Antibiotic use in the swine industry Where is it at, and where is it going?

Peter DaviesUniversity of Minnesota

Carlos Pijoan Lecture

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!

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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

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

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

‘Idealism increases in direct proportion to one’s distance from the problem’

John GalsworthyNobel Prize in Literature 1932

National Pork Board 2015 Prioritized vulnerabilities

1. Antibiotics2. Foreign animal disease3. Market preparedness4. Ethics of pork production5. Dietary guidelines

European antibiotic experiencesPhilosophy

1969 1987 2000 2006 2011

Vancomycin R Enterococci, Salmonella DT104, FQ R Campy., LA-MRSA, ESBL, CRE, mcr-1…..

Jan1, 2000 Jan1, 2017

January 1, 2017

The veterinary profession has been handed the football

January 1, 2017

We are playing in a new stadium

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 medicationof healthy and affected pigs in outbreaks

‘Production” Uses

‘Routine’ preventivemedication of ‘at risk’ pigs

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

The resistance crisis and food animalsWhat 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

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

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 USAFoodborne

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)

% of ‘non typhoid’ Salmonella resistantto >3 classes of antibiotics (NARMS 2013)

17%

9.8%

MDR more prevalent in in food animal reservoir

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 USAFoodborne and/or livestock reservoir

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

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)

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

Prevalence of VRE in nosocomial infections in intensive-care patients in

the USA (Bonten et al., 2001)

Vancomycin resistance E. faecium bacteremias in North America and Europe

(1999-2008 SENTRY Program)

(April 1, 1997 as a precautionary, protective measure)

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

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

Emergence of ST398 MRSA infections in people in Denmark

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

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

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

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

True or false?

USDA residue monitoring data show that >13% of market hogs had violative antibiotic residues?

TRUE!

In 1978

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!

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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

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

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?

>50% reduction in use associated with reduced resistance in commensals of broilers, veal calves and pigs

(modified from Dr. C. Bruschke)

3Source: Veterinary Medicines Authority: Relaties tussen antibioticagebruik en voorkomen van resistente micro-organismen (february 2016) www.sda.nl

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

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

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

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.

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

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

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

So, therefore, is the future