Combating Antimicrobial Resistance: The Way Forward - Dr. James Hughes, Professor of Medicine and Public Health with Joint Appointments in the School of Medicine and the Rollins School of Public Health at Emory University, from the 2014 NIAA Symposium on Antibiotics Use and Resistance: Moving Forward Through Shared Stewardship, November 12-14, 2014, Atlanta, Georgia, USA. More presentations at http://www.swinecast.com/2014-niaa-antibiotics-moving-forward-through-shared-stewardship

1. Combating Antimicrobial Resistance:
The Way Forward
James M. Hughes, MD
Professor of Medicine and Public Health
Emory University
Atlanta, GA
NIAA Antibiotic Symposium
November 14, 2014

2. Disclosure
No conflicts with this presentation

3. OUTLINE
 The Problem
 The Challenges
 The Opportunities

4. IOM Definition of Emerging Infections
New, reemerging or
drug-resistant
infections whose
incidence in humans
has increased within
the past two decades
or whose incidence
threatens to increase
in the near future.
1992
The Problem

5. Table. Factors contributing to the emergence of infectious
diseases according to IOM reports, 1992 and 2003
1992 IOM Report 2003 IOM Report
Human demographics and
Human susceptibility to
behavior
infection
Technology and industry Climate and weather
Economic development and
land use
Changing ecosystems
International travel and
commerce
Poverty and social inequality
Microbial adaptation and
change
War and famine
Breakdown of public health
measures
Lack of political will
Intent to harm
*Boldface indicates factors that contributed to the emergence
and spread of antimicrobial resistance.

6. The Washington Post
March 16, 1993
“In 2002, out of
89 new drugs, no
new antibiotics
were approved.”

8. The Challenges
Public Health Surveillance
 Ongoing, systematic collection, analysis,
and interpretation of outcome-specific data
 Closely integrated with the timely
dissemination of these data to those
responsible for taking public health action
to prevent and control disease or injury
Thacker SB. In: Principles and Practices of
Public Health Surveillance. New York:
Oxford University Press, 2000.

9. Resistance
World Health Day
April 7, 2011
Market Failure Innovation Gap
ESKAPE Bugs
Bad Bugs / No Drugs
“10 x ‘20”
“No Action Today,
No Cure Tomorrow”
BMJ 2010;340:1115-18
%
Drug Approvals
#
Combating Antimicrobial Resistance:
Policy Recommendations to Save Lives

10. CDC AR Threats
Urgent Threats (3)
• C. difficile
• CRE
• Resistant N. gonorrhoeae
Serious Threats (12)
• MDR Acinetobacter
• ESBLs
• MDR P. aeruginosa
• VRE
• MRSA
• Drug-resistant S. pneumoniae, NT
Salmonella, Campylobacter
Concerning Threats (3)
• VRSA
• Erythro-res GAS
• Clinda-res GBS
http://www.cdc.gov/drugresistance/threat-report-2013/

11. WHO AR Priorities
Priority Pathogens
• E. coli res to 3rd gen cephalosporins
& FQs
• K. pneumoniae res to 3rd gen
cephalosporins & carbapenems
• MRSA
• Pcn-resistant S. pneumoniae
• FQ-resistant Salmonella
• FQ-resistant Shigella
• N. gonorrhoeae with decreased
suscept to 3rd gen cephalosporins
http://www.who.int/drugresistance/documents/surveillancereport/en/

12. “A robust public health
system— in its science,
capacity, practice, and
through its collaborations
with clinical and veterinary
medicine, academia,
industry and other public
and private partners—is the
best defense against any
microbial threat.” 2003

13. IOM Forum on Microbial Threats
2010 2012
Antibiotics as a Global Public Good

14. Microbial Adaptation and Change
THE NEW YORKER, January 12, 1998 “10 x 20”

15. IDSA AR Priorities
 Drug Development Pipeline
 Bad Bugs, No Drugs
 “10 by 20”
 Increased Support for Basic and Translational
Research
 Rapid Point of Case Diagnostics
 Surveillance of Use & Resistance
 Humans and Animals
 Antimicrobial Stewardship
 Regulatory Reform for Clinical Trial Design and
New Antibacterial Drug Approval

16. Combating Antimicrobial Resistance:
Policy Recommendations to Save Lives
 Economic Incentives
 New Regulatory Approaches
 Stronger Leadership and Improved
Coordination of Federal Agencies
 Enhanced Surveillance Systems
 Strengthened Prevention & Control
Programs
 Funds for New Drug R & D
 Rapid Diagnostics R & D
 Elimination of Non-Judicious Use in
Animals, Plants, & Marine
Environments
IDSA Clin Inf Dis 2011;52(Suppl 5):S397-428

17. Preventing Antimicrobial Resistance in
Healthcare Settings and the Community

18. Core Elements
• Leadership commitment
• Accountability (single
leader)
• Drug expertise
(pharmacist)
• Action (recommendation
implementation)
• Surveillance (usage and
resistance
• Education (prescribers)
• Data sharing

19. Game Changers
 Culture Independent Diagnostic Testing
 Whole Genome Sequencing
 Bioinformatics
 Healthcare Reform
 Electronic Health Records
 Social Media
 One Health

20. The Opportunities
“One Health”
Humans
Domestic
Animals
Ecosystems
Wildlife
http://www.onehealthcommission.org/

21. Common Ground for Medical and
Veterinary Communities
 Antimicrobial resistance and usage
 Avian, animal, and pandemic influenza
 Other zoonotic diseases including those
associated with exotic pet and wildlife trade
 Foodborne disease
 Healthcare-associated infections
 Blood, organ, tissue safety
 Pathogen discovery / new diagnostics
 Drug and vaccine development
 Disease eradication
 Biosafety / Biosecurity
 Bioterrorism / Biodefense

22. President Obama
Executive Order
Combating Antibiotic-Resistant Bacteria
9/18/14
 National Security Priority
 Interagency Task Force
 Co-chairs: Secretaries of HHS, USDA, DoD
 5 year National Action Plan by 2/15/15
 Presidential Advisory Council
 Stewardship (humans & animals)
 Surveillance (repositories, curated genomic databases)
 Outbreak Response
 New Drugs
 Rapid Diagnostics
 Increased International Cooperation

23. National Strategy on
Combating Antibiotic-Resistant Bacteria
White House
September 2014
Goals
• Slow emergence / prevent spread
• Strengthen “One Health” surveillance
• Develop rapid diagnostics*
• Accelerate basic and applied R&D
• New antibiotics
• Other therapeutics
• Vaccines
• Improve international collaboration
*$20M prize for rapid PoC diagnostic for “highly resistant bacterial
infections”, co-sponsored by BARDA & NIAID
http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf

24. Report to The President on
Combating Antibiotic-Resistant Bacteria
PCAST
September 2014
Problem
• ~ 2M infections, 23K deaths
• $55 – 70B in direct & indirect costs
Recommendations
• Strong federal leadership
• Effective surveillance & response
• Genomics component
• Expanded fundamental research
• Robust clinical trial infrastructure & new
regulatory pathways
• Economic incentives for drug development,
stewardship programs, & rapid diagnostics
• Decreased use in animal agriculture
• Ensure international co-operation
http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/pcast_carb_report_sept2014.pdf

25. Ways Forward For Shared Stewardship
• Replace the use of antibiotics when possible
– Human medicine
• Prevention—vaccination, infection control, preventive
medicine
– Animal medicine and agriculture
• Vaccines, immunomodulators, farming practices

26. Ways Forward For Shared Stewardship
• Reduce the use of antibiotics when possible
– Human medicine
• Stewardship programs in healthcare—e.g., automatic
stop orders
• Outpatient physician feedback and prescriber
education—e.g., reduce prescribing for URT infections
– Animal medicine and agriculture
• Eliminate use of medically important antibiotics for
growth promotion

27. Ways Forward For Shared Stewardship
• Refine the use of antibiotics
– Human medicine
• Right drug, right dose, right duration
• NHSN antibiotic use monitoring as a quality measure
– Animal medicine and agriculture
• Require veterinary oversight
• Decrease use of critically important antibiotics
• Monitor use in animal agriculture, including
development of metrics

28. Needs for Moving Forward on
Shared Stewardship
• Shared commitment
– Continuing dialogue, willingness to listen
• Better data on use for humans and animals
– Partnership between USDA, FDA and CDC
(equivalent of NARMS for antibiotic usage) in
collaboration with healthcare and food and
pharmaceutical industries

29. Needs for Moving Forward on
Shared Stewardship
• Communication
• Adopting a One-Health approach
• Developing a shared language for human and
veterinary medicine, industry, consumers, advocates
• Research
• Better quantitation of the relationship between
agricultural use and resistance in human infections
• Alternatives to antibiotic use in human and veterinary
medicine and agriculture1
• Better ways to implement stewardship in human
medicine
1. PCAST report,
http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/pcast_carb_report_sept2014.pdf

30. Transatlantic Task Force on
Antimicrobial Resistance
• Activity #18: Establish a joint working group of
international subject matter experts to identify key
knowledge gaps in understanding the transmission to
man of antimicrobial resistance arising as a result of
the use of antimicrobial drugs in animals and on the
development of effective intervention measures to
prevent this transmission, including the development
of alternatives to antimicrobial drugs.
http://www.cdc.gov/drugresistance/pdf/TATFAR-Progress_report_2014.pdf page 17

31. Conclusions
 Move beyond “the blame game”
 Respond to and leverage Executive Order, CARB
National Strategy, and PCAST recommendations
 Identify priorities and develop metrics
 Shared commitment to antimicrobial stewardship
 Shared commitment to development of better data on
usage and resistance in various settings
 Development of a collaborative research agenda to
improve evidence base
 Shared commitment to communication and
collaboration with professional societies public /
private sector partners, and the public

32. Acknowledgements
Emory
Dianne Miller
Samantha Lammie
CDC
Steve Solomon
Rob Tauxe
Jeff Morelli