Randall Singer - Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics

Ensuring Healthy Animals & Food Safety: The Need to Preserve Antibiotics

Randall Singer, DVM, MPVM, PhD

AntibioticsLow 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?

Antibiotic Compounds

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

Antibiotic Uses at Risk

Lipsitch and Samore, Emerg Inf Dis, 2002

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



Lipsitch and Samore, Emerg Inf Dis, 2002

What this issue is NOT about

(Molbak et al., N Engl J Med, 1999)

What this issue is NOT about

(Fey et al., N Engl J Med, 2000)

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

Which Antibiotic Use Is Worse?

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

Risk Assessment

(Hurd et al., J Food Prot, 2004)

Risk Assessment

Animal Product

Macrolide-Resistant Bacteria

Quantified Risk to Humans of Treatment Failure Due to a Resistant Infection

Beef Campylobacter < 1 in 236 million per person per yr

E. faecium < 1 in 29 billion per person per yr

Poultry Campylobacter < 1 in 14 million per person per yr


Pork Campylobacter < 1 in 53 million per person per yr


(Hurd et al., J Food Prot, 2004)

“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

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

Danish Experience and Public Health

DANMAP 2008

The Danish Experience - Resistance

Fallacy of Antibiotic Tonnage

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)

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

Any Benefit from Animal Antibiotics?

𝑑𝐼𝐻𝑑𝑡 = ሾ𝑐+𝑑× 𝐼𝐴+ 𝑒ሺ1−𝐼𝐴ሻሿ× ሺ1−𝐼𝐻ሻ− ℎ× 𝐼𝐻 𝑑𝑅𝐻𝑑𝑡 = ሺ𝐴+ 𝐵ሻ× ሺ1−𝑅𝐻ሻ− 𝑞× 𝑅𝐻

Singer et al., Prev. Vet. Med., 2007

Plasmid Genomics – The Slippery Slope?

Call et al., Antimicrob. Agents Chemother., 2010

For chlortetracycline, total bacteria counts did not differ among chemostats (P = 0.51)

High-CTC chemostat selected for CTC resistance (P = 0.03)

Effects of Low Antibiotic Levels

0

2

4

6

8

10

0 2 4 6 8 10

Time (Days)

Cou

nt (l

og c

fu /

ml)

Control

8 ug / L

800 ug / L

32000 ug / L

0

2

4

6

8

10

0 2 4 6 8 10

Time (Days)

Cou

nt (l

og c

fu /

ml)

Control

8 ug / L

800 ug / L

32000 ug / L

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 distributionDanish example – veterinarians can not sell

OTC

Take Home Messages

Take Home Messages

(Singer and Hofacre, Avian Dis, 2006)

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

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

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

Return to the “Family Farm”

“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.


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


Randall Singer - Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics

Health & Medicine

Transcript of Randall Singer - Ensuring Healthy Animals and Food Safety – The Need to Preserve Antibiotics