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Antimicrobial Use, Resistance &Rules

Western Canadian Association of Bovine Practitioners

January 19, 2018

What is the concern?

• Antimicrobial use (in livestock or elsewhere)increases the risk of antimicrobial resistance

• Some of the antimicrobials used in livestockare closely related to those used in humans

• Antimicrobial resistance can be transferredamong bacteria

• This might reduce the effectiveness of drugsused in human medicine.

The beef industry’s position onantimicrobial resistance

We are not in favor of antimicrobial resistance

• We need animal health products to beeffective

• We need human drugs to be effective

• We need consumers to be confident abouthow the industry raises beef, and in thesafety of the beef they consume.

What is the perception?

• Human health is being compromised.

• Antimicrobials that are important in humanmedicine are used to promote growth orproduction in healthy beef cattle.

• This is irresponsible and encourages thedevelopment of antibiotic resistant“superbugs” that threaten human health.

What is the perception?

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CIPARS - AMU

Subtle details are important

Not all antibiotics are the same!

Very High Essential for treating serious bacterialinfections; no or limited alternatives

High

Used to treat a variety of bacterial infections(including serious); alternatives generallyavailable

MediumUsed to treat bacterial infections;Alternatives generally available

Low Not currently used in humans

Very High e.g. Excede, Baytril, A180, Excenel, Ceftiocyl

High e.g. macrolides(Tylan, Pulmotil, Micotil, Draxxin, Zuprevo, Zactran)

Medium e.g. Tetracyclines, Nuflor/Resflor

Low Ionophores, e.g. Rumensin, Bovatec, Posistac– “low” medically importance (low?)

CIPARS - AMU

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AMR 101

• Antimicrobial use doesn’t causeantimicrobialresistance.

• Antimicrobial resistance occurs naturally

• If you look for AMR bacteria you will findthem.

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CIPARS BEEF

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• The risk of AMR transferring from cattle tohuman environments and human healthappears to be greatly exaggerated

• But AMR poses a definite risk to cattle health

AMR 101

• Antimicrobial use doesn’t causeantimicrobialresistance.

• Antimicrobial resistance occurs naturally

• If you look for AMR bacteria you will findthem

• BU T antim icrobialusegreatly speedstherateatw hichantim icrobialresistancedevelopsandspreads

Anholt et al. 2017 study

• Worked with 7 feedlot practices

• 60 feedlots: samples of BRD pathogens fromcattle ill (nasal swabs) or dead (larynx, lung,pleura, heart, abscess, peritoneum, joint)

– M ycoplasm abovis

– M annheim iahaem olytica

– P asteurellam ultocida

– Histophilussom ni

– T rueperellapyogenes

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Anholt et al. 2017 study

• 90 sick, 528 mortalities

• 90% calves (8% yearlings, 2% older)

• 95% received a macrolide on arrival

• 78% ≤ 60 DOF, 22% > 60 DOF

• 34% Nuflor/Resflor, 28% Baytril, 14%Excede/Excenel

• Sick = multiple AM treatments

= selection pressure for AMR

0

10

20

30

40

50

60

70

80

90

100

AMR in BRD Pathogens

Mannheimia (223) Mycoplasma (226) Pasteurella (117) Histophilus (75) Trueperella (94)

0

10

20

30

40

50

60

70

80

90

100

tet, oxytet,chlortet

(Nuflor,Resflor)

(Micotil,Zactran,Zuprevo,Draxxin,Tylan)

Excede,Excenel,Ceftiocyl

(Baytril,A180)

AMR in CIPARS isolates from healthy slaughter cattle (2015)

E.coli Cam pylobacter

0

10

20

30

40

50

60

70

80

90

100

0 1 2 to 3 4 to 5 6 to 7 8 to 9

Multi-drug AMR in BRD Pathogens

Mannheimia (223) Mycoplasma (226) Pasteurella (117) Histophilus (75) Trueperella (94)

0

10

20

30

40

50

60

70

80

90

100

0 1 2 to 3 ≥ 4

Multi-drug AMR in CIPARS isolates from healthy slaughter cattle (2015)

E.coli Cam pylobacter

To reiterate…

• AMR and multi-drug AMR remain low inbacterial isolates collected from healthyslaughter cattle and beef through CIPARS

• AMR and multi-drug AMR can reach highlevels in severely ill or dead cattle that havebeen treated repeatedly

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&

&

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&

& &

& &

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&

AMR Does Pose a risk to Beef Cattle?

• The more (or more often) an antibiotic isused, the more likely AMR bacteria willsurvive and proliferate

• These won’t respond to treatment

• Antibiotics become less effective

• Animal health and welfare issues becomecommon and more costly

Injectable antibiotic use(36 feedlots, 2.6 million head)

0123456789

10

Highrisk

Lowrisk

Highrisk

Lowrisk

Highrisk

Lowrisk

Highrisk

Lowrisk

2009 2010 2011 2012

DDD / 1000kg

Injectable AMU in high-risk feeder cattle

0

10

20

30

40

50

60

70

80

90

100

2009 2010 2011 2012

Very High High Medium

Injectable AMU in low-risk feeder cattle

0

10

20

30

40

50

60

70

80

90

100

2009 2010 2011 2012

Very High High Medium

AMU & AMR are not just feedlot issues• Antimicrobial use on the ranch

impacts how wellantimicrobials will work in thefeedlot

• Weaning, vaccination andmarketing practices on theranch influence calf health andAMU in the feedlot

• Draxxin is not apreconditioning program or avaccine

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AMU & AMR are not just feedlot issues• Feedlot buying practices

influence the vaccination,nutrition, weaning andhealth practices on the ranch

• Everyone needs to useantimicrobials responsibly ifwe want them to keepworking

Key Actions

1.Establishandstrengthensurveillancesystem stoidentify new threatsorchangingpatternsinantim icrobialresistanceanduse,inhum anandanim alsettings.

2.S trengthentheprom otionofthe appropriateuseofantim icrobialsinhum anandveterinary m edicine.

Key Actions

3.W orkw iththeanim alagriculturesectorpartnerstostrengthentheregulatory fram ew orkonveterinarym edicinesandm edicatedfeeds,includingfacilitatingaccesstoalternativesandencouragetheadoptionofpracticesinordertoreducetheuseofantim icrobials.

4.P rom oteinnovationthrough fundingcollaborativeresearchanddevelopm enteffortsonantim icrobialresistancebothdom estically andinternationally

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• PHAC: Federal lead on the broad issue of AMR –collecting the evidence base

(CIPARS) and working on the national AMR strategy (Framework and Action

Plan)

• Health Canada-VDD: regulates the approval of antimicrobial drugs for use in

animals, and is responsible for establishing policies and standards related to the

safety of food derived from treated animals

• Provinces/Territories: regulate who can sell and distribute veterinary drugs

and the practice of veterinary medicine

• Other Players: AAFC, CFIA, CIHR, PMRA, CBSA and Industry Canada,

Veterinary Associations and Licensing Bodies, and Industry (pharma and food)

Upcoming changes• Medically important antimicrobials moving

to prescription-only

• Less impact on feeding sector (adjustmentson feed side)

• Bigger impact on cow-calf sector

– Liquamycin, many electrolytes, sulfa boluses willrequire a prescription. Maybe some implants.

– Do you stock these?

– Lots of opportunity for vets and new clients to(re)establish a focus on preventative herd healthprograms

What does the future hold?

• Questions about whether AMR bacteria andAMR genes travel through the environment?

• Ongoing questions about AMU in beef cattle– required reporting of AM prescriptions oruse?

• Continued pressure to stop or reducemetaphylaxis / mass-medication to preventdisease

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A better understanding of the respiratorymicrobiome, and

• how badly various stressors disrupt it, and

• how various management practices helpsupport a healthy respiratory microbiome

will help develop and recommend moreeffective preventative animal healthmanagement practices

What does the future hold?Accurate, rapid, cost-effective “chute side”diagnostic tests to identify:

• Whether the animal’s been effectivelyvaccinated,

• What bug’s causing the illness, and

• What antibiotics would be most effective

Would contribute to more strategic AMU

What does the future hold?

• Pressure to stop or reduce continuoususe ofantibiotics for disease prevention

• i.e. liver abscesses

Liver abscesses• Performance

losses

• Grade losses

• Condemnationlosses

• Tylan, Tylosin,tetracyclinecontinuously fedto reduceincidence

Liver abscesses• We could drastically reduce total AMU ifwe

fed less antibiotics to prevent liver abscesseson high grain diets

• But there are many unknowns:

– Bacteria responsible (vaccine?)

– When the infection starts (more strategic / notcontinuous drug use?)

– Dietary factors that increase or reduce risk(fiber/starch interactions?)

– Animal genetics?

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Antimicrobial alternatives• Immunomodulators, phages, and probiotics

are tantalizing, because they seem to suggestthat we can simply inject or feed this insteadof that, and carry on business as usual.

• If they work as well as (or better than)current options, they will be adopted

• So far, immunomodulators, phages, andprobiotics haven’t lived up to their perceivedpromise.

Antimicrobial alternatives• Just because they haven’t worked yet doesn’t

mean they won’t or never will.

• Perhaps we need to know more…

• There are also other alternatives to consider

– Better diagnostics

– Preventative vaccines

– Management – two-stage weaning, fencelineweaning, preconditioning, nutrition

• Reducing antibiotic use is a big challenge

• Antibiotics are widely used because they’recheap, easy, effective, and accessible

• I suspect the most promising antibioticalternatives will be related to adoption ofpreventative management practices, whichthe industry has known for a long time, buthasn’t had the incentive to adopt.

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