Post on 25-May-2015
description
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
Antibiotic Use and Resistance
Antibiotic Use and Resistance
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
E. faecium < 1 in 3 billion per person per yr
Pork Campylobacter < 1 in 53 million per person per yr
E. faecium < 1 in 21 billion 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
DANMAP 2008
The Danish Experience - Resistance
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.
Fallacy of Antibiotic Tonnage
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
Fallacy of Antibiotic Tonnage