**TESTIMONY OF**

**Christine Hoang, DVM, MPH**

**Assistant Director**

**American Veterinary Medical Association**

**Concerning**

**Advancements of Animal Health**

**Within the Livestock Industry**  

**Before the**

**House Subcommittee on**

**Livestock, Dairy, and Poultry**

**September 25, 2008**

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Thank you, Mister Chairman and members of the Subcommittee on Livestock,
Dairy, and Poultry, for providing the American Veterinary Medical
Association (AVMA) with the opportunity to speak about the advances in
animal health within the livestock industry.

My name is Dr. Christine Hoang, and I work as an Assistant Director in
the Scientific Activities Division of the American Veterinary Medical
Association. In addition to holding a doctorate in veterinary medicine,
I also hold a master of public health degree with concentrations in
veterinary public health policy, both national and international, as
well as epidemiology[^1]. The majority of my work focuses upon food
safety, zoonotic disease[^2], and antimicrobial resistance. As a result,
issues related to animal health, animal agriculture, and human health
have not only become topics of interest, but are topics that require a
great deal of intensive research and evaluation.

The AVMA represents nearly 77,000 U.S. veterinarians engaged in every
aspect of veterinary medicine and public health. As veterinarians, our
oath ethically charges us with promoting public health and protecting
animal health and welfare. Thus, we share many of the same concerns as
our human health counterparts. Among other things, our members protect
the health and welfare of our nation's animals, help ensure food safety,
and protect animal and human health through prevention and control of
zoonotic diseases.

The AVMA supports the use of multidisciplinary and multi-hurdle[^3]
approaches[^4] to address issues affecting public health and food
safety. For instance, in addition to supporting improved animal
husbandry and management practices, we also support the continued
availability and judicious use of antimicrobials to safeguard the
nation\'s food supply.

The veterinary profession strives to achieve optimal animal health as
well as animal welfare and human health. The fundamentals of food animal
medicine and population medicine[^5] are the same as the fundamentals of
public heath -- control and prevention of disease. While the end goal is
the same for all medical professionals -- good health -- veterinarians
are severely limited in our tools for disease control and prevention.
Regulations for drug approvals are more stringent, therapeutic agents
can be more difficult to develop, and there are fewer treatments
available. Thus, veterinarians must rely on their knowledge of clinical
medicine to determine the best course of treatment. Given the numbers of
food animal species, in addition to the diversity of disease conditions
that affect animals, a relative scarcity of labeled indications
accompanying FDA approved drugs exists. Though the FDA ,the AVMA and
others have made and continue to make significant strides in enhancing
drug availability, including legislative initiatives (such as the Minor
Use and Minor Species Act), the numbers of FDA approved drugs are
inadequate to meet veterinary medical needs, placing both animal health
and welfare -- and, potentially, human health -- at significant risk.

While it may seem intuitive to some that healthy animals are critically
important for safe food, there are few who understand the intricacies of
why. As an example, it is fairly intuitive that an effective antibiotic
will help decrease the bacterial load in food. What many do not
understand is that it is extremely difficult to ascertain whether or not
a particular animal is carrying certain bacteria. Many bacteria, such as
*Salmonella*, are shed intermittently, and cannot be easily detected by
routine testing procedures. Animals can harbor types of bacteria in
their intestinal tracts that have no effect on their health, but can
cause illness in humans. Thus, we must rely on the combination of many
different types of interventions to protect our food supply. These
interventions would range from prevention and control of disease before
it occurs in animals to post harvest interventions such as carcass
rinsing to further minimize bacterial contamination in food. Another
concept that is often misunderstood or overlooked is how seemingly
unrelated illness, such as respiratory disease in a food animal, can
affect the presence of enteric bacterial pathogens in the meat. For
example, air sacculitis is a respiratory disease that affects poultry.
It is a fairly common disease that can spread rapidly and often go
undetected until slaughter. The disease causes tissues to become more
friable[^6] and difficult to remove during food processing. The
increased handling and difficulty in processing increases the potential
for damaging the intestines and contaminating the carcass with enteric
pathogens that can be harmful to humans[^7]. By controlling this disease
through the use of antibiotics and/or other therapeutic agents,
veterinarians assist producers in maintaining a healthy flock and a safe
food supply. This example further illustrates the necessity to
continually maintain and improve animal health in the preservation of
food safety.

**Veterinarian's Role**

Veterinarians evaluate whether a therapy's benefits would outweigh its
risks to both the patient and to public health. Veterinarians have been
trained to "do no harm" as they make therapy recommendations, and they
have the duty to utilize such agents to promote animal health and
welfare in such a way that safeguards the public health. In addition,
veterinarians protect America's food supply by ensuring food animal
health from "farm to fork," including their work in clinical practice,
in state public health agencies, in the federal government, and in the
corporate sector. Healthy animals make healthy food; for veterinarians
to be effective in protecting our food supply, the appropriate tools for
preventing, mitigating, and treating disease, which include
antimicrobials, are paramount for veterinarians to be able to utilize.

Veterinarians are actively involved in research, continually looking for
new and better ways to improve animal and human health. Some
veterinarians work in research through universities, private
corporations, or through government projects, and many are actively
involved in field research. It is through this process that we have
learned so much about the nature of infectious diseases. It is through
this same process of careful study that veterinarians evaluate and
determine the efficacy of products and interventions that safeguard our
nation's food supply. With limited tools, our profession has made many
advances in animal health and food safety, including the development and
implementation of animal disease control programs, pre- and post harvest
interventions, and areas of biotechnology. Other successes through
collaborative efforts include a decline in foodborne illness from meat
and poultry products[^8] as well as a decline in the prevalence of
foodborne pathogens (including Salmonella) associated with meat and
poultry[^9] and resistance of those organisms[^10]. These are all a
result of improvements in animal health and the joint efforts of
stakeholders.

Veterinarians are in the best position to prescribe and administer the
most appropriate therapies for their patients. Veterinarians are
licensed by state authorities to practice veterinary medicine and are
authorized by both state and federal government entities to handle
potent medical agents in the course of their professional practice.
While there is governmental and regulatory oversight, veterinarians use
professional judgment to determine the best therapy for their patients:

-   Specifically, the Drug Enforcement Administration (DEA) entrusts
    registered veterinarians to prescribe controlled substances for
    animals, i.e., those drugs that are not available to the general
    public due to the potential for abuse and addiction.

-   The Environmental Protection Agency (EPA) allows veterinarians to
    use both restricted-use and conventional pesticides in the course of
    their professional practice.

-   The United States Department of Agriculture (USDA) recognizes
    veterinarians as professionals who may vaccinate animals to advance
    national animal disease control and eradication programs.

Of the tools that are available to veterinarians, one of the most
important tools that veterinarians use to protect animal health and
human health is the judicious use of antimicrobials. The continued
availability of safe, effective antimicrobials for veterinary medicine,
including the retention of currently approved drugs and future approvals
of new drugs, are critical components of ensuring a safe food supply and
essential to the improvement of animal health and welfare.

The exact quantity of antimicrobials that are used in animal agriculture
remains unknown and estimates vary greatly depending upon the source and
the classification of antimicrobials. The Union of Concerned Scientists
(UCS) estimates 24.6 million pounds of antimicrobials were used for
non-therapeutic uses (defined by UCS to include uses for prevention and
control of disease as well as for growth promotion) in cattle, swine,
and poultry in 1999.[^11] However, The Animal Health Institute (AHI) has
reported a general downward trend in total antibiotic use between 1999
and 2004, and estimates 95% therapeutic use (which includes disease
control and prevention)[^12], and therefore about 1.2 million pounds for
growth promotion or feed efficiency. Antibiotic use estimates are
equally confusing and inconsistent when evaluating human use data. AHI
reported in 2000 that 32.2 million pounds of antibiotics are used
annually in human medicine.[^13] However, the UCS estimate for human use
(for inpatient and outpatient disease treatment and as topical creams,
soaps, and disinfectants) was 4.5 million pounds. But the real issue is
not the quantity of antimicrobials that are used but the outcomes of
use.

Despite all of these figures and other available data, no one knows for
certain what role animal agriculture plays in the ecology of
antimicrobial resistance. What we do know is that we need to be able to
have as many tools as possible to uphold our oath.

The number and supply of animals that is necessary to keep up with human
demands for animal protein is rapidly increasing. The world's population
is growing, and expected to increase by a third exceeding 9 billion by
2050.[^14] With that population growth, comes an increased demand for a
safe, healthy supply of food. Ban Ki-Moon, the United Nation's secretary
general, has noted in multiple venues that global food production must
increase by 50% by 2030 to meet those demands.[^15]

In 2000, 9.7 billion animals were slaughtered for human consumption in
the United States. In that same year, the US census bureau reported a
population of approximately 281 million. The US population today is well
over 300 million, and the world's population is rapidly approaching 7
billion.[^16] Red meat production alone in the US totaled 48.8 billion
pounds last year.[^17] Today, the European Union's population is nearly
500 billion, but in 2007 slaughtered only 42 million animals for
food[^18] compared to the US's nearly 10 billion animals slaughtered
annually. While the United States is often compared to the European
Union in the discussion of differing husbandry and management practices,
few recognize the vast difference in per capita production and that the
United States has the most affordable, abundant, safe, and healthy food
supply in the world.

With the large number of animals produced for food in this country, the
topic of antimicrobial use in food production often becomes a topic of
debate. Much of the discussion revolves around a category of
antimicrobial use commonly known as growth promotion or a group of
antimicrobial uses that are poorly categorized as "non-therapeutic." The
term "non-therapeutic" has no meaning in federal regulation or common
usage. The FDA approves antimicrobials for four purposes: disease
treatment, disease prevention, disease control, and growth
promotion/feed efficiency. The FDA does not approve antimicrobials for
"non-therapeutic" uses. Also, the various organizations and people who
use the term "non-therapeutic," use it inconsistently. For example, the
Pew Commission on Industrial Farm Animal Production (PCIFAP) provides an
unclear definition of "non-therapeutic" that is different than H.R 962,
the Preservation of Antibiotics for Medical Treatment Act of 2007
(PAMTA). Additionally, the definitions use terms that are undefined,
such as "routine preventive uses and other routine uses." As a result,
the term is not commonly understood. The use of exclusionary terms, such
as "non-therapeutic", that are ill-defined serves to further confuse the
issue. We caution against the use of this term.

Instead, we believe the FDA labeled uses of antimicrobials should be
used as the terminology, i.e., treatment, prevention, control, or growth
promotion/feed efficiency. Alternatively, we advocate using the
definitions of the Codex Alimentarius Commission (an organization of the
World Health Organization and the Food and Agricultural Organization of
the United Nations), the FDA, and AVMA. All three organizations classify
treatment, prevention, and control of disease as therapeutic uses.

Not all antimicrobials or all their uses are equal in their probability
of developing resistance or creating a risk to human health. The EU's
Scientific Committee on Animal Nutrition has agreed that *possible*
theoretical human health concerns related to animal agricultural use of
antimicrobials continue to be the focus while *probable* and
scientifically based benefits to human and animal health are largely
ignored.[^19]

There is little debate on the use of antimicrobials for treatment of
disease in animals. However, few understand the importance of disease
control and prevention, and even fewer have a clear understanding of
growth promotants. Prevention and control of disease are key elements in
the practice of veterinary medicine, particularly in animal agriculture,
where the focus is on population health. This concept of disease
prevention and control through herd health is analogous to public health
efforts. Additionally, some of the growth promoting antimicrobials have
no human health equivalent and thus no human health impact. In fact,
studies show a potential health benefit from the use of growth promoting
antimicrobials.[^20]^,^[^21]^,^[^22]^,^[^23]^,^[^24]^,^[^25]^,^[^26]^,^[^27]

**Danish Experience**

The Danish experience has taught us that there can be serious negative
consequences in animal health and welfare following the withdrawal of
growth promoting antimicrobials and few, if any, improvements or
positive human health impact.

In the late 1990s, Denmark instituted a voluntary ban on the use of
antimicrobials for growth promotion (AGPs). (A complete ban of AGPs was
initiated in 2000.) The use of antimicrobials in feed and water for
controlling and treating disease was not banned. The following has
been observed as a result of the ban on the use of antibiotics for
growth promotion in Denmark:

-   There is little evidence to demonstrate a general decline in
    antimicrobial resistance in humans and there is no evidence of an
    improvement in clinical outcomes of antimicrobial treatment of
    humans, the desired consequence of the antibiotic ban in livestock.
    The results have been mixed. In fact, resistance in humans to some
    of the banned drugs has increased dramatically.

-   There has been increased death and disease in the swine herds,
    especially at the weaning stage (information inferred from DANMAP
    2005 and other reports on pigs). According to published news
    reports, there was a relative increase of 25% in the number of pigs
    that died from illnesses from 1995 to 2005.

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-   While the total quantity of antimicrobials used in food animals has
    decreased by 27%, the increase in disease has resulted in a 143%
    increase in the quantity of antimicrobials used for therapeutic
    purposes. And the antimicrobials now used are classes such as
    tetracyclines that are also used in humans.[^28]

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-   Resistance to some antibiotics has decreased in some animals while
    resistance to other antibiotics has increased

The ban on antibiotic growth promoters in Denmark has not resulted in a
significant reduction of antibiotic resistance patterns in humans. It
has, however, resulted in an increase in disease and death in the swine
herds and an increase in the use of antimicrobials for therapeutic uses
in swine herds that discontinued the use of antibiotic growth promoters.

Some important resistance trends reported by DANMAP:

-   *Salmonella* Typhimurium from human isolates[^29] has shown 34-49%
    *increase* in resistance to tetracycline, sulfonamides, and
    ampicillin from 1997-2006; increases in resistance to nalidixic acid
    and ciprofloxacin were 3.8% from 1997-2006

    -   In contrast, during the same period of time, poultry isolates
        have shown only minimal increases (2-6%) in resistance to the
        same antimicrobials.

    -   Isolates from pigs have also shown a lesser increase (25-27%) in
        resistance to tetracycline and ampicillin than human isolates
        during that time.

-   *Campylobacter jejuni* from human isolates^f^ has shown 5-11%
    *increase* in resistance to tetracycline, nalidixic acid, and
    ciprofloxacin from 1997-2006.

    -   In contrast, during the same period of time, poultry isolates
        have shown lesser increases (4-6%) in resistance to the same
        antimicrobials.

-   *Enterococcus faecium* isolates from healthy human volunteers has
    shown no increase in resistance to vancomycin (the equivalent of
    avoparcin) from 1997- 2006, and remains at 0%.

-   However, resistance to virginiamycin (quinupristin/dalfopristin,
    e.g., Synercid) had been steadily increasing (up to 25%) from 1997
    to 2005 until the definition of resistance was changed in 2006,
    bringing the level of resistance down to 0%.[^30]

    -   When the definition of resistance is standardized to the United
        States definition used by CDC and the level of resistance in
        humans in Denmark to Synercid is compared to the United States,
        we find that the level is 10 times higher in Denmark in spite of
        the Danish ban in 1998 of use in animals and the continued use
        in the United States.

-   During the same period of time, *Enterococcus faecium* isolates from
    pigs and poultry has shown 8-20% *decrease* in resistance to
    avoparcin[^31], virginiamycin, erythromycin and tetracycline from
    1997- 2006 (using the same definition of resistance as the human
    isolates from 1997-2005)

Even though the results of the Danish experiment with antimicrobial
growth promotant drug bans is very mixed, proposals within the United
States go far beyond the Danish example by proposing to ban uses for the
prevention and control of disease in addition to uses to promote growth
and feed efficiency. Evidence shows that the Danish ban has caused
animal health and welfare problems, without improving human health.

Based on the results of a limited ban enacted in Denmark (i.e., the
banning of growth promotants, not uses to prevent and control disease),
we do not believe the public would benefit from such limitations on the
use of antimicrobials. The loss of approved uses of antimicrobials will
negatively impact animal health and welfare without significantly or
predictably improving public health. Non-science based, broad bans of
preventive uses of antimicrobials have the potential to harm public
health, such as through increased foodborne disease.

Significant decisions regarding animal health need to be science- and
risk-based decisions. Decisions made without the benefit of veterinary
input as well as a thorough evaluation of risks and benefits have the
potential to further divert resources away from more appropriate disease
control measures.

# Actions Advancing Livestock Animal Health 

# AVMA's Efforts 

The AVMA has acted with three objectives in mind:

1.  Safeguarding public health,

2.  Safeguarding animal health, and the

3.  Continued availability of effective therapeutic agents, including
    antimicrobials for veterinary medicine and the retention of
    currently approved, safe drugs and biologics as well as future
    approvals of new therapeutic agents.

**[Veterinary Oversight, Judicious Use, and VCPRs]{.underline}**

Since 1998, the AVMA has actively worked to mitigate the development of
antimicrobial resistance related to the use of antimicrobials in food
animals. The AVMA Guidelines for the Judicious Therapeutic Use of
Antimicrobials were developed to safeguard public health by providing
specific recommendations for responsible and prudent therapeutic use of
antimicrobials. With support and input from the CDC, Infectious Diseases
Society of America, the FDA, and the USDA, the guidelines were
developed in collaboration with our species specific allied veterinary
organizations. These guidelines were based upon carefully reviewed,
scientifically sound research, and we believe that our members
conscientiously adhere to the principles of judicious therapeutic use of
antimicrobials to ensure the protection of human health, as well as
animal health and welfare.

We have actively encouraged and assisted our allied veterinary
organizations to use the AVMA general principles as a template to
develop more detailed guidelines appropriate to each species, disease
and type of client. The AVMA also worked with these groups to develop
and deliver a continuing education program to raise awareness within the
profession and to encourage utilization of the principles.
Fundamentally, the guidelines encourage scientifically based therapeutic
practices, the use of antimicrobials only when needed, and compliance
with all existing regulatory requirements when antimicrobials are used.

Veterinarians also strongly encourage a veterinarian-client-patient
relationship (VCPR) and veterinary consultation when implementing any
treatment regimen. Dispensing or prescribing a prescription product
(including antimicrobials) requires a VCPR. The VCPR is the basis for
interaction among veterinarians, their clients, and their patients.

The veterinarian must have sufficient knowledge of the animal(s) to
initiate at least a general or preliminary diagnosis of the medical
condition of the animal(s). This means that the veterinarian has
recently seen and is personally acquainted with the keeping and care of
the animal(s) by virtue of an examination of the animal(s), or by
medically appropriate and timely visits to the premises where the
animal(s) are kept.

Veterinarians making treatment decisions must use sound clinical
judgment and current medical information and must be in compliance with
federal, state, and local laws and regulations. The veterinarian must
also include consideration of: judicious use principles; food safety and
public health; and producer education as a part of the treatment plan.
After considerations have been made for animal, human, and the
environmental health impact, veterinary authorization is required prior
to dispensing of the prescription product.

There are older antimicrobials that are available in medicated feeds
that can be purchased without a veterinary prescription. These are
called over-the-counter or OTC drugs. OTC drugs have been approved for
marketing without a veterinary prescription and include adequate
directions for use under which a lay person can use the drugs safely and
effectively. To our knowledge, no new classes of antimicrobials have
been approved by the FDA as an OTC drug since the 1980s. A newer
category of drugs, the Veterinary Feed Directive (VFD) Drug category,
was created by the Animal Drug Availability Act of 1996 to provide
veterinary control for certain animal pharmaceuticals for use in feed
that are not suitable for OTC status. Any animal feed bearing or
containing a VFD drug shall be fed to animals only by or upon a lawful
VFD issued by a licensed veterinarian in the course of the
veterinarian\'s professional practice.

Veterinarians must balance the need for animal health and welfare with
the need of human health. We are supportive of measures to mitigate
risks to human health. Risk management measures can include any of the
following: advisory committee review of an existing approval or
application for a new animal drug approval; post-approval monitoring
through systems such as the National Antimicrobial Resistance Monitoring
System (NARMS); limitations on the extent of use (e.g., individual
animals only for short duration of use); limited or broad extra-label
use restrictions in some cases or all cases; antimicrobial use through
prescription or VFD drugs only; and, finally, non-approval or withdrawal
of a previously approved antimicrobial.

Although there are critical shortages in the veterinary workforce,
particularly in food supply veterinary medicine and veterinary public
health, veterinarians provide oversight and advice on the use of
medications, including OTC antimicrobials, on a significant percentage
of animal operations. *Feedlot '99* reports that all large operations
and nearly all (96.5%) small operations used the services of a
veterinarian. Large operations were more likely to use a veterinarian
that made regular or routine visits or employ a full-time veterinarian
on staff than small operations. Conversely, small operations were more
likely to use a veterinarian when the need for one arose. Veterinarian
recommendations had strong or moderate influence on selection of an
antimicrobial for nearly 100% of feedlots. Laboratory test results
influenced 58.8% of feedlots strongly or moderately. Veterinarian
recommendations and laboratory test results were more likely to strongly
influence selection of antimicrobials on large feedlots than small
feedlots. Almost three out of four feedlots provided formal training in
areas related to antimicrobial use.[^32]

The *USDA Swine 2006* reports approximately seven of 10 sites (69.1%)
used a veterinarian during the previous year. A higher percentage of
large and medium sites (88.1 and 85.0%, respectively) used a
veterinarian during the previous year compared to small sites (60.8%).
Nearly 5 of 10 large sites (46.8%) used an on-staff veterinarian. A
similar percentage of large sites (42.5%) used a local practitioner.
Overall, approximately half of the sites (49.5%) used a local
veterinarian during the previous 12 months. About one of four sites
(24.7%) was visited by a veterinarian five or more times. Producers used
the services of a veterinarian for many purposes during the previous 12
months. A higher percentage of large sites used a veterinarian for blood
testing, production record analysis, employee education, and quality
assurance compared to small sites. For sites that had at least one
veterinary visit during the previous 12 months, the highest percentage
of sites used a veterinarian to treat individual pigs (63.8%) and to
provide drugs or vaccines (62.6%). These are followed by vaccination
consultation (48.6%), quality assurance (47.9%), blood testing (47.6%),
nutritional consultation (19.8%), environmental consultation (19.0%),
and employee training/education (18.0%).[^33]

We believe that these numbers can be improved through the resolution of
the critical shortage of the veterinary workforce by identifying
resources and developing solutions in collaboration with key
stakeholders to ensure that veterinary needs are met. Further studies
should appropriately address the availability of veterinary services.

**[Data Collection and Review; Monitoring and Surveillance
Systems]{.underline}**

The AVMA has also continually advocated for improved, more robust
monitoring and feedback systems for foodborne disease and
antimicrobial resistance such as FoodNet and NARMS. It is unfortunate
that reporting by NARMS is not timelier. For example, the most recent
Centers for Disease Control and Prevention NARMS report that is
available to the public is for 2004 -- four years ago.

NARMS data, when combined with FoodNet data, demonstrates that the case
rate of human infections with multidrug resistant *Salmonella* spp. has
decreased 49% between the NARMS baseline years of 1996-98 and 2004 (the
most current, publicly available human data from NARMS). In addition,
there has been a 65% reduction in the case rate of penta-resistant
*Salmonella* Typhimurium infections. The case rate for *Campylobacter*
infections in humans that are resistant to ciprofloxacin have remained
constant over that period.[^34] 

Additional important resistance trends [^35] reported by NARMS[^36]
(Isolates from humans with clinical disease):

*Salmonella* spp. (non-Typhi) -- ½ as likely to be resistant in 2004 as
in 1996

-   a highly significant[^37] improvement in susceptibility[^38] (20%
    relative increase in susceptibility, from 66.2% in 1996 to 79.6% in
    2004)

*Salmonella* Typhimurium -- less than ½ as likely to be resistant in
2004 as in 1996

-   a highly significant^j^ improvement in susceptibility^k^ (60%
    relative increase in susceptibility^k^ from 37.9% in 1996 to 60.7%
    in 2004)

*Campylobacter* -- only 0.03 times more likely to be resistant in 2004
compared to 1997

-   a marginally significant^j^ increase in resistance (2% relative
    increase in resistance from 53% in 1997 to 54% in 2004)

-   However, campylobacter was significantly less likely to be resistant
    in 2003 when compared to 1997; there was a significant^j^
    improvement in relative resistance (8.2% decrease from 53% in 1997
    to 49% in 2003)

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-   *E. coli O157* -- 1/3 as likely to be resistant in 2004 compared to
    1996

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-   a highly significant^j^ improvement in susceptibility^k^ (10%
    relative increase in susceptibility)

 

In addition to trends of improved susceptibility, trends^i^ regarding
multi-drug resistance^l^ also showed improvement:

*Salmonella* spp. (non-Typhi) -- nearly ½ as likely to be multi-drug
resistant[^39] in 2004 when compared to 1996

-   a highly significant^j^ improvement (44% relative decrease) in
    multi-drug resistance^l^ (decreased from 27.0% in 1996 to 15.0%
    in 2004)  

 

*Salmonella* Typhimurium -- nearly ½ as likely to be multi-drug
resistant^l^ in 2004 when compared to 1996

-   a highly significant^j^ improvement (34% relative decrease) in
    multi-drug resistance^l^ (decreased from 56.2% in 1996 to 37.2% in
    2004)

 

*Campylobacter* -- slightly less likely to be multi-drug resistant^l^ in
2004 when compared to 1997

-   a marginally significant^j^ improvement (10% relative decrease) in
    multi-drug resistance^l^ (decreased from 15.7% in 1997 to 14.1% in
    2004)

-   However, when comparing 1997 to 2003, isolates were half as likely
    to be multi-drug resistant^l^ and there was a highly significant^j^
    improvement (46% relative decrease) in multi-drug resistance^l^
    (decreased from 15.7% in 1997 to 8.5% in 2003)

Most foodborne infections do not require treatment with antimicrobials.
Information shows that there is a decreasing trend of foodborne
diseases, thereby decreasing the potential numbers of treatments.[^40] 
The trends of increasing susceptibility/decreasing resistance mean more
successful treatments when needed. This information indicates that there
is not a public health crisis related to human pathogens that are
thought to originate in animals.

We have also advocated for more research to support scientifically based
therapeutic practices, such as epidemiological studies, that assess the
effects of antimicrobial use. In addition, we advocate for increased
resources for the FDA's Center for Veterinary Medicine (CVM) so the
agency can adequately implement its regulatory authority.

We support the scientifically valid and meaningful collection and review
of data for all uses of antimicrobials and other pharmaceuticals used in
humans and animals. We urge that such data be collected in concert with
other data necessary to explain or inform fluctuations in use, e.g.,
disease prevalence, regional data, populations of animals, etc. An
example is the USDA program, Collaboration for Animal Health, Food
Safety and Epidemiology, that is attempting to study the use of
antimicrobials on farms correlated with disease occurrence, and the
effects of antimicrobial use on antimicrobial resistance as measured
both on the farm and during processing of the meat from the specific
farm. Unfortunately, the program has not received adequate funding and
is therefore not completed or ongoing.

The AVMA provided start-up funding for projects to create a nationally
coordinated laboratory system to test for and report on resistance in
animal pathogens and to create a decision support system to assist
veterinarians when making antimicrobial use decisions. Unfortunately,
while this project received follow-on funding by the FDA, it has not
been sustained or completed.

**The FDA Role and Actions**

The FDA approves antimicrobials for four purposes:

1.  Treatment of disease,

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2.  Prevention of disease,

3.  Control of disease, and

4.  Growth promotion or feed efficiency.

The first three uses are classified as therapeutic uses by the FDA, the
AVMA, and Codex Alimentarius Commission (an organization of the World
Health Organization and the Food and Agricultural Organization of the
United Nations), and the fourth has also been shown to have
health-promoting effects.

The FDA process for the evaluation of food animal antimicrobials is at
least as stringent as, and often more stringent than, the approval
process for human antimicrobials. In addition to the testing for
efficacy and safety to the individual (human or animal) receiving the
drug that is common to the human and animal drug approval process, each
food animal antimicrobial undergoes an assessment for human and
environmental safety as part of the review by the FDA. The FDA's Center
for Veterinary Medicine uses a very strict safety assessment approval
process that requires sponsors to submit data proving the antibiotic is
safe for both humans and animals. This is a zero-risk procedure for
human safety -- benefits to animals are not weighed to offset risks to
humans, but rather, drugs that possess risks beyond "a reasonable
certainty of no harm" to human health are rejected.

Another safety measure was instituted in 2003 (Guidance for Industry
#152, "Evaluating the Safety of Antimicrobial New Animal Drugs with
Regard to Their Microbiological Effects on Bacteria of Human Health
Concern,") that outlines a comprehensive, evidence-based approach to
preventing the emergence and selection of antimicrobial-resistant
bacteria that may adversely affect human health. The Guidance requires
antimicrobial manufacturers to provide information to the FDA showing
that a proposed animal drug will not harm public health. The current FDA
risk assessment on a drug-by-drug basis provides a scientifically sound
process to protect human health. In the event that a determination is
made that human health is jeopardized, FDA will not approve the
antimicrobial or may limit the use of the antimicrobial in order to
mitigate the adverse effect.

We support GFI #152 while recognizing that it is very conservative in
ensuring that preference is given to protection of human health without
consideration of benefits to animal health and welfare. We also
recognize that the ranking of antimicrobial drugs according to their
importance in human medicine adds additional difficulty for approving
animal drugs because the ranking design includes treatment of human
diseases that are not in any manner associated with food animals. These
diseases include gonorrhea, tuberculosis caused by *Mycobacterium
tuberculosis*, neurosyphillis, meningitis, neutropenic fever, and
Legionnaire's disease.

In addition, we also recognize that the design of GFI #152 makes it
extremely difficult or impossible for FDA to approve antibiotics for use
in feed or water for treatment of groups of animals if those antibiotics
are also used in humans. This is because the extent-of-use limitations
table assigns a high ranking for intended administration to flocks or
herds of animals regardless if the duration of use is short (less than 6
days) or long (more than 21 days).

Since the mid-1990s, the FDA has coordinated the NARMS in cooperation
with the CDC and the USDA. NARMS is a multi-agency program that includes
monitoring for resistant bacteria in retail meats by the FDA, monitoring
for resistant foodborne pathogens in humans by the CDC, and monitoring
for resistant bacteria in animals on farms and animal products in
slaughter and processing facilities by the USDA. NARMS has provided a
great deal of useful information since 1996.

Therefore, the AVMA does not believe that the FDA needs new authority to
regulate the human safety of animal drugs. Instead, the FDA needs
additional resources to fulfill its existing mission.

**The USDA Role and Actions**

USDA Animal and Plant Health Inspection Services (APHIS) regulates
veterinary biologics (vaccines, bacterins, antisera, diagnostic kits,
and other products of biological origin) to ensure that the veterinary
biologics available for the diagnosis, prevention, and treatment of
animal diseases are pure, safe, potent, and effective. According to the
USDA, which regulates vaccines and other biologics for animals, over 80
billion doses of approved vaccine were produced last year.[^41]

USDA also has oversight over many national programs for animal health
monitoring and surveillance. Veterinarians in both public and private
practice actively participate in these national programs and AVMA has
consistently advocated for funding to maintain and continually improve
all of these programs.

**National Programs**

[National Animal Health Surveillance System
(NAHSS)](http://www.aphis.usda.gov/vs/nahss/) - NAHSS integrates animal
health monitoring and surveillance activities conducted by many federal
and state government agencies into a comprehensive and coordinated
system.

-   [U.S. status for reportable
    diseases](http://www.aphis.usda.gov/vs/nahss/disease_status.htm) as
    reported to the World Organization for Animal Health (OIE)

-   [NAHSS
    Outlook](http://www.aphis.usda.gov/vs/ceah/ncahs/nsu/outlook/index.htm) -
    Articles on U.S. animal health surveillance issues and developments.

[National Animal Health Monitoring System
(NAHMS)](http://www.aphis.usda.gov/vs/ceah/ncahs/nahms/) - National
studies on animal health and health management practices of U.S.
livestock and poultry.

[National Animal Health Reporting System
(NAHRS)](http://www.aphis.usda.gov/vs/ceah/ncahs/nahrs/) - Information
on the presence of reportable animal diseases in the United States.

[National Animal Identification System
(NAIS)](http://animalid.aphis.usda.gov/nais/index.shtml) - This program
coordinates and expands animal identification programs and practices in
livestock and poultry.

[National Animal Health Laboratory Network
(NAHLN)](http://www.aphis.usda.gov/vs/nahln/) - This network of state
animal health laboratories provides, among other things, laboratory data
to meet epidemiological and disease reporting needs.

[National Poultry Improvement Program
(NPIP)](http://www.aphis.usda.gov/animal_health/animal_dis_spec/poultry/index.shtml) -
National poultry health monitoring and surveillance.

[National Aquaculture Program
(NAP)](http://www.aphis.usda.gov/animal_health/animal_dis_spec/aquaculture/index.shtml) -
National aquaculture health monitoring and surveillance.

[U.S. Animal Health and Productivity Surveillance
Inventory](http://www.aphis.usda.gov/vs/nahss/inventory.htm) - Search
for surveillance programs, studies, and related information.

[Impact Assessments on Animal Health
Events](http://www.aphis.usda.gov/vs/ceah/cei/taf/current_iw.htm) -
Reports on trade and production impact of animal disease occurrences in
the U.S. and foreign countries.

[Emerging Animal Disease
Notices](http://www.aphis.usda.gov/vs/ceah/cei/taf/emergingdiseasenotice_files/notices.htm) -
Information sheets on new and emerging animal diseases.

[National Surveillance
Unit](http://www.aphis.usda.gov/vs/ceah/ncahs/nsu/index.htm) -
organization within APHIS tasked with coordinating activities related to
animal health surveillance. [^42]

**FARAD Role and Actions**

The Food Animal Residue Avoidance Databank (FARAD) program was developed
by pharmacologists and toxicologists at the university of California,
Davis, University of Florida, North Carolina State University and the
University of Illinois as a complement to the USDA Food Safety and
Inspection Service (FSIS) Residue Avoidance Program (RAP) to reduce the
rate of animal residue violations through education, and residue
mitigation rather than enforcement.

Whenever drugs are used to treat sick animals or prevent disease or when
animals are exposed to chemicals in the environment, there is a
potential that remnants of the drugs can be found in the meat or other
animal products (often known as residues). The FDA establishes
tolerances for drug residues to insure food safety. The FDA also
establishes "withdrawal times" or "withholding periods" which are times
after drug treatment when milk and eggs are not to be used for food, and
during which animals are not to be slaughtered. This allows time for the
animals to metabolize and eliminate the drugs that had been used for
treatment.

FARAD personnel collate residue avoidance information from many sources.
These data are then reviewed by residue experts to insure accuracy and
consistency, and further analysis is done by FARAD personnel at North
Carolina State University to explore novel ways in which the data may be
used to prevent residue problems. FARAD maintains an up-to-date
computerized compilation of:

-   Current label information including withdrawal times on all drugs
    approved for use in food animals in the United States and on
    hundreds of products used in Canada, Europe and Australia.

-   Official tolerances for drugs and pesticides in meat, milk, and
    eggs.

-   Descriptions and sensitivities of rapid screening tests for
    detecting chemical residues in meat, milk, and eggs.

-   Data on the fate of chemicals in food animals.

FARAD has been a chronically under-funded resource used by
veterinarians, livestock producers, and state and federal regulatory and
extension specialists to ensure that drug, environmental, and pesticide
contaminants do not end up in meat, milk, and eggs. AVMA has been a
strong supporter of FARAD and has worked diligently with Congress on the
2008 Farm Bill to include authorization for a \$2.5 million annual
appropriation for the Food Animal Residue Avoidance Databank from 2008
through 2012. [^43] However, if funding is not appropriated before
September 30, 2008, this vitally important asset to ensure food safety
may be forced to close its doors---permanently. Not only does FARAD
ensure the safety of our meat, milk, and eggs, but the U.S. researchers
from FARAD launched a global FARAD (gFARAD) initiative in response to an
increasing need from foreign countries for residue data and requests
made to FARAD to duplicate this successful program in other countries.

FARAD's efforts in establishing gFARAD have, to date, been financed
entirely by local funds in participating countries, and in the US by
private donations and use of facilities made available by the three U.S.
Universities housing the FARAD program. These exciting developments,
which have attracted collaborations (but no funding) from the Food and
Agricultural Organization (FAO) and Commonwealth Agricultural Bureaux
International (CABI), have far reaching implications for the safety of
foods imported into the United States as well as upon global food safety
and the harmonization of standards and procedures. Since 2003, the
United Kingdom, France, and Spain have initiated gFARAD sites. The
Canadian gFARAD became fully operational with significant, recurring
support from the government of Canada in 2003. In recent years, FARAD
has provided training in gFARAD techniques and databases for China, as
well as hosted the Taiwanese gFARAD consortium and South Korean delegate
visits to FARAD.

The funding lapses of U.S. FARAD in 2007 and the continued lack of
recurring support for US FARAD places the entire program in jeopardy. In
addition, the lack of continued funding and support compromises US
leadership in the continued development of a program initiated by our
own researchers. In 2007, gFARAD may have been able to assist in
mitigating the Chinese melamine crisis, however, it was a necessity for
funds to be utilized to maintain essential personnel and no funds were
available for U.S. FARAD to leverage the gFARAD consortium. Global food
safety and security will continue to be a concern for decades to come.
Support for a strong U.S. FARAD is a critical investment in continuing
relationships with our trading partners and global information sharing
between governments to mitigate agroterrorism concerns and ensure a
safe, abundant food supply.

**Risk Assessments/ Human Health Impact**

**Antibiotics as a tool to prevent and control disease in animals and
humans**

The use of drugs in animals is fundamental to animal health and
well-being. Antibiotics are needed for the relief of pain and suffering
in animals. For food animals, drugs additionally contribute to the
public health by helping keep animals healthy and thereby keeping
bacteria from entering the food supply. The hypothesis, supported by
scientific information, is that a reduction in the incidence of food
animal illness will reduce bacterial contamination on meat, thereby
reducing the risk of human
illness.[^44]^,^[^45]^,^[^46]^,^[^47]^,^[^48]^,^[^49]^,^[^50]^,^[^51]

Several risk assessments have been performed that demonstrate a very low
risk to human health from the use of antimicrobials in food animals, and
some of the models predict an increased human health burden if the use
is withdrawn. The unique farm-to-patient risk assessment performed by
Hurd demonstrates that the use of tylosin and tilmicosin in food animals
presents a very low risk of human treatment failure because of macrolide
resistance, with an approximate annual probability of less than 1 in 10
million with *Campylobacter* infections and approximately 1 in 3 billion
*E. faecium* infections.[^52] Cox performed a quantitative human health
risks and benefits assessment for virginiamycin and concluded that there
would be a significant human health risk if virginiamycin use is
withdrawn. There would be 6,660 excess cases per year of
campylobacteriosis, which far outweighs the 0.27 per year reduction of
cases of streptogramin-resistant and vancomycin-resistant *E. faecium*
(VREF) resulting from the withdrawal.[^53] Cox also performed a risk
assessment regarding macrolide and fluoroquinolone use and concluded
that withdrawal is estimated to cause significantly more illness days
than it would prevent.[^54] Cox also examined the impact of the use of
penicillin-based drugs in food animals on penicillin/ aminopenicillin
resistant enterococcal infections and concluded that not more than 0.04
excess mortalities per year (under conservative assumptions) to 0.18
excess mortalities per year (under very conservative assumptions) might
be prevented in the whole U.S. population by discontinuing current use
of penicillin-based drugs in food animals. The true risk could be as low
as zero.[^55] This equates to one potentially preventable mortality in
the U.S. population roughly every 7-25 years. Alban's risk assessment
concluded that the risk associated with veterinary use of macrolides in
Danish pigs resulted in a low risk to human health.[^56]

Others have estimated that risk management strategies that focus on
eliminating resistance are expected to create \< 1% of the public health
benefit of strategies that focus on reducing microbial loads in animals
or on foods.[^57] In another paper, the authors concluded, "We came to
some surprising conclusions that were robust to many uncertainties.
Among these were that antimicrobials that benefit animal health may
benefit human health, while regulatory interventions that seek to reduce
antimicrobial resistance in animals may unintentionally increase illness
rates (and hence antimicrobial use and resistance rates) in humans. . .
. In conclusion, our analysis suggests that the precautionary-principle
approach to regulatory risk management may itself be too risky."[^58]

Information derived from studies of organic or antibiotic-free
production practices compared to traditional production practices is
inconclusive, but there are indications that organically grown meat may
have less-resistant organisms but greater prevalence and quantities of
pathogens on the meat. Therefore, the greater risk of foodborne illness
is somewhat offset by an increased likelihood of treatment success if
treatment is necessary.[^59]^,^[^60]^,^[^61]^,^[^62]

The question of what the nature and magnitude of the risk to humans is
can only be answered by performing systematic risk assessments. Such
risk assessments must include identification of the endpoints of concern
(e.g., increased illness or mortality caused by bacteria resistant to
antibiotics used to treat the disease in humans), the nature of the
treatment protocols in food animals, the potential routes of exposure,
characterization of the population at risk, and the probability of
occurrence.

Just as in humans, resistant bacteria can and do develop in animals.
However, many of the important details regarding the transfer of that
resistant bacteria, or even resistance genes -- to the environment or
humans -- still remains in question. Simply because resistance exists in
animals, it does not necessarily equate to a human health risk. First,
the bacteria or its resistance determinants may not effectively transfer
to humans through the food chain. Secondly, the pathogen may not
colonize in humans to create a foodborne disease. Third, if a disease
does occur, antimicrobial therapy may not be needed, and the disease
resulting from the resistant bacteria is in effect no different than any
other bacteria. In the majority of cases, treatment is not needed.
Supportive therapy, such as fluids, is the only treatment that is needed
for most *Salmonella*, *Campylobacter* and *E. coli* infections. In
fact, antimicrobial therapy of *E. coli* O157 infections is
contra-indicated because such treatment makes the effects of the disease
worse. Lastly, if antimicrobial therapy is needed, the pathogen may be
susceptible to the drug of first choice. The Therapy Guidelines for
Enteric Infections for non-typhi *Salmonella* are, "In uncomplicated
infections antimicrobial therapy is not indicated because it has no
effect on clinical illness and prolongs carriage and excretion of the
organism. . . . Treatment recommended only for young infants (\< or = 6
m) and immunocompromised individuals. Resistance is common. Agents that
can be used include a fluoroquinolone or a third-generation
cephalosporin such as ceftriaxone for 5-7 days. Ampicillin and
co-trimoxazole can be used if the infecting organism remains
susceptible."[^63] NARMS[^64] reports the following resistance
percentages of non-typhi *Salmonella* to fluoroquinolone (ciprofloxacin)
-- 0.2%, third-generation cephalosporin (ceftriaxone) -- 0.6%,
ampicillin -- 12.0%, and co-trimoxazole (trimethoprim-sulfamethoxazole)
-- 1.8%. These resistance levels do not indicate a public health crisis
associated with foodborne *Salmonella*.

**Conclusion**

The American Veterinary Medical Association is committed to ensuring a
safe and healthy abundant food supply. Among other things, our
profession is dedicated to improving animal health, further safeguarding
public health and food safety, and to maintaining the long-term
effectiveness of antibiotics. The AVMA established a profession-wide
initiative to create and implement judicious use guidelines for the
therapeutic use of antimicrobials by veterinarians, and we launched an
educational campaign to raise the awareness of the profession to the
issue.  Today, we continue to review and update those guidelines to
reflect current practices and actively encourage compliance.

Foodborne illness and the spread of antibiotic resistance is a public
and animal health concern. There is no question that the public demands
a safe food supply and that the human medical profession is facing
extreme challenges because of hospital- and community-acquired resistant
human pathogens. The human medical problem with resistant nosocomial and
community-acquired infections has increased the concern of possible
development of resistant pathogens in animals that could be transferred
to humans through the food supply or environment.

The AVMA shares the concerns of the human medical community, the public
health community, governmental agencies, and the public regarding the
potential problem of resistant foodborne pathogens developing in animals
and then being transferred to humans. However, we emphasize the
importance and primacy of using these medicines to prevent and treat
diseases before they enter our food supply. Pre-emptive bans of
veterinary antimicrobials before science-based studies and risk-based
evaluations are performed would be detrimental to animal and human
health. Inappropriate reactions to a perceived problem could have
unknown and unintended consequences that negatively affect animal health
and welfare, and ultimately, could create other public health risks,
such as increased foodborne illness.

The AVMA does not believe that additional regulation of the uses of
antimicrobials or other therapeutic agents in veterinary medicine and
animal agriculture are necessary. Additional legislation and further
regulation can put animal health and welfare and public health at risk.
The FDA has adequate authority for oversight but lacks the resources to
accomplish its many priorities.

An analysis that compared the regulatory strategy of the European Union
to ban or restrict animal antibiotic uses with the United States'
approach of continued prudent use to prevent and control animal
infections, together with measures to improve food safety, has some
pertinent conclusions. Among these, prudent use of animal antibiotics
may actually improve human health, while bans on animal antibiotics,
intended to be precautionary, inadvertently may harm human health.[^65]

The AVMA supports the ongoing scientific efforts of monitoring and
surveillance of foodborne disease and resistant foodborne pathogens;
education; development of new antimicrobials, biologics, and other
treatment options; and other research to better define the challenges
presented by animal agriculture. Increased data collection and
surveillance of disease, as well as continued veterinary input
(including the appropriate use of pre- and post-harvest interventions,
and compliance with judicious use guidelines for veterinarians and
producers), may be sufficient to protect human health against the
current small risks without compromising the health of food animals.

We also support adequate funding for all efforts to improve animal
health and food safety, including efforts to combat antimicrobial
resistance. These efforts were high-priority tasks in the 2001 version
of the Public Health Action Plan to Combat Antimicrobial Resistance that
was created by a Federal Interagency Task Force on Antimicrobial
Resistance. The Action Plan reflected a broad-based consensus of federal
agencies and stakeholders on actions needed to address antimicrobial
resistance and provided a blueprint for specific, coordinated federal
actions that included the full spectrum of antimicrobial use: human
medicine, veterinary medicine and animal agriculture. We are
disappointed that the Action Plan was not adequately funded and
prioritized by Congress. We are also concerned that the new Action Plan
under development appears to not be as collaborative, broad-based or
acceptable to the diverse community of stakeholders.

 

The AVMA is committed to working in concert with the CDC, FDA, and USDA
to provide consumers -- not only in the United States, but all over the
world - with the safest food possible. The judicious use of
antimicrobials is but one of the essential components of the process
that enables animal agriculture to meet that demand. Other components
include veterinary care, good management practices, biosecurity, proper
nutrition and good husbandry.

Thank you for the opportunity to appear before you today and speak on
behalf of our profession.

[^1]: Epidemiology is a medical discipline that is the study of the
    causes, distribution, and control of disease in populations and
    serves as the foundation and
    [logic](http://en.wikipedia.org/wiki/Logic) of interventions made in
    the interest of [public
    health](http://en.wikipedia.org/wiki/Public_health) and [preventive
    medicine](http://en.wikipedia.org/wiki/Preventive_medicine).

[^2]: Zoonotic diseases are diseases that can be transmitted from
    animals to humans. CDC estimates at least 60 percent of all human
    diseases and 75 percent of all newly emerging diseases are zoonotic.

[^3]: The multi-hurdle concept refers to the interaction of factors that
    affect microbial behavior in foods. Under some circumstances these
    effects are additive. Under others the implication is that
    synergistic interactions lead to a combined effect of greater
    magnitude than the sum of constraints applied individually.

[^4]: McMeekin, T.A., Presser, K., Ratkowski, D. Ross, T., Salter, M.,
    Tienungoon, S. Quantifying the hurdle concept by modelling the
    bacterial growth/ no growth interface. International journal of food
    microbiology. [Volume 55, Issues
    1-3](http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%235061%232000%23999449998%23178169%23FLA%23&_cdi=5061&_pubType=J&view=c&_auth=y&_acct=C000069188&_version=1&_urlVersion=0&_userid=6040261&md5=e025060af42d4f943d833909a70485dc),
    10 April 2000, Pages 93-98

[^5]: Population medicine is a medical discipline focusing on the
    concepts of public health and epidemiology. In veterinary medicine,
    these concepts are incorporated to make strategic decisions to
    advance animal and herd health.

[^6]: Friable is a term used in pathology to describe tissues that are
    brittle, fragile, and easily damaged.

[^7]: Russell SM. The effect of airsacculitis on bird weights,
    uniformity, fecal contamination, processing errors, and populations
    of Campylobacter spp. and Escherichia coli. Poult Sci 2003 82:
    1326-1331

[^8]: CDC. FoodNet. Facts and Figures related to "Preliminary FoodNet
    Data on the Incidence of Infection with Pathogens Transmitted
    Commonly Through Food\-\--10 States, United States, 2007" published
    in the Morbidity and Mortality Weekly Report (MMWR) on April 11,
    2008. (Available at
    <http://www.cdc.gov/foodnet/factsandfigures.htm>)

[^9]: United States Department of Agriculture, Food Safety Inspection
    Service. [Progress Report on Salmonella Testing of Raw Meat and
    Poultry Products, 1998-2001]{.underline}.

[^10]: CDC. National Antimicrobial Resistance Monitoring System: Enteric
    Bacteria. 2004 Human Isolates Final Report. (Available at
    <http://www.cdc.gov/narms/NARMSAnnualReport2004.pdf>)

[^11]: Mellon M, Benbrook C, Benbrook KL. 2001. Hogging it: estimates of
    antimicrobial abuse in livestock. Cambridge: UCS Publications.

[^12]: \[AHI\] Animal Health Institute. 2005. Antibiotic use in animals
    rises in 2004. News release. Washington, D.C.: AHI.

[^13]: \[AHI\] Animal Health Institute. 2000. Survey indicates most
    antibiotics used in animals are used for treating and preventing
    disease. Press release., Washington D.C.: AHI.

[^14]: United Nations. Department of Economic and Social Affairs.
    Population Division. (12 October 1999). The World at Six
    Billion. ESA/P/WP.154. (Available at:
    <http://www.un.org/esa/population/publications/sixbillion/sixbilcover.pdf>)

[^15]: United Nations. Department of Public Information. News and
    Media Division. (3 June 2008). Food production must rise by 50 per
    cent, Secretary-General tells Rome high-level conference, stressing
    that crisis is chance to revisit past policies. (Available at
    <http://www.un.org/News/Press/docs/2008/sgsm11612.doc.htm>)

[^16]: United States Census Bureau. Population Division. (2008) [U.S.
    and World Population Clocks.]{.underline} (Available at
    <http://www.census.gov/main/www/popclock.html> )

[^17]: United States Department of Agriculture. National Agricultural
    Statistics Service. (24 July 2008). [Livestock and Animals -
    Slaughter Statistics]{.underline}. (Available at: 
    <http://www.nass.usda.gov/QuickStats/indexbysubject.jsp?Text1=&site=NASS_MAIN&select=Select+a+State&Pass_name=&Pass_group=Livestock+%26+Animals&Pass_subgroup=Slaughter>)

[^18]: EuroStat, European Commission. Luxembourg: Office for Official
    Publications of the European Communities, 2008. (Available at:
    <http://epp.eurostat.ec.europa.eu/cache/ITY_OFFPUB/KS-ED-08-001/EN/KS-ED-08-001-EN.PDF>)

[^19]: Phillips I. et al. Does the use of antibiotics in food animals
    pose a risk to human health? A critical review of published data. J
    of Antimicrobial Chemotherapy 2004: Vol 53, pp 28-52

[^20]: Singer RS. Modeling the Relationship between Food Animal Health
    and Human Foodborne Illness. Prev Vet Med 2007; 79: 186-203

[^21]: Russell SM. The effect of airsacculitis on bird weights,
    uniformity, fecal contamination, processing errors, and populations
    of Campylobacter spp. and Escherichia coli. Poult Sci 2003 82:
    1326-1331

[^22]: Russell SM. Ban Antibiotics In Poultry? \[Why The Policymakers
    Have It Wrong\], WATT Poultry/USA, March 2003

[^23]: Dawe J. The Relationship between Poultry Health and Food Safety.
    Poultry Informed Professional 2004; 77:1-6

[^24]: Cox LA, Ricci P. Causal regulations vs. political will: Why human
    zoonotic infections increase despite precautionary bans on animal
    antibiotics. Environ Int 2008 (in press)

[^25]: Cox LA,Popken DA. Quantifying Potential Human Health Impacts of
    Animal Antibiotic Use: Enrofloxacin and Macrolides in Chickens. Risk
    Analysis 2006; 26:135-146

[^26]: Cox LA. Potential human health benefits of antibiotics used in
    food animals: a case study of virginiamycin. Environ Int 2005;
    31:549-63

[^27]: Hurd S. et al. Potential Human Health Implications of Swine
    Health, Abstract of Oral Presentation, 2007

[^28]: DANMAP 2006. Use of antimicrobial agents and occurence of
    antimicrobial resistance in bacteria from food animals, foods and
    humans in Denmark. ISSN 1600-2032. (Available at
    [www.danmap.org](../www.danmap.org%20))

[^29]: domestically acquired clinical cases

[^30]: ^f^ domestically acquired clinical cases

    ^?^ The rationale for this change is unknown, but appears to
    introduce bias in reporting. DANMAP decided to use a preliminary
    European Committee on Antimicrobial Susceptibility Testing
    breakpoint instead of the previously used breakpoint established by
    the Clinical and Laboratory Standards Institute.

[^31]: avoparcin has never been approved for use in the United States

[^32]: United States Department of Agriculture. Animal and Plant Health
    Inspection Service. (May 2000). [Feedlot '99 -- Part I: Baseline
    Reference of Feedlot Management Practices, 1999.]{.underline}
    (#N327.0500). Fort Collins, CO: USDA/APHIS/VS/CEAH/NAHMS.

[^33]: United States Department of Agriculture. Animal and Plant Health
    Inspection Service. National Animal Health Monitoring System.
    (October 2007). [Swine 2006 - part 1: reference of swine health and
    management practices in the United States, 2006.]{.underline}
    (#N475.1007). Fort Collins, CO:USDA/APHIS/VS/CEAH/NAHMS. 

[^34]: Antimicrobial Resistance - Implications for the Food System,
    Institute of Food Technologists Expert Report, Comprehensive Reviews
    in Food Science and Food Safety, Vol 5, 2006 (Available at
    <http://members.ift.org/IFT/Research/IFTExpertReports/antimicrobial_report.htm>)

[^35]: Odds ratios were calculated based upon available data from NARMS
    assuming the reported isolates were representative of the bacterial
    population.

[^36]: CDC. National Antimicrobial Resistance Monitoring System: Enteric
    Bacteria. 2004 Human Isolates Final Report. (Available at
    <http://www.cdc.gov/narms/NARMSAnnualReport2004.pdf>)

[^37]: "Marginally significant" indicates a p-value between 0.05 and
    0.10; "significant" indicates a p-value between 0.01 and 0.05;
    "highly significant" indicates a p-value of less than 0.01

[^38]: no resistance detected to any of 5 subclasses of antibiotics

[^39]: ^i^ Odds ratios were calculated based upon available data from
    NARMS assuming the reported isolates were representative of the
    bacterial population.

    ^j^ "Marginally significant" indicates a p-value between 0.05 and
    0.10; "significant" indicates a p-value between 0.01 and 0.05;
    "highly significant" indicates a p-value of less than 0.01

    ^k^ no resistance detected to any of 5 subclasses of antibiotics

    ^?^ resistant to 2 or more antibiotic subclasses

[^40]: CDC. FoodNet. Facts and Figures related to "Preliminary FoodNet
    Data on the Incidence of Infection with Pathogens Transmitted
    Commonly Through Food\-\--10 States, United States, 2007" published
    in the Morbidity and Mortality Weekly Report (MMWR) on April 11,
    2008. (Available at
    <http://www.cdc.gov/foodnet/factsandfigures.htm>)

[^41]: United States Department of Agriculture, Animal and Plant Health
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