One Health Antibiotic Stewardship State of Science - What Do We Know? What Don't We Know? - Dr. Rick Sibbel, Executive Director, Technical Service, Food Animal Business Team, Merck Animal Health; Dr. Larry Granger, Senior Leader of Antimicrobial Resistance, USDA APHIS; Dr. Shelley Rankin, Associate Professor CE of Microbiology, School of Veterinary Medicine, University of Pennsylvania; Dr. Mark G. Papich, Professor, Clinical Pharmacology, North Carolina State University; Dr. Patrick McDermott, Director, National Antimicrobial Resistance Monitoring System, FDA Center for Veterinary Medicine, from the 2017 NIAA Antibiotic Symposium - Antibiotic Stewardship: Collaborative Strategy for Animal Agriculture and Human Health, October 31 - November 2, 2017, Herndon, Virginia, USA. More presentations at http://www.swinecast.com/2017-niaa-antibiotic-symposium-antibiotic-stewardship

1. State of the Science - What Do We Know? What
Don't We Know?
November 1, 2017
NIAA
Larry Granger, D.V.M.
larry.m.granger@aphis.usda.gov
Senior Leader – Antimicrobial Resistance
Animal and Plant Health Inspection Service
Veterinary Services

2. Ramblings of a Mad Man.
A Philosophy of Science.
40 Years
in Veterinary Medicine.
The Dedicated Public Servant.
Rantings

3. USDA National Animal Health
Monitoring System
Antimicrobial Use Studies
Kathe Bjork
U.S. Department of Agriculture
Animal and Plant Health Inspection Service
Veterinary Services – NAHMS
October, 2017
NARMS Public Meeting - October 25, 2017

4. NARMS Public Meeting - October 25, 2017
FY2017 Appropriation
• Collect on-farm data to inform policy related to appropriate antibiotic use
in agricultural settings and clinical veterinary medicine.
• Conduct on-farm surveillance, sampling and testing to enhance
understanding of levels of antibiotic use and the impact on antimicrobial
resistance levels.
USDA AMR Action Plan Objectives (2015)
•Longitudinal studies to collect data on antimicrobial use and
management practices; biological samples from the farm and at
slaughter.
•Antibiotic use, AMR patterns, management practices
•Relationships, trends over time
•Measure the effectiveness of policies and interventions in reducing AMR.

5. NARMS Public Meeting - October 25, 2017
Farm Management
Production Environment
Animal Health / Well-Being
Antimicrobial Use Antimicrobial
Resistance
Surveillance &
Monitoring
Epidemiologic
Research
Stakeholders &
Partners
Education &
Outreach

6. NARMS Public Meeting - October 25, 2017
What it takes
Survey Participants
• Operators and producers
Development and Implementation
• Animal industry
• Respondents to public notices
Operations
• Field Staff
www.aphis.usda.gov/aphis/ourfocus/animalhealth/monitoring-and-
surveillance/nahms

7. NARMS Public Meeting - October 25, 2017
Study Status
• Field operations May-September 2017
• Data collection complete September 30
• Data entry / validation
• Analysis / reports
• Final mid-2018

8. National Animal Health Laboratory Network (NAHLN)
• Pilot project design finalized for implementing AMR monitoring in veterinary
diagnostic labs
• Year 1 of the pilot project FY 2018.
• Antimicrobial susceptibility (animal pathogen testing)
• E. coli, Salmonella spp., Staphylococcus intermedius and Mannheimia haemolytica
• cattle, swine, poultry, horses, dogs and cats.
• Target at least 3000 samples across all laboratories
• Reports will be generated to inform Veterinary practitioners
• Influence prescription / stewardship behavior
• Metadata
8

9. National Veterinary Accreditation Program (NVAP)
• NVAP Module 23: Use of Antibiotics in Animals (2012)
• completed over 21,900 times by accredited veterinarians
• (G7) meeting in Germany in 2015, Module 23 was one of only two “Best Practices of Combating
Antimicrobial Resistance” from North America
• NVAP Module 29: Veterinary Feed Directive (2017)
• completed by over 4,000 accredited veterinarians, and quickly became the most viewed module in
NVAP’s training suite in early 2017.
• “agriculturalist” users exceeds veterinarian audience three-fold. Comments and questions from
these “agriculturalists” indicate that they include, but are not limited to, feed manufacturers, feed
mill owners/operators, feedlot personnel, and livestock producers.
• Beekeeping module to be completed by the summer of 2018.
• All modules are now a source of no-cost RACE-approved https://www.aavsb.org/race/
continuing education to satisfy veterinary professional license renewal requirements.
• Recognized by national associations of veterinary technicians and veterinary hospital managers
9

10. 10

12. State of the Science
• Single cell prokaryotes,
“Isolates”and cultures
• Differences (culture, WGS, SNP)
• Good bugs/Bad bugs, adaptation
• Aggregation
• Cause and effect
• Predictability
• Conformation
• Central control - bug/drug
• Repeatable
• Scientific Method
• Interconnected, multicellular
behavior
• Self similarity
• Constantly evolving, exaptation
• Dynamic, Networks of interactions
• Extremely non-linear
• Possibility, unpredictable
• Coherence
• Self organization, Emergence
• Patterns

13. The Microbial World is a Complex Adaptive
System
• Complexity is proven to be a fundamental feature of our world that is does not
provide an explanation universally acceptable to the tradition and methods of
modern science.
• Complexity can only be understood in the context of multi-disciplinary
perspectives. This is One Health. (not the “only health”)
• Open systems make it difficult or impossible to define system boundaries.
• Complex systems operate under conditions far from equilibrium, negative and
positive feedback loops.
• Complex systems have history that is responsible for their present behavior, yet
display high dependence on initial conditions.
• The behavior of the system is impossible to predict just by understanding the
traits of the individual elements or agents.
• Agents are independent actors and respond only to the information or physical
stimuli available to them locally.

14. • Antibiotic use represents a perturbation to a complex adaptive
system.
• In a population of animals affected by disease, antibiotics always
affect R0. The immune system of macrobiotic organisms is also a CAS.
• The biome is resilient over 4.5 billion years, the resistome is an
incredibly small part of that in proportion.
• Some properties of bacteria are readily apparent only when there are
enough of them communicating in such a way as for the system itself
to exhibit muliticellular behavior. (emergent properties)
The prokaryote is single celled, and it contains genetic material that it replicates
when it divides, but how and when it does that depends on nutrients and signals
from its local environment.
“All the King’s horses and all the King’s men couldn’t put Humpty Dumpty
together again”

15. Cynefin Framework Complicated
Governing Constraints
Cause and Effect, Repeatable, Knowable
Analysis, Probabilities
Realm of the Expert – similar situations produce
similar expected outcomes
Good Practice
Sense – Analyze - Respond
Simple
Rigid Constraints
Repeatable and Predictable
Well Known
Best Practices
Easy – a recipe for success
Sense – Categorize - Respond
Complex
Enabling Constraints
Cause and Effect understood only in retrospect
Unpredictable
Possibilities
Not repeatable, clearly discernable patterns
Guidelines
Probe – Sense - Respond
Chaos
Lacking Constraints
No cause and effect relationships
Unknowable
Never predictable or explainable
Authoritative intervention to achieve stability
Act – Sense - Respond
David Snowden

16. There's nothing you can know that isn't known
Nothing you can see that isn't shown
All You Need is Love, The Beatles John Lennon, Paul McCartney
Vision without action is a daydream. Action without vision is
a nightmare.
A Japanese Proverb