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
Disclosure No conflicts with this presentation
OUTLINE The Problem The Challenges The Opportunities
The Problem IOM Definition of Emerging Infections 1992 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.
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 behavior Technology and industry Economic development and land use International travel and commerce Microbial adaptation and change Breakdown of public health measures Human susceptibility to infection Climate and weather Changing ecosystems Poverty and social inequality War and famine Lack of political will Intent to harm *Boldface indicates factors that contributed to the emergence and spread of antimicrobial resistance.
The Washington Post March 16, 1993 In 2002, out of 89 new drugs, no new antibiotics were approved.
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.
% Resistance World Health Day April 7, 2011 # Drug Approvals BMJ 2010;340:1115-18 Market Failure ESKAPE Bugs Bad Bugs / No Drugs No Action Today, No Cure Tomorrow Innovation Gap 10 x 20 Combating Antimicrobial Resistance: Policy Recommendations to Save Lives
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/
WHO AR Priorities Priority Pathogens E. coli res to 3 rd gen cephalosporins & FQs K. pneumoniae res to 3 rd gen cephalosporins & carbapenems MRSA Pcn-resistant S. pneumoniae FQ-resistant Salmonella FQ-resistant Shigella N. gonorrhoeae with decreased suscept to 3 rd gen cephalosporins http://www.who.int/drugresistance/documents/surveillancereport/en/
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
IOM Forum on Microbial Threats 2010 2012 Antibiotics as a Global Public Good
Microbial Adaptation and Change THE NEW YORKER, January 12, 1998 10 x 20
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
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
Preventing Antimicrobial Resistance in Healthcare Settings and the Community
Core Elements Leadership commitment Accountability (single leader) Drug expertise (pharmacist) Action (recommendation implementation) Surveillance (usage and resistance Education (prescribers) Data sharing
Game Changers Culture Independent Diagnostic Testing Whole Genome Sequencing Bioinformatics Healthcare Reform Electronic Health Records Social Media One Health
The Opportunities One Health Humans Domestic Animals Ecosystems Wildlife http://www.onehealthcommission.org/
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
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
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
Problem Report to The President on Combating Antibiotic-Resistant Bacteria PCAST September 2014 ~ 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
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
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
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
Needs for Moving Forward on Shared commitment Shared Stewardship 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
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 agriculture 1 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
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
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
Acknowledgements Emory Dianne Miller Samantha Lammie CDC Steve Solomon Rob Tauxe Jeff Morelli