human and environmental impacts of antibiotics oh...

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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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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%

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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



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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



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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



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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



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•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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•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)



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•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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Site1- Pristine

April 13th, 2004

February 17th, 2005

August 18th, 2005

October 27th, 2005

February 17th, 2006



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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



human and environmental impacts of antibiotics oh...

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