Where are we with resistance in
veterinary medicine?
Are we having an effect on
human medicine?
Mike Apley
Kansas State Un...
Antimicrobial Timeline
2003 - Daptomycin – cyclic lipopeptides
2000 - Linezolid - oxazolidinones
1978 - Norfloxacin - fluo...
The Basics of Clinical Pharmacology
(in one slide)
•
•
•
•

Can I do some good?
Can I do any harm?
Can I get it in the ani...
First, what are we using in food
animals?
Cattle Approvals
Oral and FEED neomycin

INJ and IMM ceftiofur, IMM
cephapirin
FEED monensin, lasaslocid

29%

IMM pirlimy...
These antimicrobials are not on the list of “medically important” as defined
by the FDA/CVM in Guidance 152

Apley M, Bush...
533,973

64% of medically
important use
154,956

66% of medically
important P and T

15%

39%

46%

165,803
Are we having an effect on human
medicine?
• For me, I accept that antimicrobial use in food
animals can change bacterial ...
The responsible conversation which
will move us forward involves
discussion of specific antimicrobial
uses in relation to ...
Organisms of specific interest to me
•
•
•
•

Salmonella
Campylobacter
Staphylococcus aureus
Bacteria of animal origin fou...
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...
The Thought Process
Bacterial populations exposed to
antimicrobials on farm
Selection for resistant organisms on
farm

Rel...
Risk for foodborne effects?

Risk

Birth

Market
Timing of Antimicrobial Use
Resistance Challenges in Vet Medicine
• Weese has published an excellent review of antimicrobial
resistance issues in comp...
What about food animals?
• Bovine respiratory disease
– Mannheimia haemolytica and Pasteurella
multocida
My Definition of Judicious Use
• There is not an effective alternative to the
antimicrobial for treatment or prevention of...
My Definition of Judicious Use
• There is evidence that the antimicrobial will
be safe and effective for this use
– What i...
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

# stud...
My Definition of Judicious Use
• There is a commitment to administering the
antimicrobial according to the regimen
demonst...
My Definition of Judicious Use
• There is a constant search for alternative
management practices which would alleviate
the...
Control of Veterinary Antimicrobials…
• should be in the hands of veterinarians, and…
• training and information availabil...
Training
• Veterinary school is a good for training to start
• Post-graduate training is imperative
• What is most essenti...
Antimicrobial Use Statistics
• The Danish model?
• Reporting burden?
• What are we worried about?
Getting “policied”
• Cephalosporin ELDU prohibition in food
animals
– Retains the ability to use cephalosporins for
extral...
Direct quote
• Cephalosporin order of ELDU prohibition
• “However, the Agency believes that it is not
limited to making ri...
Immediate Gains
• Win/Win strategies
– Are we getting benefits from all of our current
uses?
– Are dosing regimens optimiz...
The Bottom Line for Veterinarians
• Will we retain our relevancy to antimicrobial
use decisions in food animals, or…
• wil...
Definitions
• Complacent: marked by self-satisfaction
especially when accompanied by unawareness
of actual dangers or defi...
How Things Work
Producer
Packer
Retail and
Restaurant
Consumer
Animal Agriculture Evolution
• Cost and availability of
–
–
–
–
–
–
–

Land
Animals
Feed
Fuel
Labor
Water
Prevention and t...
Things that are broken
• Our understanding of the relationship of
magnitude and duration of exposure with
relation to resi...
So where to from here
• Veterinarians should have control of all uses of
antimicrobials in animals.
• Emphasize veterinary...
So where to from here
• Revisit efficacy research for many of the
preventive applications (especially administered
to a gr...
Dr. Mike Apley - Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine?
Dr. Mike Apley - Where Are We With Resistance in Vet Medicine? Are We Having An Effect on Human Medicine?
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 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.

More presentations at http://www.trufflemedia.com/agmedia/conference/2013-niaa-antibiotics-bridging-the-gap-animal-health-human-health

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

  1. 1. Where are we with resistance in veterinary medicine? Are we having an effect on human medicine? Mike Apley Kansas State University
  2. 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. 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. 4. First, what are we using in food animals?
  5. 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. 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. 7. 533,973 64% of medically important use 154,956 66% of medically important P and T 15% 39% 46% 165,803
  8. 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. 9. The responsible conversation which will move us forward involves discussion of specific antimicrobial uses in relation to specific pathogens and epidemiological links
  10. 10. Organisms of specific interest to me • • • • Salmonella Campylobacter Staphylococcus aureus Bacteria of animal origin found on food products
  11. 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. 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. 13. Risk for foodborne effects? Risk Birth Market Timing of Antimicrobial Use
  14. 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. 15. What about food animals? • Bovine respiratory disease – Mannheimia haemolytica and Pasteurella multocida
  16. 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. 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. 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. 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. 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. 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. 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. 23. Antimicrobial Use Statistics • The Danish model? • Reporting burden? • What are we worried about?
  24. 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. 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. 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. 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. 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. 29. How Things Work Producer Packer Retail and Restaurant Consumer
  30. 30. Animal Agriculture Evolution • Cost and availability of – – – – – – – Land Animals Feed Fuel Labor Water Prevention and therapeutic options • Regulation • Consumers
  31. 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. 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. 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)

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