Ensuring Healthy Animals & Food Safety:
The Need to Preserve Antibiotics
Randall Singer, DVM, MPVM, PhD
Antibiotic Compounds
Antibiotics
Low molecular-weight compounds that kill or
inhibit the growth of microorganisms
Many ant...
Antibiotic Uses at Risk
Antibiotic Approvals in U.S.
Growth promotion / feed efficiency
Disease prevention
Disease control...
Antibiotic Use and Resistance

Lipsitch and Samore, Emerg Inf Dis, 2002
Antibiotic Use and Resistance
How does this relate to other situations?
Vancomycin-resistant Enterococcus sp.
Methicillin-...
Antibiotic Use and Resistance

Lipsitch and Samore, Emerg Inf Dis, 2002
What this issue is NOT about

(Molbak et al., N Engl J Med, 1999)
What this issue is NOT about

(Fey et al., N Engl J Med, 2000)
Which Antibiotic Use Is Worse?
Which is worse for resistance (and health):
long-term low dose or short-term high dose?
Dog...
Risk Assessment

Assess the potential public health risks relating
to the use of the macrolides tylosin (Tylan®) and
tilmi...
Risk Assessment
Animal MacrolideQuantified Risk to Humans of
Product Resistant Bacteria Treatment Failure Due to a
Resista...
Danish Experience and Public Health
“Based on the experience from human medicine there are good
scientific reasons to advo...
Danish Experience and Public Health
This issue is NOT about VRE or MRSA
What were the human health improvements?

Decrease...
The Danish Experience - Resistance

DANMAP 2008
The Danish Experience - Resistance

DANMAP 2008
The Danish Experience - Resistance

DANMAP 2008
Fallacy of Antibiotic Tonnage
Any Benefit from Animal Antibiotics?
Antibiotics may reduce the incidence of
clinical and subclinical disease in animals
F...
Any Benefit from Animal Antibiotics?
Mathematical model simultaneously
evaluating risks and benefits of AAU
Risk of increa...
Plasmid Genomics – The Slippery Slope?

Call et al., Antimicrob. Agents Chemother., 2010
Effects of Low Antibiotic Levels
For chlortetracycline,
total bacteria counts
did not differ among
chemostats (P = 0.51)
H...
Take Home Messages
Must stop being defensive and insist on
maintaining status quo
Look for changes that we can make that
m...
Take Home Messages

Risk assessments should include evaluations of
potential interventions for reducing the risks to
human...
Take Home Messages
Using the Danish experience as a model, is
this a trade-off?
Chlortetracycline in feed
Third-generation...
Return to the “Family Farm”
Myth – reduction in agricultural antibiotic use is
synonymous with a return to the pasture-bas...
Fallacy of Antibiotic Tonnage
“For production animals, the consumption has
increased gradually by 110% from 1998 through 2...
Fallacy of Antibiotic Tonnage
Many reports like to state the total amount of
antibiotic used in agriculture
All antibiotic...
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Randall Singer - Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics

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Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics - Randall Singer, Ph.D, DVM, Associate Professor, Epidemiology, University of Minnesota, from the 2010 Animal Ag Alliance Stakeholder's Summit: Truth, Lies and Videotape: Is Activism Jeopardizing Our Food Security?, April 28 - 29, 2010, Washington, DC, USA.

More presentations at http://www.trufflemedia.com/home/conference/2010-animal-ag-alliance-stakeholders-summit

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  • In 1913, Ehrlich publishes “Chemotherapeutics: Scientific Principles, Methods and Results” in Lancet
    He states that “treatment should hit hard and early”
    This idea was meant for tuberculosis infections
    Resistance in Mycobacterium tuberculosis is often mediated by a single point mutation
    The goal of treatment is to prevent subpopulations of mutant bacilli (the resistant ones) from emerging
  • Randall Singer - Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics

    1. 1. Ensuring Healthy Animals & Food Safety: The Need to Preserve Antibiotics Randall Singer, DVM, MPVM, PhD
    2. 2. Antibiotic Compounds Antibiotics Low molecular-weight compounds that kill or inhibit the growth of microorganisms Many antibiotics are naturally produced by bacteria or fungi What is the role of antibiotic production in nature?  Germ warfare theory  Levels are low, almost undetectable  Signaling molecules?
    3. 3. Antibiotic Uses at Risk Antibiotic Approvals in U.S. Growth promotion / feed efficiency Disease prevention Disease control Disease treatment Preservation of Antibiotics for Medical Treatment Act (PAMTA - H.R. 1549 / S. 619) Would eliminate 2 – 3 of the currently approved uses
    4. 4. Antibiotic Use and Resistance Lipsitch and Samore, Emerg Inf Dis, 2002
    5. 5. Antibiotic Use and Resistance How does this relate to other situations? Vancomycin-resistant Enterococcus sp. Methicillin-resistant Staphylococcus aureus (MRSA) Both of these are based on the acquisition of genes These resistances are unlikely to occur de novo in a single person or animal following treatment Also important to recognize that these organisms are NOT obligate pathogens
    6. 6. Antibiotic Use and Resistance Lipsitch and Samore, Emerg Inf Dis, 2002
    7. 7. What this issue is NOT about (Molbak et al., N Engl J Med, 1999)
    8. 8. What this issue is NOT about (Fey et al., N Engl J Med, 2000)
    9. 9. Which Antibiotic Use Is Worse? Which is worse for resistance (and health): long-term low dose or short-term high dose? Dogma: high doses given over short term are best Many current research studies show that high doses may select strongly for resistance and spread of resistance - advantage to resistant populations Low doses for growth and disease prevention do not alter the normal bacterial flora in the host – do not kill the susceptible population
    10. 10. Risk Assessment Assess the potential public health risks relating to the use of the macrolides tylosin (Tylan®) and tilmicosin (Pulmotil® and Micotil®) in cattle, swine and poultry Provide input for regulatory decision making by assessing the risks of using these macrolides in food animal production following FDA-CVM Guidance Document #152 (Hurd et al., J Food Prot, 2004)
    11. 11. Risk Assessment Animal MacrolideQuantified Risk to Humans of Product Resistant Bacteria Treatment Failure Due to a Resistant Infection Campylobacter Beef < 1 in 236 million per person per yr E. faecium Poultry Campylobacter < 1 in 29 billion per person per yr < 1 in 14 million per person per yr E. faecium Pork < 1 in 3 billion per person per yr Campylobacter < 1 in 53 million per person per yr E. faecium < 1 in 21 billion per person per yr (Hurd et al., J Food Prot, 2004)
    12. 12. Danish Experience and Public Health “Based on the experience from human medicine there are good scientific reasons to advocate a restrictive and selective veterinary antibiotic policy. First, such a policy will help maintain the possibilities of efficient treatment of infectious diseases in animals, and second it will reduce the risks for human health problems due to the use of antibiotics in animal husbandry.” Wegener, 1998 “The purpose of the interventions were to reduce an observed reservoir in food animals.” Aarestrup, 2010
    13. 13. Danish Experience and Public Health This issue is NOT about VRE or MRSA What were the human health improvements? Decrease in resistance in SOME bacteria to SOME antibiotics in the community and in animal populations
    14. 14. The Danish Experience - Resistance DANMAP 2008
    15. 15. The Danish Experience - Resistance DANMAP 2008
    16. 16. The Danish Experience - Resistance DANMAP 2008
    17. 17. Fallacy of Antibiotic Tonnage
    18. 18. Any Benefit from Animal Antibiotics? Antibiotics may reduce the incidence of clinical and subclinical disease in animals Fewer processing errors Reduced pathogen loads on carcass Reduced incidence of foodborne disease? Documented for airsacculitis in broilers (Russell, Poult Sci, 2003)
    19. 19. Any Benefit from Animal Antibiotics? Mathematical model simultaneously evaluating risks and benefits of AAU Risk of increased resistance Benefit of decreased human illness Potential net benefit to human health from low doses of antibiotic in feed 𝑑𝐼� ሾ 1 = ሾ + 𝑑 × 𝐼� + �ሾ − 𝐼�ሾ × ሾ − 𝐼�ሾ− ℎ × 𝐼� � 1 𝑑� 𝑑𝑅� = ሾ + �ሾ× ሾ − 𝑅� ሾ− � × 𝑅� � 1 𝑑� Singer et al., Prev. Vet. Med., 2007
    20. 20. Plasmid Genomics – The Slippery Slope? Call et al., Antimicrob. Agents Chemother., 2010
    21. 21. Effects of Low Antibiotic Levels For chlortetracycline, total bacteria counts did not differ among chemostats (P = 0.51) High-CTC chemostat selected for CTC resistance (P = 0.03)
    22. 22. Take Home Messages Must stop being defensive and insist on maintaining status quo Look for changes that we can make that might reduce some antibiotic uses Weaning age Stocking density Antibiotic prescription and distribution Danish example – veterinarians can not sell OTC
    23. 23. Take Home Messages Risk assessments should include evaluations of potential interventions for reducing the risks to human and animal health Separate the processing of treated and untreated flocks Clean the house / farm more intensively after use of an important antibiotic Have minimum waiting period until processing of treated flocks (Singer and Hofacre, Avian Dis, 2006)
    24. 24. Take Home Messages Using the Danish experience as a model, is this a trade-off? Chlortetracycline in feed Third-generation cephalosporin or fluoroquinolone in water or by injection
    25. 25. Return to the “Family Farm” Myth – reduction in agricultural antibiotic use is synonymous with a return to the pasture-based “family farm” Denmark example: between 1995 and 2005, swine operations declined from >25,000 to 10,000 Farms became larger and more industrialized
    26. 26. Fallacy of Antibiotic Tonnage “For production animals, the consumption has increased gradually by 110% from 1998 through 2008 (Table 5). During the same period, the meat production has increased by 32%, from 20.8 billion kg to 27.4 billion kg.” (DANMAP 2008) “The overall consumption increased by 1.9% in ADDkg per pig produced from 2007 to 2008, after a 22% increase occurring from 2001 through 2007.” (DANMAP 2008) In his letter to the U.S. House Committee on Agriculture, Dr. Aarestrup uses mg/kg pork produced. This number decreased by 49.8% from 1997-2008.
    27. 27. Fallacy of Antibiotic Tonnage Many reports like to state the total amount of antibiotic used in agriculture All antibiotics, all applications, and all routes of administration are not equal We hear that antibiotics given in feed to promote growth are the “bad” uses As seen in Denmark, therapeutic use of antibiotics, many of which are the EXACT SAME as those that were used in feed, went up following the ban

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