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Dr. Mike Apley - Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine?
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Dr. Mike Apley - Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine?


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Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine? - Dr. Mike Apley, Professor, Kansas State University College of Veterinary Medicine, Department of Production …

Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine? - Dr. Mike Apley, Professor, Kansas State University College of Veterinary Medicine, Department of Production Medicine/Clinical Pharmacology, from the 2013 NIAA Symposium Bridging the Gap Between Animal Health and Human Health, November 12-14, 2013, Kansas City, MO, USA.

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  • 1. Where are we with resistance in veterinary medicine? Are we having an effect on human medicine? Mike Apley Kansas State University
  • 2. Antimicrobial Timeline 2003 - Daptomycin – cyclic lipopeptides 2000 - Linezolid - oxazolidinones 1978 - Norfloxacin - fluoroquinolones 1970 – Cefalexin - cephalosporins 1959 – Virginiamycin - streptogramins 1968 - Clindamycin lincosamides 1960 – Metronidazole 1955– Vancomycin - glycopeptides 1949 - Chloramphenicol 1952 – Erythromycin - macrolides 1948 - Chlortetracycline 1935 – Prontosil (sulfanilamide) 1949 – Neomycin - aminoglycosides 1942 - Benzylpenicillin 1910 – Arsphenamine (Salvarsan) – 1912 Neosalvarsan Commercial availability for first member of major antimicrobial groups
  • 3. The Basics of Clinical Pharmacology (in one slide) • • • • Can I do some good? Can I do any harm? Can I get it in the animal(s)? What is the cost?
  • 4. First, what are we using in food animals?
  • 5. Cattle Approvals Oral and FEED neomycin INJ and IMM ceftiofur, IMM cephapirin FEED monensin, lasaslocid 29% IMM pirlimycin INJ tilmicosin, tildipirosin, tulathromycin, gamithromycin, tylosin, FEED tylosin and tilmicosin INJ and IMM penicillin G, ampicillin 42% INJ , WATER, and FEED labels INJ , WATER, and FEED labels INJ florfenicol, fluoroquinolones, FEED virginiamycin 2 Includes antimicrobial drug products which are approved and labeled for use in multiple species, including both foodand nonfood-producing animals, such as dogs and horses. ORAL (administered individually), IMM (intramammary), INJ (injected individually), FEED (administered through feed to groups), WATER (administered in water to groups
  • 6. These antimicrobials are not on the list of “medically important” as defined by the FDA/CVM in Guidance 152 Apley M, Bush E, Morrison B, Singer R, Snelson H. Use estimates of in-feed antimicrobials in swine production in the U.S. Journal of Foodborne Pathogens and Disease, 9, 2012.
  • 7. 533,973 64% of medically important use 154,956 66% of medically important P and T 15% 39% 46% 165,803
  • 8. Are we having an effect on human medicine? • For me, I accept that antimicrobial use in food animals can change bacterial population susceptibility profiles, and that this can lead to resistant pathogens and other microbiota which may then be transferred through the food chain or directly transferred to people, and… • I also accept that there a multiple safe uses of antimicrobials in food animals, which have benefits that outweigh any risks.
  • 9. The responsible conversation which will move us forward involves discussion of specific antimicrobial uses in relation to specific pathogens and epidemiological links
  • 10. Organisms of specific interest to me • • • • Salmonella Campylobacter Staphylococcus aureus Bacteria of animal origin found on food products
  • 11. My Concern • I don’t want us enact policy in the name of human health which results in harm to food animal health but with no benefit, or possibly a detrimental result, to human health.
  • 12. The Thought Process Bacterial populations exposed to antimicrobials on farm Selection for resistant organisms on farm Release Increased incidence of resistant organisms on farm Transfer through the food chain or direct transfer Exposure Presence of food animal derived resistant bacteria in a human Contribution of food animal derived resistant bacteria to human disease Treatment failure or prolonged disease course due to pathogen resistance Consequence
  • 13. Risk for foodborne effects? Risk Birth Market Timing of Antimicrobial Use
  • 14. Resistance Challenges in Vet Medicine • Weese has published an excellent review of antimicrobial resistance issues in companion animals (2008). The primary organisms addressed in this review are as follows. – Staphylococcus aureus and Staphylococcus pseudintermedius: both methicillin susceptible and resistant. – Enterococci: Enterocococcus faecium and Entercoccus faecalis. – Streptococci: Strep. zooepidemicus and Strep. Equi in horses, Strep. canis – Escherichia coli – Salmonella – Pseudomonas Animal Health Research Reviews. 9(2):169-176, 2008.
  • 15. What about food animals? • Bovine respiratory disease – Mannheimia haemolytica and Pasteurella multocida
  • 16. My Definition of Judicious Use • There is not an effective alternative to the antimicrobial for treatment or prevention of disease. – Use of an antimicrobial for therapy or control should not be the permanent solution for an infectious disease challenge
  • 17. My Definition of Judicious Use • There is evidence that the antimicrobial will be safe and effective for this use – What is the expected outcome for an antimicrobial? – Is a 30 year old infectious disease therapy or prevention claim still valid today?
  • 18. Number Needed to Treat by Disease 45 4(2) 3-6 11(5) 1-3 9(5) 2-8 30(9) 1-8 21(7) 2-40 10(7) 2-30 40 35 30 # studies (# drugs) NNT Range 25 20 15 10 7 5 5 5 3 2 2 0 0 Mastitis 1 Footrot 2 Pinkeye 3 Respiratory 4 Success Respiratory 5 Mortality Respiratory 6 Morbidity 7
  • 19. My Definition of Judicious Use • There is a commitment to administering the antimicrobial according to the regimen demonstrated to be safe and effective for this use. – We are severely lacking in information needed to optimize… • duration of therapy, and… • optimal pharmacodynamics for suppression of resistance development for many of our antimicrobial classes
  • 20. My Definition of Judicious Use • There is a constant search for alternative management practices which would alleviate the need for the antimicrobial – This requires a partnership between a veterinarian and a producer
  • 21. Control of Veterinary Antimicrobials… • should be in the hands of veterinarians, and… • training and information availability must be improved for veterinarians across all food animal practice types – Knowledge of antimicrobial clinical pharmacology varies greatly across the profession – Knowledge of regulations and commitment to following them varies across the profession
  • 22. Training • Veterinary school is a good for training to start • Post-graduate training is imperative • What is most essential is an intolerance of inappropriate activities by veterinary and producer organizations
  • 23. Antimicrobial Use Statistics • The Danish model? • Reporting burden? • What are we worried about?
  • 24. Getting “policied” • Cephalosporin ELDU prohibition in food animals – Retains the ability to use cephalosporins for extralabel indications in food animals but prohibits regimen adjustment for the ELDU – Also prohibits regimens which decrease overall exposure of food animals to cephalosporins • e.g., regional intravenous limb perfusion
  • 25. Direct quote • Cephalosporin order of ELDU prohibition • “However, the Agency believes that it is not limited to making risk determinations based solely on documented scientific information, but may use other suitable information as appropriate.’’ • We talk about benefit vs. risk, but we are regulated only on risk.
  • 26. Immediate Gains • Win/Win strategies – Are we getting benefits from all of our current uses? – Are dosing regimens optimized for our current uses? – How do we get optimal use information to veterinarians in the field? – What decision making tools can we put in the hands of veterinarians?
  • 27. The Bottom Line for Veterinarians • Will we retain our relevancy to antimicrobial use decisions in food animals, or… • will we just sign authorizations based on a regulatory formulary developed out of political pressure exerted on regulatory agencies?
  • 28. Definitions • Complacent: marked by self-satisfaction especially when accompanied by unawareness of actual dangers or deficiencies • Complicit: An individual is complicit in an illegal activity if he/she is aware of its occurrence and has the ability to report the activity, but fails to do so.
  • 29. How Things Work Producer Packer Retail and Restaurant Consumer
  • 30. Animal Agriculture Evolution • Cost and availability of – – – – – – – Land Animals Feed Fuel Labor Water Prevention and therapeutic options • Regulation • Consumers
  • 31. Things that are broken • Our understanding of the relationship of magnitude and duration of exposure with relation to resistance development, and… • our understanding of the balance between duration of therapy and treatment success/relapse rates.
  • 32. So where to from here • Veterinarians should have control of all uses of antimicrobials in animals. • Emphasize veterinary education on optimal use of these resources. • Duration of therapy research is an absolute requirement • Continue the emphasis on prevention of infectious disease
  • 33. So where to from here • Revisit efficacy research for many of the preventive applications (especially administered to a group through feed and water) to see if we actually still make a difference. • Enforce our current regulations!! • Include data and the correct analysis in the decision process • It is reasonable to monitor both antibiotic resistance and antibiotic use (also reasonable to have a plan for analysis)