This document discusses antibiotic use in the swine industry and resistance. It notes that resistance generated in animals can spread to humans and cause harm, but evidence of this is minimal. It discusses calls for measuring antibiotic use to support stewardship efforts. Voluntary monitoring programs are being developed to provide representative data while maintaining confidentiality. Overall it examines balancing prudent antibiotic use with animal health and food safety.

1. Antibiotic use in the swine industry
Where is it at, and where is it going?
Peter Davies
University of Minnesota
Carlos Pijoan Lecture

2. Resistance to medically important antibiotics
has been generated in animals…
… and is spread to humans with
the potential to cause major
harm and we..
Must take action to minimize it!
…but the evidence that it has
spread to humans and caused
major harm is minimal or non-
existent and..
No action is required!
2

3. The Antibiotic Resistance Crisis
 Antibiotics are ‘miracle’ drugs
 Efficacy of antibiotics is declining
 Medicine and agriculture have evolved with antibiotics
 Modern medicine is dependent on antibiotic use
 Surgery, transplants, chemotherapy,………
 A tribute to medical advancement
 Modern agriculture is dependent on antibiotic use
 A condemnation of agricultural practices

4. This week in Antibiotic Resistance
 FAO action plan on antibiotics in food production
 FDA call for comment on antibiotics without defined duration
 Citizen petition to FDA to withdraw medically important
antibiotics for disease prevention and growth promotion
 UK Food Systems Agency pledge to reduce use in food animals
 Detailed Dutch report on antibiotic use in food animals
 PACCARB meeting in DC
 UN General Assembly ‘high-level meeting’ Sep 21
 >60 new peer reviewed publications
 421,300 web postings
 3,090 news items

5. The ruling consensus?
 Antibiotic use in food animals is a global issue
associated with public health
 All countries should use antibiotics in food animals
more prudently
 Time to act globally to restrict or prohibit the use of
antibiotics in feed for the purpose of growth
promotion or disease prevention
Dr. Jianzhong Shen

6. ‘Idealism increases
in direct proportion
to one’s distance
from the problem’
John Galsworthy
Nobel Prize in Literature 1932

7. National Pork Board 2015
Prioritized vulnerabilities
1. Antibiotics
2. Foreign animal disease
3. Market preparedness
4. Ethics of pork production
5. Dietary guidelines

8. European antibiotic experiences
Philosophy
1969 1987 2000 2006 2011
Vancomycin R Enterococci, Salmonella DT104, FQ R Campy., LA-MRSA, ESBL, CRE, mcr-1…..

9. Jan1, 2000 Jan1, 2017

10. January 1, 2017
The veterinary profession has been handed the football

11. January 1, 2017
We are playing in a new stadium

12. The spectrum of defensibility
 Growth promotion/OTC not philosophically
defensible regardless of evidence of harm
 Defense of disease prevention and control will
require evidence of benefit to animal health and
welfare
Individual
treatment
of clinically
affected pigs
Batch medication
of healthy and
affected pigs
in outbreaks
‘Production”
Uses
‘Routine’ preventive
medication of
‘at risk’ pigs

13. What really matters?
 Are we doing harm, and how much?
 How do we use antibiotics in the swine industry?
 What is effective?
 What is necessary?
 What is philosophically defensible?
 How good is the evidence?
 Harm to public health
 Benefits to animal health and food safety
 How best to use antibiotics in food animals
 Can we do better?
13

14. The resistance crisis and food animals
What are we talking about?
 All organisms/
genes great and
small
 Vague and not
specific
 Specific pathogens
and antibiotics
 Known public
health impact
 Specific pathogens
and antibiotics
 Equivocal public
health impact

15. Antibiotic resistance threats in the USA
(CDC, Am Fam Physician. 2014 Jun 15;89(12):938-941.)
Urgent
• Clostridium difficile
• Carbapenem-resistant
Enterobacteriaceae
• Drug-resistant N. gonorrhea
Concerning
• Vancomycin-resistant S. aureus
• Erythromycin-resistant group A
Streptococcus
• Clindamycin-resistant group B
Streptococcus
Serious
• Multidrug-resistant Acinetobacter
• Drug-resistant Campylobacter
• Fluconazole-resistant Candida
• ESBL–producing Enterobacteriaceae
• Vancomycin-resistant Enterococcus
• MDR Pseudomonas aeruginosa
• Non-typhoidal Salmonella
• Salmonella serotype Typhi
• Drug-resistant Shigella
• MRSA
• MDR Streptococcus pneumoniae
• Drug-resistant tuberculosis

16. Urgent
• Clostridium difficile
• Carbapenem-resistant
Enterobacteriaceae
Concerning
• Vancomycin-resistant S. aureus
•
•
Serious
• Multidrug-resistant Acinetobacter
• Drug-resistant Campylobacter
• ESBL–producing Enterobacteriaceae
• Vancomycin-resistant Enterococcus
• Non-typhoidal Salmonella
MRSA
Antibiotic resistance threats in the USA
Foodborne

17. Relative rates of culture-confirmed infections with Campylobacter, STEC* O157,
Listeria, Salmonella, Vibrio, and Yersinia, compared with 1996–1998 rates
FoodNet 1996–2015
• ~20-30% reduction in Listeria, Campylobacter, STEC O157
• ~ 0% change in Salmonella
• ~60% reduction in Yersinia enterocolitica (swine related)

18. % of ‘non typhoid’ Salmonella resistant
to >3 classes of antibiotics (NARMS 2013)
17%
9.8%
MDR more prevalent in
in food animal reservoir

19. Urgent
• Clostridium difficile
• Carbapenem-resistant
Enterobacteriaceae
Concerning
Serious
• Multidrug-resistant Acinetobacter
• Drug-resistant Campylobacter
• ESBL–producing Enterobacteriaceae
• Vancomycin-resistant Enterococcus
• Non-typhoidal Salmonella
• MRSA
• Colistin resistant Enterobacteriaceae
Antibiotic resistance threats in the USA
Foodborne and/or livestock reservoir

20. Antibiotic resistant bacteria linked to
livestock - driving the discussion
 Vancomycin resistant enterococci (VRE)
 ‘Livestock associated’ MRSA
 ESBL Enterobacteriaceae
 Colistin resistant (mcr-1) Enterobacteriaceae
 Carbapenem resistant Enterobacteriaceae

21. Avoparcin and VRE in Europe
 Avoparcin: glycopeptide (vancomycin related)
antibiotic used for growth promotion in Europe
from early 1970s
 Never licensed in the USA
 VRE in Europe in 1990s
 High prevalence in pigs and poultry (avoparcin)
 ~10% prevalence of VRE carriage in healthy humans
 VRE clinical infections remained rare
 Sparse use of vancomycin in human medicine
 Avoparcin banned in EU in 1990s (all by 1997)

22. Vancomycin use in human medicine
in USA vs. Europe (Bonten et al., 2001)

23. Prevalence of VRE in nosocomial
infections in intensive-care patients in
the USA (Bonten et al., 2001)

24. Vancomycin resistance E. faecium
bacteremias in North America and Europe
(1999-2008 SENTRY Program)
(April 1, 1997 as a precautionary, protective measure)

25. Avoparcin and VRE
 Avoparcin use led to high VRE prevalence in food
animals and healthy humans
 VRE infections in USA attributed to high use of
vancomycin in human medicine
 No glycopeptide antibiotic use in food animals
 VRE infections emerged in Europe several years
after the banning of avoparcin

26. ST398 ‘Livestock associated’ MRSA
Generally accepted ‘facts’
 First recognized in Netherlands in 2004
 Now reported in livestock species in many countries
 High exposure risk for people with animal contact
 20-50% vs. ~ 0.5 - 2% in general populations
 Human clinical cases reported, some serious
 Very few serious infections in healthy livestock workers
 Several deaths (~10 in > 10 years) in medically
compromised people
 Low risk of exposure for the general public

27. Emergence of ST398 MRSA infections in
people in Denmark

29. Larsen et al. (Euro Surveill. 2015)
 CC398 ‘has become a major cause of human disease in
Europe, posing a serious public health challenge in countries
with intensive livestock production’
 Suggests substantial dissemination of MRSA CC398 from
livestock or livestock workers into the Danish community
 Findings strongly suggest foodborne transmission does not
play a major role in the MRSA CC398 epidemiology

30. Incidence of MRSA infections in DK in 2011
(Larsen et al., 2015)
Pig dense areas
 All MRSA
 10.9/100,000 person-years
 ST398 (no pig contact)
 0.7/100,000 person-years
Other areas
 All MRSA
 12.8/100,000 person-years
 ST398 (no pig contact)
 0.3/100,000 person-years

31. LA-MRSA in the USA
 Prevalence of LA-MRSA relatively low in US swine
 ST398, ST5, ST9 (Smith 2013, Sun 2015)
 Carriage of ST398 MRSA in IA the same (2-3%) in
people exposed and not exposed to pigs (Wardyn, 2015)
 but increased exposure to LA-MSSA variants (MDR)
 Study of human laboratories in IA (Nair, 2016)
 LA-MRSA found in 0.24% of MRSA cases
 LA-MSSA ~ 1% of S. aureus infections

32. What we know about antibiotic use (ABU)
 ABU selects for resistance in any setting
 The contribution of ABU in animals is to resistance
in human pathogens is >0
 Lack of ‘proof’ of harm is not an argument for
‘injudicious’ use
 Greater abuse in other places is not an argument
for ‘injudicious’ use
 Room for improved stewardship of antibiotics in
food animal industries

33. True or false?
USDA residue monitoring data show that >13%
of market hogs had violative antibiotic residues?
TRUE!
In 1978

34. 2014 National Residue Program
 Scheduled testing (ST) – all species
 10 of 6,021 (0.17%) animals had violative residues
 8 veal calves, 1 cow, 1 sheep
 Market hogs
 0 of 774 ST hogs had violative residues
 8 (0.05%) hogs of 17,354 ‘inspector generated’ hogs
 We have come a long way!
34

35. 35
 As we move forward as a society we create more
problems
 Higher economic growth and consumerism lead to
more stress as people work more and society falls
behind
 The more we know, the more we have to discover
 The better things become, the worse they are
perceived
Paradox of Progress

36.  It does not make sense to delay action further: the burden of proof
should be for those who oppose curtailing the use of antimicrobials in
food production to explain why, not the other way around
 Antibiotics are …a shared societal trust or property. It is not acceptable
for one group of people to abuse this trust for the purpose of perceived
economic advantage, while harming everyone else
 Many parties promote the routine use of antibiotics in livestock
specifically because they perceive (possibly incorrectly) that it enables
the meat, poultry, and drug industries to maximize production and
profits
 Thus, a group of people in society are using antibiotics injudiciously to
mask inferior management practices for perceived gains in short-term
profits, contributing to the spread of antibiotic-resistant bacteria to
other people in society

37. How good is antibiotic stewardship
in the swine industry?
How bad
‘they’ say
we are
How good
we say
we are
?
Can you manage it if you don’t measure it?

39. >50% reduction in use associated with reduced resistance in
commensals of broilers, veal calves and pigs
(modified from Dr. C. Bruschke)
3
Source: Veterinary Medicines Authority: Relaties tussen antibioticagebruik en voorkomen van resistente micro-organismen
(february 2016) www.sda.nl

40. Calls to measure antibiotic use in food
animals
 WHO policy to standardize ABU surveillance of antibiotic use in
humans and animals
 EU directive to harmonize ABU surveillance across countries as part
of an Action Plan
 EU countries (DK, NL, BE, DE,..) benchmark ABU at farm/vet level
 Consumer groups/ politicians seeking stricter regulation and
monitoring of antibiotic use in food animals
 Demands from downstream customers for assurances related to
judicious antibiotic use in the supply chain
 National Action Plan for Combatting Antibiotic Resistant Bacteria

41. National Action Plan to Combat
Antibiotic Resistant Bacteria
1. Slow the Development of Resistant Bacteria and Prevent the
Spread of Resistant Infections
2. Strengthen National One-Health Surveillance Efforts to Combat
Resistance
3. Advance Development and Use of Rapid and Innovative
Diagnostic Tests for Identification and Characterization of
Resistant Bacteria
4. Accelerate Basic and Applied R&D for New Antibiotics, Other
Therapeutics, and Vaccines
5. Improve International Collaboration and Capacities for
Antibiotic Resistance Prevention, Surveillance, Control, and
Antibiotic Research and Development

42. 1.3 Identify and implement measures to
foster stewardship of antibiotics in animals.

43. 2.4. Enhance monitoring of antibiotic-resistance patterns, as well as
antibiotic sales, usage, and management practices, at multiple points in
the production chain from food-animals on-farm, through processing,
and retail meat.
ii. Enhance collection and reporting of data regarding antibiotic
drugs sold and distributed for use in food-producing animals.
iii. Implement voluntary monitoring of antibiotic use and
resistance in pre-harvest settings to provide nationally-
representative data while maintaining producer confidentiality.

44. Measurement - steps forward
 FDA/USDA initiatives under NAP not funded
 Voluntary programs?
 ‘Barnyard’ group meetings (2015/2016)
 Dairy, beef, broilers, turkeys, layers, swine
 Major issues
 Metrics, Confidentiality, Representativeness
 Buy-in
 Market driven initiatives

45. NPB initiatives
 Increased funding for AMR/AMU research
 Sabbatical project
 Task force on measurement of antibiotic use
 Purpose: define current practices for
benchmarking and to support stewardship efforts
 Proposed pilot project in growing pigs
 5-10 systems
 Confidentiality
 Metrics

46. Looking forward
 Increasing scrutiny
 Continuous improvement
 Systems of production
 Use of antibiotics
 Measurement of use
 Evidence-based for treatment regimens
 Prevention – Control – Treatment
 Drug – route – dose – duration
 Animal health and food safety

47. So, therefore, is the future