as enhancing the health and well-being of both humans and animals; preventing the overuse and misuse of antimicrobials in animals and humans; and protecting efficacy of the drugs for future use.

Institutional versus Individual Actions 

Both institutional and individual actions are necessary to bring forth meaningful change in stewardship. Institutions, such as government agencies, can create laws, guidelines and labels that can enable individuals, such as feedlot operators, to take action. For example, in 2008/2009 the Dutch parliament set a mandate to move from being the largest to one of the lowest users of antimicrobials in the animal sector in Europe. They saw up to a 75 per cent reduction in use, especially in white veal and poultry farms. Values-based systemic intervention can be powerful. Another example is the codified ethical practice distributed to pharmaceutical companies to remove growth promotion claims. The claims were voluntarily removed from labels within three years in the United States and Canada.

“Institutions set guidelines, but individuals take actions.”

Reimagining Antimicrobial Stewardship for One Health

A single antimicrobial can target different areas in the body, which can pose different risks for resistance. For example, using antimicrobials to treat a respiratory disease can cause resistance for bacteria in the gut. Drug classes that are analogous in human and animal health, such as quinolones, third and fourth generation cephalosporins, and macrolides and ketolides, can cause concerns regarding bacterial susceptibility in both human and animal health. Studies have shown that use of antimicrobials in agriculture can lead to resistance to analogue drugs important for human use. Conversely, resistant strains from a hospital can shed into the environment through wastewater and affect food animals in agriculture.

Although there is no “technical solution to this problem,” AMS strategies are needed to preserve the effectiveness of these drugs for future use.

Keynote

Challenging Assumptions for Antimicrobial Stewardship for Human and Animal Health

Session

CCA Report on AMR in Canada: Socioeconomic Case for Stewardship

AMR jeopardizes the safety of medical procedures such as surgery and cancer therapy, and increases the burden of infectious diseases, which in turn hurts economies. To clarify the potential consequences of AMR, a question was posed by the Public Health Agency of Canada (PHAC) in 2017 to the Canadian Council of Academies: “what is the socio-economic impact of AMR for Canadians and the Canadian health care system?” To address this question, a panel of experts on human infectious diseases, veterinary diseases, and AMR coupled with economists, was assembled to write a report. 

The report begins with highlighting how AMR is a problem today with common infections having a 25 per cent resistance rate to frontline agents, resulting in about 14,000 deaths annually. Projections show that AMR will likely increase from 15 deaths a day in 2018 to 38 deaths a day in 2050 within Canada. The cost of healthcare spending related to AMR alone will also increase from $1.4 billion in 2018 to $7.6 billion in 2050 based on a mid-level rise in resistance. This rise will also impact the economy by reducing the Canadian gross domestic product (GDP) by $21 billion annually in the year 2050.

“Overall, the cumulative costs to Canada by the year 2050 if AMR increases from 26 per cent in 2018 to 40 per cent in 2050 is: 396,000 lives lost, $120 billion in healthcare costs, and $388 billion reduction in GDP.”

The way forward includes the World Health Organization’s (WHO) four pillars, with which Canada’s pillars completely align:

  • Surveillance of AMR and AMU;
  • Stewardship across the sectors of One Health;
  • Infection prevention and control; and
  • Research and innovation, not just for new drugs, but for how we use them and license them.

Despite 80-90 per cent of human antimicrobial use being in the community (general human medical practitioners (GP) clinics, pharmacies), most stewardship programs occur in hospitals. Community stewardship programs that focus on supply (prescriber guidance) and demand (user education) have the most success in reducing AMU at the human population level. These programs ideally would include: governance, education, prescribing guidelines, engagement, monitoring and research. This should be a consistent practice over the course of years across all the sectors of One Health to protect antimicrobials as a future resource.

Through a health economic analysis, it was determined that about $450 million has been saved on the cost of antimicrobials between 2005 and 2014 in BC alone due to the Antibiotic Wise program. This represents a savings of $76 for every $1 spent on community stewardship programming, which is of value to both governments and extended benefit insurers.

Apart from AMR, stewardship is necessary to prevent the harm from unnecessary AMU. Antimicrobials can cause mild to severe allergic reactions in humans. This is preventable in all cases where unneeded antimicrobials are used. Reactions that aren’t an allergy (e.g., headaches) can lead to incorrect recording of an allergy to antimicrobials and can lead to unnecessarily prescribing of second-line agents that are more likely to lead to AMR. Additionally, reducing AMU in infancy may be critical in preventing asthma. Research conducted in BC between 2000 and 2014 shows that a reduction in prescribing drugs during early childhood leads to a reduction in asthma among those exposed to pollutants and/or allergens.

“If stewardship can reduce AMR, other allergic responses, risk of common infectious diseases and possible atopic diseases, the cost benefit becomes a slam dunk.”

The stewardship program “Do Bugs Need Drugs” highlights where efforts need to be directed through surveillance: 

  • Public messaging for adults over 65 to reduce high rates of prescriptions;
  • Outreach with dentists and nurse practitioners to reduce prescriptions;
  • Continued research into the link between AMU and childhood asthma;
  • Penicillin allergy de-labelling in the community for safer and narrower spectrum first-line antimicrobials; and
  • Direct online accredited Continuing Medical Education (CME) for primary care.

“Recommendations that are not influenced by industry are available online on bugsanddrugs.org for professionals.”

Session

CCCA Report on AMR in Canada: Socioeconomic Case for Stewardship

Session

Alberta’s AMR Strategy

The Alberta AMR strategy was developed from a One Health perspective to enable joint ownership and effect meaningful action on the ground at a provincial level through partner and stakeholder engagement. This was a joint initiative between Alberta Health and Alberta Agriculture and Forestry.

To help develop the strategy, a jurisdictional scan and literature review were completed to identify strategies for addressing AMR across different sectors through One Health approaches. The overall findings included:

  • International consensus on strategic recommendations to address the threat of AMR through collaborative One Health policy approaches;
  • Insufficient policies focused on environmental AMR containment strategies; 
  • A shortage of evaluations of the impact of AMS programs in animals;
  • A minimal number of One Health reviews examining cross-species impacts of AMR; and
  • Gaps in human stewardship programs for community-based care.

“These findings reinforced the need to improve intersectoral collaboration to contain the threat of AMR.”

The results of the scan indicated that Alberta should adopt a One Health approach given the province’s capacity of human and animal health expertise, and robust livestock industries.

To further develop the provincial strategy, 48 stakeholders participated in a variety of ways: interviews, focus groups, questionnaires and workshops to identify current gaps in areas of AMR and AMS, and provided suggestions on how the findings can be addressed. Stakeholders included the agricultural industry, government, health services organizations, veterinary services and post-secondary education. This engagement effort found that there is broad support for One Health approaches to AMR, a gap in education for frontline antimicrobial users, a need for intersectoral collaboration between agriculture, health and environment, and also between government, academia and industry.

Alberta’s AMR strategy aims to outline the provincial government’s commitment to taking action to address the threat of AMR and taking concrete steps to prevent and contain the spread of AMR while preserving the effectiveness of antimicrobial treatments. Alberta’s goal is to provide leadership, harness the expertise of Albertans and direct a coordinated response to AMR. The mission and vision of the strategy speak to collaboration, tapping into collective resources, preventing and containing the threat, and promoting stewardship.

The six core principles that will guide the work include:

  • Social good: benefiting the public interest of communities and ensuring needs of individuals are met;
  • Collaboration: government and stakeholders working together;
  • Ongoing engagement: communicating and consulting stakeholders continually;
  • Incremental change: gradual improvements over time to solve issue;
  • Shared accountability: working together across industry and sectors;
  • Mitigating risk: minimize threats of AMR to our health, economy and environment; and
  • Implementation plan of strategy: the government is the steward of the strategy and a key actor within the strategy.

“The Albertan strategy is built upon three foundational pillars: stewardship, surveillance, and infection prevention and control. Cross-cutting themes across these pillars include education and awareness, and research and innovation.”

The next steps for this strategic plan include finalizing the strategy through consultations with stakeholders, and completing internal assessments on the proposed implementation plan to move forward.

Session

Alberta’s AMR Strategy

Session

Pan-Canadian AMR Action Plan

AMR remains a priority for the Government of Canada, which advances AMR actions and initiatives guided by One Health approaches through surveillance, knowledge brokering, facilitation, public health capacity building, laboratory science leadership, regulatory responsibilities and international engagement.

Thus far, the federal government has advanced AMS through:

  • Human health – supporting initiatives and organizations to promote prudent AMU and introducing requirements for inclusion of precautionary statements in product labelling for prescription antimicrobials for human use.
  • Animal health/agri-food – supporting development of national biosecurity standards and introducing new pathways to facilitate access to veterinary health products to improve animal health and wellness.
  • Integrated, One Health surveillance of AMR and AMU in the human and animal health, as well as agriculture sectors.

The 2017 Pan-Canadian Action Framework and Plan on AMR and AMU sets out the policy foundation for collaborative efforts to address AMR in Canada. This framework supports a coordinated pan-Canadian response to AMR, covering the core pillars of Surveillance, Stewardship, Infection Prevention and Control, and Research and Innovation. The vision and goals of the plan include: protecting the health of humans, animals and the environment by limiting emergence and the spread of drug resistant microorganisms, preserving the effectiveness of antimicrobials and innovating to discover new antimicrobials, alternative therapies, vaccines, methods and tools to combat AMR.

Most recently, engagement sessions were held with stakeholders across all sectors in early 2020 but COVID-19 has impacted the federal government’s capacity to move forward. The Public Health Agency of Canada plans to re-engage provinces, territories and other stakeholders in the private sector to finalize the action plan.

Session

Pan-Canadian AMR Action Plan

Session

Stewardship: The Big Picture – The Environmental Dimension of Antibiotic Resistance and its Mobilization

AMR has been around in the environment for as long as bacteria have been present. Resistance genes, such as vancomycin resistance elements, have been around long before humans started using vancomycin as therapeutic agents. More recent is the AMR presence and amplification in society through selective pressures and extensive use of antimicrobials in humans and animals, and dissemination and spread of AMR genes through the environment.

“Water serves as an interface between how AMR and bacteria move through the environment.”

The two take home messages include:

  1. Fecal resource management and protecting source waters from fecal contaminations are a critical control point in mitigating AMR in the environment.

    Fecal materials are reservoirs for resistant bacteria and resistance genes entering the environment. Through a multi-year study conducted at South Tobacco Creek, MB, high concentrations of AMR gene marker, class 1 integron-integrase, were found in a holding pond on a cattle farm when compared to other surrounding water sampling sites. The gene, class 1 integron-integrase, serves as a proxy for general AMR genes. This study found that holding ponds effectively capture runoff released from agriculture into the environment and can control the contamination of AMR in the environment. Such beneficial management practices can mitigate AMR spread in agriculture environments by preventing bacteria, which, in many cases, contain AMR genes, from entering the general watershed.

  2. There is a lack of a global standardized surveillance system for measuring risks of AMR in the environment, with promising, engaging advances from genomic technologies. 

    Surveillance frameworks are important to mitigate environmental sources of AMR and to evaluate effectiveness — measuring not just bacteria, but also specific genes coding for resistance determinants.

    A critical target for AMR surveillance is plasmids — mobile genetic elements found in bacteria that can contain AMR genes and are important for monitoring AMR in the environment. They have a core set of genes but can acquire additional genes that code for various resistances (e.g., to metal). Many negative clinical outcomes from AMR infections can be attributed to resistance genes resting in plasmids carried by pathogens. Class 1 integrons are excellent proxies that can be used for surveillance for resistant genes that are often found in plasmids.

    “Bacteria are like smartphones and mobile genes such as plasmids are like apps that confer a specialized function. Bacteria can take up new plasmids, get new functions or delete them.”

    A recent Canadian project will develop a framework for a comprehensive model of mobile AMR in Canadian environments. It will study plasmid existence, movement through, and change in, human and animal environments, and the implications of plasmid contamination in drinking water, for example. A key deliverable of this project is to develop a “plasmidome” database that tracks the types of AMR plasmids in the environment, how they move between different environments, how long they persist, driving environmental factors and the associated risks with certain plasmid types.

    Antimicrobial resistance genes and bacteria are considered pollutants. Therefore, it is important to monitor pollutant levels in water and the environment and define an acceptable emission level based on evidence of risks (e.g., Quantitative Microbial Risk Assessment data).

Session

Stewardship: The Big Picture - The Environmental Dimension of Antibiotic Resistance and its Mobilization

Day 1 Panel Discussion Summary

Antimicrobial Stewardship - The Big Picture

This discussion period covered a variety of themes and questions put forth by the audience for the panel members.

What is the objective of antimicrobial stewardship?

During the One Health workshop series held in fall of 2020, Dr. Susan Rogers proposed that the long-term objective of AMS should be sustainable access to effective antimicrobials for everyone. This includes access for all people and animals, especially for those in low- and middle-income countries that may not have access currently; conservation of the effectiveness of existing drugs; and innovation for new drugs and strategies.

Additionally, a key objective of stewardship should also be avoidance of harms of unnecessary antimicrobial exposure. 

What is the current status of Alberta’s AMR strategy?

On the animal side, a lot of work has been done and is currently ongoing with partnerships established, partnering on messaging, and prescription changes. To track current AMU, more data is needed for accurate surveillance. Although there is a national plan and national participation in Alberta campaigns, it is important for the province to continue working with PHAC and Health Canada to put forward the business case for investing in each and every health system in the country.

The agriculture market currently does not reward reducing antimicrobial use. Should we incentivize this, and who would pay for this?

Antimicrobials should not be withheld from animals if they need them for their health, but incentivizing at an enterprise level through an open process is something to consider. Currently the US is creating a One Health label for drugs. While there is criticism from advocacy groups that it should be zero use rather than judicious use, messaging that zero use is not feasible nor sustainable and that overuse is also irresponsible, is critical.

Additionally, the environmental sector has a role to play in terms of helping producers become good environmental stewards. With certain fast-food chains, it might reach a stage where farmers have to show reduced AMR in their water supply and/or dugouts. For this, monitoring will play a big role.

Questions about environmental aspects: research conducted on the impact of human waste, fecal and otherwise, on water contamination; impact of inappropriate disposal of unused pharmaceuticals into waterways and water supply; pharmaceutical disposal strategies in countries in the context of AMR. 

In Canada, the management of fecal materials, raw manure and composted manure was explored by Agriculture and Agri-food Canada as part of an investigation of the different risks and benefits of using managed manure on different types of food crops. Although more research is needed on this subject, appropriate regulations that require treatment of manure can reduce levels of pathogens and genes.

AMR is a global problem and requires global collaboration to address it. Antimicrobials should be purchased from companies that manufacture globally with good practices — we cannot dispose of antimicrobials and/or their residues in bodies of water (e.g., rivers). In India, regulation does not appear to be controlling the effluent from pharmaceutical factories, resulting in the subcontinent becoming a hotbed for natural selection for severe types of resistance. Through international trade agreements, governments around the world are going to need to develop ways to help pharmaceutical companies and ensure they have the resources necessary for effluent control.

How do we engage the environment sector in the stewardship and policy conversation?

Conferences such as the One Health Antimicrobial Stewardship Conference are an important platform to create engagement across the sectors. Additionally, increased collaboration between and across government ministries, agencies and departments is crucial. 

From a US perspective, the US National Antimicrobial Resistance Monitoring System expanded from the CDC to include the US Department of Agriculture, Food and Drug Administration, and the Environmental Protection Agency. 

Overall, there is a lot of antimicrobial use that goes beyond human and animal health, with the environment playing an important reservoir and transmission role for AMR. Formalizing the role of the environment in  stewardship and policy make AMR the prototypical One Health issue.

Where are we at in Canada with promoting implementation science around stewardship across all three sectors, realizing that they all look a bit different?

Health promotion is the art and science of trying to change the public’s behaviour, which has to be a big focus. When looking at physician prescribing patterns, audits and feedback systems have been a core method of initiating behavioural change in hospital stewardship. Apart from physicians, the general public should be a focus for health promotion because most feedback received on physician prescriptions comes from patients. If the patient is upset over a lack of prescription, the physician may give in and start prescribing antimicrobials.

On the animal production side, financial incentives go a long way. Industry-developed programs will continue to be a big driver. Fast food companies and grocery store chains have the power and ability to drive change in AMU. 

In the short term, what do you recommend to mitigate the tensions between health professionals, policy makers, livestock producers and consumers to move this forward? 

Generally, there is a tendency for groups to entrench in what they will or will not change. Mapping out common ground across sectors and roles in terms of their beliefs about antimicrobials would work towards measurable change in the way people are practicing AMU.

As we emerge from COVID with a public that’s primed about public health threats, is the timing right to drive the conversation with governments about AMR and AMS? Also, disease management with COVID has brought attention to pharmaceutical manufacturing domestically, so is this a window of opportunity to work with government on the development of manufacturing capacity and responsible use?

The scenario of extreme antimicrobial resistance might be more easily understood by the public and government now. Through new technology and opportunity for discovery, it is crucial to get back on course. Post-pandemic government budgets will see significant deficits, which will affect future funding. Moving forward on AMR and AMS will need to be strategic to provide the “greatest bang for buck.” The business case that this will save money in the long run is important. Another important narrative for public outreach should include that COVID-19 vaccines came from long-term foundational research. The same narrative applies to tackling AMR.

Panelists

Day 1 Trainee Presentations

The following trainees were selected to present their projects during Day One of the conference (see the Appendix for abstracts):

Day 2:
Antimicrobial Stewardship Challenges

Rapid fire: Stewardship Challenges from Specific Sectors – Challenging the Status Quo
Session

Removing Barriers to Antimicrobial Stewardship in Companion Animal Medicine

AMS can be thought of as “right drug, right dose and right duration to maximize positive treatment outcomes, minimize adverse side effects and reduce the risk of AMR.”  

“AMS programs are formalized hospital-based initiatives that incorporate stewardship principles and concepts into clinical practice.” These programs are intended to improve patient care and safety, reduce treatment failure, promote correct prescribing, and reduce AMR. In the US, these programs are well established in human medicine but are largely missing in animal medicine.

Within the US, the following barriers exist for stewardship programs in animal medicine:

  • The lack of external drivers for incorporating and creating stewardship programs which are required in human hospitals;
  • Absence of veterinary models of stewardship programs;
  • Limited training and exposure to AMS for animal medicine;
  • Limited number of animal health specialists, such as veterinary clinical pharmacists;
  • Concerns over clients’ expectations of antimicrobial use; and 
  • Existing clinic culture where staff may or may not be familiar with stewardship.

To address this gap in animal medicine, a group at OSU-CVM developed a veterinary model for AMS. Using the model, they launched a program in 2018 with the following goals:

  • Educate students and incorporate stewardship principles in the veterinary medical centre;
  • Create antimicrobial guidelines as educational tools for students to provide guidance when creating treatment plans for best practices in AMU; 
  • Partner with clinicians to identify last-resort drugs that should have additional approval for use in veterinary patients to ensure they are not being used empirically but used judiciously, and to maintain efficacy of drugs in patient populations; and
  • Surveillance through monthly sampling in the veterinary medical centre to identify resistant bacteria of concern, monitoring prescribing practices of clinicians to assess impact of and improve stewardship programs, and using antibiograms to guide empiric therapy and track susceptibility of key pathogens to drugs of interest.

Components of this program can be incorporated into companion animal practice:

  • Drug expertise: consulting veterinary clinical pharmacists at educational institutions over the phone for prescribing for difficult cases; 
  • Action: incorporating stewardship by creating standard operating procedures for how antimicrobials are used and tracking use to provide feedback to the veterinarians in the clinic; 
  • Tracking: monitoring for trends in pathogens of concerns and their susceptibility to drugs being used in the clinic; 
  • Reporting: identifying areas for improvements (e.g., infection control, cleaning/disinfection, etc.); and
  • Education: providing education to clinicians, staff and clients on AMR through lunch and learns, educational posters, handouts, etc.

The group has also launched a certification program called Buckeye ASP to provide AMS resources and expertise to private veterinary practices in Ohio. This certification program helps private practices establish their own in-house stewardship programs. The group’s hope is for other states and counties to adopt their model to develop new animal stewardship programs.

Session

Removing Barriers to Antimicrobial Stewardship in Companion Animal Medicine

Session

Dairy Selective Dry Cow Treatment

Mastitis prevention and treatment, including antimicrobial dry cow therapy, accounts for the vast majority of antimicrobial use on Canadian dairy farms. This could lead to emergence, maintenance and horizontal transfer of AMR bacteria, with adverse effects on animal health and welfare, and dairy farm sustainability. 

As lactation ends, cows enter a dry period where they all receive intramammary antimicrobials to treat and prevent infections. Selective dry cow therapy (DCT) attempts to only treat cows who would benefit from antimicrobials. Currently, about 35 per cent of dairy producers practice selective DCT, indicating a need for further antimicrobial stewardship in the Canadian dairy industry.

Selective DCT should only be used for herds with:

  • Low incidence of mastitis;
  • Low bulk milk somatic cell count, which is used as a proxy for identifying subclinical mastitis infection;
  • Hygienic dry-off procedure/housing; and
  • Good record keeping

High-risk cows are identified during the dry-off period using bacteriological culture or somatic cell count thresholds. 

There are a variety of factors that impact dry cow management:

  • Social determinants of AMU
  • Product availability
  • Cow environment
  • Milk reduction before dry-off
  • Nutrition
  • Housing
  • Culling 
  • Use of teat sealant

Recent literature shows that selective DCT with careful selection criteria and appropriate dry cow management does not appear to have disadvantages or cause significant health impacts in dairy cattle. Additionally, no major differences in milk production were seen when using selective DCT.

“It is unknown if long-term and wide-spread selective DCT will reduce AMR prevalence or mitigate its development, but effects of AMU are widespread and the potential benefits of reducing AMU shouldn’t be overlooked. Overall, industry attempts to reduce AMU on dairy farms could yield benefits to producers, animal health, consumer perception and potential reduction in AMR.”

There are many drivers for and barriers to implementing selective DCT including:

  • For producers: economic considerations, previous experiences, societal pressures and/or perception of risk.
  • For veterinarians: public health safety, obligation to ease suffering, financial dependency on clients, economic limitations and/or producer compliance.

“With increasing scrutiny of prophylactic use, selective DCT could rise in popularity. Development of a national selective DCT guideline would provide producers with the tools to implement selective DCT protocols with limited negative consequences in animal health and welfare.”

Session

Dairy Selective Dry Cow Treatment

Session

Opportunities and Barriers for Stewardship in the Swine Industry

The Canadian Pork Sector is a diverse model made up of:

  • The Canadian Pork Council that includes commercial pork production that accounts for 90-95 per cent of all Canada’s pork;
  • Small holder pork producers that are independent producers and not part of Canadian Pork Council;
  • Pet pigs; and
  • Wild pigs.

AMS in this sector is diverse and can be advanced through biosecurity, regional vaccination and drug use policies (DUP). Alternatively, AMS can be hindered through factors such as lack of veterinary awareness of swine, sectors with limited resources and market signals.

The Canadian Pork Excellence (CPE) programs offered by the Canadian Pork Council are the basis of the verified Canadian pork brand that is recognized worldwide. There are three programs: 

  1. PigSAFE focuses on food safety, including DUP and biosecurity programs;
  2. PigCARE focuses on animal care, including care and handling, and stocking density; and
  3. PigTRACE focuses on traceability for swine diseases.

The CPE DUP objectives include food safety, mitigating AMR and practicing AMS. Within this policy, there are strict restrictions for AMU, information on growth promotion prohibition and guidance on extra-label drug use.

Much effort has been put into the biosecurity programs for keeping diseases out (external biosecurity) and managing diseases (internal biosecurity), all of which impact on AMU. Biosecurity efforts include the 2010 National biosecurity standard, truck wash and wash facility audit, transporter biosecurity audit and a biosecurity module in the CPE program. Research shows that viral pathogens of swine are spreading around the world through feed ingredients, a newly recognized contamination pathway. With no in-feed mitigants labelled in Canada, this poses a challenge to biosecurity in the swine industry. Both contaminated feed ingredients and contaminated packaging can potentially carry infectious virus, so holding feed ingredients in storage prior to feeding is recommended to reduce viral survival (100 days at 10°C, 200 days at 20°C).

The Pork Council recently produced the Small Lot Swine Producer Management and Production manual to advance biosecurity in small herds who typically don’t have the same well-developed relationships with veterinarians.

“Animal health is a core driver of AMU. Host, pathogen, barn/environment, producers, processors and government all play a role in animal health across Canada.”

A growing challenge within the pork sector is influenza A due to multiple changing strains and ongoing human introduction of virus into farms. Within Canada, commercial influenza vaccines for swine are out of date and not effective against common strains as there is no mechanism within the commercial sector to update the vaccines on an annual basis. Because autogenous vaccine regulation in Canada is farm specific, it could take months to get a vaccine produced, allowing the virus to spread in that time. “There is a strong need for regional influenza vaccine solutions that are proactive and preventive.”

Currently, there is no national influenza database or surveillance system in Canada. To address this gap, a pilot project was launched in Ontario that has identified the most common circulating strains in swine farms and has led to the development of an autogenous vaccine that can be used across multiple sites.

With vaccine deficits for various diseases such as Streptococcus suis, Brachyspira sp. and PRRS virus, many challenges for AMU arise. For successful stewardship, continuing education for AMU and AMR within the pork sector is necessary.

Session

Opportunities and Barriers for Stewardship in the Swine Industry

Session

Responsible Antibiotic Use: Chicken Farmers of Canada’s Strategy

The Chicken Farmers of Canada is a national association that represents Canada’s chicken farmers. They develop strategic direction and policies on production issues, including food safety, animal health and care, and AMU. AMU and AMR are key priorities that have been part of CFC’s strategic plan since 2014. Deliverables of this plan include implementing an antibiotic reduction strategy and decreasing the use of antibiotics important for human medicine.

The drivers for development of this strategy were market demands by retail and restaurants, surveillance results through Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) that highlighted resistance issues in chickens for category I drugs, understanding that there was a need for a strategy to ensure long-term effectiveness of antimicrobials being used and to maintain consumer confidence.

The key elements of AMU developed by the CFC that drive initiatives are: 

  • Reduction: the CFC antibiotic reduction strategy is not a Raised without Antimicrobial strategy. The focus is on reducing or eliminating prophylactic use of drugs of human importance (category I, II and III). Thus far, the CFC has implemented policies to eliminate prophylactic use of category I antibiotics (specifically cephalosporin) and category II antibiotics. Their next goal is to implement a policy to eliminate preventive use of category III antibiotics (specifically bacitracin).
  • Maintain the use of antimicrobials for treatment and the use of ionophores (Category IV) and coccidiostats for prevention.
  • Surveillance: surveillance occurs through CIPARS at the farm level for both AMU and AMR. It helps understand use patterns for policy development and helps understand the impact of policies. CIPARS has reported effective elimination of the use of category I and II drugs, and reduced resistance at the processing level and retail.
  • Research: reduction of AMU is a priority of the research conducted. It focuses on vaccines, feed and water additives as alternatives and the impact of eliminating preventative use, among other things. 
  • Education: the implementation and enforcement of reduction policies is put in place through the CFC Raised by a Canadian Farmer On-Farm Food Safety Program. This is mandatory for 100 per cent of farmers with provincial enforcement.

A key goal of the CFC antimicrobial education strategy is to “provide our customers a sustainable means of meeting expectations while protecting animal health.” 

In developing and moving forward with this strategy, communication has been a key factor with farmers, veterinarians, stakeholders and consumers. This has occurred through videos, podcasts, case studies, magazine series and a website.

Session

Responsible Antibiotic Use: Chicken Farmers of Canada’s Strategy

Session

Equine Practice

Nationally, there are various challenges in equine AMS:

  • Some antimicrobials have specific labels for equine use but can also be used off label;
  • Canada has limited access to some antimicrobials specifically labelled for horses. This leads to the use of extra-label or compounded antimicrobials or human antimicrobial tablets. This can lead to antimicrobial residues in the environment and unintentional exposure to the people mixing the drugs; 
  • Antimicrobials are used for both prevention (e.g., penicillin when doing arthroscopy of the hock) and treatment (e.g., sepsis);
  • Culture and susceptibility (C/S) are performed frequently;
  • C/S test methods and recognized MIC cut points for equine pathogens.

The equine community is critically thinking about AMU, and spending time on investigating different diagnostic methods. To promote stewardship moving forward, the equine community can improve on client education, use less ceftiofur in general practice as it has human importance, and conduct more research in equine and industry sectors.

Session

Equine Practice

Session

Opportunities and Barriers for Antimicrobial Stewardship in the Aquaculture Industry

Globally, Norway and Chile are the largest salmon producers. In Canada, BC is a large salmon producer — it is the province’s number one agriculture export. Managing disease is one if the challenges in the finfish aquaculture industry. In Norway, viral diseases pose a challenge, while bacterial diseases are limited. In BC, viral diseases are very limited but bacterial diseases are prevalent.

The BC aquaculture industry was able to reduce AMU from the mid-to-late 1990s to now through the introduction of vaccines and the screening of brood stock for vertically transmitted diseases. Use was reduced from approximately 500 grams of antimicrobials per metric tonne of salmon produced to 100 grams per metric tonne. 

Regulation of AMU in aquaculture is governed by Fisheries and Oceans Canada (DFO), CFIA and the province, with each individual treatment being reported to DFO at time of prescribing. The most commonly prescribed antimicrobial is florfenicol due to its short half-life in salmon, lack of use in human health and slower levels of resistance in target finfish pathogens compared to other molecules.  

In BC farms, the most common reason for antimicrobial prescription is the disease Yellow Mouth, which is caused by the bacterium Tenacibaculum maritimum. To manage AMU for this disease, vaccines are being tested; whole genome sequencing for different strains; biofilm sequencing to determine if the bacteria can be altered; and toxin research to  understand how the bacteria actually kill the fish. Environmental levels of AMU are monitored through testing antibiotic levels in the feed and benthic samples.

Another common disease is Salmonid Rickettsial Septicaemia (SRS), which is caused by Piscirikettsia salmonis. Although it is only occasionally seen in BC, it is most common in Chile. Currently, SRS vaccines are available in Chile to curb AMU.

Session

Opportunities and Barriers for Antimicrobial Stewardship in the Aquaculture Industry

Session

Beef Industry for Bovine Respiratory Disease and Liver Abscess Management

An ideal antimicrobial steward would administer antimicrobials to animals only if they needed it, and would not administer them otherwise. The benefits of AMU include safe, ethical and affordable food for society, as well as farm profitability. However, the risks include AMR and associated costs. In the beef industry, there is higher consumption of macrolides and tetracyclines compared to other antimicrobials. To reduce use, these two antimicrobials should be the priority.

When it comes to AMU decision making in farmers, the following factors are considered:

  • AMU is economically beneficial
  • Risk factors of diseases
  • Farmer’s attitude
  • Institutional influences (e.g., consumer pressures)

Keeping these in consideration, the following strategies could be used to reduce usage:

    • Medical prevention
      • Liver abscesses: vaccines existed previously for this disease but were not adopted by the market. To reduce AMU, use of this vaccine could be encouraged.
      • Bovine respiratory disease (BRD): vaccination of cattle at arrival is not very effective, but people are still vaccinating the animals. There is a need to understand the rationale of continued use and determine how to use the vaccine more effectively.
    • Substitutes/adjuvants
      • Liver abscesses: the use of yeast shows promising results, although more studies are needed. 
      • BRD: currently, there is no good substitute or alternative to antimicrobials to manage this multifactorial disease complex.
    • Dose optimization
      • Liver abscesses: an option is to modify the number of days of antimicrobial treatment.
      • BRD: to reduce use, the daily single dose could be decreased but this alternative should be investigated more. 
    • Improved management strategies
      • Liver abscesses: feeding low-grain, high-forage ratio would be a good option but it is not economically viable.
      • BRD: farmers could select low risk calves but would need to define a phenotype for BRD first. Another option is to encourage pre-conditioning and vaccination programs for the animals prior to entering the feedlot. This measure is currently poorly adopted although is it economically beneficial. There are many structural bottlenecks in the beef supply chain that slowed down the adoption of pre-conditioning. These include:
        • The structure of the system not facilitating risk management
        • Feedlots being better off economically by purchasing high risk calves and using AM 
        • Feedlots benefiting from AMU reduction but farmers having to take actions.

To successfully reduce AMU in the beef supply chain, individual commitments, coordination of actors, transparency and structural modification are all needed. Additionally, emerging technology is also needed to improve capability to predict and detect disease and decrease AMU.

Session

Beef Industry for Bovine Respiratory Disease and Liver Abscess Management

Session

Diagnostic and Treatment, Urinary Tract Infection Stewardship

To effect real and sustained change in stewardship, knowledge, perception and system barriers all need to be addressed. For example, changing someone’s knowledge can only be sustained by changing their perception to create a new lore. For innovation, a good knowledge base is needed in conjunction with awareness of what the system barriers are to work through them. Lastly, having the perception that system barriers can be overcome gives the buy in and persistence to work through the barriers.

Knowledge-related barriers:
  • Entrenched beliefs/lore: there is a cognitive bias toward establishing a new status quo. Building concise and engaging initiatives helps to break the lore. It is also important to have reminders in place to ensure new resources and tools are being used.
  • Impractical guidelines can lead to new knowledge not being applied.
  • Dissociated practices: for example, urinary tract infections (UTIs) could be treated differently depending on the department consulted. Having non-standard antimicrobial use practices can lead to confusion about which practice to use.
Perception-related barriers:
  • Prescribing etiquette is well established and hard to change.
  • Clinicians are compelled to take action to treat a patient instead of following “watchful waiting.”
  • While exceptions exist, in general, humans share pathology and biology that guidelines are built upon. Perception of “unique practices” needs to be overcome.
  • Deflection to other professionals for who is responsible for stewardship
  • Previous negative outcomes causing hesitancy to adopt new guidelines
  • Indifference to stewardship.
System-related barriers:
  • Order sets/routines result in firmly embedded practices that make change difficult.
  • Volume and workload are high for clinicians, making it hard to introduce change that adds more work.
  • Staff turnover leads to the need for continuous education reminders for new staff.
  • Lack of knowledge translation resources: there are many continuous changes in the systems, leading to competing priorities.
  • Lack of change management resources: a lot of cost goes into staff training, and since the benefits of stewardship are downstream and hard to measure, it’s hard to get support.
Session

Diagnostic and Treatment, Urinary Tract Infection Stewardship

Session

Long Term Care UTI Stewardship

In LTC, there are various problems associated with effective AMU. Approximately, 30-56 per cent of prescriptions for UTIs in LTCs do not meet the criteria for requiring a prescription. With tremendous overuse of antimicrobials, up to 10 per cent of LTC residents are taking antimicrobials at any given time, half of which are unnecessary.

Using Antibiotics Wisely (funded by PHAC) was launched through Choosing Wisely Canada, the national voice for reducing unnecessary tests and treatments in healthcare. Urinary tract infections in LTC were a focus within this initiative. As a result, practice change recommendations were developed to reduce unnecessary use of antimicrobials for UTIs. The practice change recommendations went through extensive revisions and had wide input from different organizations, such as Alberta Health Services and Public Health Ontario.

The nine practice change recommendations are:

  • New admission/periodic health examinations/new referrals in LTC: don’t perform screening urinalysis/urine dipstick and/or urine culture and sensitivity for residents on admission, during periodic health examinations, or prior to new specialist referrals.
  • Use of urine dipstick or urinalysis: don’t perform urine dipstick/urinalysis to diagnose UTI.
  • Assessment of residents with changes in health status (e.g. change in urine odour or colour): don’t assume a UTI is the cause of any change in health status. Don’t send a urine culture unless the change noted is accompanied by minimum criteria for a UTI. Do perform clinical assessments to identify alternate causes. Do complete comprehensive delirium workups. Do encourage increased fluid intake. Do document and reassess.
  • Substitute decision maker/family requests to submit a urine culture or treat a UTI: don’t collect a urine culture upon request without first seeking to understand and address resident/substitute decision maker/family concerns. Provide a differential diagnosis and a rationale.
  • Management of residents with clinical criteria for a UTI: don’t order a urine culture unless the minimum criteria for a UTI are present.
  • Management of residents with positive urine culture: don’t prescribe antimicrobials unless the minimum criteria for a UTI are met.
  • Selecting antibiotic and duration for residents with clinical criteria for a UTI: don’t treat a UTI for excessive durations.
  • Follow-up assessment of residents with clinical criteria for a UTI: don’t forget to reassess the need for antimicrobial therapy within three days of starting antimicrobials. Antimicrobial therapy should be stopped if the result of the urine culture is negative.
  • Residents transferred to the emergency department: don’t routinely screen residents from LTC homes with a urinalysis/urine dipstick unless minimum criteria for a UTI are present. Look for alternate explanations for change in clinical status.

Implementation of these recommendations has been stalled due to COVID-19. In the meantime, websites and social media have been populated with knowledge projects for staff and families to refer to. Additionally, work with partner associations and key stakeholders has continued, along with physician engagement.

Session

Long Term Care UTI Stewardship

Session

Human Hospital Stewardship

Current Landscape of AMS in Hospitals

Accreditation Canada has a required stewardship program to optimize AMU for inpatient acute care, inpatient cancer, inpatient rehabilitation and complex continuing care. This program emphasizes accountability and reporting structures, interventions focus on optimizing antimicrobial prescribing, and includes important criterion on monitoring and reporting AMU.

In the US, Medicare and Medicaid require participating hospitals to have AMS as part of the patient care improvement impetus. The Joint Commission made this program a requirement for acute care hospitals and ambulatory care settings.

The US Centers for Disease Control and Prevention (CDC) developed core elements that should be included in hospital AMS programs. These include:

  • Hospital leadership commitment
  • Accountability
  • Pharmacy Expertise
  • Action
  • Tracking
  • Reporting
  • Education

Interventions within these core elements include:

  • Prospective audit and feedback/post-prescription review
  • Optimizing the choice, route and duration, as well as tailoring of antimicrobial therapy
  • Locally developed guidelines/pathways
  • De-labelling penicillin allergy in self-reported patients
  • Monitoring and reporting of AMU

Public Health Ontario has a dashboard with an AMS Program comparison tool. It displays which hospitals are participating in the program, how many hospitals are in the process of implementing it, which hospital is doing what and who you can contact to share tips and expertise.

New Frontiers for Hospital-Based AMS

Recently, a lot of research has been done on a specialized patient population — immunocompromised hosts, including hematologicaloncology, stem cell transplant recipients and solid organ transplant recipients. The conventional practice for this population group was “more is better, longer is better, and double coverage is always preferred over monotherapy.” This approach was deemed unnecessary antimicrobial use. To improve patient outcomes, the Infectious Diseases Society of America recommended having local guidelines for neutropenic fever and anti-fungal stewardship interventions in this population. 

The rationale behind anti-fungal stewardship is that invasive fungal infections cause significant morbidity and mortality, with immunocompromised patients being affected the most. There are limited treatment options with only three classes of antifungals in circulation for use, from which two out of three are highly toxic. Additionally, patients require long treatment courses that are expensive. To address these barriers, new guidelines have emerged from research. Recommendations include:

  • bundled intervention,
  • monitoring and reporting of use,
  • pursuing non-culture based diagnostic strategy because they have a faster turnaround time, and
  • emphasis on accountability.

Apart from guidelines, metrics have also broadened from consumption (quantity of use) to appropriateness (quality of use). The first step to decide on appropriate use of antimicrobial regimens is to see if there are guidelines that could be used as a benchmark — local or published. If guidelines are not available for particular syndromes, refer back to first principles, which include assessing the patient factor, the infectious syndrome, the microbiology and the choice of antimicrobial regimen. 

COVID-19 Effects on AMS

Currently, there is a debate on what impact COVID-19 will have on AMR:

  • Increase: COVID-19 will result in an increase in AMR due to bacterial co-infections and increased prevalence of AMU. The use of immunomodulatory therapy could lead to secondary infections, causing pre-emptive use of antimicrobials.
  • Decrease: COVID-19 will not result in an increase in AMR due to improved infection control practices, uptake of influenza vaccine, travel restrictions, physical distancing and reduction in other respiratory infections that reduce secondary bacterial infections and antimicrobial exposure. 

Overall, the impact of the pandemic remains uncertain.

Session

Human Hospital Stewardship

Session

Primary Care

In Canada, approximately 90 per cent of all antimicrobials are used in the community, with only 10 per cent use in the hospital sector. The biggest group of prescribers are family physicians, with two-thirds of all prescriptions in the community. 

While reducing unnecessary use and prescriptions is important, another emerging factor is the duration of AMU. Studies have shown that shorter treatment days (3-5) have an equivalent efficacy to longer treatment days (7-10). A study also found that the biggest predictor for prescribing prolonged durations of antimicrobial treatments is a physician’s career stage. Those who have been in practice for more years tend to prescribe for longer, irrespective of antimicrobial type. This highlights an area for targeted improvement.

Between 2019 and 2020, there was an overall 30 per cent reduction in community AMU across Canada, including family physicians and non-family physicians. This change was more drastic in children with a 70 per cent reduction, and a 20 per cent reduction in adults. In Ontario, there was also an overall 28 per cent drop in total family physician visits between January to July 2020 during the COVID-19 pandemic. There was a decline in in-person visits during the initial months of the pandemic but a 56 per cent increase in virtual visits. There is still more work needed to be done with these trends to determine the impact on resistance.

Stewardship in primary care is very challenging and can lead to difficulties in creating positive change. There is an imbalance in factors related to antimicrobial prescribing in primary care:

  • Factors driving prescription: belief that patient wants antimicrobials, perception that it is easier and quicker to prescribe than explain why it is unnecessary, habitual behaviour and worry about serious complications with a “just to be safe” mentality.
  • Factors deterring: risks of adverse reactions and drug interactions, recognizing the need for stewardship, desire to deter low-value care and decrease unnecessary healthcare spending and preference to follow guidelines.   

A study in the US looking at antimicrobial prescribing among primary care practices for acute respiratory tract infections tested different intervention methods that decreased rates of prescriptions. These included:

  • accountable justification where physicians had to write in the electronic medical records why they were prescribing the antimicrobials, and
  • peer comparison feedback where physicians would receive monthly emails telling them if they were good or poor performers in the previous month. 

A randomized control trial conducted in Ontario included high-prescribing physicians. One group of physicians received an initiation letter outlining appropriate prescribing practices for antimicrobials for respiratory infections. The other group received a duration letter that included the appropriate durations of antimicrobial therapy. There was a small but significant reduction in both total prescriptions and prolonged duration prescriptions in the group that received the duration letter. A simple intervention such as the duration letter could save as much as $2.7 million per year from drug costs alone.

Session

Primary Care

Session

CPSA Antimicrobial Utilization

The Physician Prescribing Practices Program (PPP) is a quality improvement program that provides educational support to physicians to optimize quality of care provided to Alberta patients. This program uses data to enable audit and feedback-based activities (e.g., individualized prescribing profiles), and proactively identifies at-risk prescribing patterns to intervene before patient harm or a complaint occurs. The program has a tiered approach starting with broad-based/self-directed initiatives, moving to targeted feedback (e.g., letters) and, lastly, directed feedback if failure to improve.

The TPP Alberta is the province’s long-standing prescription monitoring program that monitors medications prone to non-medical or inappropriate use, such as opioids. It works with stakeholders to enable system level change to ensure appropriate use of monitored medications. TPP Alberta is administered through CPSA. 

TPP Alberta, working with a group of practitioners, researchers, data science consultants and clinical experts, developed the Antibiotic Prescription Atlas which provides an overview of human antimicrobial utilization in the community. This report includes data from 2017 to 2019 on utilization of prescription antimicrobials, patients receiving drugs by age and sex, analysis of utilization by prescriber type and analysis on days of antimicrobial therapy. 

Where we are now:
  • Antimicrobials have been formally added as a monitored drug to the TPP Alberta drug list. 
  • The PPP is working on incorporating antimicrobial data into the individualized prescribing reports, called an MD Snapshot.
  • The PPP is also in the early planning stages for developing tools for providing directed education and support at the individual physician level.
Session

CPSA Antimicrobial Utilization

Session

Do Bugs Need Drugs

There are many challenges when it comes to community AMS. These include:

  • Decentralized prescribing environment with a lot of prescriptions for acute issues
  • Long-term relationships between patients and prescribers
  • Prescribing antimicrobials on an outpatient basis is an unremarkable act that is recorded but not reviewed
  • From a centralized office, how do you show that AMS is important?

To address some of these challenges, Do Bugs Need Drugs — a community AMS program that is run independently in BC and Alberta — was developed. The program has two different streams:

  1. A community health promotion program to support wise use of antimicrobials through the use of:
    1. Handwashing materials: to be used in any community setting and as tools to support HCPs who are working in these settings
    2. Guide to Wise Use of Antibiotics: a public-facing resource aimed at improving prescribing, public knowledge, and communication between patient and prescriber
  2. An initiative to support proper outpatient and prescribing of antimicrobials through translation and dissemination of evidence-based materials
    1. Materials for this initiative are for multiple purposes, with information that is useful for prescribers, primary health care administration and the general public
    2. The initiative also includes targeted outreach to healthcare professionals through a non-specific approach, providing materials where relevant and keeping AMS on the table. Different sorts of organizations will have different entry points.
Session

Do Bugs Need Drugs

Session

Human Pharmacy

Pharmacists are recognized members of integrated multidisciplinary health care teams. Depending on the province/territory, they have a varying ability to prescribe for ailments for patients. They are independent in their patient assessments and collaborative in their practice. However, there are barriers to this integrated care, including access to complete patient information (diagnosis, laboratory results and other medication history) and the recognition of the role of a pharmacist (patient’s lack of clarity on the pharmacist’s role in care).

Hospital Pharmacy Practice
  • A pharmacist’s role is integrated, with proactive care more well-established.
  • Access to patients, caregivers and clinical data
  • National network supporting and promoting advanced scope of practice
Community Pharmacy Practice
  • Pharmacists are often physically removed from the diagnostician
    • Reactive intervention
    • Delay in time from original decision
    • Limited access to labs and other diagnostics that help with decision making
  • Competitive environment
    • May hinder broad professional scope of practice recognition

COVID-19 has become a new and unique barrier to AMS. The distance between patients and their caregivers as virtual visits have become the norm and has created new challenges to good stewardship. COVID-19 itself has led to an increase in antimicrobial prescribing when patients are admitted to a hospital, especially in the early stages of the pandemic. Hospital pharmacists play a key role in ensuring unnecessary antimicrobial therapies are stopped in patients in their care.

Hope for the Future
  • Movement of prescriptions from paper to ePrescribing
  • Shared electronic health records to allow for greater collaboration across healthcare professionals (e.g., netCARE in Alberta)
  • Connect Care in Alberta will link the electronic health patient records across all hospitals and levels of care.
Session

Human Pharmacy

Day 2 Trainee Presentations

The following trainees were selected to present their projects during Day Two of the conference (see the Appendix for abstracts):

Day 3:
The Vision for Antimicrobial Stewardship: How Do We Move Forward?

Session

Social Science – How Do We Influence People to Change?

Often, the impact of human behaviour on mitigating AMR is underestimated. In livestock production, the beliefs, values and attitudes of producers and veterinarians are all critical to AMU, AMR and stewardship. 

In the US, beef cattle feedlot veterinarians have found that the factors influencing metaphylaxis prescribing include:

  • Economic pressure 
  • Social expectation of other veterinarians, pharmaceutical companies and veterinary professional organizations 
  • Moral obligation 
  • Trust in antimicrobial information
    • Confidence that government agencies base their recommendations on good science
    • Confidence in regimens and recommendations of nutritionists, feedlot operators, over-the-counter drug outlets, and consumer and advocacy groups

On the other hand, antimicrobial usage in the Netherlands was found to be influenced by the knowledge of the livestock producers about the spread of resistant bacteria, their referent beliefs, perceived risk and undesired attitude towards regulations.

A study in Germany on AMR perceptions and attitudes looked at various population groups. The study found that general human medical practitioners (GPs) and hospital physicians strongly agreed that their prescribing behaviour influences AMR development within their region. Veterinary practitioners and pig farmers had a more neutral view of this. The general population did not think their behaviour influenced AMR development. Additionally, GPs and hospital physicians thought agriculture should be the targeted audience to reduce AMR, while veterinarians and pig farmers thought human health should be the target. These perspectives could complicate the process to bring in policies that will truly address AMR. To find meaningful solutions, it is important that all stakeholders understand that they contribute to AMR. 

On a global scale, while focusing on dairy cattle, barriers for AMU reduction include lack of knowledge of the producers on how and when specific antimicrobials should be used, poor environmental conditions for cattle and poor herd health management. To help reduce antimicrobial consumption in food animals by 2030, a combination of regulations, reduction in meat consumption by humans and user fees would all have the biggest impact. This finding could work as a starting point for conversations on how to alter human behaviour to reduce AMU in livestock.

On the human health side, a successful intervention in Australia found that there was a dramatic reduction in the number of prescriptions filled for GPs who received peer comparison feedback compared to those who received education letters.  

We currently do not know enough to understand what the fundamental barriers and enablers of changing antimicrobial use behaviour might be. There needs to be a feedback loop after the first round of research on this subject to inform producers and veterinarians, find out how they respond to the results and conduct analysis on a broader range of policy approaches to find out which ones will not have any impact based on the behavioural characteristics of the particular sector.

Session

Social Science - How Do We Influence People to Change?

Session

Individual barriers – What makes us tick: Psychosocial drivers for antimicrobial prescribing behaviour

AMS interventions aiming to improve prescribing in human medicine have shown success through a decrease in length of stay at hospitals without an increase in risk of death. Over the last few years, public campaigns have shifted from correcting misinformation to addressing the emotional component of interventions, but these alone are not successful. Targeting interventions for healthcare workers is also important because the public usually sees prescription decisions as belonging to the health care worker, not the patient. Often, health care workers feel pressured by patients to prescribe, especially in pediatrics, which can be disproportionate to the actual expectation of the patient or caregiver.

Prescribing happens in the context of a complicated society. For example, hospitals are their own society with their own social norms. If a provider takes over a new patient’s care who is on antimicrobials, the provider might not want to change the treatment to avoid getting into a conflict. The need to avoid conflicts can overpower change. Status inequality is also a big factor. People tend to defer decision making to those perceived to have more experience, which could have a huge impact on medical trainees who look to their attending as the source of information for prescribing. Additionally, the psychology of the group also makes a difference. Whether or not people feel optimistic that they can make a change in AMR can make a difference to prescribing behaviour. Lastly, the act of prescribing consists of emotions that include fear of consequences and diagnostic uncertainty. Very few studies that look at AMS interventions and prescribing behaviours have focused on applying behaviour change theories. If they do, the interventions tend to work well because they address culture and psychosocial factors, and engage multidisciplinary staff.

Characteristics of successful interventions in prescribing include:

  • Implementation in the context of real clinical experiences
  • Role modelling: target staff physicians so trainee physicians can also improve
  • Having actions for accountability or justification and peer comparison
  • Face-to-face components: fostering a culture of collaboration and more judicious prescribing
  • Focusing on developing collegial relationships based on trust to increase engagement (shared sense of mission/motivation)
  • Using positive communication tools. Stewards should come across as:
    • Non-aggressive
    • Showing concern for prescriber experience
    • Knowing when and for what to intervene
    • Seeking to understand, asking questions, making space for dialogue

Social determinants of prescribing can be used to help develop interventions. These include:

  • Relationships between clinicians
  • Relationships between clinicians and patients
  • (Mis)perception of the problem
  • Risk, fear, identity and emotion around the act of prescribing

Using social determinants and the theoretical domain framework, Dr. Constantinescu described facilitators and barriers to prescribing in the pediatric intensive care unit (PICU) and clinical teaching unit (CTU):

  • Facilitators: collaboration, trust and shared decision making; local and easily accessible guidelines, feeling optimistic as a team; doing right by the patients and feeling optimistic as a prescriber
  • Barriers: norm of non-interference and professional comparisons; inadequate training, group pessimism, fear of clinical consequences and diagnostic uncertainty; pejorative monitoring system; environmental restrictions

A stepwise approach was then created by Dr. Constantinescu to promote stewardship and develop intervention programs:

  1. Who is the audience and what is the behaviour you are trying to change
  2. Develop a needs assessment based on who the audience is, and explore what and how they need to know
  3. Understand what drives the behaviour
  4. Develop an intervention and implementation plan tailored to the audience using effective communication
  5. Develop an evaluation tailored to the audience

To further promote stewardship among healthcare workers, Dr. Constantinescu developed a Stewardship Intervention Communication Framework using the acronym VOTE:

  • V: Validate what their aims are and what emotions are behind the action
  • O: Offer to share your knowledge about the facts and your understanding of the situation
  • T: Tailor the recommendations to the specific patient and their health concerns
  • E: Evaluate how they are responding to your recommendations. Plant the seed of re-evaluation

Stewardship interventions aimed at correcting prescribing have been shown to benefit without adverse outcomes of increased mortality. Prescribing is a highly social and emotional act; therefore, interventions need to include a multifaceted approach. It is important to know the aim, needs and behaviour determinants, and tailor the intervention and evaluation. VOTE for effective communication to build common ground and trust.

Session

Individual barriers - What makes us tick: Psychosocial drivers for antimicrobial prescribing behaviour

What is the Vision for Antimicrobial Stewardship?

Session

International perspective on stewardship in Animal Health

To tackle AMR using a global approach, organizations such as the World Health Organization (WHO), the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (OIE) have addressed AMR within their activities and mandates. Many countries look to these organizations for guidance on how to respond to a multitude of human, animal and environmental concerns.

The WHO released a global action plan in 2015 (WHO, 2015) on AMR development informed by countries and key stakeholders. The goal is to ensure continuity of successful treatment and prevention of infectious diseases with effective and safe medicines that are accessible to all who need them. The report includes five strategic objectives:

  • Improve awareness and understanding of AMR
  • Strengthen knowledge through surveillance and research
  • Reduce incidence of infection
  • Optimize use of antimicrobials agents
  • Develop the economic case for sustainable investment taking into account the needs of all countries, and
  • increase investment in alternative health products and medical interventions.

In 2015, the FAO adopted a resolution on AMR that recognizes AMR poses an increasingly serious risk to public health and sustainable food production. To support the implementation of this resolution, an action plan (FAO, 2016) was developed that addressed four major areas:

  • Improve awareness on AMR and related threats
  • Develop capacity for surveillance and monitoring of AMR and AMU in food and agriculture
  • Strengthen governance related to AMU and AMR in food and agriculture
  • Promote good practices and prudent use of antimicrobials in food and agriculture systems

This plan supports the WHO global action plan and is in line with a One Health approach.

The OIE developed a strategy (OIE, 2016), intergovernmental standards and a list of antimicrobials to combat AMR in 2016. This strategy also aligns with the WHO plan and uses a One Health approach. It outlines goals and tactics the OIE has in place to support member countries and encourages national ownership and implementation of international standards. The intergovernmental standards promote responsible and prudent AMU and provide methodology to address the risk of emergence or spread of disease resulting from the use of antimicrobial agents in food producing animals. The goal of these initiatives is to preserve antimicrobial efficacy and prolong use in animals and humans. Finally, the list of agents of veterinary importance includes criteria used to determine the degree of importance, which is in parallel with the WHO list for human medicine.

To demonstrate how different countries and regions impose antimicrobial requirements, Dr. Thompson presented two case studies:

Case Study #1: Canada

Canada approaches AMR from a One Health perspective by coordinating efforts across multiple sectors, including human health, animal health and agri-food. As there are approximately 24 times more animals than people in Canada, 1.4 times more antimicrobials are sold for use in production animals compared to humans after adjusting for the animal population and their weights. To promote responsible use of antimicrobials and increase oversight, Canada has made significant progress in building an evidence-based approach towards stewardship. Recent regulatory and policy changes to strengthen Canada’s framework for veterinary antimicrobials include new labelling requirement, import controls for veterinary drugs and data collection. More specifically:

  • Regulatory amendments
    • Increased oversight of antimicrobials important to human health
    • Increased oversight on importation and quality of veterinary active pharmaceutical ingredients
    • Facilitating access to low-risk veterinary health products
    • Requiring reports of veterinary antimicrobial sales volume
  • Policy changes
    • Removing growth promotion claims from medically important antimicrobials (MIAs)
    • Switching from over-the-counter to prescription status for all remaining MIAs
  • Veterinary drug AMR initiatives
    • Re-evaluating MIAs being used in animals
    • Regulatory requirement for sharing 2018/19 antimicrobial sales data to support surveillance and inform policy decisions
    • Continued facilitation of access to low-risk veterinary health products

Canada plays an active role in international efforts through membership on the Codex Ad hoc Intergovernmental Task Force on AMR and the Transatlantic Task Force on AMR (TATFAR), and working with various international agencies on their AMR initiatives such as the WHO.

Do domestically based initiatives, such as Canada’s, shape the global agenda and create progressive movement for AMS or do countries need to work on controls and enforcements that apply to imports and trading partners? This is addressed in the second case study.

Case Study #2: European Union

The European Union (EU) released three major initiatives to combat AMR:

  • EU One Health Action Plan against AMR, developed in 2017
    • The three pillars of the plan include making the EU a best practice region; boosting research, development and innovation; and shaping the global agenda
  • Farm to Fork strategy which aims to make food systems fair, healthy and environmentally friendly, released in 2020
    • Aims to position EU as a global leader in sustainable agriculture
    • One of the objectives is reduction of sales of antimicrobials for farmed animals and in aquaculture by 50 per cent by 2030
  • Regulations on medicated feed and veterinary medicinal products
    • Medicated feed: ban AMU for prophylaxis and growth promotion; restrict veterinary prescription with antimicrobials; establish limits for AMU in feed; harmonize standards for manufacturing medicated feed; and create a legal framework for manufacturing and distribution of medicated feed for pets
    • Veterinary medical products (VMPs): harmonize internal market for VMPs; reduce administrative burden; enhance internal market; stimulate innovation; and provide incentives to increase availability of VMPs

The EU also developed regulations for animal or animal byproduct imports from other countries that list certain antimicrobials banned for animal use and the ban of AMU for growth promotion and increasing yield. The EU is not only  relying on withdrawal periods or maximum residue limit from antimicrobials, but are requiring live animals and animal byproducts entering the EU to not have had any of the antimicrobials that the EU reserves for human use, nor those with growth promotion claims during their entire lifespan, production cycle or value chain. The EU is still working on the criteria for the designation of antimicrobials reserved for human use, the list of antimicrobials reserved for human use and the import rules for trading partners. Benefits of these regulations for trading partners could include the increase of prudent and responsibleAMU, the increased use of alternative health products, stimulating animal welfare advances, stimulating global process and innovation and limiting AMU. Some concerns include trade impacts, ambiguity on which substances are banned and inconsistent definition of antimicrobials between the EU and importing countries.

Overall, it is important to recognize the global differences of AMU as different levels of disease prevalence or environmental conditions can lead to greater importance of antimicrobials in one country compared to another. Considerations from all levels of stakeholders and trading partners is necessary for global forward progress of AMR that is feasible.

Session

International perspective on stewardship in Animal Health

Session

Pharmaceutical industry

To align with the first four strategic objectives of the WHO’s global action plan on AMR, which include improving awareness and understanding of AMR, strengthening knowledge through surveillance and research, reducing incidence of infection and optimizing use of antimicrobials agents, Boehringer Ingelheim carries out the following AMS activities in Canada:

  • Education to increase end user awareness: develop education materials for farmers to better inform them on the antimicrobial drugs used on farms and their importance in human medicine based on Health Canada’s categorization
  • Awareness through small group farmer training: work with clinics to provide training on AMU and help change farmer AMU behaviour
  • Support applied research to evaluate use and efficacy of drugs: sponsor investigative trials done by other institutions, such as universities, and support publications in scientific journals to maintain confidence that research is independent and credible
  • Emphasize the importance of prevention: market products intended to reduce the risk of infectious diseases (e.g., internal teat sealant for use in dairy cows to reduce mastitis infections), and develop multiple vaccines for use in cattle, swine and poultry
  • Optimization of use: work with farms who volunteered to use the COMPASS app to track and benchmark their own AMU. COMPASS can be used to collect AMU data in multiple ways:
    • Type of administration of the medication (e.g., injectables)
    • Where on the farm the medication is used (e.g., sows)
    • Classes of antimicrobials used, if farms want to change their pattern of AMU (e.g., class 1)
  • Sponsorship to facilitate dialogue and distribution of knowledge and information: sponsor various events such as conferences in Western Canada, and organizations like the Canadian Roundtable for Sustainable Beef and Alberta Farm Animal Care Association.
Session

Pharmaceutical industry

Session

Environment

The environmental health paradigm is made up of the following steps:

  • Exposure
  • Internal dose
  • Biologically effective dose
  • Early biological effects
  • Altered structure and function
  • Clinical disease

By focusing on these steps, stewardship practices can reduce exposures to prevent animal and human disease. Interventions may target any step but most often target exposure.

From an AMR perspective, pathogens infecting a host result in more AMU, which can cause increased shedding of drug-resistant pathogens and non-target organisms into the environment (food, soil, air, dust, water). This brings us to the concept of the “resistome,” which includes all the genetic determinants of resistance present in a community of organisms. Resistance spreads between organisms by horizontal genetic transfer of elements of the resistome, while antimicrobial selective pressure expands the resistome. As microbes are being shed into the environment, they might interact with non-pathogenic bacteria, making them reservoirs for resistance genes that can persist in the environment for longer.

Resistant bacteria transmission pathways can occur within multiple settings such as agriculture or hospitals. Use in any setting can increase selection pressure for drug-resistant organisms or the AMR genes themselves. However, human or animal exposure to resistant organisms can occur through various environmental pathways, such as manure application on fields, water, processing of food, and through the occupational context, such as farm worker exposure. For example, in US hog operations, a study on occupational exposure found that multidrug and tetracycline resistant S.aureus isolates were present in the air and dust of conventional operations (farms using antimicrobials) while none were detected in antimicrobial-free operations. Transmission clusters of resistant S.aureus strains between pigs and humans where similar resistance phenotypes and AMR genes were present in both populations were also found.

Another study evaluated Klebsiella urinary tract infections of foodborne origin. They found that multidrug resistant strains of Klebsiella among predominantly meat-source isolates were the same as those found in human urinary tract infections.

Looking at multidrug resistant organism contamination in meats from conventional sources compared to organic meats, where uses are curtailed but not fully antimicrobial free, a study found that organic meats had lower proportion of contamination with resistant isolates. They identified the three processing pathways in the US: conventional, split and organic. Organic-only processing plants are very rare but researchers found no major difference in resistance between the split and conventional plants. The study also looked at travel distance and discovered that meats that travelled further distances had higher contamination with resistant organisms. This includes chicken, ground beef, pork chops and ground turkey.

Two crucial intervention strategies for stewardship include:

  1. Animal vaccines
    1. Vaccines can prevent animal disease, where appropriate, and significantly reduce the need for AMU, thereby reducing environmental contamination with resistant organisms/resistance genes and ultimately in food for human and animal consumption.
  2. Regulation of AMU
    1. Ontario and Quebec poultry farms found that both E.coli and S.heidelberg carry plasmids that encode for resistance to ceftiofur. Following the voluntary withdrawal of ceftiofur in Quebec, there was a decrease in resistant isolates in chickens and humans.
    2. Changes in AMU regulations in the US were implemented with ease by large producers compared to small and medium size producers who struggled to make the changes. This highlights the importance of providing strategies that can help support producers of different segments of the production chain to implement regulations.

Shifting from agriculture, hospital environments require strategies that harmonize AMS in both the human and animal sectors, and consider environmental interventions to help hygiene-based solutions to prevent exposure or to help eliminate contact with pathogens. Examples of interventions include manual cleaning (disinfectant) of surfaces/objects and using no touch technology (UV light). The occupational health control strategy is another great intervention. Within this, the hierarchy of controls found that the most effective strategies focus on elimination, substitution or engineering controls. When only administrative controls (contact isolation) or personal protective equipment (PPE) are used, the strategies are less successful because of the dependence on human behaviour.

Bringing together other environments, households are a nexus where hospital, agriculture, food and community sources all come together in terms of the occupants interacting with each other and the environment. A study looked at methicillin-resistant S.aureus (MRSA) in home dust to see if there is a link between AMU in humans or pets in the home and outcomes of multidrug resistant (MDR) MRSA. They found that AMU was associated with higher prevalence of MDR MRSA but clindamycin use, in specific, was associated with lower odds of MDR MRSA; rural households at baseline that used EPA-listed MRSA-cidal disinfectant were also associated with higher odds of MDR MRSA; and that index patients with MRSA in households with no positive reservoirs (no pets, other people, environmental contamination) had faster rates to clearance and more complete clearance than those with one or two positive reservoirs. Similarly, those with no positive reservoirs also had no or slower recolonization rates than those with one or two positive reservoirs.

The following findings of interventions for MRSA in humans can also apply to veterinary medicine:

  • Household-wide decolonization of people is marginally successful
  • Environmental contamination with a colonizing or infecting strain was associated with presumed intra-household transmission
  • Children in the home are also associated with transmission
  • Case reports describing home cleaning suggest the need to use extreme measures for some people with persistent colonization
  • Replacement of mattresses
  • Low-temperature laundering is effective
  • Detergents generally are effective

Lastly, recommendations for interventions for resistant pathogens include:

  • Good hygiene in the home
  • Treatment of both people and pets on a case-by-case basis
  • Contact isolation/social distancing
  • Daily laundering of bedding and clothes concurrent with treatment of people and/or pets
  • Starting with topical therapies whenever possible, such as chlorhexidine, given concerns with selection for AMR
  • Household decontamination
    • Chlorine and quaternary ammonium-based cleaners effective
Session

Environment

Session

What is the vision for antimicrobial stewardship in Human Medicine: Disruption, Growth and Progress?

In 1997, expert panel guidelines and stewardship teams in hospitals and long-term care facilities proposed to make stewardship in Canada part of the accreditation standard. Due to lack of progress, the Canadian Committee on Antibiotic Resistance (CCAR) released a national action plan in 2004 focusing on surveillance, infection prevention and control, optimal antimicrobial use and research. This plan was one of the first to mention bringing together the ministries of Health and Agriculture. In 2007, there was a review of AMR programs published that found a lack of articulated objectives, centralized data access, comparability and targets. They found that local-provincial programs across Canada are not linked with each other and that the most common mode of dissemination of information was at scientific meetings. Lastly, it highlighted a lack of a comprehensive AMR surveillance program in Canada. In 2010, pan-Canadian stakeholder consultations on AMR highlighted the need for enforcement of appropriate use in human and animal sectors, which was a novel recommendation at that time. 

Between 2014 and 2016, there were two separate reports published: one on the evaluation of integrated AMR/AMU surveillance by Dr. Saxinger and colleagues through the National Collaborating Centre for Infectious Diseases, and one on AMU surveillance in the animal sector by Dr. Simon Otto and colleagues for The Canadian Council of Chief Veterinary Officers. In 2019, Drs. Otto and Saxinger led a review to assess progress made to address the gaps noted in these two reports [1] [2]. Their work found that the “patchwork” of AMR/AMU surveillance identified in 2014 had become more cohesive with some important developments, such as the Canadian Antimicrobial Resistance Surveillance System centralized reporting, expansion of existing flagship programs, the Canadian Nosocomial Infection Surveillance Program and the Canadian Integrated Program for AMR Surveillance (CIPARS). Ongoing development of the nascent AMRNet holds promise for surveillance of evolving community resistance and the potential for development of a clear One Health focus with inclusion of animal pathogens. The challenges identified include prioritization within government, dedicated and stable surveillance infrastructure and funding/resources, and lack of policy to enable standardized transnational surveillance.

Developing stewardship to tackle AMR should be considered “a wicked problem” because the solution requires a great number of people to change their mindsets and behaviours. It could be difficult because there is incomplete or contradictory knowledge, there is a large economic burden and there is an interconnected nature of this problem with other problems. Wicked problems cannot be solved by the application of standard or known methods. Solution model options include:

  • Authoritative/central control: few people responsible for solving the problem, but they might not have an appreciation of all the perspectives needed for a solution
  • Competitive model: opposing viewpoints argue it out until a solution is chosen. This approach might discourage effective knowledge sharing
  • Collaborative model: engage all stakeholders to find a solution but is a time-consuming process

Other ways to solve this wicked problem include:

  • Shifting the goal of action from “solution” to “intervention”
    • This recognizes that actions occur in an ongoing process, and further actions will always be needed
  • Creating managed networks to tackle federal/provincial/territorial and public/private challenges:
    • This may be the “least bad” way of making wicked problems governable
    • Manage change by charging new networks with meeting national policy standards
    • Draw energized clinical professionals into hybrid-clinical-managerial roles, operate with self-regulation but intervention for lower performers

The following models could be implemented in Canada for integrated stewardship:

  • A model where there is federal control, and resourcing of stewardship follows a central control model
  • A formal collaborative model could offer a way to knit together parallel and similar work across provinces and territories. This could offer some synergy and cohesion through autonomy and self-regulation to work toward common goals
    • Provinces and territories would have groups involved in food animal production and veterinary medicine, medical hospitalization, medical community and pharmacy stakeholders
    • The federal role would be as a centralized network support system where the group develops the goals and evaluation occurs

Currently within Canada, models like CIPARS have been a flagship for bringing together data from different groups and establishing surveillance in different One Health areas. CIPARS has a centralized infrastructure that engages the groups who are doing the work. This is already a mini version of a managed network model. A full federated network could reduce duplicate efforts between provinces through real-time information flow and better dialogue between separate communities of practices, such as policy makers and experts in the field. Additionally, a federal coordinating Council could improve cohesion, transparency and public communication.

Session

What is the vision for antimicrobial stewardship in Human Medicine: Disruption, Growth and Progress?

Day 3 Panel Discussion Summary

What is the Vision for Antimicrobial Stewardship?

This discussion period covered a variety of themes and questions put forth by the audience for the panel members.

The definition, vision and perception of stewardship can be variable. How do we bring these stewardship definitions together – what does this look like?

Many people have perceived needs and have articulated them in remarkably similar ways. There is a great common understanding. A big concept in stewardship is sustainability, where the value of antimicrobials is important. The infrastructure required to thoughtfully design a collaborative stewardship network is possible. Being able to bring these activities together across the different domains of human health, public health, veterinary public health, veterinary medicine, animal agriculture and environmental health is critical. We need to use out-of-the box thinking and engage with non-traditional stakeholders, starting at a grassroots level, trying to move away from recommendations and move to more of a sense of engagement and support. This applies to both the public and private sectors. In order for interventions to be feasible long-term, we need to understand that different groups already know their needs well and have ideas on how to approach those needs. When speaking of stewardship, there has been a change from a top-down to bottom-up approach, but in the animal health regulatory field this is still being directed in black and white ways through policing antimicrobial use and resistance rather than bringing together stakeholders to have important conversations to develop something feasible at the global level. Regulations need to be feasible for compliance, and government agencies need to work together.

PHAC is funding a group to develop an AMR Network. Does Canada’s Federal-Provincial/Territorial (FPT) structure require political buy-in or political distance to make this successful? In Alberta, the political will is for made-in-Alberta solutions, for example. How do we deal with potential political division?

Some of what we have now is working because it is separate from politics. In CIPARS, there is academic collaboration that forms a de-facto network that skips the FPT level, but skipping that level weakens the structure. We have not tried to tackle that head on, but during this global COVID-19 public health challenge could be the time to take it into a political arena. We have to have a cohesive response. The message does not seem to get through politically, no matter how many different approaches we take. The made-in-Alberta suggestion begs the question of “do you understand the scope of the problem?” 

Is Canada ready to set targets for reductions in volume of antimicrobial use? Global solutions are required, but we act at national levels and must also act within our FPT structure in Canada.

The concept of thresholds is most relevant where robust data are available to inform what a reasonable amount of use is, or examples from elsewhere where decreasing AMU has not had significant negative impacts. People can respond to a target — it is a palpable thing, so it depends on the scenario. Stewardship should not just be about the drugs and/or tools, it needs to be about the population in question, and the microbes as well. 

Stewardship is not a quick fix, but quick wins that individuals can identify within their own context are important. How can we pursue this? It feels like an imperative in a rapidly changing and dynamic environment that is distracted by so many other factors.

It took the global pandemic for governments to realize that vaccine confidence and hesitancy are a big deal and this one-size approach of telling people to take the vaccine did not fit. We have to realize that everybody has different reasons for hesitancy. This is a complex issue but in order to build trust for people to buy in, we definitely need the government/political buy-in. However, on the ground you need people with common ground to build trust — those are the local champions within the various fields. Implementation science, or process-based approaches where you are able to set metrics for your progress toward a goal, are really useful from the high-level perspective. Relating to the people who do not think that AMR and AMS mean anything to them, personally or professionally, is critically important. It is hard for government when this is not one particular organization from the industry side to communicate to the general producer or general public. 

Who should be educating the public on the critical impact of AMR and stewardship, and where is the opportunity for public education campaigns like “Do Bugs Need Drugs”? How important is it to get the general public involved in understanding stewardship and what’s the best way to do it?

People are increasingly and incredibly engaged in public health and biomedical research over the last year. Although this interest was born out of desperation and necessity, it has become normal to have scientists, epidemiologists and doctors talking about high-end scientific concepts on a regular basis. Is there a way we can leverage this level of public engagement? When all of the communication around the pandemic finally ends, there will be a void during which there will still be an activated public and that provides an opportunity to work with them. The public is somewhat used to being lectured about not taking antimicrobials, so we have to make sure the message remains fresh and more sophisticated because it is a more sophisticated group now. We need public outreach but maybe we need to move away from decision making and have the sustainable approach be the default. An example is removing triclosan from soap. There is varied knowledge across groups so there is a certain requirement of education. In addition to public engagement, there is a need for discussion at the point of care when consideration of use of an antimicrobial is happening. The prescriber needs to be primed to discuss this with members of the public as well. A lot of people know about AMR or stewardship in some form, but there is a worry that things will only happen if there is a regulatory requirement that needs to be met.

How do you actually evaluate the impacts of a specific intervention when you have got these things happening at the same time or with complicated measurements?

If you are going to have an intervention, you should have something you can follow and measure. If you do a targeted intervention that involves audit and feedback in a particular domain, you can follow that. When we look at the large-scale desires of stewardship in terms of overall antimicrobial use, small changes in a lot of different areas might make a larger collective difference in terms of antimicrobial exposure that is clinically meaningful. You have to make sure the metric makes sense for what you are looking at.

Do we need Canadian manufacturing to support vaccines and other interventions for a real made-in-Canada solution? In a world where cradle-to-grave interests are growing, what is the increasing responsibility of product stewardship by manufacturers regarding product lifecycle?      

We do not even have that for plastics and other macro scale waste, much less things that are very difficult to see, such as antimicrobials. If we had that kind of approach, what would it take to incentivize industry to be able to build those costs in and to follow products all the way through to disposal? Not just antimicrobial return programs. How do we handle, for example, excretion of antimicrobials by animals into the environment? In Canada we have recovery of unused medicines but it is hard to know how efficient that is. When a product is sold, you have no idea how much actually goes into an animal and where unused product ends up.

Dr. Constantinescu talked about a hierarchy of experience being an impediment to prudent decision making and use. How might a managed network approach consider this?

A managed network requires a feedback loop so that quality assurance is monitored and unintended consequences can be identified. You have to pass on control in terms of evaluation and implementation in order to remove hierarchy.

Where does maternal-fetal health fit into the stewardship spectrum and does antimicrobial use during pregnancy affect resistance in the mother and the baby and are there any gains there we should be thinking of? 

There are a lot of unknowns, lack of data, etc. We have our short list of safe drugs and we try to use medications very responsibly in pregnancy to minimize exposure because of those unknowns. Part of the issue is we do not really know who “owns” this area. We know that if moms are on antimicrobials during pregnancy, we do see higher rates of resistance in babies when they come in with invasive infections. There are huge implications to the microbiome — how huge, we do not know. Pregnant women are notoriously not included in studies and this may be why recommendations take so long to change in this field. 

Realizing that there are some differences between WHO, OIE and Health Canada’s antimicrobial categorization, how can we build on or apply stewardship groups for human health in the Canadian context?

The concept of the groupings came forward from trying to de-emphasize certain antimicrobials from widespread use in animal health because of their potential impacts of resistance in human health. There has been a default categorization that is starting to evolve when we think about the stewardship of specific antimicrobials in human health (i.e., fluoroquinolones are now the bad guys and trying to de-emphasize them in first-line therapy). So, there is some categorization but we are limited because in human health we are always reacting with both empirical and targeted therapy. Antimicrobial studies should include more ecologic data on the incidence of resistance that happens when you use that antimicrobial in terms of that person’s flora. 

Can the stewardship of antimicrobials be tied to changes in animal stewardship or husbandry? Is the public willing to pay the resulting cost for reduction in antimicrobial use for some of these stewardship changes?

We are seeing food price increases related to animal feed and a variety of other things. If we do get carbon taxes incorporated properly into food prices, then consumers will recognize this cost. 

Use the term antimicrobial footprint as carbon footprint is used. Everyone using/giving antimicrobials leaves a footprint.

Again, this is a global problem because we export a lot of food to countries that are protein or other deficient and we do not want to exacerbate food security problems in low-income countries by raising the cost of food or reducing production due to animal disease. At the same time, we have to recognize that we cannot continue to create externalities from our food production system. They have to be costed properly. In some countries, the connection between antimicrobial use and animal welfare/husbandry has not been communicated well.

Panelists

Call to Action

A One Health antimicrobial stewardship approach is fundamental to enacting and sustaining change over time. The issue of Stewardship has progressed significantly in the last several years, but we are not at the finish line and collaborated efforts must continue moving forward.

Stakeholders on this issue need to consider next steps, including ongoing mechanisms for networking and communicating (future western Canadian events), and the development of a national communications and surveillance network.

Appendix

Other Resources

NCCID (2014-2019)

Progress on Integrated Antimicrobial Resistance and Antimicrobial Use Surveillance in Canada (2014-2019):
https://nccid.ca/publications/progress-on-integrated-antimicrobial-resistance-and-antimicrobial-use-surveillance-in-canada/

Frontiers in Public Health (2021) Novel Tool for Evaluating Integrated, One Health Antimicrobial Resistance and Antimicrobial Use Surveillance Programs: https://www.frontiersin.org/articles/10.3389/fpubh.2021.693703/

A second peer-reviewed manuscript on the results of the evaluation is in press, jointly, at the Canadian Veterinary Journal and the Canadian Journal for Public Health

NCCID (2014) Surveillance of Antimicrobial Resistance and Antimicrobial Utilization in Canada https://nccid.ca/publications/surveillance-of-antimicrobial-resistance-and-antimicrobial-utilization-in-canada/

FAO. (2016). (rep.). The FAO Action Plan on Antimicrobial Resistance 2016-2020.

Retrieved from
http://www.fao.org/3/i5996e/i5996e.pdf

OIE. (2016). (rep.). The OIE Strategy on Antimicrobial Resistance and the Prudent Use of Antimicrobials.

Retrieved from
https://www.oie.int/app/uploads/2021/03/en-oie-amrstrategy.pdf

WHO. (2015). (rep.). Global action plan on antimicrobial resistance.

Retrieved from
https://www.who.int/publications/i/item/9789241509763

Useful Links

https://nccid.ca/
At the National Collaborating Centre for Infectious Diseases, we specialize in forging connections between those who generate and those who use infectious disease public health knowledge. Working across disciplines, sectors and jurisdictions, NCCID is uniquely situated to facilitate the creation and operation of networks and partnerships.

www.climatechangeandglobalhealth.com
The Climate Change and Global Health Research Group conducts community-based, participatory epidemiology at the social-environment-health nexus, in the context of global environmental change. Our group’s current research focus involves working with intersectoral partners to respond to the grand challenge of developing an evidence base for policies, interventions, and actions needed to moderate future climate change impacts on health outcomes around the world.

www.heat-amr.com
The Human-Environment-Animal Transdisciplinary Antimicrobial Resistance (AMR) Research Group conducts research on the One Health epidemiology of AMR at the intersection of human, environmental and animal health.
The core focus of HEAT-AMR is to develop an evidence base to inform policies, interventions and actions that utilize a One Health approach to tackle AMR.

https://research.ucalgary.ca/one-health
One Health at UCalgary (OH@UC) was founded in 2019 with funding as an emerging, cross-cutting research theme from the Office of the Vice-President (Research). We are committed to tackling complex problems at the convergence of people, animals, and the environment and the underlying economic and social factors that determine the opportunities for health across all ecosystems. Using a One Health approach we will develop research, training, and community engagement programs to meet that commitment.

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