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Responsible Use of Antimicrobials in Veterinary Medicine:

The EU vs. USA Approachto AGPs

Dr Shabbir SimjeeTechnical Advisor

Microbiology & AntimicrobialsElanco Animal HealthBasingstoke, Englandsimjeess@elanco.com

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Resistance & Food Safety

There are public concerns that people may acquirefoodborne illnesses that cannot be appropriately treatedwith antibiotics as a result of antibiotic-resistant bacteriathat are derived fromfood animals that have been treatedwith antibiotics

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Veterinarian’s Oath(Approved by HOD, 1954; Revision approved by HOD, 1969; Revision approved by the Executive Board 1999, 2010, 2011)

Being admitted to the profession of veterinary medicine, I solemnly swear to use my scientific knowledge and skills for the benefit of society through the

protection of animal health and welfare, the prevention and relief of animal suffering, the conservation of animal resources, the promotion of public health,

and the advancement of medical knowledge.

I will practice my profession conscientiously, with dignity, and in keeping with the principles of veterinary medical ethics.

I accept as a lifelong obligation the continual improvement of my professional knowledge and competence.

https://www.avma.org/KB/Policies/Pages/veterinarians-oath.aspx

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Why Are Antibiotics Used?

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The Danish Experiment

1995 National ban on avoparcin

1998 National ban on virginiamycin

1999 Voluntary agreement to discontinue antibiotic growth promoter (AGP’s) for finishing swine

2000 Voluntary ban of AGP in piglets

Responsible Use vs. Precautionary Principle

AGP misconception: feed efficiency and reduced rates of infection

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Has the Danish Experiment Been Beneficial?

1. Decrease antibiotic use?

2. Public Health Benefit?

Reduced illness

Reduced resistance inhuman isolates

3. Animal Health?

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Card

System

Taxes

Denmark – GP v. Rx

Increased NE poultry / dysentery in swine, consequently cost of production and food price increase

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Resistance among Salmonella typhimurium in pigs and humans

Reverse seen in USA as they still have AGPs

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Did the Danish

Experiment work?

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Summary of the Danish Experiment

• Decrease antibiotic use? – Depends…

– Danish therapeutic antibiotic use is on the rise

– Unintended consequence - increase treatment antibiotic use, including human use antibiotics

• Public Health Benefit? – None shown yet

– No decrease in Salmonellaillness

– Increased resistance in Salmonella Typhimurium

• Antibiotics are still a necessary tool used in raising pigs!

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12Decade plus after EU AGP decision FDA decision on AGP (Precautionary P vs. Science)

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WHO Critical Antibiotics List

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Use of The Three Categories of Antibiotics

Medically Important Antibiotics

None Medically Important Antibiotics

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Marketing Status TransitionTherapeutic and/or Performance Indications

OTC VFD

Macrolides (except Tilmicosin)PenicillinTetracyclineStreptograminsAminoglycosidesLincosamidesSulfonamidesOther veterinary use only agents (e.g. Ionophores)

Current

Macrolide (Tilmicosin)Phenicol (Florfenicol)

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Marketing Status TransitionTherapeutic Indications VFD

Performance Indications and/or Therapeutic Indications OTC

OTC VFD

MacrolidesPenicillinAvilamycin (Therapeutic)TetracyclineStreptograminsAminoglycosidesLincosamidesSulfonamidesPhenicol

Avilamycin (AGP)IonophoresBacitracinBambermycinCarbadox (MA Removable Recommended)Other veterinary use only agents

After

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Need for Harmonisation

Franklin A, Acar J, Anthony F, Gupta R, Nicholls T, Tamura Y, Thompson S, Threlfall EJ, Vose D, van Vuuren M, White DG, Wegener HC &Costarrica ML (2001). Antimicrobial resistance: harmonisation of national antimicrobial resistance monitoring andsurveillance programmes inanimals and in animal-derived food. Revue scientifique et technique (International Office of Epizootics) 20, 859-870

Franklin et al (2001) published a guideline on the harmonisation ofsurveillance programmes in animals on behalf of the Office International desEpizooties (OIE)a) animal species/categories (including age) to be sampledb) for food sampling, the relative merits of sampling at the abattoir and retail outlet should beconsidered. In addition to food of domestic origin, food of foreign origin may also be considered,possibly at the port of entry of the productsc) sampling strategy to be employed, for example: active or passive collection of samples; random,stratified or systematically collected samples; statistically based sampling or opportunistic samplingd) samples to be collected (faeces, carcass, raw and/or processed food)e) bacterial species to be isolatedf) antimicrobials to be used in susceptibility testingg) standardised susceptibility testingh) quality control – quality assurancei) type of quantitative data to be reportedj) database design for appropriate data extractionk) analysis and interpretation of datal) reporting (consideration of transparency of reporting and interests of stakeholders)

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At the outset it is important to emphasise that all of the reviewedsurveillance systems have merit, especially when consideringresistance trends within the countries in which the surveillance hasbeen instigated

The major challenge when analysing data across surveillancesystems is a lack of harmonisation in sampling, susceptibilitytesting methods and in such basic terms as defining resistance

All these factors can confound data interpretation even whenanalysing data vertically within a country but in horizontal analysis,across countries, it can be become almost impossible

Need for Harmonisation

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National surveillance schemes do not all define resistance in thesame way, there is considerable variability in what is defined as“resistant”

This means that it is not possible to simply compare resistant ratesfrom different surveillance schemes as they are not measuring thesame parameter

Indeed even within national surveillance schemes methods ofanalysis have changed over time such that % resistance values needto be viewed with caution

Definition of Resistance

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Clinical vs. Epidemiologic

� Clinical Resistance� Isolates are not inhibited by the usually achievable

concentrations of the agent with normal dosage schedulesand/or fall in the range where specific microbial resistancemechanisms are likely (e.g.β-lactamases), and clinicalefficacy has not been reliable in treatment studies

� Epidemiological (Resistance)� Isolate is defined as non-wild type (NWT) by the presence

of an acquired or mutational resistance mechanismto theantibiotic. Isolates may or may not respond clinically toantimicrobial treatment

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Clinical vs. Epidemiologic

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Clinical vs. Epidemiologic

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Clinical vs. Epidemiologic

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Lets Compare Datawithin a country

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Lets Compare Datawithin a country

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In MARAN 2004, ciprofloxacin resistance in allSalmonella(n =2195) was reported to be 0.3%, applying aclinical breakpoint ofgreater than 2 µg/ml

In MARAN 2005 ciprofloxacin resistance in allSalmonella(n =2238) was reported to be 10.1%, as theepidemiological cut-offvalue of 0.06 µg/mlwas used

Lets Compare Datawithin a country

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EFSA Journal 2011;9(7):2154

SCIENTIFIC REPORT OF EFSA AND ECDC

The European Union Summary Report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in the

European Union in 2009

European Food Safety AuthorityEuropean Centre for Disease Prevention and Control

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ABSTRACTThe European Food Safety Authority and the European Centre forDisease Prevention and Control have analysed the information onantimicrobial resistance among zoonotic and indicator bacteria in2009 submitted by25 European Union Member States. Thisinformation covers antimicrobial resistance inSalmonella andCampylobacter isolates fromhumans, food and animals, and inindicator Escherichia coli and enterococciisolates fromanimalsand food.

Page 17:“The results must therefore be interpreted with care and no directcomparison between countries should be made. Where countrieshave used the same method over the time period covered by thereport, then an evaluation of trends is likely to be valid, though maylack sensitivity dependent on the specific breakpoint used.”

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Summary of National Action Plans

1. Formulation of national Responsible Use Guidelines

2. Establishment of a harmonised resistance monitoring program

3. Establishment of a harmonised antibiotic usage monitoring program

4. Risk Assessment based regulatory Control

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Thank you!Questions?