One Health Antibiotic Stewardship Science and Practice - What are the Major Gaps in Knowledge or Translation? How Do We Find the Answers to What We Don't Know? - Dr. Kerry Keffaber, Chief Veterinarian, Scientific Affairs and Policy, Elanco Animal Health; Dr. Jeff Bender, Professor, Environmental Sciences, University of Minnesota; Dr. Nora Schrag, Clinical Assistant Professor/Agricultural Practices, Kansas State University; Mr. Joe Swedberg, Chairman of the Board, Farm Foundation, Hormel Foods Corporation (retired); Dr. David G. White, Associate Dean for Research, University of Tennessee Institute of Agriculture, 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. Can We Build the Perfect One
Health AMR Intersection
David G. White, Ph.D.
2017 NIAA Antibiotic Symposium

2. 2017 NIAA Antibiotic Symposium
• What are the Major Gaps in Knowledge
or Translation?
• How Do We Find the Answers to What
We Don't Know?

3. 2017 NIAA Antibiotic Symposium
• What are the Major Gaps in Knowledge
or Translation?

4. The Antimicrobial Resistome
The resistome comprises all the
antimicrobial resistance genes and
their precursers in pathogenic and
non-pathogenic bacteria (including
antibiotic-producing bacteria)
Wright, G. 2007. Nature Reviews Microbiol. 5:175-186.
ancient, diverse and widespread

5. Genes Move Laterally Through
the Resistome
G.D. Wright, 2012, Antibiotic Resistance, A.R.M Coates, Editor, Handbook of Experimental Pharmacology, Vol. 211.
AMR genes
do not respect
boundries
Very large
gene pool
Canica, M. Res Microbiol. 166:594-600. 2015.

6. Major Gaps
• How do resistance mechanisms evolve over time?
– Origins of resistant genes/organisms
• Resistome
– Diverse selection pressures (heavy metals,
disinfectants, other)
– Establishment and sustainability
• How is resistance transferred and how often
– Mobile elements (plasmids, transposons, integrons)
• Mobilome
– Gene linkage (chimeras)

7. Major Gaps
• What is the contribution of the normal microbiomes
to antimicrobial resistance?
– Disruption consequences
– Return of susceptible populations
– Innocent bystanders
• What factors contribute to the selection and
dissemination of resistant microbes
– Appropriate PK/PD parameters
• Dose, frequency of dose, route of administration, duration
• Optimize therapy while minimizing resistance development
– Organism and host factors

8. Major Gaps
• How important is the environmental dimension of
antimicrobial resistance?
– Anthropogenic impacts in soil and water
– What can be done?
• What are the niches where pathogens and
environmental organisms co-exist
– What drives gene exchange in the environment?
– Are there bottlenecks or can we create ones to prevent
gene transfer
• CTX-M beta-lactamases in Kluyvera
• qnr genes in waterborne Vibrio, Shewanella and Aeromonas

9. 2017 NIAA Antibiotic Symposium
• How Do We Find the Answers to What
We Don't Know?

10. Finding Answers
• Strengthen the Knowledge base
– Identify and prioritize data gaps
• Research, stewardship, infection prevention and control,
diagnostics, product development, alternatives, integrated
surveillance, education/outreach, national policy and guidance,
risk analysis
• Share and align priorities where possible
– Publish findings to various audiences in a timely manner
– Use data to formulate science based pubic health policy
• Develop metrics for success
• Reevaluate over time
– Seek international harmonization and coordination where
possible
– Coordinate and direct resources collaboratively

11. Finding Answers
• Create strategic public-private partnership(s) and
coordinated road maps
– Bridge different sectors and disciplines – gather and
integrate information
– Strengthen partnerships and leverage resources
• Academia
• Industry
• Federal government
• Professional organizations
• Consumer advocacy organizations
• Citizens
– Global consortiums where appropriate
– Develop funding mechanisms
– Action plans – move knowledge to implementation

12. The Future is Round
Building a One Health AMR
Roundabout
Building a One Health AMR
Intersection