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

1. Ensuring Healthy Animals & Food Safety:
The Need to Preserve Antibiotics
Randall Singer, DVM, MPVM, PhD

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. 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. Antibiotic Use and Resistance
Lipsitch and Samore, Emerg Inf Dis, 2002

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. Antibiotic Use and Resistance
Lipsitch and Samore, Emerg Inf Dis, 2002

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

8. What this issue is NOT about
(Fey et al., N Engl J Med, 2000)

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. 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. 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. 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. 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. The Danish Experience - Resistance
DANMAP 2008

15. The Danish Experience - Resistance
DANMAP 2008

16. The Danish Experience - Resistance
DANMAP 2008

17. Fallacy of Antibiotic Tonnage

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. 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. Plasmid Genomics – The Slippery Slope?
Call et al., Antimicrob. Agents Chemother., 2010

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. 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. 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. 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. 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. 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. 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