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Amy Pruden
College of Engineering
Colorado State University
March 28, 2008
Human and Environmental
Impacts of Antibiotics R1
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Tetracycline
Colorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research InstituteColorado Water Resources Research Institute
Award #: 057342
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1.) Agricultural Antibiotic Use
2.) Problem of Antibiotic Resistance
3.) Potential Human/ Environmental Impacts
This presentation focuses on potential human and environmental impacts of agricultural antibiotics
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Therapeutic Use: When animal is sick
Sub-therapeutic Use: Prevent Disease and Promote Weight Gain
1.) Antibiotics are Widely Applied to Livestock in the U.S.
>50%
?
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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2.) Antibiotic Resistance is a Growing Human Health Problem
•~98,000 people in the U.S. die annually from hospital acquired infections
• Up from 13,000 in 1992
• 70% are resistant to antibiotics
•Examples:
– Methicillin Resistant Staphlococcus aureus(MRSA)
– Vancomycin Resistant Enterococci (VRE)
– Multi-drug Resistant Tuberculosis
MRSA
MRSA Infection
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How Do Bacteria Resist Antbiotics?
Target Modification
Antibiotic Degradation
Antibiotic
Inactivation
Efflux
Antibiotic
Target
Antibiotic
Efflux
pump
Enzyme
Enzyme
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Bacteria Can Share Antibiotic Resistance Genes in
Several Ways
Antibiotic Resistance
Horizontal Gene
TransferSpontaneous
mutation
in the chromosome
* Conjugation
“mating” that results in
the exchange of DNA
between bacteriaTransformation
free DNA is taken up
by the bacterium
Transduction
DNA is transferred
from one organism to
another via a virus
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Add “Miracle-mycin”
Credit: Thomas Eugene
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Current Strategies to Contain Antibiotic Resistance
�The World Health Organization (WHO) has called on a global strategy to contain antibiotic resistance
�The Center for Disease Control (CDC) launched a 4 part strategy in effect since 1999 (USDA is one of many partners):
� Surveillance
� Research
� Product Development
� Prevention, Control & Public Education
�National Antimicrobial Resistance Monitoring System (NARMS) monitors antimicrobial resistance trends in human, animal, and retail meat
�Potential environmental routes of spreading antibiotics and resistance are only recently being considered
� e.g., The White House issued a proclamation in November recommending that unused pharmaceuticals no longer be flushed down the toilet
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Public Education Examples
CDC/DHHSNHS
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Calls to Restrict Antibiotic Use in Animal
Agriculture in the U.S.
�The EU banned all antibiotic growth promoters in 2006
The American Society for Microbiology, the American Public Health Association and the American Medical Association have called for substantial restrictions on antibiotic use in food animal production including an end to all non-therapeutic uses.
Federal bills (S. 549 and H.R. 962) are aimed at phasing out non-therapeutic antibiotics in US food animal production. These bills are endorsed by many public health and medical organizations including the American Nurses Association (ANA), the American Academy of Pediatrics (AAP), and the American Public Health Association (APHA).
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3.) Antibiotics Spread in the Environment via
Multiple Pathways- Impacts?Human and animal excretions
Food and potable water for human consumption
Natural processes (run-off, leaching)
Human directed applications and disposals
Animal
Agriculture
Plant
Agriculture
Veterinary
Medicine
Human
Aquaculture
Drinking
Water
Treatment
Agricultural
Fields
Surface water
and
Groundwater
Wastewater
Treatment
Plant
Lagoons
Composting
Stockpiling
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Antibiotics Have Relatively Low Toxicity and are
Not Known to be Endocrine Disruptors
•H. Ramsdell (CSU)- Monensin toxicity study:
Planaria
LD50 = 20ppm in sediment
Fathead minnow
LD50 = 1ppm in sediment
Hyallela
LD50 = 5 ppm in water
•Much lower concentrations may stimulate antibiotic resistance
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Greater Concern is the Potential to Contribute to the
Emergence & Spread of Resistant Bacteria
–In 1945, Alexander Fleming warned,
“…the greatest possibility of evil in self-
medication is the use of too-small doses, so that instead of clearing up the infection, the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred…”
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Disposal of
AntibioticsExcretion
Excretion
Person-to-Person
Fomite-
mediated
Contact
Contact
?Natural
Selection Run-off
Leaching
Wastewater-Mediated
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Food-Mediated
Manure-Mediated
Storage and
Application
of Manure
Irrigation
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Irrigation
Treatment
Treatment
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Potential Routes of Spread of Antibiotic Resistance
Animal-to-Person
Animal-to-Person
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Some Antibiotic Resistant Infections in Humans
Have Been Linked to Agriculture
•In 2005, Fluoroquinolone use was banned in poultry because of links to ciprofloxacin-resistant Campylobacter infections in humans
•The judge summarized the following findings:
> one million people annually suffer from Campylobacterinfections
Poultry is a source of Campylobacter infections
The use of enrofloxacin (Baytril™) in poultry results in the emergence and dissemination of fluoroquinolone-resistant Campylobacter
Fluoroquinolone-resistant Campylobacter in poultry can be transferred to humans and ‘can contribute to’fluoroquinolone-resistant Campylobacter infections in humans
Campylobacter
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Some Antibiotic Resistant Infections in Humans
Have Been Linked to Agriculture
•Links of resistant infections in humans to agriculture:
– Quinolone-resistant S. typhimurium DT104 infections in the UK traced to a dairy where fluoroquinolone used the month before the outbreak (Walker et al., 2000)
– Tetracycline-resistant Salmonella infections traced to the ‘top-dressing’ of cattle feed with tetracycline (Holmberg et al., 1987)
– Illegal chloramphenicol use on a dairy linked to resistant infections in California (Spika et al., 1987)
Salmonella
17 NARMS Executive Report, 2003
Increasing Ceftiofur Resistance in Salmonella from
Production Animal Species
Ceftiofur is a 3rd generation cephalosporin largely used to treat bovine respiratory disease
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Some Antibiotic Resistant Infections in Humans
Have Been Linked to Agriculture
•Vancomycin is typically used as a last resort
•Avoparcin, also a glycopeptide, was used widely as a growth promoter in Europe in the 1970s
– Genotyping suggested high similarity among VRE strains isolated from pigs, chickens, healthy humans and hospitalized patients
– Avoparcin was banned by Denmark in 1995 and the EU in 1997
– Marked reductions in VRE were noted in broiler chicken, and later in swine when tylosin was also banned. Reductions in VRE carriage in healthy humans has been quantified, but still not clear if number of infections has decreased
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Vancomycin Resistant Enterococci (VRE)
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Some Antibiotic Resistant Infections in Humans
Have Been Linked to Agriculture
•In Germany, shortly after nourseothricin was introduced as a growth promoter in swine, resistant determinants found in livestock operators, employees, and in neighboring communities (Hummel et al., 1986), including Salmonella and Shigella isolates (Witte et al., 2000)
•The first reported case of ceftriaxone-resistant Salmonella in the US involved the child of a veterinarian treating several herds for Salmonella (Fey et al., 2000)
Transfer of resistance to agricultural operators
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Potential Environmental Pathways: The Poudre
River (Colorado) as a Model for Relative Inputs
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Antibiotic Resistance Genes in Poudre River
Associated with Land-Use
Copy of ARG/Copy of 16S rRNA Genes
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April 13th, 2004
February 17th, 2005
August 18th, 2005
October 27th, 2005
February 17th, 2006
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast
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Potential On-Farm Treatment Options for Antibiotic
Resistance
•Lagoons
•Composting
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Elevated levels of antibiotic resistance are associated with agricultural operations
Potential environmental pathways have been identified
Best management practices may help reduce resistance
Questions?
Conclusion: Antibiotic Use in Agriculture May Play a Role in the Rise of Antibiotic Resistance
Livestock and Poultry Environmental Learning Center Webcast Series March 28, 2008
Archived presentation available at: http://www.extension.org/pages/Antibiotics_and_Hormones_in_Animal_Manure_Webcast