This is the accessible text file for GAO report number GAO-04-490 
entitled 'Antibiotic Resistance: Federal Agencies Need to Better Focus 
Efforts to Address Risk to Humans from Antibiotic Use in Animals' which 
was released on May 24, 2004.

This text file was formatted by the U.S. General Accounting Office 
(GAO) to be accessible to users with visual impairments, as part of a 
longer term project to improve GAO products' accessibility. Every 
attempt has been made to maintain the structural and data integrity of 
the original printed product. Accessibility features, such as text 
descriptions of tables, consecutively numbered footnotes placed at the 
end of the file, and the text of agency comment letters, are provided 
but may not exactly duplicate the presentation or format of the printed 
version. The portable document format (PDF) file is an exact electronic 
replica of the printed version. We welcome your feedback. Please E-mail 
your comments regarding the contents or accessibility features of this 
document to Webmaster@gao.gov.

This is a work of the U.S. government and is not subject to copyright 
protection in the United States. It may be reproduced and distributed 
in its entirety without further permission from GAO. Because this work 
may contain copyrighted images or other material, permission from the 
copyright holder may be necessary if you wish to reproduce this 
material separately.

Report to Congressional Requesters: 

April 2004: 

ANTIBIOTIC RESISTANCE: 

Federal Agencies Need to Better Focus Efforts to Address Risk to Humans 
from Antibiotic Use in Animals: 

[Hyperlink, http://www.gao.gov/cgi-bin/getrpt?GAO-04-490]: 

GAO Highlights: 

Highlights of GAO-04-490, a report to congressional requesters

Why GAO Did This Study: 

Antibiotic resistance is a growing public health concern; antibiotics 
used in animals raised for human consumption contributes to this 
problem. Three federal agencies address this issuethe Department of 
Health and Human Services (HHS) Food and Drug Administration (FDA) and 
Centers for Disease Control and Prevention (CDC), and the Department of 
Agriculture (USDA). GAO examined (1) scientific evidence on the 
transference of antibiotic resistance from animals to humans and extent 
of potential harm to human health, (2) agencies efforts to assess and 
address these risks, (3) the types of data needed to support research 
on these risks and extent to which the agencies collect these data, (4) 
use of antibiotics in animals in the United States compared with its 
key agricultural trading partners and competitors, and (5) information 
on how use has affected trade.

What GAO Found: 

Scientific evidence has shown that certain bacteria that are resistant 
to antibiotics are transferred from animals to humans through the 
consumption or handling of meat that contains antibiotic-resistant 
bacteria. However, researchers disagree about the extent of harm to 
human health from this transference. Many studies have found that the 
use of antibiotics in animals poses significant risks for human health, 
but a small number of studies contend that the health risks of the 
transference are minimal.

Federal agencies have expanded their efforts to assess the extent of 
antibiotic resistance, but the effectiveness of their efforts to reduce 
human health risk is not yet known. FDA, CDC, and USDA have increased 
their surveillance activities related to antibiotic resistance. In 
addition, FDA has taken administrative action to prohibit the use of a 
fluroquinolone in poultry. FDA has identified animal drugs that are 
critically important for human health and begun reviewing currently 
approved drugs using a risk assessment framework that it recently 
issued for determining the human health risks of animal antibiotics. 
However, because FDAs initial reviews of approved animal drugs using 
this framework have focused on other drugs and have taken at least 2 
years, FDAs reviews of critically important drugs may not be completed 
for some time.

Although federal agencies have made some progress in monitoring 
antibiotic resistance, they lack important data on antibiotic use in 
animals to support research on human health risks. These data, such as 
the type and quantity of antibiotics and purpose for their use by 
species, are needed to determine the linkages between antibiotic use in 
animals and emerging resistant bacteria. In addition, these data can 
help assess human health risks from this use and develop and evaluate 
strategies for mitigating resistance.

The United States and several of its key agricultural trading partners 
and competitors differ in their use of antibiotics in animals in two 
important areas: the specific antibiotics allowed for growth promotion 
and availability of antibiotics to producers (by prescription or over 
the counter). For example, the United States and Canada allow some 
antibiotics important in human medicine to be used for growth 
promotion, but the European Union (EU) and New Zealand do not. 
Regarding over the counter sales of antibiotics, the United States is 
generally less restrictive than the EU. 

Antibiotic use in animals has not yet been a significant factor 
affecting U.S. international trade in meat and poultry, although the 
presence of antibiotic residues in meat has had some impact, according 
to government and industry officials. Instead, countries raise other 
food safety issues, such as hormone use and animal diseases. However, 
according to these officials, antibiotic use in animals may emerge as a 
factor in the future. They particularly noted that the EU could object 
to U.S. use of antibiotics for growth promotion as its member countries 
are phasing out that use. 

What GAO Recommends: 

GAO recommends that (1) FDA expedite its risk assessments of drugs used 
in animals that are critical for human health and (2) USDA and HHS 
develop and implement a plan to collect data on antibiotic use in 
animals. USDA and HHS generally agreed with GAOs findings. With 
respect to the recommendations, HHS agreed that it is important to 
review animal drugs that are critical to human health and both agencies 
discussed ways to better collect antibiotic use data.

www.gao.gov/cgi-bin/getrpt?GAO-04-490.

To view the full product, including the scope and methodology, click on 
the link above. For more information, contact Anu Mittal at (202) 
512-3841 or Marcia Crosse at (202) 512-7119.

[End of section]

Contents: 

Letter: 

Results in Brief: 

Background: 

Antibiotic-Resistant Bacteria Have Been Transferred from Animals to 
Humans, but Researchers Disagree About the Extent of Potential Harm to 
Human Health: 

Federal Agencies Have Increased Surveillance of Antibiotic Resistance 
from Animals to Assess Human Health Risk; Effectiveness of Risk 
Reduction Efforts Is Not Yet Known: 

Federal Agencies Do Not Collect Data Needed to Address the Risk of 
Antibiotic Resistance Associated with Use in Animals: 

The United States and Its Key Trading Partners and Competitors Differ 
in the Restrictions They Place on the Use of Antibiotics in Animals: 

Antibiotic Use in Animals Has Not Significantly Affected U.S. Trade but 
Could Be an Issue in the Future: 

Conclusions: 

Recommendations for Executive Action: 

Agency Comments and Our Response: 

Appendixes: 

Appendix I: Objectives, Scope, and Methodology: 

Appendix II: Studies of the Economic Impacts of Restricting Antibiotic 
Uses in Animals: 

Appendix III: FDA's Procedures for Evaluating the Importance of an 
Animal Drug for Human Health: 

Appendix IV: Information on Selected Countries' Activities to Address 
Animal-Related Antibiotic Resistance: 

Appendix V: Antibiotics Frequently Used in Animals: 

Antibiotic Use in U.S. Feedlot Cattle Production: 

Antibiotic Use in U.S. Swine Production: 

Antibiotic Use in U.S. Broiler Production: 

Appendix VI: Comments from the U.S. Department of Agriculture: 

GAO's Responses to USDA's Comments: 

Appendix VII: Comments from the Department of Health and Human Services: 

Appendix VIII: GAO Contacts and Staff Acknowledgments: 

GAO Contacts: 

Acknowledgments: 

Tables: 

Table 1: Federal Surveillance Activities Related to Antibiotic 
Resistance and Foodborne Disease or Animal Health: 

Table 2: Economic Studies That Estimate the Effects of Restrictions on 
Antibiotic Use: 

Table 3: Antibiotic Sales and Meat Production, 2002: 

Table 4: Antibiotics Frequently Used in Feedlot Cattle, 1999: 

Table 5: Antibiotics Frequently Used in Swine, 2000: 

Table 6: Antibiotics Frequently Used in Feed for Broiler Chickens, 1995-
2000: 

Figures: 

Figure 1: Swine Confinement Facility: 

Figure 2: Possible Spread of Antibiotic-Resistant Bacteria from Animals 
to Humans: 

Figure 3: Sources of Data from Surveillance Activities about Antibiotic 
Resistance and Foodborne Disease or Animal Health: 

Abbreviations: 

ADG: average daily weight gain: 

ADP: antibiotics used for disease prevention: 

AGP: antibiotics used for growth promotion: 

CAHFSE: Collaboration in Animal Health, Food Safety, and Epidemiology: 

CDC: Centers for Disease Control and Prevention: 

DT: definitive type: 

DNA: deoxyribonucleic acid: 

EU: European Union: 

FAO: Food and Agriculture Organization of the United Nations: 

FAS: Foreign Agricultural Service: 

FCR: feed conversion ratio: 

FDA: Food and Drug Administration: 

FoodNet: Foodborne Diseases Active Surveillance Network: 

HIV: human immunodeficiency virus: 

HHS: Department of Health and Human Services: 

MR: mortality rate: 

NAHMS: National Animal Health Monitoring System: 

NARMS: National Antimicrobial Resistance Monitoring System--Enteric 
Bacteria: 

NRC: National Research Council: 

OIE: Office International des Epizooties: 

Q/D: quinupristin/dalfopristin: 

USDA: U.S. Department of Agriculture: 

WHO: World Health Organization: 

WTO: World Trade Organization: 

Letter April 22, 2004: 

The Honorable Olympia J. Snowe: 
Chair, Committee on Small Business and Entrepreneurship:
United States Senate: 

The Honorable Tom Harkin:
Ranking Democratic Member: 
Committee on Agriculture, Nutrition, and Forestry: 
United States Senate: 

The Honorable Edward M. Kennedy: 
Ranking Minority Member: 
Committee on Health, Education, Labor, and Pensions: 
United States Senate: 

Antibiotic resistance is a serious and growing public health 
problem.[Footnote 1] As resistance to antibiotics develops in disease-
producing bacteria, it can become difficult to treat diseases that were 
formerly treatable with antibiotics, and this can have deadly 
consequences. Treating antibiotic-resistant infections often requires 
the use of more expensive drugs and can result in longer hospital 
stays. According to Institute of Medicine estimates, the annual cost of 
treating antibiotic-resistant infections may be as high as $3 billion. 
Experts cite the widespread use of antibiotics in human medicine as the 
principal cause of resistance, but they identify the use of antibiotics 
in animals raised for human consumption as contributing to antibiotic 
resistance in humans. It is generally agreed that a large proportion of 
the antibiotics used in the United States is administered to animals 
raised for human consumption.

While antibiotic use in animals poses potential human health risks, it 
also reduces the cost of producing these animals, which in turn helps 
reduce the prices consumers pay for food. Antibiotics are an integral 
part of animal production in the United States and many other countries 
where large numbers of livestock and poultry are raised in confined 
facilities, which increases the likelihood of disease. Antibiotics are 
used to treat animal diseases; to prevent the spread of diseases that 
are known to occur during those phases of production when animals are 
at a high risk of disease (e.g., when animals have been transported to 
a new location); and to increase animals' growth rate. Consumer groups 
argue that antibiotic use would be reduced if different animal 
production methods were used. Public health officials are particularly 
concerned about the use of antibiotics in animals to promote growth 
because antibiotics used for growth promotion are administered in low 
doses over long periods of time to large groups of animals that are not 
sick. This practice can allow animals to become reservoirs of 
antibiotic-resistant bacteria. If a person becomes ill from handling or 
ingesting meat or poultry contaminated with antibiotic-resistant 
bacteria, the infection may be resistant to treatment not only with the 
antibiotic of choice for that infection but also with other antibiotics 
in the same class of drugs. Use of antibiotics in animals also may lead 
to the transference of resistance from one type of bacteria to another 
type.

Three federal agencies are primarily responsible for protecting 
Americans from the health risk associated with the transfer of 
antibiotic-resistant bacteria from meat and poultry to the humans who 
handle or consume these products. The Department of Health and Human 
Services' (HHS) Food and Drug Administration (FDA) approves for sale 
and regulates the manufacture and distribution of antibiotics used in 
animals. HHS's Centers for Disease Control and Prevention (CDC) 
conducts surveillance and other research to assess the extent of 
antibiotic resistance in humans from animals. The U.S. Department of 
Agriculture (USDA) gathers data on antibiotic resistance in animals, 
conducts surveillance, and funds epidemiologic and other research on 
antibiotic resistance in humans, animals, and the environment. In 
addition, internationally, the World Health Organization (WHO) and the 
Office International des Epizooties (OIE) have been examining these 
issues.[Footnote 2]

In 1999, we reported that the development and spread of antibiotic-
resistant bacteria is a worldwide phenomenon and that the widespread 
use of various antibiotics has created the potential for U.S. public 
health costs to increase.[Footnote 3] We further reported that the 
extent to which the agricultural use of antibiotics contributes to 
antibiotic-resistant bacteria in humans is uncertain and recommended 
that HHS and USDA work together to develop and implement a plan with 
specific goals, time frames, and resources needed for determining the 
safe use of antibiotics in agriculture.[Footnote 4] In response, in 
January 2001, the federal Interagency Task Force on Antimicrobial 
Resistance, which is composed of FDA, CDC, and USDA, and several other 
agencies,[Footnote 5] issued an action plan to address antibiotic 
resistance issues, including those associated with antibiotic use in 
animals. Subsequently, in June 2003, the task force issued a status 
report that described the agencies' progress in implementing the 
activities outlined in the action plan.

You asked us to examine the (1) scientific evidence regarding the 
transference of antibiotic resistance from animals to humans through 
consuming or handling contaminated meat and poultry and the extent of 
potential harm to human health, (2) progress federal agencies have made 
in assessing and addressing the human health risk of antibiotic use in 
animals, (3) types of data that federal agencies need to support 
research on the human health risk of antibiotic use in animals and the 
extent to which these data are collected, (4) use of antibiotics in 
animals in the United States compared with antibiotic use by its key 
agricultural trading partners and competitors, and (5) information that 
is available on the degree to which antibiotic use in animals has 
affected U.S. trade.

For the purpose of this report, the term "animal" refers to animals 
raised for human consumption, such as cattle, sheep, swine, chickens, 
and turkeys; the term "meat" refers to beef, lamb, pork, chicken, and 
turkey; and the term "contaminated meat" refers to meat that contains 
antibiotic-resistant bacteria. We limited the scope of our work to the 
transference of antibiotic-resistant bacteria from animals to humans 
through the consumption or handling of meat. Specifically, we looked at 
the evidence for transference of antibiotic-resistant foodborne 
intestinal pathogens from these animals to humans. We did not examine 
issues related to antibiotics used on plants and seafood, antibiotic 
residues in animals, or the effects of antibiotics present in the 
environment because of the application of animal waste to agricultural 
lands.

To identify scientific literature on the transmission of antibiotic-
resistant bacteria from animals to humans, we searched medical, social 
science, and agricultural databases, which included HHS's National 
Institutes of Health's National Library of Medicine, for studies 
published in professional journals. We identified articles published 
since the 1970s on antibiotic use and resistance in animals and humans, 
as well as articles on antibiotic-resistant foodborne illnesses.

To examine federal agencies' progress in assessing and addressing the 
human health risk of antibiotic use in animals, we examined documents 
from FDA, CDC, and USDA. These documents include reports on results 
from the federal government's antibiotic resistance surveillance 
program and on the progress of the federal Interagency Task Force on 
Antimicrobial Resistance, documents presented in an FDA administrative 
proceeding concerning the agency's proposal to withdraw the approval of 
the use of a certain antibiotic used in poultry that is also an 
important antibiotic in human medicine, and FDA's framework to assess 
the human health risk of antibiotic use in animals.

To examine the types of data that federal agencies need on antibiotic 
use in animals to support research on the human health risk and the 
extent to which these data are collected, we reviewed federal agencies' 
documents and reports and interviewed FDA, CDC, and USDA officials. We 
reviewed foreign government reports to determine how other countries 
use data on antibiotic use for research and international reports from 
WHO and OIE, which provide guidelines on the types of antibiotic use 
data that countries should collect. We also interviewed officials from 
Denmark, which collects extensive data on antibiotic use in animals, 
and from Canada, which plans to implement a data collection system. We 
discussed the availability of data on U.S. antibiotic use in animals 
with officials from pharmaceutical companies, industry associations, 
state veterinary offices, firms that collect data on antibiotic use in 
animals, and public health advocacy groups.

To compare the United States' use of antibiotics in animal production 
with that of its key trading partners and competitors, we reviewed 
information on antibiotic use in animals for these countries. We 
reviewed FDA regulations on antibiotic use in animals in the United 
States and visited livestock and poultry farms in Georgia, Maryland, 
and Pennsylvania. Using international trade data, we identified the 
European Union (EU) and 11 countries--Australia, Brazil, Canada, China, 
Denmark,[Footnote 6] Hong Kong, Japan, Mexico, New Zealand, Russia, and 
South Korea--as key U.S. trading partners or competitors. We identified 
relevant documents on these countries' policies concerning antibiotic 
use in animals and obtained further information through discussions 
with USDA's Foreign Agricultural Service officials, as well as through 
a questionnaire we sent to the agency's attachs stationed in those 
countries. We examined these policies and identified the similarities 
and differences between countries. In addition, we discussed antibiotic 
use and policies with government officials from Canada, a leading U.S. 
trading partner and competitor, and Denmark, a leading U.S. trading 
partner and competitor that took significant actions to curtail 
antibiotic use in animals during the late 1990s. We also reviewed USDA 
and other reports on antibiotic use in animal production. We did not 
independently verify the information we received in response to our 
questionnaire; other documents, including laws and regulations from the 
foreign countries; or other reports on antibiotic use in the United 
States.

To examine the available information on the degree to which antibiotic 
use in animals has affected U.S. trade, we examined USDA records on 
foreign countries' meat import standards and reviewed reports by USDA 
and international food safety organizations on international trade 
issues related to food safety. In addition, we discussed international 
trade issues with officials from the Office of the U.S. Trade 
Representative, USDA's Foreign Agricultural Service, and meat industry 
trade associations.

We discussed the matters in this report with government officials, 
public interest groups, pharmaceutical manufacturers, and 
international and academic experts. Appendix I provides additional 
information on our scope and methodology. We conducted our work from 
May 2003 through April 2004 in accordance with generally accepted 
government auditing standards.

Results in Brief: 

Antibiotic-resistant bacteria have been transferred from animals to 
humans, and many of the studies we reviewed found that this 
transference poses significant risks for human health. Studies have 
shown two types of evidence related to the transfer of antibiotic-
resistant bacteria from animals to humans. First, some studies have 
provided evidence of associations between changes in antibiotic use in 
animals and resistance to antibiotics in humans. For example, 
researchers have found that antibiotic-resistant Escherichia coli (E. 
coli) and campylobacter bacteria increased in humans as use of the 
antibiotics commonly used to treat infections caused by those bacteria 
has increased in animals. Second, studies that have examined the 
genetic makeup of the bacteria have provided evidence of a stronger 
link and have established that antibiotic-resistant campylobacter and 
salmonella bacteria are transferred from animals to humans. In those 
studies, strains of antibiotic-resistant bacteria infecting humans were 
indistinguishable from those found in animals, leading the researchers 
to conclude that the animals were the source of infection. Researchers 
disagree about the extent of the human health risk caused by this 
transference. Many studies have found that the use of antibiotics in 
animals poses significant risks for human health. However, a small 
number of studies contend that health risks of the transference are 
minimal.

Federal agencies have expanded their surveillance of antibiotic 
resistance from the use of antibiotics in animals to assess the risk to 
human health, but it is too early to determine the effectiveness of 
their efforts to reduce this risk. FDA, CDC, and USDA have increased 
their surveillance activities related to antibiotic resistance in 
animals, humans, and retail meat by studying more types of bacteria, 
increasing the geographic areas studied, and adding new programs. In 
addition, all three agencies have funded or conducted research on 
antibiotic resistance in animals. As the regulatory agency responsible 
for animal drugs, FDA has determined that antibiotic resistance in 
humans resulting from the use of antibiotics in animals is an 
unacceptable risk to the public health and has taken a variety of 
recent actions. For example, FDA has taken action to prohibit the use 
of the fluoroquinolone antibiotic enrofloxacin in poultry because of 
what the agency asserts is strong evidence that the use of these 
antibiotics has led to the transference of antibiotic-resistant 
bacterial diseases from poultry to humans. A challenge from the drug's 
manufacturer has led to administrative proceedings that have lasted 
more than 3 years, and the product remains on the market pending the 
final outcome of this case. In addition, FDA has issued guidance 
recommending a risk assessment framework for determining the human 
health risk of animal antibiotics and has begun to apply this framework 
in its reviews of manufacturers' applications for approval of new 
animal drugs. FDA has also begun reviewing currently approved animal 
antibiotics using this same framework. However, the approved drugs that 
it has reviewed to date using this approach have not included those 
that FDA identified in its guidance as critically important to human 
health, and the reviews have taken at least 2 years to complete. 
Therefore it may be some time before FDA completes its reviews of 
critically important drugs in order to determine if enforcement action 
to protect human health is warranted.

Although they have made some progress in monitoring antibiotic 
resistance, federal agencies do not collect the critical data on 
antibiotic use in animals that they need to support research on the 
human health risk. The data that could help this research include the 
types and quantities of antibiotics sold for use in animals, the 
purpose of their use (such as disease treatment or growth promotion), 
the species in which they are used, and the method used to administer 
them. These types of data are needed to study the linkages between 
antibiotic use in animals and the human risk from antibiotic resistance 
and to develop and evaluate strategies for mitigating resistance. Such 
data could also help researchers assess the human risk from using 
antibiotics in animals. At this time, FDA is not collecting data on 
antibiotic use in animals, and USDA's data collection activities are 
limited to a few swine farms. In Denmark, where detailed data on 
antibiotic use are collected, scientists have been able to research the 
effects of antibiotic use in animals on the development of resistant 
bacteria in animals, food, and humans and to develop mitigation 
strategies that minimize the potential human health risk.

The United States and several of its key trading partners and 
competitors, such as the EU, Canada, Australia, South Korea, and New 
Zealand, differ in their use of antibiotics in animals in two key 
areas: the specific antibiotics that can be used for growth promotion 
and the availability of antibiotics to producers (by prescription or 
over the counter). For example, the United States and Canada allow some 
antibiotics important in human medicine to be used for growth 
promotion. In contrast, New Zealand and the EU have banned this use in 
feed for those antibiotics that are important in human medicine. The EU 
has also issued a regulation requiring that member nations prohibit the 
use of all other antibiotics in feed for growth promotion by 2006. With 
regard to the availability of antibiotics to producers, the United 
States allows older antibiotics to be sold over the counter but 
requires a veterinarian's prescription for newer antibiotics, such as 
fluoroquinolones. Some other countries, including Canada, also allow 
certain antibiotics to be sold over the counter. In contrast, Danish 
producers need prescriptions for all antibiotics, while other EU 
countries generally require prescriptions.

To date, antibiotic use in animals has not been a significant factor 
affecting the United States' international trade in meat products, 
although the presence of antibiotic residues in meat has had some 
impact, according to officials from USDA, the Office of the U.S. Trade 
Representative, and industry. In addition, these officials told us, 
foreign governments have raised other food safety concerns as trade 
issues, including hormone use in animals and animal diseases, such as 
bovine spongiform encephalopathy (commonly known as mad cow disease) 
and avian influenza. However, according to government officials, a USDA 
report, and a Canadian government report, antibiotic use in animals may 
emerge as a factor in U.S. trade negotiations in the future. The 
officials particularly noted that the EU could object to the United 
States' use of antibiotics for growth promotion because member 
countries are phasing out that use.

We are making recommendations to federal agencies to better focus their 
efforts to reduce the risk to human health from the transfer of 
antibiotic-resistant bacteria from meat. We recommend that FDA expedite 
its risk assessments of the antibiotics used in animals that are 
critically important to human health to determine if regulatory action 
is necessary. We also recommend that the Secretaries of Agriculture and 
of Health and Human Services develop and implement a plan to collect 
data on antibiotic use in animals that will adequately (1) support 
research on the relationship between this kind of antibiotic use and 
emerging resistant bacteria, (2) help assess the human health risk 
related to antibiotic use in animals, and (3) help the agencies develop 
and evaluate strategies to mitigate antibiotic resistance.

In commenting on a draft of this report, USDA and HHS generally agreed 
with our findings. With respect to our recommendations, HHS agreed that 
it is important to review animal drugs that are critical for human 
health, and both agencies discussed ways to better collect antibiotic 
use data.

Background: 

For over 50 years, antibiotics have been widely prescribed to treat 
bacterial infections in humans. Many antibiotics commonly used in 
humans have also been used in animals for therapeutic and other 
purposes, including growth promotion. Resistance to penicillin, which 
was the first broadly used antibiotic, started to emerge soon after its 
widespread introduction. Since that time, resistance to other 
antibiotics has emerged, and antibiotic resistance has become an 
increasing public health problem worldwide.

Development of Antibiotic Resistance: 

Antibiotics kill most, if not all, of the susceptible bacteria that are 
causing an infection, but leave behind--or select, in biologic terms--
the bacteria that have developed resistance, which can then multiply 
and thrive. Infection-causing bacteria that were formerly susceptible 
to an antibiotic can develop resistance through changes in their 
genetic material, or deoxyribonucleic acid (DNA). These changes can 
include the transfer of DNA from resistant bacteria, as well as 
spontaneous changes, or mutations, in a bacterium's own DNA. The DNA 
coding for antibiotic resistance is located on the chromosome or 
plasmid of a bacterium.[Footnote 7] Plasmid-based resistance is 
transferred more readily than chromosomal-based resistance. Once 
acquired, the genetically determined antibiotic resistance is passed on 
to future generations and sometimes to other bacterial species. The 
dose of antibiotic and length of time bacteria are exposed to the 
antibiotic are major factors affecting whether the resistant bacteria 
population will dominate. Low doses of antibiotics administered over 
long periods of time to large groups of animals, such as doses used for 
growth promotion in animals, favor the emergence of resistant 
bacteria.[Footnote 8]

Investigating the Impact of Antibiotic Resistance on Human Health: 

To investigate the impact on human health of antibiotic use in animals, 
researchers have used both epidemiologic studies alone and 
epidemiologic studies combined with molecular subtyping of bacterial 
isolates.[Footnote 9] Epidemiologic studies examine patterns of health 
or disease in a population and the factors that influence these 
patterns. These studies help to identify the cause of a disease and the 
factors that influence a person's risk of infection. Many studies 
investigating antibiotic-resistant bacteria and their impact on human 
health combine epidemiologic studies with molecular subtyping--also 
called "DNA fingerprinting"--a technique that translates bacteria's 
genetic material into a "bar code" that can be used to identify 
specific pathogens and link them with disease outbreaks. For example, 
following an outbreak of a diarrheal disease among people in a 
community, an epidemiologic study would determine all the common 
exposures among the people with the disease, and molecular subtyping of 
bacterial isolates could determine what pathogens were responsible for 
the disease.

Use of Antibiotics in Animals: 

While the use of antibiotics in animals poses potential human health 
risk, it is also an integral part of intensive animal production in 
which large numbers of poultry, swine, and cattle are raised in 
confinement facilities. (See fig. 1.) Antibiotics are used in animals 
to treat disease; to control the spread of a disease in a group of 
animals when disease is present in some of the animals; to prevent 
diseases that are known to occur during high-risk periods, such as 
after transport, when the animals are stressed; and to promote growth-
-that is, to allow animals to grow at a faster rate while requiring 
less feed per pound of weight gain.[Footnote 10] This use of 
antibiotics is commonly referred to as growth promotion and generally 
entails using low doses of antibiotics over long periods of time in 
large groups of animals. Many animal producers believe the use of 
antibiotics for growth promotion also prevents disease. Antibiotics are 
generally administered by injection to individual animals and in feed 
or water to groups of animals.

Figure 1: Swine Confinement Facility: 

[See PDF for image]

[End of figure]

Possible Spread of Antibiotic-Resistant Bacteria from Animals to 
Humans: 

Figure 2 shows how antibiotic-resistant bacteria that develop in 
animals can possibly be transferred to humans, who may then develop a 
foodborne illness, such as a salmonella infection, that is resistant to 
antibiotic treatment.[Footnote 11] Once the resistant bacteria develop 
in animals, they may be passed to humans through the consumption or 
handling of contaminated meat. An animal or human may carry antibiotic-
resistant bacteria but show no signs or symptoms of an illness. 
Resistant bacteria may also be spread to fruits, vegetables, and fish 
products through soil, well water, and water runoff contaminated by 
waste material from animals harboring these bacteria, although such 
routes are beyond the focus of this report.

Figure 2: Possible Spread of Antibiotic-Resistant Bacteria from Animals 
to Humans: 

[See PDF for image]

[End of figure]

Debate Regarding Public Health Impact of Use of Antibiotics in 
Agriculture: 

Researchers in human medicine have debated the public health impact of 
antibiotic use in agriculture for many years. In the United States the 
debate intensified before FDA approved the first fluoroquinolone 
antibiotic for use in animals in 1995. At that time, drugs from the 
fluoroquinolone class had already been used for humans for nearly a 
decade. Debate focused on whether development of resistance to the drug 
approved for use in animals could, through cross-resistance,[Footnote 
12] compromise the effectiveness of other drugs in the fluoroquinolone 
class that were valuable in treating human diseases.

Efforts have been made to address the spread of antibiotic resistance 
by providing education to change behaviors of physicians and the 
public, but researchers differ on whether changes in agricultural 
practices are also needed. CDC has undertaken educational efforts aimed 
at physicians and the public. CDC is encouraging physicians to reduce 
prescribing antibiotics for infections commonly caused by viruses, such 
as ear and sinus infections. Patients are being taught that antibiotics 
are only for bacterial infections, not viral infections. Many 
researchers contend that efforts to reduce the use of antibiotics in 
animals are also needed to preserve the effectiveness of antibiotics 
necessary for treatment of bacterial diseases in humans and animals and 
to decrease the pool of resistant bacteria in the environment. However, 
agricultural industry officials argue that antibiotic use in animals is 
essential to maintaining the health of animals and therefore the safety 
of food.

Professional organizations and associations differ on the use of 
antibiotics in animals. Many professional organizations that have 
studied the human health implications of antibiotic use in animals--
including WHO and, in the United States, the Institute of Medicine of 
the National Academy of Sciences and the Alliance for the Prudent Use 
of Antibiotics--have recommended either limiting or discontinuing the 
use of antibiotic growth promoters.[Footnote 13] Many of the 
professional associations for human medicine--such as the American 
Medical Association, the American College of Preventive Medicine, the 
American Public Health Association, and the Council of State and 
Territorial Epidemiologists--have position statements for limiting 
antibiotic use in animals for nontherapeutic purposes, such as growth 
promotion, for antibiotics that are important for both human and animal 
health. Many of the professional associations for veterinary medicine-
-such as the American Veterinary Medical Association and the American 
Association of Swine Practitioners--agree on the goal of reducing the 
use of antibiotics in animals but differ on the means to achieve this 
goal. These associations are calling for veterinarians to work with 
owners of animals to implement judicious use guidelines.

While limiting the use of antibiotics in animals for growth promotion 
may reduce the human health risk associated with antibiotic-resistant 
bacteria, such restrictions also may increase the cost of producing 
animals and the prices consumers pay for animal products. For example, 
a 1999 economic study estimated that a hypothetical ban on all 
antibiotic use in feed in swine production would increase U.S. 
consumers' costs by more than $700 million per year.[Footnote 
14],[Footnote 15] However, the increase in consumer costs would be much 
smaller if--as the Institute of Medicine proposed in 2003--producers 
were allowed to continue to use some antibiotics for growth promotion 
and only antibiotics that are used in humans were banned for growth 
promotion. Moreover, in other animal species, such as beef cattle or 
chickens, the economic impacts of growth promotion restrictions would 
likely be smaller than in swine because antibiotic use for growth 
promotion is less prevalent in the production of these other species. 
Appendix II summarizes studies of the economic effects of banning 
antibiotic use for growth promotion and other proposed restrictions on 
antibiotic uses in animals.

Federal Agency Responsibilities and Authority: 

The three federal agencies responsible for protecting Americans from 
health risk associated with drug use in animals are FDA, CDC, and USDA. 
These agencies have a variety of responsibilities related to 
surveillance, research, and regulation. All three agencies collaborate 
on surveillance activities, such as the National Antimicrobial 
Resistance Monitoring System--Enteric Bacteria (NARMS), which was 
initiated in 1996 because of public health concerns associated with the 
use of antibiotics in animals. In addition, FDA's primary 
responsibilities as a regulatory body focus on human health and animal 
drug safety. CDC primarily conducts research and education that focus 
on human health. USDA oversees the retail meat trade, including related 
farm and slaughter operations. USDA activities may include studies of 
healthy farm animals, evaluations of diagnostic data involving sick 
animals, and biological sampling from slaughter and meat processing 
plants. USDA also conducts research and education related to antibiotic 
resistance.

In addition, FDA approves for sale and regulates the manufacture and 
distribution of drugs used in veterinary medicine, including drugs 
given to animals from which human foods are derived. Prior to approving 
a new animal drug application, FDA must determine that the drug is safe 
and effective for its intended use in the animal. It must also 
determine that the new drug intended for animals is safe with regard to 
human health. FDA considers a new animal antibiotic to be safe if it 
concludes that there is reasonable certainty of no harm to human health 
from the proposed use of the drug in animals. FDA may also take action 
to withdraw an animal drug from the market when the drug is no longer 
shown to be safe.[Footnote 16]

These three agencies also participate in the federal Interagency Task 
Force on Antimicrobial Resistance. Task force activities focus on 
antibiotic resistance from use of antibiotics in animals, as well as 
the human use of antibiotics. In January 2001, the task force developed 
an action plan based on advice from consultants from state and local 
health agencies, universities, professional societies, pharmaceutical 
companies, health care delivery organizations, agricultural producers, 
consumer groups, and other members of the public. The action plan 
includes 84 action items, 13 of which have been designated as top-
priority items and cover issues of surveillance, prevention and 
control, research, and product development.[Footnote 17] A federal 
agency (or agencies) is designated as the lead for each action item.

International Trade Issues: 

The United States is one of the world's leading exporters of meat. In 
2002, U.S. meat exports accounted for about $7 billion. The World Trade 
Organization (WTO), of which the United States is a member, provides 
the institutional framework for conducting international trade, 
including trade in meat products. WTO member countries agree to a 
series of rights and obligations that are designed to facilitate global 
trade. When a country regulates imports, including imported meat, WTO 
guidelines stipulate that member countries have the right to determine 
their own "appropriate levels of protection" in their regulations to 
protect, among other things, human and animal health. Member countries 
must have a scientific basis to have levels of protection that are 
higher than international guidelines. To encourage member countries to 
apply science-based measures in their regulations, WTO relies on the 
international standards, guidelines, and recommendations that its 
member countries develop within international organizations, such as 
the Codex Alimentarius Commission for food safety and the OIE for 
animal health and the safety of animal products for human consumption.

While ensuring that food products are safe and of high quality usually 
promotes trade, one country's food safety regulations could be 
interpreted by another country as a barrier to trade. It is difficult, 
however, to distinguish between a legitimate regulation that protects 
consumers but incidentally restricts trade from a regulation that is 
intended to restrict trade and protect local producers, unless that 
regulation is scientifically documented.

Antibiotic-Resistant Bacteria Have Been Transferred from Animals to 
Humans, but Researchers Disagree About the Extent of Potential Harm to 
Human Health: 

Research has shown that antibiotic-resistant bacteria have been 
transferred from animals to humans, but the extent of potential harm to 
human health is uncertain. Evidence from epidemiologic studies suggests 
associations between patterns of antibiotic resistance in humans and 
changes in antibiotic use in animals. Further, evidence from 
epidemiologic studies that include molecular subtyping to identify 
specific pathogens has established that antibiotic-resistant 
campylobacter and salmonella bacteria are transferred from animals to 
humans. Many of the studies we reviewed found that this transference 
poses significant risks for human health. Researchers disagree, 
however, about the extent of potential harm to human health from the 
transference of antibiotic-resistant bacteria.

Antibiotic-Resistant Bacteria Have Been Transferred from Animals to 
Humans: 

Antibiotic-resistant bacteria have been transferred from animals to 
humans. Evidence that suggests that this transference has taken place 
is found in epidemiologic studies showing that antibiotic-resistant E. 
coli and campylobacter bacteria in humans increase as use of the 
antibiotics increases in animals. Evidence that establishes 
transference of antibiotic-resistant bacteria is found in epidemiologic 
studies that include molecular subtyping. These studies have 
demonstrated that antibiotic-resistant campylobacter and salmonella 
bacteria have been transferred from animals to humans through the 
consumption or handling of contaminated meat. That is, strains of 
antibiotic-resistant bacteria infecting humans were indistinguishable 
from those found in animals, and the researchers concluded that the 
animals were the source of infection.

Epidemiologic Evidence Suggests That Patterns of Antibiotic Resistance 
in Humans Are Associated with Changes in Antibiotic Use in Animals: 

Evidence from epidemiologic studies that do not include molecular 
subtyping indicates that patterns of antibiotic resistance in humans 
are associated with changes in the use of particular antibiotics in 
animals. For example, work conducted in the United States in the 1970s 
showed an association between the use of antibiotic-supplemented animal 
feed in a farm environment and the development of antibiotic-resistant 
E. coli in the intestinal tracts of humans and animals.[Footnote 18] In 
the study, isolates from chickens on the farm and from people who lived 
on or near the farm were tested and found to have low initial levels of 
tetracycline-resistant E. coli bacteria. The chickens were then fed 
tetracycline-supplemented feed, and within 2 weeks 90 percent of them 
were excreting essentially all tetracycline-resistant E. coli bacteria. 
Within 6 months, 7 of the 11 people who lived on or near the farm were 
excreting high numbers of resistant E. coli bacteria. Six months after 
the tetracycline-supplemented feed was removed, no detectable 
tetracycline-resistant organisms were found in 8 of the 10 people who 
lived on or near the farm when they were retested. Another 
study,[Footnote 19] based on human isolates of Campylobacter jejuni 
submitted to the Minnesota Department of Health, reported that the 
percentage of Campylobacter jejuni in the isolates that were resistant 
to quinolone increased from approximately 0.8 percent in 1996 to 
approximately 3 percent in 1998.[Footnote 20]

There is also evidence to suggest that antibiotic-resistant 
enterococcus has developed from the use of antibiotics in animals. 
Vancomycin[Footnote 21] resistance is common in intestinal enterococci 
of both exposed animals and nonhospitalized humans only in countries 
that use or have previously used avoparcin (an antibiotic similar to 
vancomycin)[Footnote 22] as an antibiotic growth promoter in animal 
agriculture.[Footnote 23] Since the EU banned the use of avoparcin as a 
growth promoter, several European countries have observed a significant 
decrease in the prevalence of vancomycin-resistant enterococci in meat 
and fecal samples of animals and humans.

Evidence Shows That Antibiotic-Resistant Campylobacter and Salmonella 
Bacteria Have Been Transferred to Humans: 

Epidemiologic studies that include molecular subtyping have 
demonstrated that antibiotic-resistant campylobacter and salmonella 
bacteria have been transferred from animals to humans through the 
consumption or handling of contaminated meat. That is, strains of 
antibiotic-resistant bacteria infecting humans were indistinguishable 
from those found in animals, and the authors of the studies concluded 
that the animals were the source of infection.

Campylobacter Bacteria: 

The strongest evidence for the transfer of antibiotic-resistant 
bacteria from animals to humans is found in the case of 
fluoroquinolone-resistant campylobacter bacteria. Campylobacter is one 
of the most commonly identified bacterial causes of diarrheal illness 
in humans. The strength of the evidence is derived in part from the 
fact that the particular way fluoroquinolone resistance develops for 
campylobacter bacteria makes it easier to identify the potential source 
of the resistance. Most chickens are colonized with campylobacter 
bacteria, which they harbor in their intestines, but which do not make 
them sick. Fluoroquinolones are given to flocks of chickens when some 
birds are found to have certain infections caused by E. coli. In 
addition to targeting the bacteria causing the infection, treatment of 
these infections with fluoroquinolones almost always replaces 
susceptible campylobacter bacteria with fluoroquinolone-resistant 
campylobacter bacteria. Because fluoroquinolone resistance is located 
on the chromosome of campylobacter, the resistance is generally not 
transferred to other species of bacteria. Therefore when 
fluoroquinolone-resistant campylobacter bacteria are detected in human 
isolates, the source is likely to be other reservoirs of campylobacter 
bacteria, including animals. In some cases, molecular subtyping 
techniques have shown that fluoroquinolone-resistant isolates of 
campylobacter from food, humans, and animals are similar.

Fluoroquinolone-resistant Campylobacter jejuni in humans has increased 
in the United States and has been linked with fluoroquinolone use in 
animals. CDC reported that in the United States the percentage of 
Campylobacter jejuni in human isolates that were resistant to 
fluoroquinolones increased from 13 percent in 1997 to 19 percent in 
2001.[Footnote 24] A study in Minnesota found that fluoroquinolone-
resistant Campylobacter jejuni was isolated from 14 percent of 91 
chicken products obtained from retail markets in 1997.[Footnote 25] 
Through molecular subtyping, the strains isolated from the chicken 
products were shown to be the same as those isolated from nearby 
residents, thereby bolstering the case that the chickens were the 
source of the antibiotic resistance.

During the 1980s, the resistance of campylobacter bacteria to 
fluoroquinolones increased in Europe. European investigators 
hypothesized that there was a causal relationship between the use of 
fluoroquinolones in animals and the increase in fluoroquinolone-
resistant campylobacter infections in humans. For example, an 
epidemologic study that included molecular subtyping in the Netherlands 
found that among different strains of campylobacter bacteria, the 
percentage of fluoroquinolone-resistant strains in isolates tested had 
risen from 0 percent in both human and animal isolates in 1982 to 11 
percent in human isolates and 14 percent in poultry isolates by 
1989.[Footnote 26] The authors concluded that the use of two new 
fluoroquinolones, one in humans in 1985 and one in animals in 1987, was 
responsible for the quinolone-resistant strains. The authors asserted 
that the extensive use of fluoroquinolones in poultry and the common 
route of campylobacter infection from chickens to humans suggest that 
the resistance was mainly due to the use of fluoroquinolones in 
poultry.

Salmonella Bacteria: 

Several epidemiologic studies using molecular subtyping have linked 
antibiotic-resistant salmonella infections in humans, another common 
foodborne illness, to animals. For example, in 1998 bacteria resistant 
to ceftriaxone were isolated from a 12-year-old boy who lived on a 
cattle farm in Nebraska.[Footnote 27] Molecular subtyping revealed that 
an isolate from the boy was indistinguishable from one of the isolates 
from the cattle on the farm. No additional ceftriaxone-resistant 
salmonella infections were reported in that state or adjoining states 
that could have been the cause of the infection. Similarly, an 
epidemiologic study in Poland from 1995 to 1997 using molecular 
subtyping found identical profiles for ceftriaxone-resistant 
salmonella bacteria in isolates from poultry, feed, and 
humans.[Footnote 28] The researchers concluded that the salmonella 
infections were introduced in the poultry through the feed and reached 
humans through consumption of the poultry. Researchers in Taiwan also 
found that Salmonella enterica serotype choleraesuis bacteria that were 
resistant to ciprofloxacin in isolates collected from humans and swine 
were closely related and, following epidemiologic studies, concluded 
that the bacteria were transferred from swine to humans.[Footnote 29]

Researchers have also documented human infections caused by multidrug-
resistant strains of salmonella linked to animals. In 1982, researchers 
used molecular subtyping to show that human isolates of multidrug-
resistant salmonella bacteria were often identical or nearly identical 
to isolates from animals.[Footnote 30] In the mid-1990s, NARMS data 
showed a rapid growth of multidrug resistance in Salmonella enterica 
serotype Typhimurium definitive type (DT) 104 among humans.[Footnote 
31] Molecular subtyping found that human isolates with this strain of 
multidrug resistance in Salmonella enterica serotype Typhimurium DT104 
in 1995 were indistinguishable from human isolates with this strain 
tested in 1985 and 1990. These results indicated that the widespread 
emergence of multidrug resistance in Salmonella enterica serotype 
Typhimurium DT104 may have been due to dissemination of a strain 
already present in the United States. Because food animals are the 
reservoir for most domestically acquired salmonella infections and 
transmission from animals to humans occurs through the food supply, the 
researchers concluded that the human infections were likely from the 
animals.

Recently, there has been an emergence of multidrug-resistant Salmonella 
enterica serotype Newport infections that include resistance to 
cephalosporins,[Footnote 32] such as cefoxitin.[Footnote 33] Based on 
molecular subtyping, multidrug-resistant salmonella isolates from 
cattle on dairy farms were found to be indistinguishable from human 
isolates. An epidemiologic study found that the infections in humans 
were associated with direct exposure to a dairy farm, and the authors 
hypothesized that the infections were associated with handling or 
consuming the contaminated foods.

Many Studies Have Found That Transference of Antibiotic-Resistant 
Bacteria from Animals to Humans Is a Human Health Risk, but Researchers 
Disagree About the Extent of Risk: 

The extent of harm to human health from the transference of antibiotic-
resistant bacteria from animals is uncertain. Many studies have found 
that the use of antibiotics in animals poses significant risks for 
human health, and some researchers contend that the potential risk of 
the transference is great for vulnerable populations. However, a small 
number of studies contend that the health risks of the transference are 
minimal.

Many Researchers Contend That Antibiotic Use in Animals Poses 
Significant Risk for Human Health: 

Some studies have sought to determine the human health impacts of the 
transference of antibiotic resistance from animals to humans. For 
example, the Food and Agriculture Organization of the United Nations 
(FAO), OIE, and WHO recently released a joint report based on the 
scientific assessment of antibiotic use in animals and agriculture and 
the current and potential public health consequences.[Footnote 34] The 
report states that use of antibiotics in humans and animals alters the 
composition of microorganism populations in the intestinal tract, 
thereby placing individuals at increased risk for infections that would 
otherwise not have occurred. The report also states that use of 
antibiotics in humans and animals can also lead to increases in 
treatment failures and in the severity of infection.

Similarly, a recent review of studies regarding increased illnesses due 
to antibiotic-resistant bacteria found significant differences in 
treatment outcomes of patients with antibiotic-resistant bacterial 
infections and patients with antibiotic-susceptible bacterial 
infections.[Footnote 35] For example, one study found that 
hospitalization rates of patients with nontyphoidal salmonella 
infections were 35 percent for antibiotic-resistant infections and 27 
percent for antibiotic-susceptible infections. That study also found 
that the length of illness was 10 days for antibiotic-resistant 
infections versus 8 days for antibiotic-susceptible infections. Another 
study found diarrhea from Campylobacter jejuni infections lasted 12 
days for antibiotic-resistant infections versus 6 days for susceptible 
infections. Also, based on this review, the authors estimated that 
fluoroquinolone resistance likely acquired through animals leads to at 
least 400,000 more days of diarrhea in the United States per year than 
would occur if all infections were antibiotic-susceptible. The authors 
estimated that antibiotic resistance from nontyphoidal salmonella 
infections mainly arising from animals could account for about 8,700 
additional days of hospitalization per year.

Experts are especially concerned about safeguarding the effectiveness 
of antibiotics such as vancomycin that are considered the "drugs of 
last resort" for many infections in humans. Evidence suggests that use 
of the antibiotic avoparcin in animals as a growth promoter may 
increase numbers of enterococci that are resistant to the similar 
antibiotic vancomycin. A particular concern is the possibility that 
vancomycin-resistant enterococci could transfer resistance to other 
bacteria. Some Staphylococcus aureus infections found in hospitals are 
resistant to all antibiotics except vancomycin, and human health can be 
adversely affected, as treatment could be difficult, if not impossible, 
if these strains develop resistance to vancomycin, too. Recently, two 
human isolates of Staphylococcus aureus were found to be resistant to 
vancomycin.

With the increase in infections that are resistant to vancomycin, the 
streptogramin antibiotic quinupristin/dalfopristin (Q/D, also known as 
Synercid) has become an important therapeutic for life-threatening 
vancomycin-resistant enterococcus infections.[Footnote 36] 
Virginiamycin, which is similar to Q/D, has been used in animals since 
1974, and Q/D was approved for human use in 1999. NARMS data from 1998 
to 2000 indicate that Q/D-resistant Enterococcus faecium has been found 
in chicken and ground pork purchased in grocery stores, as well as in 
human stools.[Footnote 37] Experts hypothesize that use of 
virginiamycin in poultry production has led to Q/D-resistant bacteria 
in humans because the antibiotics are very similar, but the human 
health consequences of this have not been quantified.[Footnote 38]

Experts are also concerned about risks to vulnerable populations such 
as individuals with compromised immune systems or chronic diseases, who 
are more susceptible to infections, including antibiotic-resistant 
infections. For example, salmonella infections are more likely to be 
severe, recurrent, or persistent in persons with human immunodeficiency 
virus (HIV). Another concern is that people with resistant bacteria 
could inadvertently spread those bacteria to hospitalized patients, 
including those with weakened immune systems.

Other Researchers Contend That Evidence of Human Health Risk from 
Antibiotic Use in Animals Is Lacking: 

Although it is generally agreed that transference is possible, some 
researchers contend that the health risks of the transference are 
minimal.[Footnote 39] Proponents of this view note that not all studies 
have shown an increase in antibiotic-resistant bacteria. For example, 
one study conducted between 1997 and 2001 found no clear trend toward 
greater antibiotic resistance in salmonella bacteria.[Footnote 40]

Proponents of this view also assert that restricting the use of 
antibiotics in animal agriculture could lead to greater levels of 
salmonella and campylobacter bacteria reaching humans through meat, 
thus increasing the risk of human infections. Conversely, some of these 
researchers also argue that the risk to humans of acquiring these 
infections from animals can be eliminated if meat is properly handled 
and cooked. They also cite a few studies that have concluded that the 
documented human health consequences are small. For example, they noted 
that one study estimated that banning the use of virginiamycin in 
animals in the U.S. would lower the number of human deaths by less than 
one over 5 years.[Footnote 41]

Federal Agencies Have Increased Surveillance of Antibiotic Resistance 
from Animals to Assess Human Health Risk; Effectiveness of Risk 
Reduction Efforts Is Not Yet Known: 

FDA, CDC, and USDA have increased their surveillance activities related 
to antibiotic resistance in animals, humans, and retail meat since 
beginning these activities in 1996. New programs have been added, the 
number of bacteria being studied has increased, and the geographic 
coverage of the sampling has been expanded. In addition, all three 
agencies have sponsored research on the human health risk from 
antibiotic resistance in animals. FDA has taken several recent actions 
to minimize the human health risk of antibiotic resistance from 
animals, but the effectiveness of its actions is not yet known. These 
activities include administrative action to prohibit the use of the 
fluoroquinolone enrofloxacin (Baytril) for poultry and the development 
of a recommended framework for conducting qualitative risk assessments 
of all new and currently approved animal drug applications with respect 
to antibiotic resistance and human health risk.

Federal Surveillance Activities for Antibiotic Resistance in Animals 
and Humans Have Increased: 

FDA, CDC, and USDA have six surveillance activities ongoing to identify 
and assess the prevalence of resistant bacteria in humans, animals, or 
retail meat. (See table 1.) Since 1996, these activities have expanded 
to include additional bacteria, greater geographic coverage, and new 
activities. Two of these activities--NARMS and Collaboration in Animal 
Health, Food Safety and Epidemiology (CAHFSE)--focus on antibiotic 
resistance from animals. The other four activities--Foodborne Diseases 
Active Surveillance Network (FoodNet), PulseNet, PulseVet, and National 
Animal Health Monitoring System (NAHMS)--focus on foodborne disease or 
animal health in general, not antibiotic resistance, but are 
nevertheless relevant to issues of antibiotic resistance. Figure 3 
shows how these different surveillance activities provide data about 
various aspects of antibiotic resistance.

Table 1: Federal Surveillance Activities Related to Antibiotic 
Resistance and Foodborne Disease or Animal Health: 

Activity: Focus on antibiotic resistance; National Antimicrobial 
Resistance Monitoring System--Enteric Bacteria (NARMS); 
Purpose: To monitor antimicrobial resistance among foodborne bacteria 
isolated from humans, animals, and retail foods and perform research to 
further evaluate resistance, including molecular analysis, and develop 
special projects to better understand resistance. Implement response 
activities to mitigate the resistance and perform epidemiologic 
studies; 
Lead agency: CDC (Human NARMS); 
Bacteria: 
* Salmonella Typhi; 
* non-Typhi Salmonella; 
* Campylobacter; 
* E. coli O157: H7; 
* Enterococcus; 
* Shigella; 
Source of bacteria isolates: Humans.
Lead agency: USDA (Animal NARMS); 
Bacteria: 
* Non-Typhi Salmonella; 
* Campylobacter; 
* generic E. coli; 
* Enterococcus; 
Source of bacteria isolates: Animals: on farm, diagnostic, slaughter/
processing.
Lead agency: FDA (Retail Meat NARMS); 
Bacteria: 
* Non-Typhi Salmonella; 
* Campylobacter; 
* generic E. coli; 
* Enterococcus; 
Source of bacteria isolates: Retail samples of ground beef, ground 
turkey, pork chops, chicken breasts[A].

Activity: Focus on antibiotic resistance; Collaboration in Animal 
Health, Food Safety and Epidemiology (CAHFSE); 
Purpose: To assess the presence of bacteria, relate the onset and 
duration of infection with antibiotic use patterns in animals, and 
describe on-farm trends in the prevalence of bacteria; 
Lead agency: USDA; 
Bacteria: 
* Salmonella; 
* Campylobacter; 
* generic E. coli; 
* Enterococcus; 
Source of bacteria isolates: Swine (on farm), expanding to include 
slaughter/processing.

Activity: Focus on foodborne disease or animal health; Foodborne 
Diseases Active Surveillance Network (FoodNet); 
Purpose: To determine the incidence of foodborne diseases, monitor 
foodborne disease trends, and determine the proportion of foodborne 
diseases attributable to specific foods and settings; 
Lead agency: CDC; 
Bacteria: 
* Salmonella; 
* Campylobacter; 
* Shigatoxin-producing E. coli (e.g., E. coli O157: H7); 
* Shigella; 
* Listeria; 
* Vibrio; 
* Yersinia; 
* Cryptosporidium; 
* Cyclospora; 
Source of bacteria isolates: Humans.

Activity: Focus on foodborne disease or animal health; PulseNet; 
Purpose: To provide data on the extent and relatedness of outbreaks and 
individual isolates of foodborne disease; 
Lead agency: CDC; 
Bacteria: 
* Non-Typhi Salmonella; 
* E. coli O157: H7; 
* Listeria; 
* Shigella; 
* Campylobacter; 
Source of bacteria isolates: Humans and food[B].

Activity: Focus on foodborne disease or animal health; PulseVet; 
Purpose: To conduct DNA fingerprinting of animal bacteria; 
Lead agency: USDA; 
Bacteria: 
* Salmonella; 
Source of bacteria isolates: Animals from slaughter/processing.

Activity: Focus on foodborne disease or animal health; National Animal 
Health Monitoring System (NAHMS); 
Purpose: To collect, analyze, and disseminate data on animal health, 
management, and productivity; 
Lead agency: USDA; 
Bacteria: 
* Salmonella; 
Source of bacteria isolates: Animals on farm. 

Source: GAO.

[A] The retail meat program of NARMS, with USDA, will also look at 
susceptibilities of recovered E. coli and salmonella bacteria obtained 
from their produce surveys.

[B] PulseNet includes any type of food, not just retail meat.

[End of table]

Figure 3: Sources of Data from Surveillance Activities about Antibiotic 
Resistance and Foodborne Disease or Animal Health: 

[See PDF for image] 

Note: 
CAHFSE = Collaboration in Animal Health, Food Safety and Epidemiology; 
NARMS = National Antimicrobial Resistance Monitoring System--Enteric 
Bacteria; 
NAHMS = National Animal Health Monitoring System; 
FoodNet = Foodborne Diseases Active Surveillance Network.

[End of figure] 

NARMS and CAHFSE Focus on Antibiotic Resistance: 

NARMS monitors changes in susceptibilities of bacteria in humans and 
animals to antibiotics. To assess the extent of changes in levels of 
resistance, NARMS collects animal and human isolates of six different 
bacteria, specifically non-Typhi Salmonella, Campylobacter, E. coli, 
Enterococcus, Salmonella Typhi, and Shigella.[Footnote 42] These 
activities are conducted under three independent, yet coordinated, 
programs, with FDA serving as the funding and coordinating agency. The 
human program gathers isolates from humans and is led by CDC. The 
animal program, led by USDA, gathers isolates from animals on farms, 
from slaughter and processing plants, and from diagnostic laboratories. 
The retail meat program gathers samples of meat purchased at grocery 
stores and is run by FDA. The agencies work together to standardize 
results through ongoing quality control efforts.

NARMS has expanded in three major ways--range of bacteria tested, 
geographic coverage, and number of programs--since it was established 
in 1996. For example, human NARMS started by looking at two bacteria 
and now studies six bacteria.[Footnote 43] Further, NARMS also assessed 
the potential of other bacteria to become sources of resistance by 
collecting and assessing listeria and vibrio isolates in pilot 
studies.[Footnote 44] With regard to geographic coverage, the number of 
participating health departments has increased from 14 state and local 
health departments in 1996 to all 50 states and Washington, D.C., in 
2003.[Footnote 45] Finally, the retail meat program was added in 2002. 
Initially, 5 states participated in the retail meat program, but by 
2004, 10 states were participating. Despite this recent expansion, all 
of NARMS experienced budget cuts in fiscal year 2004, calling into 
question future expansion efforts. For example, the USDA budget for the 
animal program was cut 17.6 percent for 2004.

NARMS has also produced collaborative research efforts among FDA, CDC, 
and USDA and helped further scientific understanding of antibiotic 
resistance. For example, data from NARMS led CDC to conclude that the 
proportion of campylobacter isolates resistant to ciprofloxacin in 2001 
was 2.4 times higher than in 1997.[Footnote 46] Similarly, FDA and CDC 
officials reported that NARMS data were used to evaluate antibiotic 
resistance to fluoroquinolones, and CDC officials told us that after 
NARMS data showed an increased number of cases of Salmonella Newport 
infections in humans, researchers at CDC and USDA shared human and 
animal isolates to determine whether the same pattern existed in 
animals.

CAHFSE, established by USDA in 2003, collects samples from animals on 
farms to identify changes in antimicrobial resistance over time. The 
first animals that are being tested in the program are swine. USDA 
conducts quarterly sampling of 40 fecal and 60 blood samples from 
animals from farms in four states. As of March 2004, 40 farms were 
participating in CAHFSE. In addition to the laboratory analyses, there 
are plans for risk analyses, epidemiologic studies, and field 
investigations, as well as analysis of samples collected at slaughter, 
and the addition of more species, funding permitted.

Other Activities Focus on Foodborne Disease or Animal Health: 

FoodNet, PulseNet, PulseVet, and NAHMS focus on foodborne disease or 
animal health rather than antibiotic resistance. FoodNet, the principal 
foodborne disease component of CDC's Emerging Infections Program, is a 
collaborative project with 10 states (referred to as FoodNet sites), 
USDA, and FDA.[Footnote 47] The goals of FoodNet are to determine the 
incidence of foodborne diseases, monitor foodborne disease trends, and 
determine the proportion of foodborne diseases attributable to specific 
foods and settings. FoodNet data are derived from specimens collected 
from patients. Isolates from these specimens are sent to NARMS for 
susceptibility testing. CDC officials reported that one of every 20 
patients with a specimen in FoodNet also has an isolate in NARMS.

A recent development has been the linking of the NARMS and FoodNet data 
systems. For example, FoodNet data can be used to determine whether an 
individual was hospitalized, and NARMS data can reveal whether the 
bacteria that infected the person were resistant to antibiotics. CDC 
officials reported that because of the linked databases, they were able 
to determine whether, for example, someone with an antibiotic-resistant 
salmonella infection was more likely to be hospitalized than someone 
with an antibiotic-susceptible salmonella infection. FoodNet also has a 
role in the retail meat program of NARMS. The FoodNet sites purchase 
the meat samples from grocery stores, examine the samples for the 
prevalence or frequency of bacterial contamination, and forward 
isolates of the bacteria to FDA for susceptibility testing for 
antibiotic resistance.

PulseNet is CDC's early warning system for outbreaks of foodborne 
disease. USDA recently established a similar animal program, called 
PulseVet. PulseNet studies isolates from humans and suspected food, and 
PulseVet studies isolates from animals.[Footnote 48] Both PulseNet and 
PulseVet conduct DNA fingerprinting of bacteria[Footnote 49] and 
compare those patterns to other samples in order to identify related 
strains. The PulseNet and PulseVet isolates are tested for antibiotic 
resistance at CDC and USDA, respectively. FDA also performs DNA 
fingerprinting on salmonella and campylobacter isolates obtained from 
the retail meat program of NARMS and submits these data to PulseNet.

NAHMS, which focuses on healthy animals, was initiated by USDA in 1983 
to collect, analyze, and disseminate data on animal health, management, 
and productivity across the United States. Since 1990, USDA has 
annually conducted studies on animal health, including information 
about antibiotic use, through NAHMS. Each study focuses on different 
animals, including swine, cattle (both dairy and beef), and sheep. 
NAHMS provides only a snapshot of a particular species or commodity; it 
does not track changes over time. While NAHMS contributes information 
about healthy animals, a USDA official told us that it also includes 
information about antibiotics used and may include information on the 
route of administration and the reason for treatment, which can be 
useful in further understanding NARMS findings. In addition, 
researchers and veterinarians are able to access the NAHMS database for 
studies of disease incidence, risk assessment, and preventive treatment 
techniques. Further, bacteria samples obtained from NAHMS have been 
added to the NARMS database.

Federally Funded Research Is Under Way to Study the Human Health Risk 
of Antibiotic Resistance in Food Animals: 

Under the federal Interagency Task Force on Antimicrobial Resistance 
action plan, FDA, CDC, and USDA have initiated a number of research 
efforts that are relevant to antibiotic use in animals and human 
health. These ongoing research efforts focus on defining the effects of 
using various animal drugs on the emergence of antibiotic-resistant 
bacteria and identifying risk factors and preventive measures. Through 
CDC, FDA currently has cooperative agreements with four veterinary 
schools to study ways to reduce antibiotic-resistant bacteria in 
animals and is assessing the prevalence of antibiotic-resistant DNA in 
feed ingredients.[Footnote 50] In addition, FDA annually issues a 3-
year research plan that describes research focusing on, among other 
things, antibiotic resistance in animals and its consequences for human 
health. Current studies include efforts to examine the consequences of 
antibiotic use in animals, the transmission of antibiotic resistance, 
and the processes underlying the spread of antibiotic resistance. In 
total, CDC has funded three projects under its Antimicrobial Resistance 
Applied Research extramural grant program. One of these grants, for 
example, is to study the prevalence of antibiotic-resistant E. coli in 
chicken and ground beef products, examine the risk factors for human 
colonization with a resistant strain of E. coli, and compare 
characteristics of antibiotic-susceptible and antibiotic-resistant 
isolates from meat with those of antibiotic-susceptible and antibiotic-
resistant isolates from humans. Similarly, USDA has funded studies of 
antibiotic resistance in chicken, turkey, pork, and dairy products. 
These studies have provided additional sources of isolates to FDA for 
risk assessment purposes. Also, USDA's Cooperative State Research, 
Education, and Extension Service has funded over 30 studies related to 
antibiotic resistance since 2000 and awarded an additional $8 million 
in grants in 1999 and 2000. Funded research includes studies on the 
prevalence, development, and possible transmission of antibiotic 
resistance; the epidemiology of antibiotic resistance; and the 
evaluation of management practices and potential prevention/
intervention strategies for antibiotic resistance.

FDA Has Taken Action to Minimize the Potential Human Health Risk of 
Antibiotic Resistance from Animals, but It Is Too Early to Determine 
Effectiveness: 

FDA has taken a variety of actions to minimize the risk to the public 
health of antibiotic resistance in humans resulting from the use of 
antibiotics in animals, although it is still too early to determine the 
effectiveness of these actions. First, FDA has taken action to prohibit 
the use of an already approved animal drug for poultry because of 
concerns about human health risk. Second, the agency developed a 
recommended framework for reviewing all new animal antibiotic 
applications with respect to antibiotic resistance and human health 
risk. Third, FDA has begun reviewing antibiotics currently approved for 
use in animals according to its new framework to determine whether FDA 
needs to act to ensure that the drugs are safe. It is too early to 
determine the effectiveness of FDA's review of currently marketed 
drugs. FDA has not made drugs used in animals that are critically 
important for human health its top priority for review, and any 
remedial actions pursued by the agency may take years to complete.

FDA Has Initiated Action to Prohibit the Use of Enrofloxacin in 
Poultry, but Proceedings Not Yet Complete: 

On October 31, 2000, FDA proposed withdrawing the approval of 
enrofloxacin (Baytril), a fluoroquinolone drug used in 
poultry,[Footnote 51] after human health risks associated with the use 
of the drug in chickens and turkeys were documented by, among others, 
NARMS. Enrofloxacin is administered to flocks of poultry in their water 
supply to control mortality associated with E. coli and Pasteurella 
multocida organisms. FDA had found that new evidence, when evaluated 
with information available when the application was approved, 
demonstrated that enrofloxacin used with poultry flocks has not been 
shown to be safe for humans. Specifically, FDA determined that the use 
of enrofloxacin in poultry causes the development of a fluoroquinolone-
resistant strain of campylobacter in poultry, which, when transferred 
to humans, is a significant cause of fluoroquinolone-resistant 
campylobacter infections in humans.

Before proceeding with formal efforts to withdraw approval for use of 
enrofloxacin with poultry flocks, FDA considered a number of 
alternative actions. For example, the agency determined that changing 
the label to limit use to the treatment of individual birds and 
limiting use to one time or one treatment per individual bird were 
impractical. The agency also considered and rejected the establishment 
of a registry that would require veterinarians to demonstrate the need 
for the drug. FDA proceeded with its efforts to withdraw approval of 
enrofloxacin for use in poultry because FDA knew that there were 
alternative effective drugs for treating these illnesses in poultry.

In February 2002, FDA announced that a hearing would be held on the 
proposal to withdraw approval of enrofloxacin.[Footnote 52] Since FDA's 
proposed action to ban the use of enrofloxacin in poultry, 
representatives of both FDA and Bayer, the manufacturer of Baytril, as 
well as numerous experts, have provided testimony on the question of 
its safety. Submission of written testimony was due in December 2002, 
and cross-examination of witnesses took place from late April 2003 
through early May 2003. The final posthearing briefs and responses were 
delivered in July and August 2003. On March 16, 2004, an FDA 
administrative law judge issued an initial decision withdrawing the 
approval of the new animal drug application for Baytril. This decision 
will become final unless it is appealed to the FDA Commissioner by 
Bayer or another participant in the case or the Commissioner chooses to 
review it on his own initiative.[Footnote 53] If the Commissioner 
reviews and upholds the initial decision, Bayer or another participant 
may choose to appeal in court.[Footnote 54]

Effectiveness of FDA's Framework for Reviewing New Animal Drugs Is Not 
Yet Known: 

FDA has determined that the human health risk from antibiotic use in 
animals is not acceptable, and the agency may initiate risk management 
strategies to contain such risk. In October 2003, as part of its 
efforts to approve and regulate animal drugs, FDA issued Guidance for 
Industry #152. The guidance outlines a framework for determining the 
likelihood that an antibiotic used to treat an animal would cause an 
antibiotic resistance problem in humans who consume meat or other food 
products from animals. The guidance's risk assessment framework is 
based on three factors--the probability that resistant bacteria are 
present in the target animal, the probability that humans would ingest 
the bacteria in question from the relevant food commodity, and the 
probability that human exposure to resistant bacteria would result in 
an adverse health consequence. The resulting overall risk estimate is 
ranked as high, medium, or low.

Because the guidance is new, it is not yet known how the results of a 
risk assessment conducted according to the guidance will influence 
FDA's decisions to approve new drug applications. Agency officials told 
us that FDA has never denied a new or supplemental animal drug 
application because of evidence that the drug caused antibiotic 
resistance in humans. In addition, the risk assessment guidance states 
that drugs with high risk may still be approved, though with specific 
use restrictions, if there is a reasonable certainty of no harm to 
human health when the drug is approved. These restrictions might 
include availability only by prescription, restrictions on uses not 
specified on the label (known as extralabel use), limitations for use 
in individual animals (versus groups of animals) for fewer than 21 
days, and requirements for postapproval monitoring. FDA has previously 
used these kinds of restrictions with some drugs. While agency 
officials told us that the extralabel use prohibitions for animal drugs 
have generally reduced unauthorized use, such use restrictions may not 
prevent human health risk. For example, while FDA had earlier limited 
fluoroquinolones to use by or under the order of a veterinarian and 
prohibited the extralabel use of fluoroquinolones, the agency has now 
concluded that a human health risk exists despite these restrictive 
measures.

FDA officials reported that the agency has reviewed about seven new 
drug applications using the risk assessment framework in Guidance for 
Industry #152. Some of those drugs have been approved. Other drugs have 
been approved but with label claims different from those requested in 
the application. FDA officials have not denied approval to any of these 
new drug applications.

Timing and Effectiveness of FDA Plans to Review Currently Marketed 
Animal Antibiotics for Human Health Risk Are Uncertain: 

To determine whether future regulatory actions may be necessary, FDA is 
conducting risk assessments for drugs currently used in animal 
agriculture that are also important for human medicine. FDA began with 
two quantitative risk assessments for drugs ranked as critically 
important for human health at the time the assessments were initiated. 
FDA completed the assessment for fluoroquinolones in October 2000 and 
expects to complete the assessment for virginiamycin, a streptogramin 
drug related to Synercid, its counterpart for humans, in 2004.[Footnote 
55] The quantitative risk assessments calculate estimates of the number 
of cases of infection. Agency officials told us that they had hoped 
that the quantitative risk assessment approach would provide a template 
for future risk assessments. However, FDA decided that it did not.

FDA officials told us that as a result, the agency plans to review 
other currently marketed antibiotics using the qualitative risk 
assessment framework outlined in Guidance for Industry #152, which uses 
broad categories to assess risk. An FDA official reported that if the 
information necessary to complete any section of the qualitative risk 
assessment were unavailable, the agency would assign a higher score to 
the product, to err on the side of caution. After outlining possible 
risk management steps, if any, the agency would allow a drug's sponsor 
(generally pharmaceutical firms) to provide additional information to 
help FDA reconsider its risk estimate. Generally, these qualitative 
risk assessments are considered to be a starting point for examining 
human health risk for some drugs.

FDA has not made drugs that are critically important for human health 
its top priority for review.[Footnote 56] (See app. III for more detail 
on evaluating the importance of an animal drug for human health.) 
Instead, the agency focused its first qualitative risk assessments on 
subtherapeutic penicillin and tetracycline drugs.[Footnote 57] These 
assessments are expected to be completed by April 2004. FDA officials 
told us that the agency will then conduct qualitative risk assessments 
for therapeutic penicillin and tetracycline drugs, followed by 
assessments for those drugs that are defined in Guidance for Industry 
#152 as critically important for human health. As of March 2004, there 
were four such categories of drugs.[Footnote 58]

For a number of reasons, it is not known whether FDA's new framework 
for reviewing currently approved and marketed animal drugs will be able 
to effectively identify and reduce any human health risk. First, under 
this plan, it may take years for FDA to identify and reduce any human 
risk of acquiring antibiotic resistance from meat. FDA has not 
developed a schedule for conducting the qualitative risk assessments on 
the currently approved drugs, and the assessments may take a 
significant amount of time to complete. For example, based on the 
current schedule, FDA officials told us they expect the qualitative 
risk assessment of subtherapeutic penicillins and tetracyclines, which 
were begun in 2002, to take nearly 2 years to complete. Second, FDA 
officials told us that the risk estimation from the qualitative risk 
assessments will only use data already available in the original new 
drug application and any supplemental drug applications, rather than 
actively seeking new evidence. However, FDA told us that new evidence 
was an important factor in its risk assessment of fluoroquinolones. 
Finally, while FDA can pursue a number of enforcement options if its 
reviews uncover a human health risk, it is not known if they will be 
effective or how long it will take for such changes to take effect. As 
the enrofloxacin case demonstrates, risk management strategies may not 
mitigate human health risk, and administrative proceedings can extend 
for several years after FDA decides to take enforcement action.
[Footnote 59] An FDA official also told us that if the drug sponsor 
voluntarily cooperates in implementing risk management strategies, 
lengthy administrative proceedings may be avoided.

Federal Agencies Do Not Collect Data Needed to Address the Risk of 
Antibiotic Resistance Associated with Use in Animals: 

Although they have made some progress in monitoring antibiotic 
resistance associated with antibiotic use in animals, federal agencies 
do not collect data on antibiotic use in animals that are critical to 
supporting research on the human health risk. Data on antibiotic use 
would allow agencies to link use to the emergence of antibiotic-
resistant bacteria, help assess the risk to human health, and develop 
strategies to mitigate resistance. FDA and USDA do not collect these 
data because of costs to the industry and other factors. Countries that 
collect antibiotic use data, depending on the amount and type of data 
collected, have been able to conduct more extensive research than U.S. 
agencies.

Federal Agencies Do Not Collect Needed Data: 

According to FDA, CDC, and USDA, more data are needed on antibiotic use 
in animals in order to conduct further research on antibiotic 
resistance associated with this use. In particular, FDA has stated that 
it needs information on the total quantity of antibiotics used in 
animals, by class; the species they are used in; the purpose of the 
use, such as disease treatment or growth promotion; and the method used 
to administer the antibiotic. WHO and OIE have also recommended that 
countries collect such data. This information could be used for the 
following: 

* To link antibiotic use to emerging strains of antibiotic-resistant 
bacteria. Antibiotic use information would clarify the relationship 
between resistance trends in NARMS and the actual use of antibiotics. 
For example, detailed on-farm data on antibiotic use and other 
production practices that are linked to bacteria samples from animals 
could help identify the conditions under which resistant bacteria 
develop.

* To help assess risk to human health. Information on antibiotic use 
would help assess the likelihood that humans could be exposed to 
antibiotic-resistant bacteria from animals. This potential exposure is 
important in determining the risk that antibiotic use in animals may 
pose to human health.

* To develop and evaluate strategies to mitigate resistance. Data on 
antibiotic use would help researchers develop strategies for mitigating 
increased levels of resistant bacteria in animals, according to CDC 
officials. Strategies could be developed based on such factors as the 
way the drug is administered, dosage levels, or use in a particular 
species. In addition, unless data are available for monitoring the 
effects of these interventions, researchers cannot assess the 
strategies' effectiveness.

FDA recognizes that additional data on antibiotic use in animal 
production would facilitate research on the linkages to human 
resistance. To that end, FDA had considered a plan that would have 
required pharmaceutical companies to provide more detailed information 
on antibiotics distributed for use in animals.[Footnote 60] This 
information would have been reported as a part of FDA's ongoing 
monitoring of these antibiotics after their approval. However, 
according to FDA officials, this more detailed reporting would have 
resulted in significant costs to the pharmaceutical industry.[Footnote 
61] Consequently, FDA is analyzing other options to minimize the burden 
to the industry.

In addition, the information that USDA collects through NAHMS is of 
limited use for supporting research on the relationship between 
antibiotic use in animals and emerging antibiotic-resistant bacteria. 
NAHMS was not designed to collect antibiotic use data; instead, as 
previously discussed, its main goal is to provide information on U.S. 
animal health, management, and productivity. Through NAHMS, USDA does 
collect some data on antibiotic use, but only periodically and only for 
certain species. For example, it has studied the swine industry every 5 
years since 1990 but has not yet studied broiler chickens--the most 
common type of poultry Americans consume.

USDA's Collaboration in Animal Health, Food Safety and Epidemiology 
(CAHFSE) is a new program designed to enhance understanding of bacteria 
that pose a food safety risk. USDA plans to monitor, over time, the 
prevalence of foodborne and other bacteria, as well as their resistance 
to antibiotics on farms and in processing plants. These data are 
expected to facilitate research on the link between agricultural 
practices, such as the use of antibiotics, and emerging resistant 
bacteria. Currently, however, CAHFSE does not provide information on 
the impact of antibiotic use for species such as poultry and cattle and 
for a significant portion of the swine industry. According to USDA, 
CAHFSE funding comes primarily from a limited amount of funding that is 
redirected from other USDA programs, and the program would need 
additional funding before it could expand to cover processing plants, 
more swine operations, or other species. USDA officials told us they 
plan to coordinate data collection and analysis efforts for CAHFSE with 
NARMS activities at FDA and CDC.

According to the officials we spoke with at market research firms, 
private companies also collect some data on antibiotic use, but this 
information is developed for commercial purposes and is not always 
available for public research. These companies collect information on 
animal production practices, including antibiotic use, and sell this 
information to producers, who use it to compare their production costs 
and practices with those of other producers. They also sell these data 
to pharmaceutical companies, which use the information to estimate the 
future demand for their products. In any case, the market research 
firms do not design their data collection efforts to assist research on 
antibiotic resistance.

Other Countries Collect Data That Are Useful for Conducting Research on 
Antibiotic Use and Developing Strategies to Mitigate Antibiotic 
Resistance: 

Unlike the United States, other countries, such as Denmark, New 
Zealand, and the United Kingdom, collect more extensive data on 
antibiotic use in animals. Among the countries we examined, Denmark 
collects the most comprehensive and detailed data, including 
information on the quantities of antibiotics used in different animal 
species by age group and method of administration. According to Danish 
researchers, these data have allowed them to take the following 
actions: 

* Link antibiotic use in animals to emerging strains of antibiotic-
resistant bacteria. Danish researchers have been able to determine how 
changes in the consumption of antibiotics in animals affect the 
occurrence of antibiotic-resistant bacteria. In addition, researchers 
began collecting additional data on antibiotic-resistant bacteria in 
humans in 2002, allowing them to explore the relationship between 
levels of antibiotic-resistant bacteria in animals, food, and humans.

* Develop strategies to mitigate resistance. By monitoring trends in 
antibiotic use and levels of antibiotic-resistant bacteria, Denmark has 
been able to adjust national veterinary use guidelines and revised 
regulations to minimize potential risk to human health.

Other countries, such as New Zealand and the United Kingdom, have data 
collection systems that are not as comprehensive as Denmark's. 
Nevertheless, these nations collect data on total sales for antibiotics 
used in animals by class of antibiotic. The United Kingdom is also 
working to more accurately track the sales of antibiotics for use in 
different species. These data show trends in use over time and identify 
the importance of different antibiotic classes for the production of 
livestock and poultry. According to the official responsible for the 
United Kingdom's data collection system, collecting these data requires 
few resources. In addition, Canadian officials told us Canada is 
collecting some data on antibiotic use on farms and expects to collect 
data on sales of antibiotics used in animals. Canada also plans to 
develop comprehensive methods to collect use data and integrate these 
data into its antibiotic resistance surveillance system. According to 
Canada's first annual report on antibiotic resistance, issued in March 
2004, its next annual report will include some information on 
antibiotic use in animals. See appendix IV for information on other 
countries' data collection systems.

The United States and Its Key Trading Partners and Competitors Differ 
in the Restrictions They Place on the Use of Antibiotics in Animals: 

The United States and several of its key trading partners, such as 
Canada and South Korea, and its competitors, such as the EU, differ in 
their use of antibiotics in animals in two important areas: the 
specific antibiotics that can be used for growth promotion and the 
availability of antibiotics to producers (by prescription or over the 
counter).[Footnote 62]

With respect to growth promotion in animals, the United States, as well 
as Australia, Canada, Japan, and South Korea, allow the use of some 
antibiotics from classes important in human medicine.[Footnote 63] 
However, the United States and Australia are currently conducting risk 
assessments to determine whether to continue to allow the use of some 
of these antibiotics for growth promotion. Canada plans to conduct 
similar risk assessments, and Japan is reviewing the use of antibiotics 
for growth promotion if those antibiotics are from classes used in 
humans. In contrast, New Zealand has completed its risk assessments of 
antibiotics used for growth promotion and no longer allows the use of 
any antibiotics for growth promotion that are also related to 
antibiotics used in human medicine. Similarly, the EU has prohibited 
its member countries from using antibiotics in feed for growth 
promotion if those antibiotics are from antibiotic classes used in 
human medicine. In addition, the EU has issued a regulation that will 
prohibit the use of all other antibiotics in feed for growth promotion 
by 2006.[Footnote 64]

We found differences among the United States' and other countries' use 
of antibiotics for growth promotion in the following four antibiotic 
classes that FDA has ranked as critically or highly important in human 
medicine: 

* Macrolides. The United States, Canada, and South Korea allow 
antibiotics from the macrolide class for growth promotion, but the EU 
and New Zealand do not.[Footnote 65] In the United States, tylosin, a 
member of this class, is among the most commonly used antibiotics for 
growth promotion in swine. As of March 2003, Australia allowed 
antibiotics from the macrolide class for growth promotion, but it had a 
review under way on some antibiotics in this class, including tylosin, 
to determine if growth promotion use should continue.

* Penicillins and tetracyclines. The United States, Canada, and South 
Korea allow certain antibiotics from these two classes to be used for 
growth promotion, but Australia, the EU, Japan, and New Zealand do not. 
Furthermore, as mentioned earlier, the United States is currently 
conducting risk assessments on these two classes to determine whether 
to continue allowing their use for growth promotion.

* Streptogramins. The United States, Canada, and South Korea allow the 
use of virginiamycin, an antibiotic from this class, for growth 
promotion, but the EU and New Zealand do not. The United States is 
conducting a risk assessment on the use of virginiamycin for growth 
promotion and disease prevention. As of April 2003, Australia permitted 
virginiamycin for growth promotion, but the Australian agency that 
regulates antibiotic use in animals has recommended that approval of 
this use be withdrawn.

Appendix V lists antibiotics--including antibiotics from the above 
classes--that are frequently used in U.S. animal production.

With regard to the availability of antibiotics to livestock and poultry 
producers, public health experts advocate requiring a veterinarian's 
prescription for the sale of antibiotics. They believe that this 
requirement may help reduce inappropriate antibiotic use that could 
contribute to the emergence of antibiotic-resistant bacteria in animals 
and the human health risk associated with these resistant bacteria.

The United States and Canada permit many antibiotics to be sold over 
the counter, without a veterinarian's prescription, while the EU 
countries and New Zealand are more restrictive regarding over-the-
counter sales.[Footnote 66] The United States and Canada generally 
allow older antibiotics, such as sulfamethazine, to be sold over the 
counter, but they require a prescription for newer antibiotics, such as 
fluoroquinolones. In addition, with regard to the availability of 
antibiotics from antibiotic classes that are important in human 
medicine, the United States and Canada allow livestock and poultry 
producers to purchase several antibiotics over the counter, including 
penicillins, tetracyclines, tylosin, and virginiamycin. However, 
Canada is considering changing its rules to require prescriptions for 
antibiotics used in animals for all antibiotic uses except growth 
promotion.

In contrast, the EU countries and New Zealand are more restrictive 
regarding over-the-counter sales of antibiotics for use in animals. 
Unlike the United States and Canada, the EU does not allow penicillins, 
tetracyclines, tylosin, and virginiamycin to be sold over the counter 
and will end all over-the-counter sales by 2006. Denmark, an EU member, 
already prohibits all over-the-counter sales. Similarly, New Zealand 
requires producers to have a veterinarian's prescription for 
antibiotics that it has determined are associated with the development 
of resistant bacteria in humans.

Appendix IV contains additional information on the key U.S. trading 
partners and competitors discussed in this section, including, as 
previously mentioned, their systems for collecting data on antibiotic 
use.

Antibiotic Use in Animals Has Not Significantly Affected U.S. Trade but 
Could Be an Issue in the Future: 

To date, antibiotic resistance associated with use in animals has not 
been a significant factor affecting U.S. trade in meat 
products,[Footnote 67] according to officials of USDA's Foreign 
Agricultural Service, the Office of the U.S. Trade Representative, the 
U.S. Meat Export Federation, and the U.S. Poultry and Egg Export 
Council. However, the presence of antibiotic residues in meat has had 
some impact on trade.[Footnote 68] In particular, Russia has previously 
banned U.S. poultry because of the presence of tetracycline residues. 
Furthermore, these officials indicated that other issues have been more 
prevalent in trade discussions, including the use of hormones in beef 
cattle and animal diseases such as bovine spongiform encephalopathy 
(commonly referred to as mad cow disease) and avian influenza. For 
example, the EU currently bans U.S. beef produced with hormones. Many 
other nations ban the import of U.S. beef because of the recent 
discovery of an animal in the United States with mad cow disease.

Although federal government and industry officials stated that 
antibiotic use in animals has not significantly affected U.S. trade to 
date, we found some indication that this issue might become a factor in 
the future. As USDA reported in 2003,[Footnote 69] antibiotic use in 
animals could become a trade issue if certain countries apply their 
regulations on antibiotic use in animals to their imports. For example, 
according to some government and industry officials, the United States' 
use of antibiotics could become a trade issue with the EU as it phases 
out its use of all antibiotics for growth promotion by 2006. However, 
the EU is not currently a significant market for U.S. meat because of 
trade restrictions, such as its hormone ban that effectively disallows 
U.S. beef. Similarly, a Canadian task force reported in June 2002 that 
the issue of antibiotic resistance and differences in antibiotic use 
policies could become a basis for countries to place trade restrictions 
on exports of meat from countries that have less stringent use 
policies.[Footnote 70]

The issue of antibiotic use in animals and of the potential human 
health risk associated with antibiotic-resistant bacteria have also 
received international attention. For example, in 2003, the Codex 
Alimentarius Commission, an international organization within which 
countries develop food safety standards, guidelines, and 
recommendations, issued draft guidance for addressing the risk of 
antibiotic resistance in animals. Codex also requested that a group of 
experts assess the risk associated with antibiotic use in animals and 
recommend future risk management options. In December 2003, these 
experts concluded that the risk associated with antibiotic-resistant 
bacteria in food represents a significantly more important human health 
risk than antibiotic residues--an issue that countries have already 
raised as a trade concern.[Footnote 71]

Conclusions: 

Antibiotics have been widely prescribed to treat bacterial infections 
in humans, as well as for therapeutic and other purposes in animals. 
Resistance to antibiotics is an increasing public health problem in the 
United States and worldwide. Published research results have shown that 
antibiotic-resistant bacteria have been transferred from animals to 
humans. In evaluating the safety of animal drugs, FDA considers their 
effect on human health. Such drugs are safe in this regard if there is 
reasonable certainty of no harm to humans when the drug is used as 
approved. Using this critieria, FDA has determined that the potential 
health risk from transference of antibiotic resistance from animals to 
humans is unacceptable and must be a part of FDA's regulation of animal 
antibiotics.

FDA, CDC, and USDA have made progress in their efforts to assess the 
extent of antibiotic resistance from the use of antibiotics in animals 
through both individual and collaborative efforts, including work 
through the Interagency Task Force. However, the effectiveness of these 
efforts remains unknown. FDA has developed guidance to evaluate 
antibiotics used in animals and intends to review all new drug 
applications and antibiotics currently approved for use with animals 
for this risk to determine if it needs to act to ensure that the drugs 
are safe. Although FDA has recently begun the reviews using this 
approach, its initial reviews have been for drugs other than those that 
are critically important for human health. FDA officials do not know 
how long each review will require. In addition, it is not yet known 
what actions FDA would take if concerns became evident. Although the 
agency has the authority to deny or withdraw approval of new or 
approved animal antibiotics that pose such a risk, FDA also has a 
variety of other options available. However, FDA action to prohibit the 
use of fluoroquinolone antibiotics in poultry has continued for more 
than 3 years.

Finally, researchers and federal agencies still do not have critical 
data on antibiotic use in animals that would help them more 
definitively determine any linkage between use in animals and emerging 
resistant bacteria, assess the relative contribution of this use to 
antibiotic resistance in humans, and develop strategies to mitigate 
antibiotic resistance. The experience of countries such as Denmark 
indicates that data collection efforts are helpful when making risk-
based decisions about antibiotic use in animals. While we recognize 
that there are costs associated with collecting additional data on 
antibiotic use in animals, options exist for collecting these data that 
are not cost-prohibitive. For example, the United Kingdom's efforts to 
collect national sales data on antibiotic use in animals use relatively 
few resources. In addition, existing federal programs, such as FDA's 
ongoing monitoring of approved antibiotics and USDA's CAHFSE, can 
provide a data collection framework that can be expanded to begin 
collecting the needed data. FDA, CDC, and USDA recognize the importance 
of such information and have taken some steps to collect data, although 
they have not yet developed an overall collection strategy. Until the 
agencies have implemented a plan to collect critical data on antibiotic 
use in animals, researchers will be hampered in their efforts to better 
understand how this use affects the emergence of antibiotic-resistant 
bacteria in humans, and agencies will be hampered in their efforts to 
mitigate any adverse effects.

Recommendations for Executive Action: 

Because of the emerging public health problems associated with 
antibiotic resistance in humans and the scientific evidence indicating 
that antibiotic-resistant bacteria are passed from animals to humans, 
we recommend that the Commissioner of FDA expedite FDA's risk 
assessments of the antibiotics used in animals that the agency has 
identified as critically important to human health to determine if 
action is necessary to restrict or prohibit animal uses in order to 
safeguard human health.

Additionally, because more data on antibiotic use in animals--such as 
the total quantity used, by class; the species in which they are used; 
the purpose of the use, such as disease treatment or growth promotion; 
and the method used to administer--are needed to further address the 
risk of antibiotic resistance, we also recommend that the Secretaries 
of Agriculture and of Health and Human Services jointly develop and 
implement a plan for collecting data on antibiotic use in animals that 
will adequately (1) support research on the relationship between this 
use and emerging antibiotic-resistant bacteria, (2) help assess the 
human health risk related to antibiotic use in animals, and (3) help 
the agencies develop strategies to mitigate antibiotic resistance.

Agency Comments and Our Response: 

We provided USDA and HHS with a draft of this report for review and 
comment. We also provided segments of the draft related to trade 
matters to the Department of State and the Office of the U.S. Trade 
Representative. In their written comments, USDA and HHS generally 
agreed with the report and provided comments on certain aspects of our 
findings.

USDA stated that our report recognized the many issues and complexities 
of efforts to address the risk to humans from antibiotic use in 
animals. The department also provided information on the extent of 
research related to antibiotic resistance that it has funded since 
1998. We added this information to the report. Regarding our conclusion 
that antibiotic-resistant salmonella and campylobacter bacteria have 
been transferred from animals to humans, USDA agreed that it is likely 
that a transfer has occurred. However, USDA suggested that some of the 
studies we cited to support that conclusion were, by themselves, 
inadequate to support a causal link. We believe that our conclusion is 
firmly supported by a body of scientific evidence, but we have 
clarified our description of some studies in response to USDA's 
comments. On the issue of human health risks, USDA commented that we 
cited few sources of scientific evidence to support the view that the 
human health risks from the transference of antibiotic-resistant 
bacteria are minimal. We found that only a few studies have concluded 
that the risk is minimal, while many studies have concluded that there 
is a significant human health risk from the transference. With respect 
to our recommendation that USDA and HHS jointly develop and implement a 
plan for collecting data on antibiotic use in animals, USDA stated that 
our report highlights the importance of the data that the CAHFSE 
program could provide on the impact of antibiotic use in various animal 
species. However, USDA pointed out that additional funding resources 
would be needed to expand CAHFSE and other data collection and research 
efforts. We revised the report to better reflect USDA's concern about 
funding.

HHS agreed with our finding that antibiotic-resistant salmonella and 
campylobacter bacteria have been transferred from food animals to 
humans. HHS provided references to additional research studies that 
support our conclusion. We were aware of all of the studies cited by 
HHS, but we did not include them in the report because we believe that 
our conclusion was already amply supported. Regarding our conclusion 
that researchers disagree about the extent of human health risk caused 
by the transference of antibiotic resistance, HHS provided information 
from an unpublished study that found that the course of illness was 
significantly longer for persons with antibiotic-resistant 
campylobacter cases than for those with antibiotic-susceptible 
infections. Most of the studies we identified found modest but 
significant human health consequences, similar to those in the 
unpublished study described in HHS's comments. Regarding our 
recommendation that the agencies jointly develop and implement a plan 
for collecting data on antibiotic use in animals, HHS stated that the 
most useful and reliable antibiotic use data are those maintained by 
pharmaceutical companies. HHS said current regulations would have to be 
revised to put the data that pharmaceutical companies are required to 
report to FDA in a more relevant format for research on antibiotic 
resistance. As the two agencies develop and implement their plan to 
collect the relevant data, if they agree that pharmaceutical companies 
are an important source, they should take whatever regulatory actions 
might be necessary if the sources they identify will not provide the 
data voluntarily. HHS also proposed that discussions between HHS and 
USDA for improving antibiotic use data collection be conducted through 
the Interagency Task Force on Antimicrobial Resistance.

We note that while USDA's comments on antibiotic use data emphasized 
collecting on-farm data through its new CAHFSE program, HHS's comments 
focused on obtaining data on antibiotic use in animals from 
pharmaceutical companies. We believe these differing approaches 
illustrate the need for USDA and HHS to jointly develop and implement a 
plan to collect data. We agree with HHS that the Interagency Task Force 
could serve as a forum for discussions between USDA and HHS on this 
matter.

USDA's written comments and our more detailed responses to them are in 
appendix VI. HHS's written comments are in appendix VII. In addition, 
HHS, USDA, the Department of State, and the Office of the U.S. Trade 
Representative provided technical comments, which we incorporated into 
the report as appropriate.

As agreed with your offices, unless you publicly announce the contents 
of this report earlier, we plan no further distribution until 30 days 
from the date of this letter. At that time, we will send copies of this 
report to the Secretaries of Agriculture and of Health and Human 
Services and of State; the U.S. Trade Representative; and other 
interested officials. We will also provide copies to others upon 
request. In addition, the report will be available at no charge on 
GAO's Web site at [Hyperlink, http://www.gao.gov.].

If you have any questions about this report, please call Marcia Crosse 
at (202) 512-7119 or Anu Mittal at (202) 512-3841. Other contacts and 
key contributors are listed in appendix VIII.

Signed by: 

Marcia Crosse: Director, Health Care--Public Health and Military 
HealthCare Issues: 

Signed by: 

Anu K. Mittal: 
Director, Natural Resources and Environment: 

[End of section]

Appendixes: 

Appendix I: Objectives, Scope, and Methodology: 

This report examines the (1) scientific evidence regarding the 
transference of antibiotic resistance from animals to humans through 
the consumption or handling of contaminated meat, and the extent of 
potential harm to human health, (2) progress federal agencies have made 
in assessing and addressing the human health risk of antibiotic use in 
animals, (3) types of data that federal agencies need to support 
research on the human health risk of antibiotic use in animals and the 
extent to which these data are collected, (4) use of antibiotics in 
animals in the United States compared with antibiotic use by its key 
agricultural trading partners and competitors, and (5) information that 
is available on the degree to which antibiotic use in animals has 
affected U.S. trade.

We used the term "animal" to refer to animals raised for human 
consumption, such as cattle, sheep, swine, chickens, and turkeys; the 
term "meat" to refer to beef, lamb, pork, chicken, and turkey; and the 
term "contaminated meat" to refer to meat that contains antibiotic-
resistant bacteria. We limited the scope of our work to the 
transference of antibiotic-resistant bacteria from animals to humans 
through the consumption or handling of contaminated meat. Specifically, 
we looked at the evidence for transference of antibiotic-resistant 
foodborne intestinal pathogens from animals to humans. We did not 
examine issues related to antibiotics used on plants and seafood, 
antibiotic residues in animals, or the effects of antibiotics present 
in the environment because of the application of animal waste to 
agricultural lands.

To examine the scientific evidence regarding the transference of 
antibiotic resistance from animals to humans through the consumption or 
handling of contaminated meat, and the extent of harm to human health, 
we searched medical, social science, and agricultural databases, which 
included the Department of Health and Human Services' (HHS) National 
Library of Medicine, for studies published in professional journals. We 
identified articles published since the 1970s on antibiotic use and 
resistance in animals and humans, as well as articles on antibiotic-
resistant foodborne illnesses. We interviewed officials from HHS's Food 
and Drug Administration (FDA) and Centers for Disease Control and 
Prevention (CDC) and the U.S. Department of Agriculture (USDA) to 
determine how these agencies are assessing the human health risk of 
antibiotic use in animals. We also reviewed reports related to the 
human health risk of antibiotic use in animals. Finally, we interviewed 
officials from relevant professional organizations (e.g., the American 
Medical Association) and public health advocacy groups (e.g., the 
Center for Science in the Public Interest) to identify other data or 
studies on the issue of human health risk from antibiotic use in 
animals.

To determine federal agencies' progress in assessing and addressing the 
human health risk of antibiotic use in animals, we examined documents 
from FDA, CDC, and USDA. These documents include reports on results 
from the federal government's antibiotic resistance surveillance 
program and on the progress of the federal Interagency Task Force on 
Antimicrobial Resistance, documents presented in an FDA administrative 
court concerning the agency's proposal to withdraw the approval of the 
use of a certain antibiotic used in poultry that is also an important 
antibiotic in human medicine, and FDA's framework to assess the human 
health risk of antibiotic use in animals.

To examine the types of data that federal agencies need concerning 
antibiotic use in animals in order to support research on the human 
health risk and the extent to which these data are collected, we 
reviewed federal agency documents and reports and interviewed FDA, CDC, 
and USDA officials. In particular, we discussed the status of FDA's 
efforts to collect data on U.S. antibiotic use in animals, the status 
of USDA's programs that collect data on antibiotic use, and CDC's 
initiatives that would benefit from use data. We reviewed foreign 
government reports to determine how other countries use antibiotic use 
data for research; we also reviewed international reports from the 
World Health Organization (WHO) and the Office International des 
Epizooties (OIE), which provide guidelines on the types of use data 
that countries should collect. We also interviewed officials from 
Denmark, which collects extensive data on antibiotic use in animals, 
and from Canada, which plans to implement a data collection system. We 
discussed the availability of data on U.S. antibiotic use in animals 
with officials from pharmaceutical companies, industry associations, 
state veterinary offices, firms that collect data on antibiotic use in 
animals, and public health advocacy groups.

To examine how the use of antibiotics in animals in the United States 
compares with antibiotic use by its key agricultural trading partners 
and competitors, we obtained and reviewed information on antibiotic use 
in animals for the United States and its key partners and competitors 
in international meat trade.[Footnote 72] Using international trade 
data, we identified the European Union (EU) and 11 countries--
Australia, Brazil, Canada, China, Denmark,[Footnote 73] Hong Kong, 
Japan, Mexico, New Zealand, Russia, and South Korea--as key U.S. 
trading partners or competitors.[Footnote 74] We obtained information 
on countries' antibiotic use in animals through discussions with 
officials of USDA's Animal and Plant Health Inspection Service and 
Foreign Agricultural Service (FAS) and literature searches to identify 
relevant documents. In addition, we discussed antibiotic use in animals 
with government officials from Canada, a leading U.S. trading partner 
and competitor, and Denmark, a leading U.S. trading partner and 
competitor that took significant actions to curtail antibiotic use in 
animals during the late 1990s. We also e-mailed a questionnaire to FAS 
agricultural attachs in the EU and the key trading partner or 
competitor countries, except Canada and Denmark. For Canada and 
Denmark, we obtained responses to this questionnaire from Canadian and 
Danish government officials as part of our visits to these countries. 
We did not send this questionnaire to government officials of the EU 
and the other nine countries because of Department of State and FAS 
officials' concerns that antibiotic use in animals may be a sensitive 
issue for some foreign governments and that some governments may be 
suspicious about the questionnaire's underlying purposes; for the same 
reasons, in completing this questionnaire, the FAS agricultural 
attachs were instructed to not contact foreign government officials. 
As a result, the amount of information we obtained varies by country, 
and we were able to obtain only very limited information on antibiotic 
use in Brazil, China, Hong Kong, Japan, Mexico, Russia, and South 
Korea. We did not independently verify the information reported in 
responses to this questionnaire or other documents, including laws and 
regulations, from the foreign countries.

To obtain information on antibiotic use in U.S. animal production, we 
reviewed FDA regulations;[Footnote 75] USDA's National Animal Health 
Monitoring System reports on management practices, including antibiotic 
use practices in beef cattle and swine production; a University of 
Arkansas study of antibiotic use in broiler chickens; the Animal Health 
Institute's annual reports on antibiotic use in animals; and a Union of 
Concerned Scientists report.[Footnote 76],[Footnote 77] We did not 
independently verify the information contained in these reports. In 
addition, we spoke with officials from state veterinarians' offices and 
from agricultural industry organizations, including the American 
Veterinary Medicine Association, the National Pork Producers Council, 
the American Meat Institute, the National Cattlemen's Beef Association, 
the U.S. Poultry and Egg Export Council, the National Chicken Council, 
and pharmaceutical and poultry companies. We also visited livestock and 
poultry farms in Georgia, Maryland, and Pennsylvania.

We compared the United States' policies regulating antibiotic use in 
animals with the policies of those key trading partners and competitors 
for which this information was available. In addition, we summarized 
available information on countries' activities to address antibiotic 
resistance associated with antibiotic use in animals, and, for the 
United States, we developed a list of the antibiotics most commonly 
used in beef cattle, swine, and broiler chickens.

To examine information that is available on the degree to which 
antibiotic use in animals has affected international trade, we reviewed 
reports on trade and food safety issues from USDA's Economic Research 
Service and FAS, foreign governments, and international organizations. 
We also examined records of USDA's Food Safety and Inspection Service 
to identify countries that have requirements concerning antibiotic use 
for the meat they import. In addition, we reviewed the reports and 
standards of international trade organizations, such as the World Trade 
Organization, the Codex Alimentarius Commission, and OIE. We discussed 
antibiotic use and other potential trade issues with officials from the 
Office of the U.S. Trade Representative, FAS, and meat industry trade 
associations.

We also identified several studies on estimates of the potential 
economic impacts of restrictions on antibiotics used in meat 
production. These are described in detail in appendix II.

We conducted our work from May 2003 through April 2004 in accordance 
with generally accepted government auditing standards.

[End of section]

Appendix II: Studies of the Economic Impacts of Restricting Antibiotic 
Uses in Animals: 

In this appendix we identify and summarize eight recent studies that 
provide estimates of the potential economic impacts of restrictions on 
antibiotics used in livestock production. Specifically, these studies 
estimate the economic effects of a partial and/or total ban of 
antibiotics used in animals. For several decades, antibiotics have been 
used for a variety of production management reasons, from therapeutic 
uses to increased productivity, such as feed efficiency or weight gain. 
In economic terms, higher productivity results in more final product 
supplied to the market, at a lower cost to consumers. Despite the use 
of a variety of economic models, assumptions about model parameters, 
and data sets, the economic impacts on consumers and producers of the 
studies that we identified were generally comparable. Overall, the 
studies conclude that a ban or partial ban on antibiotics in animal 
production would increase costs to producers, decrease production, and 
increase retail prices to consumers. For example, the studies indicate 
that the elimination of antibiotic use in pork production could 
increase costs to producers ranging from $2.76 to $6.05 per 
animal,[Footnote 78] which translates into increased consumer costs for 
pork ranging from $180 million per year to over $700 million per year. 
Table 2 summarizes the eight studies.

Table 2: Economic Studies That Estimate the Effects of Restrictions on 
Antibiotic Use: 

Economic study: World Health Organization (WHO), Impacts of 
Antimicrobial Growth Promoter Termination in Denmark; 
Purpose of the study: To review the economic impacts resulting from the 
Danish ban of the use of antibiotics for growth promotion purposes in 
swine and poultry production; 
Year: 2003; 
Economic impacts: Producers: Cost increase of $1.04 per swine or 1 
percent of total production costs; No cost changes for poultry; 
Economic impacts: Consumers: [Empty].

Economic study: Hayes and Jensen, "Lessons from the Danish Ban on Feed-
Grade Antibiotics,"; 
Center for Agricultural and Rural Development; 
Purpose of the study: To determine the economic impacts of a ban on 
antibiotics in pork production in the United States from the experience 
with such a ban in Denmark; 
Year: 2003; 
Economic impacts: Producers: Costs increase by $4.50 per head in first 
year; 
Total 10- year cost over $700 million; 
Economic impacts: Consumers: Retail price increases by 2%.

Economic study: Miller et al., "Productivity and Economic Effects of 
Antibiotics Used for Growth Promotion in U.S. Pork Production," Journal 
of Agricultural and Applied Economics; 
Purpose of the study: To estimate the net benefit of antibiotics used 
for growth promotion to swine producers in the United States using the 
1990 and 1995 NAHMS swine survey data.[A]; 
Year: 2003; 
Economic impacts: Producers: Increased profits of $0.59 per marketed 
swine or 9% profitability; 
Economic impacts: Consumers: [Empty].

Economic study: Miller et al., "Producer Incentives for Antibiotic Use 
in U.S. Pork Production," American Agricultural Economics Association 
Annual Meetings; 
Purpose of the study: To validate the productivity and economic impacts 
of antibiotic use for swine producers at the farm level using the NAHMS 
2000 survey; 
Year: 2003; 
Economic impacts: Producers: Four scenarios: [B]; 
* Ban on AGP: profits decrease by $3,813; 
* Ban on ADP: profits increase by $2703; 
* Ban on AGP and ADP: profits decrease by $1128; 
* Limitation of AGP and ADP: Profits increase by $12,438; 
Economic impacts: Consumers: [Empty].

Economic study: Brorsen, Lehenbauer, Ji, and Conner, "Economic Impacts 
of Banning Subtherapeutic Use of Antibiotics in Swine Production," 
Journal of Agricultural and Applied Economics; 
Purpose of the study: To estimate the economic impacts on producers and 
consumers of a ban on the use of antibiotics in swine production; 
Year: 2002; 
Economic impacts: Producers: Costs would increase by $2.37 - $3.11 per 
hog with an average of $2.76 per hog; 
Total costs would be $153.5 million per year in the short run and $62.4 
million per year in the long run; 
Economic impacts: Consumers: Costs to consumers increase by $89 million 
per year in the short run to $180 million per year in the long run.

Economic study: Mathews, Jr., "Economic Effects of a Ban Against 
Antimicrobial Drugs Used in U.S. Beef Production," Journal of 
Agricultural and Applied Economics; 
Purpose of the study: To examine the economic effects of a ban on 
antibiotic use in U.S. beef production on two policy alternatives--a 
partial ban and a full ban; 
Year: 2002; 
Economic impacts: Producers: Partial ban: Cattle prices increase by 
0.49 percent. Producer income declines by $15 million.[D]; 
Full ban: Cattle prices increase by 3.32 percent. Producer income 
declines by $113.6 million.[D]; 
Economic impacts: Consumers: Partial ban: Costs to consumers increase 
by $54.7 million.[D]; 
Full ban: Costs to consumers increase by about $361 million.[D].

Economic study: Hayes, Jensen, Backstom, and Fabiosa, "Economic Impact 
of a Ban on the Use of Over-the-Counter Antibiotics," Center for 
Agricultural and Rural Development; 
Purpose of the study: To estimate the likely economic impacts of a ban 
on antibiotics in the U.S. pork industry based on the impacts of such a 
ban in Sweden; 
Year: 1999; 
Economic impacts: Producers: Costs would increase by $5.24 - $6.05 per 
head; 
Net profit declines by $0.79/head; 
Total net present value of forgone profits over 10 years declines by 
$1.039 billion; 
Economic impacts: Consumers: Retail price would increase by 5 cents per 
pound; 
Nationally, annual increase of consumer costs of $748 million.

Economic study: National Research Council, "Costs of Eliminating 
Subtherapeutic Use of Antibiotics" in The Use of Drugs in Food Animals: 
Benefits and Risk; 
Purpose of the study: To examine the economic costs to consumers of the 
elimination of subtherapeutic use of antibiotics for poultry, beef, and 
pork; 
Year: 1999; 
Economic impacts: Producers: [Empty]; 
Economic impacts: Consumers: Retail meat price increases (cents per 
pound): [C]; 
Chicken: (1 - 3); 
Turkey: (2 - 3); 
Pork: (3 - 6); 
Beef: (3 - 6); 
Total consumer costs for pork: $382 million - $764 million per year; 
For all meat products, consumer costs increase by $1.2 billion to $2.5 
billion per year. 

Source: GAO analysis of sources cited.

[A] NAHMS is the National Animal Health Monitoring System.

[B] Within these scenarios, Miller et al. define AGP as antibiotics 
used for growth promotion and ADP as antibiotics used for disease 
prevention. The annual estimates of economic impacts for these 
scenarios are for a producer that has a 1,020-head barn of swine. A 
swine producer could have many such barns in his/her operation.

[C] The National Research Council estimates of retail price increases 
are ranges based on whether consumers would substitute other meat. The 
lower change in price assumes that substitution of other meat mitigates 
the price impact by 50 percent, while the higher change in retail price 
assumes no substitution.

[D] These estimates are in 1984 dollars.

[End of table]

While these market effects are important to both producers and 
consumers of livestock products, they must be balanced against the 
health care costs of antibiotic resistance due to agricultural uses of 
antibiotics. Potential health costs imposed by increased antibiotic 
resistance include more hospitalizations, higher mortality rates, and 
higher research costs to find new and more powerful drugs.[Footnote 79] 
From the point of view of proposals to reduce antibiotic use, these 
potential costs represent the benefits from reduced antibiotic use. 
These costs to society, however, are difficult to measure because of 
limited data on antibiotic use and resistance as well as the 
problematic nature of measuring the value of a human life. Moreover, 
while there are some estimates of the costs of antibiotic resistance 
from both medical and agricultural sources, no estimates exist that 
directly link the human health costs of antibiotic resistance with 
antibiotics used in animal production. Nevertheless, studies that have 
examined the costs of antibiotic resistance from all sources have found 
a wide range of estimates running into the millions and billions of 
dollars annually.[Footnote 80] For example, one recent study (2003) 
estimated that the health cost to society associated with resistance 
from only one antibiotic, amoxicillin, was $225 million per 
year.[Footnote 81]

We discuss the eight studies we reviewed in reverse chronological 
order, from 2003 to 1999. Most examine restrictions on antibiotics in 
the swine industry, but a few look at the beef and poultry industries 
as well. All of the studies measure the economic impacts of antibiotic 
restrictions on domestic U.S. markets, except the WHO study of the 
antibiotic restrictions recently imposed by Denmark. Also, most studies 
estimate only domestic economic impacts, not impacts on international 
trade.

WHO (2003) Review of the Economic Impacts of Antibiotics for Growth 
Promotion in Denmark: 

In 2002, WHO convened an international expert panel to review, among 
other issues, the economic impact resulting from the Danish ban of 
antibiotics for growth promotion, particularly in swine and poultry 
production.[Footnote 82] As part of this effort, Denmark's National 
Committee for Pigs estimated that the cost of removing antibiotic 
growth promoters in Denmark totaled about $1.04 per pig, or a 1 percent 
increase in total production costs. In the case of poultry, however, 
there was no net cost because the savings associated with not 
purchasing these antibiotics offset the cost associated with the 
reduction in feed efficiency. Components of these costs included excess 
mortality, excess feeding days, increased medication, and increased 
workload.

A subsequent study by Jacobsen and Jensen (2003) used these costs as 
part of the agriculture sector of a general equilibrium model to 
estimate the impact on the Danish economy of the termination of 
antibiotic growth promoters.[Footnote 83] The model used these cost 
assumptions in a baseline scenario that projects the likely development 
of the Danish economy to 2010.

The results of the model indicated a small reduction in pig production 
of about 1.4 percent per year and an increase in poultry production of 
about 0.4 percent. The authors explain that the increase in poultry 
production occurred because of the substitutability of these meats in 
consumption. In addition, this research included estimates of the 
consequences of removing antibiotic growth promoters on the export 
market. The model showed that exports of pork were forecast to be 1.7 
percent lower than they would be in the absence of these growth 
promoters, while poultry exports would increase by about 0.5 percent.

The authors explained that some costs associated with modifications to 
production systems were difficult to measure and were not included in 
the analysis, although they may have been substantial for some 
producers. They also stated that the analysis does not take into 
account the possible positive effect that the removal of antibiotic 
growth promoters may have had on consumer demand, both in the domestic 
and in the export markets. Moreover, they added that any costs must be 
set against the likely human health benefits to society.

Hayes and Jensen (2003) Study Based on the Danish Ban of Feed-Grade 
Antibiotics in the Pork Industry: 

In 2003, using a 1999 study by Hayes et al. of the potential economic 
impacts of a U.S. ban based on the ban in Sweden, as described below, 
and a recent ban on feed-grade antibiotics in Denmark, Hayes and Jensen 
estimated the economic impacts of a similar ban in the United 
States.[Footnote 84] In 1998, the Danish government instituted a 
voluntary ban on the use of antibiotics in pork production at the 
finishing stage, and in 2000 it banned antibiotics for growth promotion 
at both the weaning and the finishing stages. The results of the ban in 
Denmark, however, may be more applicable than the Swedish experience 
because, like the United States, Denmark is one of the largest 
exporters of pork and has somewhat similar production 
practices.[Footnote 85] The authors compared the econometric results of 
a U.S. baseline without a ban with projected results based on 
assumptions taken from the ban in Denmark. Many of the same technical 
and economic assumptions that were used in the Swedish study were also 
used for the impacts based on the Danish ban. For instance, the authors 
included a sort-loss cost of $0.64 per animal, a similar assumption for 
loss of feed efficiency, and decreases in piglets per sow.[Footnote 86] 
Other key assumptions and features unique to the study include the 
following: 

* the use of only one case or scenario--a "most-likely" scenario--
unlike the study based on the Swedish ban;

* increased costs of $1.05 per animal at the finishing stage and $1.25 
per animal at the weaning stage;

* a vaccine cost of $0.75 per animal; and: 

* a capital cost of about $0.55 per animal;

According to the study, a major economic impact in the U.S. pork market 
of a ban similar to the Danish ban would be a cost increase of about 
$4.50 per animal in the first year. Across a 10-year period, the total 
cost to the U.S. pork industry was estimated to be more than $700 
million. With a lower level of pork production, retail prices would 
increase by approximately 2 percent. The authors conclude that a ban at 
the finishing stage would create very few animal health concerns, while 
a ban at the weaning stage would create some serious animal health 
concerns and lead to a significant increase in mortality. They also 
note that, as happened immediately following the ban at the weaning 
stage in Denmark, the total use of antibiotics in the United States at 
this production stage may rise.

Miller et al. (2003) Study Using 1990 and 1995 NAHMS Data on the 
Economic Effects of Antibiotics Used for Growth Promotion in U.S. Pig 
Production: 

Miller et al. (2003) used 1990 and 1995 National Animal Health 
Monitoring System (NAHMS) swine survey data to estimate the net benefit 
of antibiotics used for growth promotion to swine producers.[Footnote 
87] The NAHMS database provides statistically valid estimates of key 
parameters related to the health, management, and productivity of swine 
operations in the United States.[Footnote 88] The authors used 
econometric methods to estimate the relationships between growth-
promoting antibiotics and productivity measures, such as average daily 
weight gain (ADG) and feed conversion ratio (FCR), for grower/finisher 
pigs. Using these productivity measures, predictions on performance 
were then generated for an independent, medium-sized, midwestern 
farrow-to-finish pork producer in 1995. The performance figures were 
expressed in economic terms, such as profitability, using a swine 
enterprise budgeting model. The study includes the following key 
features and assumptions: 

* The productivity measures estimated were ADG, FCR, and mortality rate 
(MR) during the grower/finisher stage of swine production.

* Explanatory variables included in the model were regional 
identifiers, size of operation, market structure variables, number of 
rations, mortality rate, number of days antibiotics were administered, 
number of antibiotics fed, number of diseases diagnosed in last 12 
months, among others.

* The ADG and FCR equations were estimated jointly using the seemingly 
unrelated regression procedure.

* Because the theory as to an exact specification was unknown, the MR 
equation was estimated using a backward-stepwise linear regression.

The authors estimated that increases in annual returns above costs from 
antibiotics for a 1,020-head finishing barn was $1,612, or $0.59 per 
swine marketed. This represents an improved profitability of 
approximately 9 percent of net returns in 2000 for Illinois swine 
finishing operations. The authors also found that there is 
substitutability between antibiotics as growth promoters and other 
production inputs (such as number of rations) that could reduce the 
negative influence of removing antibiotics.

Miller et al. (2003) Study Using 2000 NAHMS Data to Estimate the 
Productivity and Economic Impacts of Antibiotic Use in U.S. Pig 
Production: 

In an updated study, Miller et al. (2003) estimated the combined 
effects of antibiotics used for growth promotion (AGP) and antibiotics 
used for disease prevention (ADP) in pork production using the NAHMS 
2000 swine survey.[Footnote 89] Specifically, the authors measured the 
productivity and the economic impacts of these antibiotics on grower/
finisher pigs for individual swine producers. The authors evaluated 
four scenarios, using varying degrees of bans of both AGP and ADP: (1) 
a ban on AGP, (2) a ban on ADP, (3) a ban on both AGP and ADP, and (4) 
a limitation on AGP and ADP to levels that maximize production. These 
scenarios were chosen because antibiotics that are used for different 
purposes have different impacts on productivity, improving it on one 
dimension while possibly diminishing it on another. First, the authors 
estimated four pork productivity dimensions related to the use of 
antibiotics using an econometric model. Second, using the estimated 
productivity measures from the econometric model, they estimated 
economic impacts to pork producers for each antibiotic ban scenario 
using a spreadsheet farm budget model. The study includes the following 
key features and assumptions: 

* Pork productivity was measured using four measures of productivity, 
including average daily weight gain, feed conversion ratio, mortality 
rate, and lightweight rate.

* These productivity measures were estimated using seemingly unrelated 
regression analysis and are modeled from the perspective of possible 
structural relationships among the measures.

* The study used the NAHMS 2000 study, which provides the most recent 
data available to investigate productivity impacts and impacts on farm 
costs and profitability.

Overall, the authors confirmed their earlier findings that a ban would 
likely cause substantial short-term losses to producers. However, 
decreasing the use of certain antibiotics to a more desirable level may 
be implemented without major losses. For scenario 1, a total ban on AGP 
would cost producers $3,813 in profits annually.[Footnote 90] For 
scenario 2, a ban on ADP would slightly improve profits by a gain of 
$2703 annually. For scenario 3, a ban on both AGP and ADP would lower 
producer profits by $1128 annually. For scenario 4, where AGP and ADP 
are applied at levels where swine productivity is maximized, producers 
would gain $12,438 annually compared with no antibiotic use. The 
authors conclude that restrictions on classes of AGP, the amount of 
time antibiotics are fed, and restrictions on ADP many be implemented 
by producers without major losses. However, they also note that some 
time dimensions ignored in their study may be important and that their 
use of nonexperimental data requires careful interpretation.

Brorsen et al. (2002) Study on Economic Effects of a Ban on the Use of 
Antibiotics for Growth Promotion in Swine Production: 

Brorsen et al. (2002) used a model similar to one developed by 
Wohlgenant (1993) to estimate the economic impacts on producers and 
consumers of a ban on antibiotics used for growth promotion in swine 
production.[Footnote 91] The authors used a model that allowed for 
feedback between beef and pork markets and measured changes in producer 
and consumer surplus resulting from shifts in both supply and demand. 
Moreover, the authors extended their two-commodity beef and pork model 
to include poultry. In their model, changes in production costs due to 
banning the use of antibiotics for growth promotion are measured 
indirectly by the net benefits from their use. The study includes the 
following key features and assumptions: 

* The ban considered in this model is a complete ban on all antibiotics 
in feed.

* The effects of using antibiotics for growth promotion were assumed to 
be from improvements in (1) feed efficiency over drug cost, (2) reduced 
mortality rate, and (3) reduced sort-loss at marketing.

* The authors assumed a $45.00 per hundredweight market price for hogs.

* All parameters (i.e., demand and supply elasticities) used to solve 
the model were based on other economic studies, except the parameter 
that represented the change in production costs. Once these were 
obtained, retail quantity, retail price, farm quantity, and farm price 
were determined simultaneously.

* An econometric model was used to obtain the economic benefit from the 
improvement in feed-to-gain conversions in swine production.

* The mortality benefit in swine was assumed to range from 0 percent, 
to 0.75 percent (most likely), to 1.5 percent.

* Net benefits of the use of antibiotics for growth promotion were 
estimated by summing the results of a simulation exercise based on the 
probability distributions of the three sources of economic benefits at 
the industry level.

The authors estimated that economic costs to swine producers from a ban 
on antibiotics used for growth promotion would range from $2.37 per hog 
to $3.11 per hog, with an average cost of $2.76 per hog. For swine 
producers, the estimated annual costs would be approximately $153.5 
million in the short run to $62.4 million in the long run. Estimated 
annual costs to pork consumers would increase by about $89 million in 
the short run to $180 million in the long run.

Mathews, Jr. (2002) Analysis of the Economic Effects of a Ban on 
Antibiotics in U.S. Beef Production: 

Mathews, Jr. (2002) examined the economic effects of a ban on 
antibiotic use in U.S. beef production using two policy alternatives--
a partial ban and a full ban.[Footnote 92] To estimate these effects, 
the author developed a series of economic models, including a firm-
level, cost-minimization model that minimizes the cost of feeding 
cattle to final output weights for a base case, a full ban, and a 
partial ban (banning only selected antibiotics) scenario. Imbedded in 
this model is a growth function that incorporates the interaction 
between the growth rate of cattle and feed efficiency. The firm-level 
effects were then aggregated across firms in a partial equilibrium 
framework to estimate national cattle supply, price, and value of 
production for the three scenarios. The study includes the following 
key features and assumptions: 

* Variables included in the growth function were lagged average daily 
weight gain, feed efficiency, seasonal variables, and an interaction 
variable of average weight gain and feed efficiency. The growth model 
forms a "dynamic" link to the cost-minimization model by accounting for 
the impacts of recent feeding experiences.

* In the cost-minimization model, feed costs were minimized, subject to 
protein levels and other feed constraints. The model finds the minimum 
cost for feeding a steer to a final weight estimated from the embedded 
growth function.

* The resulting model allowed final cattle weights, feeding costs, and 
the number of cattle fed per year to vary, resulting in livestock 
supplies that are endogenous to the model.

* In the partial-ban scenario, substitute antibiotics were assumed to 
be functionally equivalent to and twice as costly as in the base 
scenario.

* Data for the aggregate analysis included annual average all-cattle 
prices and commercial beef production for the period 1975 through 1990. 
A base scenario was estimated using parameter and final steer weight 
estimates from the growth model for each quarter over an 11-year 
period, from January 1990 through January 2001.

Results of the partial-ban scenario indicated that aggregate annual 
income would decrease by nearly $15 million for producers, while annual 
consumer costs would increase by $54.7 million.[Footnote 93] For the 
full ban, a 4.2 percent decline in beef production would yield a 3.32-
percent increase in the price of cattle, from $42.60 to $47.12 per 
hundredweight. Also, the full ban translates into an annual consumer 
cost increase of $361 million. The author noted that the study did not 
take into account any effects of a ban or partial ban on trade in beef 
products.

Hayes et al. (1999) Study Based on the Swedish Ban of Antibiotics in 
the Pork Industry: 

A study issued in 1999 by Hayes et al. at Iowa State University 
estimated the potential economic impacts of a ban on the use of 
antibiotics in U.S. pork production based on assumptions from a Swedish 
ban in 1986.[Footnote 94] To estimate baseline results, the authors 
used a simultaneous econometric framework of the U.S. pork industry 
that included several production and marketing segments: live inventory 
and production, meat supply, meat consumption, meat demand, and retail 
price transmission. The baseline results, or results with no change in 
antibiotic use, were compared to a range of estimates of a ban on 
antibiotics in pork production in the United States based on a set of 
technical and economic assumptions taken from the Swedish experience. 
These simulations included three different scenarios: a "most likely," 
a "best-case," and a "worst-case" scenario if the ban were to be 
implemented in the United States. The key features and assumptions of 
the model for the "most likely" case included the following: 

* a 10-year projection period from 2000 to 2009 from a 1999 baseline, 
with deviations from the baseline in the projection period reflecting 
the technical and economic assumptions taken from the Swedish ban;

* the pork, beef, and poultry markets, although the model assumed no 
change in the regulation of antibiotics on beef and poultry;

* technical assumptions: feed efficiency for pigs from 50 to 250 pounds 
declines by 1.5 percent, piglet mortality increases by 1.5 percent, and 
mortality for finishing pigs increases by 0.04 percent. Also, the "most 
likely" case extends weaning age by 1 week and piglet per sow per year 
decrease by 4.82 percent.

* veterinary and therapeutic costs would increase by $0.25 per pig, net 
of the cost for feed additives;

* additional capital costs would be required because of additional 
space needed for longer weaning times and restricted feeding, including 
$115 per head for nursery space and $165 per head for finishing space;

* an estimated penalty of $0.64 per head for sort-loss costs; and: 

* input markets, such as the cost of antibiotics, are exogenous or not 
a part of the modeling system.

The authors in their "most likely" scenario estimated that the effects 
of a ban on the use of antibiotics would increase production costs by 
$6.05 initially and $5.24 at the end of the 10-year period modeled. 
Because the supply of pork declines, however, net profit to farmers 
would decline by only $0.79 per head. Over a 10-year period, the net 
present value of forgone profits would be about $1.039 billion. For 
consumers, the retail price of pork increases by $0.05 per pound, which 
sums to a yearly cost of about $748 million for all consumers.

The authors also cited four important limitations to their study: (1) 
the estimated impacts represent an "average" farm and may mask wide 
differences across farms; (2) technical evidence from the Swedish 
experience must be regarded with caution as an indicator of what might 
happen in the United States; (3) consumers only respond to changes in 
the price of pork; however, the model does not take into account how 
such a ban would affect the prices of beef and poultry; and (4) there 
was no attempt to factor in the positive effects of such a ban on 
consumer willingness to pay for pork produced without the use of feed-
grade antibiotics.

National Research Council's (1999) Economic Analysis of the Costs of 
Eliminating Subtherapeutic Use of Antibiotics in Animals: 

The National Research Council (NRC) examined the economic costs to 
consumers of the elimination of all subtherapeutic use of antibiotics 
in a chapter of a 1999 report entitled The Use of Drugs in Food 
Animals: Benefits and Risks.[Footnote 95] Instead of measuring the 
consequences of eliminating antibiotics on farm costs and profits, NRC 
decided that a more viable alternative would be to measure costs to 
consumers in terms of the higher prices that would be passed on to 
consumers. According to NRC, this measurement strategy was followed for 
several reasons: changes in production costs do not necessarily 
translate into lower profits; depending on management practices, not 
all producers rely on these antibiotics to the same extent and would 
not all be equally affected by a ban; and some producers, for example 
those who produce for special niche markets, may actually benefit from 
such a ban.[Footnote 96] The study includes the following key features 
and assumptions: 

* All cost increases are passed on to consumers in terms of percentage 
price changes.

* The model measures how much consumers would need to spend in order to 
maintain a similar level of consumption as before the ban.

* No change in consumption because of a ban on antibiotics would occur.

* Per capita costs are estimated as the product of three items: (1) 
percentage increase in annual production costs, (2) retail prices, and 
(3) per capita annual retail quantity sold.

* Annual costs of a ban were estimated for four domestic retail 
markets--chicken, turkey, beef, and pork--as well as a total cost for 
all meat.

NRC estimated that the average annual cost per capita to consumers of a 
ban on all antibiotic use was $4.84 to $9.72. On a commodity retail 
price basis, the change in price for poultry was lowest, from $0.013 
per pound to $0.026 per pound; for pork and beef, prices ranged from 
$0.03 per pound to $0.06 per pound. Retail pork price increases ranged 
from $0.03 per pound to $0.06 per pound. Total national additional 
costs per year for pork consumption ranged from $382 million to $764 
million, depending on assumptions about meat substitutes. As for all 
meat products combined, total consumer cost increases ranged from $1.2 
billion to $2.5 billion per year. Finally, NRC noted that the reduction 
in profits and industry confidence that would result from such a ban 
may cause a reduction in research, and that society would lose the 
research benefits. Also, to determine whether this cost increase would 
be justified, the amount should be compared with the estimated health 
benefits.

[End of section]

Appendix III: FDA's Procedures for Evaluating the Importance of an 
Animal Drug for Human Health: 

As part of the risk estimation outlined in Guidance for Industry #152, 
FDA developed a framework for evaluating the importance of an 
antibiotic to human medicine. FDA has ranked antibiotics as either 
critically important, highly important, or important. These rankings 
are based on five criteria, which are ranked from most (criterion 1) to 
least important (criterion 5): 

1. The antibiotic is used to treat enteric pathogens that cause 
foodborne disease.

2. The antibiotic is the sole therapy or one of the few alternatives to 
treat serious human diseases or is an essential component among many 
antibiotics in the treatment of human disease.

3. The antibiotic is used to treat enteric pathogens in nonfoodborne 
disease.

4. The antibiotic has no cross-resistance within the drug class and an 
absence of linked resistance with other drug classes.[Footnote 97]

5. There is difficulty in transmitting resistance elements within or 
across genera and species of organisms.

Antibiotics that meet both of the first two criteria are considered by 
FDA to be critically important to human medicine. Drugs that meet 
either of the first two criteria are considered highly important to 
human medicine. Drugs that do not meet either of the first two criteria 
but do meet one or all of the final three criteria are considered 
important to human medicine. Of the 27 classes of animal drugs relevant 
to human health, 4 were ranked critically important, 18 highly 
important, and 5 important. The status of a particular antibiotic may 
change over time. For example, a drug may be considered to be 
critically important to human health because it is the sole therapy. 
Later, if new antibiotics become available to treat the same disease or 
diseases, the drug may be downgraded in its importance to human health.

[End of section]

Appendix IV: Information on Selected Countries' Activities to Address 
Animal-Related Antibiotic Resistance: 

This appendix provides information on efforts to address antibiotic 
resistance associated with antibiotic use in animals for the United 
States and some of its key trading partners and competitors. For the 
United States, more detailed information on these activities is in the 
letter portion of this report. For the United States' key trading 
partners and competitors, to the extent that information was available, 
we summarized the countries' activities and described antibiotic 
resistance surveillance systems and antibiotic use data collection 
systems.

In addition, table 3 presents information on the total amount of 
antibiotics sold or prescribed for use in animals for the United States 
and three trading partners and competitors for which this information 
was available. Specifically, it shows 2002 antibiotic sales data for 
the countries that we identified as having government data collection 
systems on antibiotic use with the available data. Although the United 
States does not have a government system, we included information 
collected by the Animal Health Institute for comparison. Total meat 
production is also shown to represent the size of the animal production 
industries in these countries.

Table 3: Antibiotic Sales and Meat Production, 2002: 

Denmark[A]; Antibiotic sales (metric tons of active ingredient): 94; 
Metric tons of meat production (in millions): 2.1; 
Percent of world total meat production: 1.

New Zealand; Antibiotic sales (metric tons of active ingredient): 106; 
Metric tons of meat production (in millions): 1.3; 
Percent of world total meat production: 1.

United Kingdom; Antibiotic sales (metric tons of active ingredient): 
433; 
Metric tons of meat production (in millions): 3.3; 
Percent of world total meat production: 1.

United States; Antibiotic sales (metric tons of active ingredient): 
5,896; 
Metric tons of meat production (in millions): 39.0; 
Percent of world total meat production: 16.

Source: Danish Integrated Antimicrobial Resistance Monitoring and 
Research Programme, Veterinary Institute, the New Zealand Food Safety 
Authority, the United Kingdom Veterinary Medicines Directorate, the 
Animal Health Institute, and the Food and Agriculture Organization of 
the United Nations.

Note: The antibiotic amounts do not include ionophores, an 
antibacterial that is a unique drug product developed for animal 
production and not related to traditional antibiotics.

[A] Denmark's information is based on actual use of antibiotics. The 
other information is based on antibiotics sold for use in animals and 
includes limited use in other species.United States: 

[End of table]

Overview of activities. In 1999, federal agencies formed the 
Interagency Task Force on Antimicrobial Resistance to address 
antibiotic resistance issues.[Footnote 98] In October 2003, FDA issued 
guidelines for assessing the safety of animal drugs (Guidance for 
Industry #152). FDA is conducting risk assessments of some antibiotics 
important in human medicine.

Antibiotic-resistance surveillance systems. FDA, CDC, and USDA collect 
information on antibiotic-resistant bacteria in humans, retail meat, 
and animals through the National Antimicrobial Resistance Monitoring 
System (NARMS).

Antibiotic use data collection systems. The Animal Health Institute, a 
trade association representing veterinary pharmaceutical companies, 
publishes the only publicly available data on the amount of antibiotics 
sold annually for use in animals. The Animal Health Institute collects 
these data from its member companies, which represent about 85 percent 
of the animal drug sales in the United States. The data show the amount 
of antibiotics sold by antibiotic class, but certain classes are 
reported together to abide by company disclosure agreements. See table 
3 for information on the amount of antibiotics sold in the United 
States during 2002. In addition, the United States collects some on-
farm data through USDA's National Animal Health Monitoring System 
(NAHMS) and Collaboration in Animal Health, Food Safety, and 
Epidemiology (CAHFSE) programs.

Australia: 

Overview of activities. In 1998, Australia established the Joint Expert 
Technical Advisory Committee on Antibiotic Resistance to provide 
independent expert scientific advice on the threat to human health of 
antibiotic-resistant bacteria caused by use in both animals and 
humans.[Footnote 99] Australia has begun to review the approved uses of 
antibiotics important in human medicine to determine if changes are 
needed. Australia's review process includes performing a public health 
and an efficacy assessment. Like the United States' risk assessment 
approach, Australia's public health assessment considers the hazard, 
exposure, and potential impact of the continued use of the antibiotic 
on public health. The efficacy assessment considers whether the 
antibiotic is effective in animals for the purpose claimed and whether 
the label contains adequate instructions. As of April 2003, Australia 
had completed its assessment of virginiamycin, a member of the 
streptogramin class, and was considering a recommendation to ban its 
use for growth promotion. In addition, as of March 2003, Australia was 
assessing the risk of the macrolide antibiotic class, including 
tylosin.

Antibiotic resistance surveillance systems. The committee's 1999 report 
recommended establishing a comprehensive surveillance system to monitor 
antibiotic-resistant bacteria in animals. As of March 2003, a strategy 
for developing an antimicrobial resistance surveillance system was 
being completed.

Antibiotic use data collection systems. Australia uses import data to 
monitor the annual quantity of antibiotics used in animals because all 
of the antibiotics used in the nation are imported. The data, which 
include information on the quantity of antibiotics imported by 
antibiotic class and end use, are not usually released publicly. A 
potential problem with this data collection method is that importers 
are not always able to anticipate how producers will use the 
antibiotic.

Canada: 

Overview of activities. Like the United States, Canada plans to do risk 
assessments of antibiotics important in human medicine and to make 
changes in approved antibiotic uses as appropriate based on these risk 
assessments. Canadian officials expect to initially focus on growth 
promotion uses of several antibiotic classes and antibiotics, including 
penicillins, tetracyclines, tylosin, and virginiamycin. Canada plans to 
use risk assessment methods similar to those used in the United States; 
however, Canada may also consider other factors, such as the benefits 
associated with antibiotic use. In addition, Canada is considering the 
adoption of a prescription requirement for all antibiotic uses in 
animals except growth promotion.

Antibiotic resistance surveillance systems. The Canadian Integrated 
Program for Antimicrobial Resistance Surveillance, started in 2002 and 
designed to use resistance surveillance methods consistent with the 
United States' NARMS, collects information on antibiotic resistance 
from the farm to the retail levels. Canada issued the first annual 
report from this surveillance system in March 2004.

Antibiotic use data collection systems. Canada is integrating the 
collection of data on antibiotic use in humans and animals into its 
surveillance system and plans to use this information to support risk 
analysis and policy development. Collection of on-farm data on 
antibiotic use in animals through pilot projects is ongoing, and 
collection of data from pharmaceutical companies, importers, and 
distributors, such as feed mills and veterinarians, is planned.

The European Union: 

Overview of activities. In 1999, an EU scientific committee on 
antibiotic resistance recommended that the growth promotion use of 
antibiotics from classes that are or may be used in human medicine be 
banned. Later that year, the EU completed action on this recommendation 
and banned the use of these antibiotics in feed for growth promotion. 
The scientific committee also recommended that the four remaining 
antibiotics used for growth promotion be replaced with other 
alternatives. In 2003, the EU issued a regulation adopting this 
recommendation, which banned the use of these antibiotics as of January 
1, 2006.[Footnote 100] In addition, Denmark, an EU member, ended the 
use of all antibiotics for growth promotion in 2000.

Antibiotic resistance surveillance systems. Most EU members have a 
program to monitor antibiotic resistance, but the EU as a whole does 
not have a harmonized system that allows comparison of data across 
nations. A November 2003 directive from the European Parliament and the 
Council of the European Union set forth general and specific 
requirements for monitoring antibiotic resistance. Among other things, 
member countries must ensure that the monitoring system includes a 
representative number of isolates of Salmonella spp., Campylobacter 
jejuni, and Campylobacter coli from cattle, swine, and poultry. In 
particular, Denmark's surveillance system, the Danish Integrated 
Antimicrobial Resistance Monitoring and Research Programme, monitors 
resistance in these and other bacteria in animals, meat, and humans.

Antibiotic use data collection systems. The EU has proposed that its 
members collect data on antibiotic use in animals. EU countries' 
efforts to collect this information are at varying stages of 
development. For example, while some EU countries are just developing 
programs to collect antibiotic use data, the United Kingdom and Denmark 
currently collect this information.

The United Kingdom's Veterinary Medicines Directorate collects data 
from veterinary pharmaceutical companies on the amounts of different 
antibiotics and other animal drugs sold in the United Kingdom. The 
directorate then separates these data into chemical groups, 
administration methods, and target species. For certain antibiotics 
that are sold for use in more than one species, it is not possible to 
determine the species in which they were used. However, the directorate 
is working to more accurately assign sales quantities to each species. 
See table 3 for information on the amount of antibiotics sold in the 
United Kingdom during 2002.

Denmark collects extensive data on the use of antibiotics in animals. 
In particular, through its VetStat program, Danish officials can obtain 
data on all medicines prescribed by veterinarians for use in animals. 
This program provides detailed information on antibiotic use, such as 
the quantity used, class of antibiotic used, species, age of animal, 
and the purpose of use, as well as the disease the antibiotic was used 
to treat. In addition, VetStat allows researchers to calculate the 
average daily doses that animals receive of various antibiotics. See 
table 3 for information on the amount of antibiotics used in Denmark 
during 2002.

Hong Kong: 

Antibiotic resistance surveillance systems. Hong Kong has an antibiotic 
resistance surveillance system. We did not obtain additional 
information on this system.

Antibiotic use data collection systems. Hong Kong has an antibiotic use 
data collection system. We did not obtain additional information on 
this system.

Japan: 

Overview of activities. Japan is currently reviewing the use of 
antibiotics for growth promotion if those antibiotics are from classes 
used in humans. According to an April 2004 report from the Office of 
the U.S. Trade Representative, the Japanese government has stated that 
these reviews will be based on science.

Antibiotic resistance surveillance systems. Japan has an antibiotic 
resistance surveillance system. We did not obtain additional 
information on this system.

Antibiotic use data collection systems. Japan has an antibiotic use 
data collection system. We did not obtain additional information on 
this system.

Mexico: 

Antibiotic resistance surveillance systems. In 2000 and 2001, FDA 
undertook a pilot study with Mexico to monitor the antimicrobial 
resistance of salmonella and E. coli isolates obtained from human 
samples. In September 2001, the pilot study was expanded into a 3-year 
cooperative agreement to include both human and animal monitoring. The 
primary objective of the agreement was to establish an antimicrobial 
resistance monitoring system for foodborne pathogens in Mexico 
comparable to the United States' NARMS program.

New Zealand: 

Overview of activities. New Zealand established an Antibiotic 
Resistance Steering Group primarily to coordinate a program to gather 
and analyze information on the use of antibiotics in feed (including 
antibiotics for growth promotion), assist in developing a policy 
concerning this use, and assess the potential transfer of resistant 
bacteria from animals to humans.[Footnote 101] New Zealand has 
completed its risk assessments of antibiotics for growth promotion and 
no longer allows the growth promotion use of any antibiotics that are 
also related to antibiotics used in human medicine. New Zealand did not 
carry out a comprehensive risk analysis for any of the antibiotics 
being used for growth promotion because the available information was 
not sufficient. Instead, New Zealand used consistent rationale, 
including the mechanisms and potential for antibiotic resistance and 
the potential for that resistance to be transferred from animals to 
humans, in assessing each antibiotic (or class, such as the macrolide 
class).

Antibiotic resistance surveillance systems. New Zealand is working to 
implement a comprehensive antibiotic resistance surveillance program. 
According to a January 2003 antibiotic resistance progress report, New 
Zealand has programs to monitor specific pathogens in animals, but the 
programs do not gather information specific to antibiotic resistance. 
While the government informally monitors the antibiotic resistance of 
E. coli and Staphylococcus aureus, the program provides very limited 
data.

Antibiotic use data collection systems. Since 2001, New Zealand has 
collected antibiotic sales data from a formal survey of pharmaceutical 
companies. The companies report the data voluntarily. Annual reports 
provide antibiotics sales statistics by antibiotic class, method of 
administration, type of use (including growth promotion), and animal 
species. The data are only indicative of use because antibiotics are 
used for multiple purposes, and it is impossible to know the exact use 
of all the antibiotics. New Zealand has considered changes to its data 
collection system to provide additional information. See table 3 for 
information on the amount of antibiotics sold in New Zealand during 
2002.

South Korea: 

Antibiotic use data collection systems. The Korea Animal Health 
Products Association, an industry group, monitors the quantity of 
antibiotics produced and sold by its members. The data are available on 
a monthly basis and, at a minimum, provide total antibiotic use 
quantities by species, specific antibiotic, and antibiotic class.

[End of section]

Appendix V Antibiotics Frequently Used in Animals: 

This appendix provides information available on the antibiotics that 
are frequently used on farms that produce feedlot cattle, swine, and 
broiler chickens in the United States.

Antibiotic Use in U.S. Feedlot Cattle Production: 

In 1999, USDA's National Animal Health Monitoring System (NAHMS) 
collected data on antibiotic use in beef cattle raised in feedlots. 
Table 4 lists the antibiotics identified as having at least 10 percent 
of feedlots using them in feed or water, or by injection, and the most 
frequent purpose of use, when this information is available. NAHMS 
provided only limited information on how the antibiotics were 
administered, so this information is not included in the table. The 
table also presents information on FDA's rankings of the importance of 
the antibiotic class in human medicine. (See app. III for further 
information on FDA's ranking system.) For those antibiotics not found 
in these rankings, we listed them as not important. In particular, over 
half of the feedlots surveyed used chlortetracycline in feed or 
water,[Footnote 102] about one-third used tilmicosin to prevent 
disease, and over half used tilmicosin, florfenicol, and tetracyclines 
to treat disease. In addition, about one-third used cephalosporins, 
fluoroquinolones, and penicillins/amoxicillin to treat disease. 
However, the feedlots using these antibiotics do not administer them to 
all cattle. For example, although 42 percent of feedlots use 
antibiotics to prevent respiratory disease, only 10 percent of feedlot 
cattle receive antibiotics for this purpose.

Table 4: Antibiotics Frequently Used in Feedlot Cattle, 1999: 

Antibiotic class: Cephalosporin (third generation); 
Importance of antibiotic class in human medicine: Critically important.
Antibiotic: Ceftiofur[A]; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Fluoroquinolone; 
Importance of antibiotic class in human medicine: Critically important.
Antibiotic: Enrofloxacin[A]; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Macrolide; 
Importance of antibiotic class in human medicine: Critically important.
Antibiotic: Tilmicosin; 
Most frequent purpose of use: Disease treatment, disease prevention. 
Antibiotic: Tylosin[A]; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Penicillin/Aminopenicillin; 
Importance of antibiotic class in human medicine: Highly important.
Antibiotic: Penicillins/amoxicillin; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Phenicol; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Florfenicol; 
Most frequent purpose of use: Disease treatment, disease prevention. 

Antibiotic class: Sulfonamide; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Sulfamethazine[B]; 
Most frequent purpose of use: Not specified. 

Antibiotic class: Tetracycline; 
Importance of antibiotic class in human medicine: Highly important.
Antibiotic: Chlortetracycline; 
Most frequent purpose of use: Not specified. 
Antibiotic: Oxytetracycline; 
Most frequent purpose of use: Disease treatment, disease prevention. 

Source: GAO analysis of USDA and FDA data.

[A] The National Animal Health Monitoring System cited this antibiotic 
as an example for the class.

[B] Used in a combination with chlortetracycline.

[End of table]

Antibiotic Use in U.S. Swine Production: 

In 2000, NAHMS collected data on antibiotic use in swine. Table 5 lists 
the antibiotics identified as those that at least 10 percent of 
producers use in feed or water or by injection for either nursery-age 
or older swine, the most frequent method of administration for these 
antibiotics, and the most frequent purpose of use. The table also 
presents information on FDA's ranking of the importance of the 
antibiotic class in human medicine. For those antibiotics not found in 
these rankings, we listed them as not important. In particular, about 
half of the producers surveyed used tylosin and chlortetracycline in 
feed. In addition, about one-third of the producers surveyed used a 
penicillin to treat disease and bacitracin to promote growth. However, 
the producers using these antibiotics do not administer them to all of 
their swine.

Table 5: Antibiotics Frequently Used in Swine, 2000: 

Antibiotic class: Cephalosporin (third generation); 
Importance of antibiotic class in human medicine: Critically important.
Antibiotic: Ceftiofur; 
Most frequent method of administration: Injection; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Lincosamide; 
Importance of antibiotic class in human medicine: Highly important.
Antibiotic: Lincomycin; 
Most frequent method of administration: Injection; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Macrolide; 
Importance of antibiotic class in human medicine: Critically important.
Antibiotic: Tylosin; 
Most frequent method of administration: Feed, injection; 
Most frequent purpose of use: Disease treatment, disease prevention, 
growth promotion. 

Antibiotic class: Penicillin; 
Importance of antibiotic class in human medicine: Highly important.
Antibiotic: Procaine Penicillin G; 
Most frequent method of administration: Injection; 
Most frequent purpose of use: Disease treatment. 
Antibiotic: Penicillin Benzathine; 
Most frequent method of administration: Injection; 
Most frequent purpose of use: Disease treatment. 
Antibiotic: Penicillin[A]; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Growth promotion. 

Antibiotic class: Pleuromutilin; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Tiamulin; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Growth promotion. 

Antibiotic class: Polypeptide; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Bacitracin; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Growth promotion. 

Antibiotic class: Sulfonamide; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Sulfathiazole[A]; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Growth promotion. 

Antibiotic class: Tetracycline; 
Importance of antibiotic class in human medicine: Highly important.
Antibiotic: Chlortetracycline; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Disease treatment, disease prevention, 
growth promotion; 
Antibiotic: Oxytetracycline; 
Most frequent method of administration: Injection; 
Most frequent purpose of use: Disease treatment. 

Antibiotic class: Other; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Carbadox; 
Most frequent method of administration: Feed; 
Most frequent purpose of use: Growth promotion. 

Source: GAO analysis of USDA and FDA data.

[A] A chlortetracycline/penicillin/sulfathiazole combination is used 
for growth promotion.

[End of table]

Antibiotic Use in U.S. Broiler Production: 

USDA has not collected any data on antibiotic use in broiler chickens 
through NAHMS. However, a University of Arkansas study used data from a 
corporate database to track patterns of antibiotic use in broiler 
chickens from 1995 through 2000.[Footnote 103] This study focused on 
the use of antibiotics in feed to promote growth and to prevent 
disease. Over the period of the study, the percentage of production 
units using antibiotics in feed decreased, in part because antibiotics 
did not prove to be as cost-effective as other feed additives that 
promote growth.[Footnote 104] The study did not analyze data on 
antibiotics used in chickens for disease treatment. According to 
industry officials, producers seldom treat chickens for diseases.

Table 6 lists the antibiotics identified by the study as being used by 
at least 10 percent of broiler production units and their purpose of 
use. Table 6 also presents information on FDA's ranking of the 
importance of the antibiotic class in human medicine. For those 
antibiotics not found in these rankings, we listed them as not 
important.

Table 6: Antibiotics Frequently Used in Feed for Broiler Chickens, 
1995-2000: 

Antibiotic class: Other; 
Importance of antibiotic class in human medicine: Not important.
Antibiotic: Bambermycin; 
Most frequent purpose of use: Growth promotion/disease prevention.

Antibiotic class: Polypeptide; 
Most frequent purpose of use: Not important.
Antibiotic: Bacitracin; 
Most frequent purpose of use: Growth promotion/disease prevention.

Antibiotic class: Streptogramin; 
Most frequent purpose of use: Highly important.
Antibiotic: Virginiamycin; 
Most frequent purpose of use: Growth promotion/disease prevention. 

Source: GAO analysis of industry and FDA data.

[End of table]

[End of section]

Appendix VI: Comments from the U.S. Department of Agriculture: 

United States Department of Agriculture
Food Safety and Inspection Service
Washington, D.C. 20250:

Ms. Anu K. Mittal, 
Director:
Natural Resources and Environment, 
United States General Accounting Office, 
441 G Street, NW:

Washington, DC 20548:

APR 5 2004:

Dear Ms. Mittal:

In your letter dated March 16, 2004, you requested the U.S. Department 
of Agriculture (USDA) written comments on the Draft report GAO-04-490 
"Antibiotic Resistance: Federal Agencies Need to Better Focus Efforts 
to Address Risk to Humans from Antibiotic Use in Animals." Thank you 
for the opportunity to provide comments on the draft report.

We generally agree with the report. The report recognizes the many 
issues and complexities of efforts to address the risk to humans from 
antibiotic use in animals. We believe that the Animal National 
Antimicrobial Resistance Monitoring System (NARMS) and the 
Collaboration for Animal Health and Foods Safety Epidemiology (CAHFSE) 
are essential programs. These programs provide data that will protect 
the public health and assure consumers of the safety of their food. The 
report highlights the importance of the CAHFSE project and its 
contribution in supplying antimicrobial use data and information on the 
impact of antibiotic use in various animal species.

General Comments:

1. The report should note that CAHFSE is funded with limited base 
agency resources and that new funding would need to be considered 
before expanding it to slaughter/processing plants, more swine 
operations, or other species. To a large extent, the existence of 
CAHFSE is the result of redirected internal funding from other program 
areas.

2. Although the report identified several opportunities (on page 10, 
2nd paragraph, and page 45, 2nd paragraph) to strengthen data 
collection and research efforts, the report should explicitly state 
that new funding would need to be considered before these activities 
could be supported.

3. Throughout the document you may want to reconsider when it is 
appropriate to use the terms "antibiotic resistance in humans" or 
"antibiotic resistant bacteria in humans." Suppositions or conclusions 
by authors of studies should be supported with appropriate references. 
Moreover, many statements in the report about definitive 
findings (for example on page 21, 151paragraph) are redundant, and 
should make reference to scientific literature.

4. On page 21, paragraph 1, and elsewhere in the report the collection 
of antimicrobial use data at the macro (aggregate) level seems to be 
emphasized. While such data are useful for generating hypotheses about 
the relationships between antimicrobial use and antimicrobial 
resistance, they do not provide sufficient information upon which to 
take specific action or to evaluate appropriate mitigation strategies. 
As pointed out in the report, antimicrobials can be used in many ways; 
and without knowing more specifically how they are used, it is 
impossible to determine which of the uses is responsible for any trends 
that may be seen in the outcomes being monitored.

5. The Highlights section opening paragraph states, "Some research has 
shown that use of antibiotics in food animals poses significant risks 
for human health, but other researchers contend that the clinical 
consequences of the transference, if it occurs, are small." The report 
cites many references supporting the first position, "use of 
antibiotics in food animals poses significant risks for human 
health...", but not the second position, "...the clinical consequences 
of the transference, if it occurs, are small." GAO should consider 
including more scientific evidence to support the second position.

6. The report provides a comprehensive overview of several surveillance 
programs pertaining to antimicrobial resistance throughout the Federal 
government such as NARMS and CAHFSE. The report would be more complete 
if it included an overview of research efforts related to antimicrobial 
resistance. The Cooperative State Research, Education, and Extension 
Service (CSREES) funded over 30 studies since 2000 related to 
antibiotic resistance. CSREES awarded an additional $8 million in 
grants related to antibiotic resistance in 1999 and 2000. Funded 
studies include research into the prevalence, development, and possible 
transmission of antibiotic resistance; the epidemiology of antibiotic 
resistance; risk factors for persistence of antibiotic resistance in 
the animal and the environment as well as risk factors for 
transmission; the evaluation of management practices and potential 
prevention and intervention strategies for antibiotic resistance. In 
addition, USDA has partnered with FDA to fund education and training 
programs.

7. Information significantly impacting conclusions or limitations 
regarding studies advocating that agricultural use of antimicrobials 
promotes development of antimicrobial-resistant bacterial populations 
in humans are not reported, leading the reader to assume that 
agriculture use is responsible for increases, when scientific evidence 
may not conclusively support this assumption.

A few specific examples include:

* The report fails to mention that increases in fluoroquinolone 
resistance in a Minnesota study (page 22) were associated in largest 
part with foreign travel. 

* The report mentions avoparcin use in food 
animals may lead to increased numbers of vancomycin-resistant 
enterococci, but fails to mention that 
emergence of vancomycin-resistant enterococci in the US occurred 
despite the fact that avoparcin (page 28) has never been used in food 
animals in the US. 

* The report mentions on page 21 that the finding of 
genetically-related organisms in food derived from animals and in 
humans established definitive evidence of transfer antimicrobial-
resistant pathogens from food animals to humans. Though it is likely 
that a transfer of antimicrobial-resistant pathogens occurred, 
epidemiological studies described only provide circumstantial 
evidence. Many of the studies mentioned in the report are case-control 
studies which can only reveal associations, not establish cause and 
effect.

Please find enclosed additional specific USDA comments on the draft 
report.

Sincerely,

Signed for: 

Ronald F. Hicks, 
Assistant Administrator 
Office of Program Evaluation, Enforcement and Review:

Enclosure:  

GAO's Responses to USDA's Comments: 

The following are our comments on the USDA letter, dated April 5, 2004.

1.We revised the report to include USDA's concerns that additional 
funding would be needed to expand CAHFSE.

2.We clarified our discussion of some studies. References are cited in 
footnotes for studies discussed in the report.

3.We agree that the collection of both aggregate and detailed data on 
antibiotic use in animals is useful and that researchers need to know 
specifically how antibiotics are used in order to determine which of 
the uses is responsible for trends in antibiotic resistance. The report 
discusses both aggregate and detailed data. As USDA states, the report 
highlights the CAHFSE program, through which USDA is collecting 
specific, on-farm data on swine. In addition, the report discusses 
Denmark's system, which collects detailed data on how antibiotics are 
used in animals.

4.We found that only a few studies have concluded that the risk is 
minimal, while many studies have concluded that there is a significant 
human health risk from the transference.

5.We revised the report to include information on research funded by 
USDA's Cooperative State Research, Education, and Extension Service.

6.We clarified the report to reflect comments on specific studies. In 
addition, we clarified the report to indicate which results were from 
epidemiologic studies alone, and which results were from epidemiologic 
studies that included molecular subtyping techniques.

[End of section]

Appendix VII: Comments from the Department of Health and Human 
Services: 

DEPARTMENT OF HEALTH & HUMAN SERVICES	
Office of Inspector General:

Washington, D.C. 20201:

APR 7 2004:

Ms. Marcia Crosse 
Director, Health Care 
Public Health and Military Health Care Issues 
United States General Accounting Office 
Washington, D.C. 20548:

Dear Ms. Crosse:

Enclosed are the Department's comments on your draft report entitled, 
"Antibiotic Resistance: Federal Agencies Need to Better Focus Efforts 
to Address Risk to Humans from Antibiotic Use in Animals" (GAO-04-490). 
The comments represent the tentative position of the Department and are 
subject to reevaluation when the final version of this report is 
received.

The Department provided several technical comments directly to your 
staff.

The Department appreciates the opportunity to comment on this draft 
report before its publication.

Sincerely,

Signed by: 

Dara Corrigan:

Acting Principal Deputy Inspector General:

Enclosure:

The Office of Inspector General (OIG) is transmitting the Department's 
response to this draft report in our capacity as the Department's 
designated focal point and coordinator for General Accounting Office 
reports. OIG has not conducted an independent assessment of these 
comments and therefore expresses no opinion on them.

GENERAL COMMENTS BY THE DEPARTMENT OF HEALTH AND HUMAN SERVICES ON THE 
U.S. GENERAL ACCOUNTING OFFICE'S DRAFT REPORT, "ANTIBIOTIC RESISTANCE: 
FEDERAL AGENCIES NEED TO BETTER FOCUS EFFORTS TO ADDRESS RISK TO HUMANS 
FROM ANTIBIOTIC USE IN ANIMALS" (GAO-04-490):

The Department of Health and Human Services (HHS) appreciates the 
opportunity to review and comment on the General Accounting Office's 
(GAO) draft report. HHS concurs with the findings of this report and 
considers it to be very thorough and generally accurate.

The Food and Drug Administration (FDA) and the Centers for Disease 
Control and Prevention (CDC) have been and will continue to be actively 
engaged in: research on the relationship between antibiotic use in 
agriculture and emerging resistant bacteria, assessing the human health 
consequences of antibiotic use in food animals, and developing 
strategies to mitigate antibiotic resistance. We believe these agencies 
can make important contributions to the scientific knowledge on this 
issue through agency specific projects as well as through 
interdepartmental and extramural collaborations.

The draft report presents or refers to significant and growing evidence 
demonstrating the human health consequences of drug resistant 
infections related to antibiotic use in agriculture. We discuss below 
11 additional studies that GAO did not reference in their draft report. 
While some of these studies date back to 1971, they remain relevant to 
this issue. These studies, along with those cited in the GAO report, 
all demonstrate a relationship between the use of antimicrobials in 
food-producing animals, antibiotic resistance in humans, and adverse 
human health consequences as a result. We believe that there is a 
preponderance of evidence that the use of antimicrobials in food-
producing animals has adverse human consequences.

There is little evidence to the contrary. GAO cites one study and one 
article published in the Journal ofAntimicrobial Chemotherapy. [NOTE 1] 
We believe GAO should note in its report that the article they cite was 
written by an advisory group to the Animal Health Institute.

Recent studies have demonstrated that antimicrobial resistance among 
foodbome bacteria, primarily Salmonella and Campylobacter, may cause 
prolonged duration of illness, and increased rates of bacteremia, 
hospitalization, and death. Other studies have determined that the 
majority of antimicrobial resistant Salmonella and Campylobacter 
infections in developed countries are due to antimicrobial use in food 
animals, findings that GAO does not dispute. Therefore, the studies 
described here can be used as evidence that adverse human health 
outcomes are associated with resistant bacteria due to the use of 
antimicrobials in food animals, although not all of these studies 
specifically addressed the origin of the resistant bacteria.

Holmberg et al. reviewed Salmonella outbreaks investigated by the 
Centers for Diseases Control and Prevention (CDC) between 1971 and 1983 
and found a higher case fatality 
rate for patients infected with antimicrobial-resistant Salmonella 
(4.2%) than for those with antimicrobial-sensitive infections 
(0.2%).[NOTE 2] In a later study (1987) of 28 Salmonella outbreaks, 
greater hospitalization and case-fatality rates were associated with 
outbreaks caused by antimicrobial-resistant Salmonella as compared to 
susceptible infections.[NOTE 3] A more recent CDC study of 24 
Salmonella outbreaks that occurred between 1984 and 2002 also found 
that outbreaks caused by antimicrobial-resistant Salmonella resulted in 
higher hospitalization rates than outbreaks caused by susceptible 
Salmonella.[NOTE 4]

Studies of salmonellosis cases not limited to outbreaks have also 
demonstrated that resistance is associated with higher morbidity and 
mortality. In a prospective CDC study of 758 salmonellosis cases, 
patients with resistant infections were significantly more likely be 
hospitalized than were those with susceptible infections, even after 
accounting for underlying illness and prior antimicrobial exposure 
using multivariate techniques. Patients with resistant infections also 
tended to be ill longer (median, 10 vs. 8 days) and hospitalized longer 
(median, 5 vs. 4 days) than patients with susceptible infections.[NOTE 
5]

More recent studies, which have utilized epidemiological and/or 
statistical methodologies to account for potentially confounding 
factors including serotype and age, have provided further support for 
the association between resistance in Salmonella and increased 
morbidity and mortality. Varma et al. [NOTE 6] studied Salmonella cases 
diagnosed in the United States between 1996-2000 and found that 
antimicrobial resistance was associated with increased hospitalization 
and bloodstream infections. Patients with Salmonella isolates resistant 
to any antimicrobial agent or to commonly used agents (cephalosporins, 
quinolones, or amino glycosides) were hospitalized more often than 
patients with pan-susceptible isolates even after controlling for age, 
race, surveillance site, serotype, and bloodstream infection in a 
multivariate analysis. [NOTE 7] Resistance to any antimicrobial or to 
commonly used agents was also associated with an increase in 
bloodstream infection compared to pan-susceptible isolates after 
controlling for age and serotype.[NOTE 7]

Helms et al. [NOTE 8] conducted a large matched 
cohort study in Denmark to determine mortality rates associated with 
different drug resistance patterns in S. Typhimurium. Each patient 
diagnosed between 1995 and 1999 was matched by age, sex, and county to 
10 people in the general Danish population. By survival analysis, the 
2-year mortality rates for patients were compared with mortality rates 
in the general population after the data were adjusted for differences 
in co morbidity. Patients with pan-susceptible strains of S Typhimurium 
were 2.3 times more likely to die within two years than the general 
Danish population, whereas patients infected with R-type ACSSuT 
(resistance to ampicillin, chloramphenicol, streptomycin, 
sulfonamides, and tetracycline) were 4.8 times more likely to die. 
Resistance to nalidixic acid was associated with even higher mortality 
(resistance to nalidixic acid often foreshadows reduced susceptibility 
to the fluoroquinolones); patients infected with nalidixic acid 
resistant strains were 10.3 times more likely to die than the general 
population, while those infected with strains resistant to nalidixic 
acid as well as ampicillin, chloramphenicol, streptomycin, 
sulfonamides, and tetracycline (ACSSuT) were 13.1 times more likely to 
die. [NOTE 8] Another recently completed study in Denmark found that 
among patients with culture-confirmed S. Typhimurium infections between 
1995 and 2000, patients with nalidixic acid-resistant infections were 
more likely to have bloodstream infections or die in the 90 days 
following specimen collection than those with susceptible infections. 
[NOTE 4]

A study conducted in Canada in 1999 and 2000 investigated the 
relationship between increased burden of illness in patients with S 
Typhimurium and both definitive phage type 104 (DT104) and 
antimicrobial resistance.[NOTE 9] In this study, after controlling for 
significant risk factors and confounding variables, including age, 
hospitalization was 2.3 times more likely to occur among patients whose 
infections were resistant to at least ampicillin, kanamycin and/or 
chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (R-
type AK/CSSuT) compared with AK/CSSuT-susceptible patients (p=0.003) 
and 3.6 times more likely to occur among patients with non-DT 104 R-
type AKSSuT infections compared with patients with non-DT104 R-type 
AKSSuT-susceptible infections (p=0.005). [NOTE 9]

The evidence is not limited to Salmonella infections. Several 
Campylobacter case-control studies in the United States and Denmark 
have demonstrated a relationship between quinolone resistance and 
prolonged duration of illness. GAO does mention the Smith et al. study 
in Minnesota, [NOTE 10] but there are several others that GAO ignores. 
In a 1996-1997 study in Denmark, Neimann et al. found that among 
Campylobacter cases treated with fluoroquinolones or other antibiotics, 
the median duration of illness was 14 days in patients infected with 
ciprofloxacin-resistant strains compared to 9 days in patients with 
susceptible isolates. [NOTE 11]

Nelson et al. conducted a multistate case-control study of sporadic 
Campylobacter cases in the United States in 1998 and 1999. [NOTE 12] 
Among patients who did not take antidiarrheal medications, patients 
with ciprofloxacin-resistant infections had a longer mean duration of 
diarrhea than those with ciprofloxacin-susceptible infections (9 vs. 7 
days, p=0.04). The difference in mean duration of diarrhea between 
ciprofloxacin-resistant and ciprofloxacin-susceptible infections was 
even more pronounced among persons who did not take antidiarrheals or 
antimicrobials (12 vs. 6 days, p=0.04), suggesting that resistant 
Campylobacter may be more virulent than susceptible strains. In a 
multivariate model controlling for antimicrobial, antidiarrheal, and 
antacid use, the mean duration of diarrhea was longer for patients with 
ciprofloxacin-resistant infections than for patients with susceptible 
infections (p=0.01) and the effect was independent of foreign travel. 
[NOTE 12]

A recently completed study in Denmark evaluated the relationship 
between resistance in Campylobacter and increases in both bacteremia 
and mortality. Among patients with culture-confirmed 
campylobacteriosis from 1995 to 2000, those with fluoroquinolone-
resistant or erythromycin-resistant Campylobacter infections were more 
likely to have a bloodstream infection or die in the 90 days following 
specimen collection than those with susceptible infections. [NOTE 4]

GAO should change the title and update the section in the draft report 
to read, "FDA's Center for Veterinary Medicine Has Initiated Action to 
Prohibit the Use of Enrofloxacin in Poultry, but Proceedings Not Yet 
Complete." Since GAO issued its draft report the Administrative Law 
Judge issued an initial decision, find that: 1) "poultry is in fact a 
major source of fluoroquinolone-resistant Campylobacte"; 2) "the use of 
Baytril in poultry acts as a selection pressure for fluoroquinolone-
resistant Campylobacter and results in the emergence and dissemination 
of fluoroquinolone-resistant Campylobacter"; 3) "fluoroquinolone-
resistant Campylobacter are transferred from poultry to humans and 
contribute to Campylobacter infections in humans"; 4) "fluoroquinolone-
resistant Campylobacter results in an increased severity of 
campylobacteriosis in humans." 
http://www.fda.gov/ohrms/dockets/dailys/04/marO4/031604/
00n-1571-idf0001-vol389.pdf:

Recommendations:

1. FDA expedite its risk assessments of drugs used in food animals that 
are critically important for human health to determine if regulatory 
action is necessary:

GAO recommends that FDA expedite its review of the currently approved 
antimicrobials for food-producing animals using GFI 152 and focusing on 
the antimicrobials that are critically important for human health. FDA 
agrees that this review is important and has devoted considerable 
resources to this process. It is important to point out, however, that 
if CVM develops sufficient evidence to initiate a withdrawal proceeding 
under the Federal Food, Drug and Cosmetic Act, this withdrawal 
proceeding can be quite lengthy. As GAO noted, CVM proposed to withdraw 
approval of the new animal drug for Baytril use in poultry in October 
2000, yet Baytril remains on the market.

2. Better data is needed on antimicrobial drug use in food animals:

GAO is correct that drug use data are essential to evaluate the 
development of antimicrobial resistance and to target mitigation 
strategies intended to prolong the effectiveness of antimicrobials used 
in food-producing animals. Data generated from monitoring antimicrobial 
usage can be used in conjunction with surveillance of antimicrobial 
resistance to inform and educate all stakeholders, to develop national 
and international policies for the containment of antimicrobial 
resistance, and to evaluate the impact of the implementation of the 
prudent use of antimicrobials and other interventions designed to 
mitigate or contain antimicrobial resistance.

GAO recommends that HHS and USDA develop and implement a plan to 
collect data on antibiotic use in food animals. However, the most 
useful and reliable data are those maintained by the drug sponsors. 
Currently, the drug companies are required under 21 CFR 514.80(b)(4)(i) 
to report quantities of product marketed to FDA on the anniversary date 
of approval of their new animal drug application (NADA or ANADA). 
Sponsors typically provide a quantity for each of the dosage forms 
marketed but the information is not differentiated by animal species, 
label indication(s), route of administration or geographic region. The 
data collection requirements would need to be modified to make the data 
more relevant for the purposes described above. This would require 
notice and comment rulemaking to revise the current regulation.

We propose that the forum for discussions between HHS and USDA for 
improving and creating surveillance for drug use in agriculture should 
be the Interagency Task Force on Antimicrobial Resistance. The 
appropriate agencies of HHS are members. USDA is represented as a 
department, but personnel from specific relevant agencies within USDA 
can participate in discussions and planning through this group as they 
did during the drafting of A Public Health Action Plan to Combat 
Antimicrobial Resistance.

END NOTES:

[1] Phillips 1, Casewell M, Cox T, et al. Does the use of antibiotics 
in food animals pose a risk to human health? A critical review of 
published data. J Antimicrob Chemother 2004;53:28-52.

[2] Holmberg SD, Wells JG, Cohen ML. Animal-to-man transmission of 
antimicrobial-resistant Salmonella: investigations of U.S. outbreaks, 
1971-1983. Science 1984;225:833-5.

[3] Holmberg SD, Solomon SL, Blake PA. Health and economic impacts of 
antimicrobial resistance. Rev Infect Dis 1987; 9:1065-78.

[4] World Health Organization. Joint FAO/OIE/VVHO Expert Workshop on 
Non-Human Antimicrobial Usage and Antimicrobial Resistance: Scientific 
Assessment. Geneva, 1-5 December, 2003. Available online at: http://
www.who.int/foodsafety/micro/meetings/nov2003/en/:

[5] Lee LA, Puhr ND, Maloney K, et al. Increase in antimicrobial-
resistant Salmonella infections in the United States, 1989-1990. J 
Infect Dis 1994;170:128-34.

[6] Varma J, Molbak K, Rossiter S, et al. Antimicrobial resistance in 
Salmonella is associated with increased hospitalization; NARMS 1996-
2000. International Conference on Emerging Infectious Diseases. March 
2002. Atlanta, GA.

[2] Varma J, Molbak K, Rossiter S, et al. Antimicrobial resistance in 
non-typhoidal Salmonella is associated with increased hospitalization 
and bloodstream infection--United States, 1996-2000. 51st Annual EIS 
Conference. April 22-26, 2002. Atlanta, GA.

[8] Helms M, Vastrup P, Gerner-Smidt P, Molbak K. Excess mortality 
associated with antimicrobial drug-resistant Salmonella Typhimurium. 
Emerg Infect Dis 2002;8:490-5.

[9] Martin L, Fyfe M, Dore K, et al. Increased burden of illness 
associated with antimicrobial-resistant Salmonella enterica serotype 
Typhimurium infections. J Infect Dis 2004;189:377-84:

[10] Smith KE, Besser JM, Hedberg CW, et al. Quinolone-resistant 
Campylobacter jejuni infections in Minnesota, 1992-1998. N Engl J Med 
1999;340:1525-32.

[11] Neimann J, Molbak K, Engberg J, et al. Longer duration of illness 
among Campylobacter patients treated with fl uoroquinolones. 11th 
International Workshop on Campylobacter, Helicobacter, and Related 
Organisms, 1-S September, 2001. Freiburg, Germany.

[12] Nelson JM, Smith KE, Vugia DJ, et al. Prolonged diarrhea due to 
ciprofoxacin-resistant Campylobacter infections. J Infect Dis 2004; in 
press.

[End of section]

Appendix VIII: GAO Contacts and Staff Acknowledgments: 

GAO Contacts: 

Martin T. Gahart, (202) 512-3596 J. Erin Lansburgh, (202) 512-3017: 

Acknowledgments: 

In addition to those named above, Gary Brown, Diane Berry Caves, Diana 
Cheng, Barbara El Osta, Ernie Jackson, Julian Klazkin, Carolyn Feis 
Korman, Deborah J. Miller, Sudip Mukherjee, Lynn Musser, Roseanne 
Price, and Carol Herrnstadt Shulman made key contributions to this 
report.

(360314): 

FOOTNOTES

[1] Antibiotics are substances that destroy microorganisms or inhibit 
their growth. They are used extensively to treat bacterial infectious 
diseases in plants, animals, and humans. Some scientists refer to 
synthetic antibiotics as antimicrobials. In this report, we use the 
term antibiotics to mean both natural and synthetic types.

[2] The Office International des Epizooties is also known as the World 
Organization for Animal Health and, among other things, helps ensure 
the safety of foods produced from animals.

[3] U.S. General Accounting Office, Antimicrobial Resistance: Data to 
Assess Public Health Threat from Resistant Bacteria Are Limited, GAO/
HEHS/NSIAD/RCED-99-132 (Washington, D.C.: Apr. 28, 1999).

[4] U.S. General Accounting Office, Food Safety: The Agricultural Use 
of Antibiotics and Its Implications for Human Health, GAO/RCED-99-74 
(Washington, D.C.: Apr. 28, 1999).

[5] The other task force agencies are the National Institutes of 
Health, the Agency for Healthcare Research and Quality, the Centers for 
Medicare and Medicaid Services, the Health Resources and Services 
Administration, the Department of Defense, the Department of Veterans 
Affairs, the Environmental Protection Agency, and since 2001, the U.S. 
Agency for International Development.

[6] Although Denmark is an EU member, we included it in addition to the 
EU because it is a major U.S. competitor in pork exports.

[7] Chromosomes are linear threads made of DNA in the nucleus of a 
cell. Plasmids are circular pieces of DNA that are smaller than 
chromosomes and are often called extra-or mini-chromosomes.

[8] Stuart B. Levy, "Multidrug Resistance--A Sign of the Times," New 
England Journal of Medicine, vol. 338, no. 19 (1998): 1376-1378.

[9] A bacterial isolate is a population of organisms that come from a 
sample, such as diseased tissue from animals or humans.

[10] Although scientists do not fully understand how antibiotics 
promote growth in animals, they believe antibiotics work through 
mechanisms such as increasing the absorption of nutrients in feed and 
suppressing subclinical bacterial infections.

[11] Foodborne illnesses generally cause gastrointestinal symptoms, 
such as nausea, vomiting, abdominal cramps, and diarrhea. There are 
more than 250 foodborne diseases, and most are caused by bacteria, 
viruses, and parasites.

[12] Cross-resistance is the phenomenon in which a microbe, such as a 
bacterium, that has acquired resistance to one drug through direct 
exposure, also turns out to have resistance to one or more other drugs, 
typically in the same drug class, to which it has not been exposed.

[13] World Health Organization, Department of Communicable Disease 
Surveillance and Response, WHO Global Principles for the Containment of 
Antimicrobial Resistance in Animals Intended for Food (Geneva, 
Switzerland, 2000); Alliance for the Prudent Use of Antibiotics, "The 
Need to Improve Antimicrobial Use in Agriculture: Ecological and Human 
Health Consequences." Clinical Infectious Diseases, vol. 34, suppl. 3 
(2002): S76-S77; and Institute of Medicine of the National Academies of 
Sciences, Microbial Threats to Health: Emergence, Detection, and 
Response (Washington, D.C., 2003): 16-17.

[14] Dermot J. Hayes, Helen H. Jensen, Lennart Backstrom, and Jay 
Fabiosa, "Economic Impact of a Ban on the Use of Over-the-Counter 
Antibiotics," Staff Report 99-SR 90, Center for Agricultural and Rural 
Development, Iowa State University, Ames, Iowa, December 1999.

[15] However, FDA's authority to withdraw a currently approved animal 
antibiotic use is generally limited to human health considerations and 
does not concern the economic impacts of such a withdrawal. See 21 
U.S.C. 360b(e)(2000).

[16] 21 U.S.C. 360b(e)(1)(2000).

[17] See http://www.cdc.gov/drugresistance/actionplan/(downloaded 
Apr. 11, 2003).

[18] Stuart B. Levy, George B. Fitzgerald, and Ann B. Macone, "Spread 
of Antibiotic-Resistant Plasmids from Chicken to Chicken and from 
Chicken to Man," Nature, vol. 260, no. 5546 (1976): 40-42; and Stuart 
B. Levy, George B. Fitgerald, and Ann B. Macone, "Changes in Intestinal 
Flora of Farm Personnel after Introduction of a Tetracycline-
Supplemented Feed on a Farm," New England Journal of Medicine, vol. 295 
(1976): 583-588.

[19] Kirk E. Smith, John M. Besser, Craig W. Hedberg, Fe T. Leano, 
Jeffrey B. Bender, Julie H. Wicklund, Brian P. Johnson, Kristine A. 
Moore, Michael T. Osterholm, and the investigation team, "Quinolone-
resistant Campylobacter jejuni infections in Minnesota, 1992-1998," New 
England Journal of Medicine, vol. 340, no. 20 (1999). 

[20] These percentages are from isolates from people who acquired the 
infections in the United States. There was a greater increase in the 
number of quinolone-resistant human isolates when infections acquired 
from foreign travel and from people who took fluoroquinolones prior to 
the collection of stool samples were included. Noting this, the 
percentage change between 1996 and 1998 of the domestically acquired 
infections was found to be statistically significant. FDA approved the 
use of fluoroquinolones in animals in 1995.

[21] The antibiotic vancomycin has been reserved to treat infections, 
such as enterococcus infections, in humans that are resistant to 
antibiotics normally used for treatment.

[22] Avoparcin has never been approved for food animal use in the 
United States.

[23] Anthony E. van den Bogaard and Ellen E. Stobberingh, "Epidemiology 
of Resistance to Antibiotics Links between Animals and Humans," 
International Journal of Antimicrobial Agents, vol. 14 (2000): 327-335.

[24] Centers for Disease Control and Prevention, National Antimicrobial 
Resistance Monitoring System: Enteric Bacteria 2001 Annual Report 
(2003): 10.

[25] Kirk E. Smith, John M. Besser, Craig W. Hedberg, Fe T. Leano, 
Jeffrey B. Bender, Julie H. Wicklund, Brian P. Johnson, Kristine A. 
Moore, Michael T. Osterholm, and the investigation team, "Quinolone-
resistant Campylobacter jejuni Infections in Minnesota, 1992-1998," New 
England Journal of Medicine, vol. 340, no. 20 (1999).

[26] Hubert Ph. Endtz, Gijs J. Ruijs, Bert van Klingeren, Wim H. 
Jansen, Tanny van der Reyden, and R. Peter Mouton, "Quinolone 
Resistance in Campylobacter Isolated from Man and Poultry Following the 
Introduction of Fluoroquinolones in Veterinary Medicine," Journal of 
Antimicrobial Chemotherapy, vol. 27 (1991): 199-208.

[27] Paul D. Fey, Thomas J. Safranek, Mark E. Rupp, Eileen F. Dunne, 
Efrain Ribot, Peter C. Iwen, Patricia A. Bradford, Frederick J. Angulo, 
and Steven H. Hinrichs, "Ceftriaxone-Resistant Salmonella Infection 
Acquired by a Child from Cattle," New England Journal of Medicine, vol. 
342 (2000): 1242-1249.

[28] Andrzej Hoszowski and Dariusz Wasyl, "Typing of Salmonella 
enterica subsp. enterica serovar Mbandaka Isolates," Veterinary 
Microbiology, vol. 80 (2001): 139-148.

[29] Po-Ren Hsueh, Lee-Jene Teng, Sung-Pin Tseng, Chao-Fu Chang, Jen-
Hsien Wan, Jing-Jou Yan, Chun-Ming Lee, Yin-Ching Chuang, Wen-Kuei 
Huang, Dine Yang, Jainn-Ming Shyr, Kwok-Woon Yu, Li-Shin Wang, Jang-Jih 
Lu, Wen-Chien Ko, Jiunn-Jong Wu, Feng-Yee Chang, Yi-Chueh Yang, Yeu-Jun 
Lau, Yung-Ching Liu, Cheng-Yi Liu, Shen-Wu Ho, and Kwen-Tay Luh, 
"Ciprofloxacin-Resistant Salmonella enterica Typhimurium and 
Choleraesuis from Pigs to Humans, Taiwan," Emerging Infectious 
Diseases, vol. 10, no. 1 (2004): 60-68.

[30] Thomas F. O'Brien, John D. Hopkins, Elaine S. Gilleece, Antone A. 
Medeiros, Ralph L. Kent, Billie O. Blackburn, Marion B. Holmes, Joseph 
P. Reardon, James M. Vergeront, Wendy L. Schell, Eleanor Christenson, 
Marjorie L. Bissett, and Erskine V. Morse, "Molecular Epidemiology of 
Antibiotic Resistance in Salmonella from Animals and Human Beings in 
the United States," New England Journal of Medicine, vol. 307, no. 1 
(1982): 1-6.

[31] Efrain M. Ribot, Rachel K. Wierzba, Frederick J. Angulo, and 
Timothy J. Barrett, "Salmonella enterica serotype Typhimurium DT104 
Isolated from Humans, United States, 1985, 1990, and 1995," Emerging 
Infectious Diseases, vol. 8, no. 4 (2002): 387-391.

[32] Cephalosporins are antibiotics that are commonly used, especially 
in children, to treat severe salmonella infections.

[33] Amita Gupta, John Fontana, Colleen Crowe, Barbara Bolstorff, 
Alison Stout, Susan Van Duyne, Mike P. Hoekstra, Jean M. Whichard, 
Timothy J. Barrett, Frederick J. Angulo, for the National Antimicrobial 
Resistance Monitoring System PulseNet Working Group, "Emergence of 
Multidrug-Resistant Salmonella enterica Serotype Newport Infections 
Resistant to Expanded-Spectrum Cephalosporins in the United States," 
Journal of Infectious Diseases, vol. 188 (2003): 1707-1716.

[34] Food and Agriculture Organization of the United Nations, Office 
International des Epizooties, and World Health Organization, Joint FAO/
OIE/WHO Expert Workshop on Non-Human Antimicrobial Usage and 
Antimicrobial Resistance: Scientific Assessment (Geneva, Switzerland, 
Dec. 1-5, 2003).

[35] Karin Travers and Michael Barza, "Morbidity of Infections Caused 
by Antimicrobial-Resistant Bacteria," Clinical Infectious Diseases, 
vol. 34, suppl. 3 (2002): S131-S134.

[36] Vancomycin-resistant enterococcus infections are easily 
transmitted in health care settings and are difficult to treat.

[37] J. McClellan, K. Joyce, S. Rossiter, T. Barrett, F. J. Angulo, and 
the NARMS Enterococci Working Group, "High-Level Gentamicin Resistant 
Enterococci and Quinupristin/Dalfopristin Resistant E. faecium from 
Ground Pork Purchased from Grocery Stores" (paper presented at the 41st 
Interscience Conference on Antimicrobial Agents and Chemotherapy annual 
meeting, Chicago, Ill., 2001), and K. Gay, K. Joyce, J. Stevenson, F. 
Angulo, T. Barrett, and the NARMS Working Group, "Quinupristin/
Dalfopristin-Resistant Enterococcus faecium Isolated from Human 
Stools, Retail Chicken, and Retail Pork: EIP Enterococci Project" 
(paper presented at the International Conference on Emerging Infectious 
Diseases, Atlanta, Ga., March 2002).

[38] Joshua R. Hayes, Angela C. McIntosh, Sadaf Qaiyumi, Judith A. 
Johnson, Linda L. English, Lewis E. Carr, David D. Wagner, and Sam W. 
Joseph, "High-Frequency Recovery of Quinupristin-Dalfopristin-
Resistant Enterococcus faecium Isolates from the Poultry Production 
Environment," Journal of Clinical Microbiology, vol. 39, no. 6 (2001): 
2298-2299; and D. L. Smith, J. A. Johnson, A. D. Harris, J. P. Furuno, 
E. N. Perencevich, and J. G. Morris Jr., "Assessing Risks for a Pre-
Emergent Pathogen: Virginiamycin Use and the Emergence of Streptogramin 
Resistance in Enterococcus faecium," The Lancet Infectious Diseases, 
vol. 3 (2003): 241-249.

[39] I. Phillips, M. Casewell, T. Cox, B. De Groot, C. Friis, R. Jones, 
C. Nightingale, R. Preston, and J. Waddell, "Does the Use of 
Antibiotics in Food Animals Pose a Risk to Human Health? A Critical 
Review of Published Data," Journal of Antimicrobial Chemotherapy, vol. 
53, no. 1 (2004): 28-52.

[40] Jennifer M. Stephen, Mark A. Toleman, Timothy R. Walsh, Ronald N. 
Jones, and the SENTRY Program Participants Group, "Salmonella 
Bloodstream Infections: Report from the SENTRY Antimicrobial 
Surveillance Program (1997-2001)," International Journal of 
Antimicrobial Agents, vol. 22 (2003): 395-405.

[41] I. Phillips, M. Casewell, T. Cox, B. De Groot, C. Friis, R. Jones, 
C. Nightingale, R. Preston, and J. Waddell, "Does the Use of 
Antibiotics in Food Animals Pose a Risk to Human Health? A Critical 
Review of Published Data," Journal of Antimicrobial Chemotherapy, vol. 
53, no. 1 (2004): 42.

[42] Two of the bacteria studied in NARMS--Salmonella Typhi and 
Shigella--do not occur in food animals but are acquired by humans as a 
result of poor hygiene. As a result, they are not tested in the animal 
or retail meat programs of NARMS.

[43] NARMS began testing human non-Typhi salmonella and E. coli O157: H7 
isolates. As of early 2004, NARMS tests Salmonella Typhi, non-Typhi 
salmonella, E. coli, campylobacter, enterococcus, and shigella 
isolates.

[44] Because little antibiotic resistance was found in these isolates, 
these bacteria are no longer tested for antibiotic susceptibility. 

[45] In 1999, testing of campylobacter isolates was limited to seven of 
these departments. By 2003, 10 states were participating in 
campylobacter testing. 

[46] CDC, National Antimicrobial Resistance Monitoring System for 
Enteric Bacteria (NARMS): 2001 Annual Report, Atlanta, Ga: HHS, CDC, 
2003.

[47] CDC officials reported that USDA and FDA provide one-third of the 
funding for FoodNet, and the agencies and states each have 
representatives on FoodNet's steering committee.

[48] PulseNet fingerprints salmonella, E. coli, listeria, and shigella 
isolates, and PulseVet fingerprints salmonella and plans to include, as 
funding allows, campylobacter, enterococcus, and generic E. coli 
isolates.

[49] DNA fingerprinting is performed through genetic relatedness 
studies using pulsed-field gel electrophoresis.

[50] Animal feeds may include animal products or parts which have DNA. 
For example, cattle feed, may include blood and blood products, among 
others. See 21 C.F.R.  589.2000(a)(1),(7),(b)(2003).

[51] 65 Fed. Reg. 64954 (Oct. 31, 2000). There were two 
fluoroquinolones approved at that time: sarafloxacin hydrochloride and 
enrofloxacin.

[52] After the original notice of FDA's plans to withdraw approval of 
enrofloxacin for poultry, the only other manufacturer of an approved 
fluoroquinolone for poultry, Abbott Laboratories, voluntarily 
requested withdrawal of the approval for its drug sarafloxacin 
hydrochloride (SaraFlox).

[53] The only other participant in the case is the Animal Health 
Institute.

[54] See 21 C.F.R.  12.120-12.140(2003).

[55] Virginiamycin is no longer considered a critically important drug. 
Synercid, was the first antibiotic approved for the treatment of 
vancomycin-resistant Enterococcus faecium bacteremia and was the only 
drug available for treatment when the risk assessment began. Since that 
time, other drugs have been developed, and the status of virginiamycin 
has been reduced from critically important to highly important for 
human health.

[56] FDA has rated classes of animal drugs as critically important, 
highly important, or important to human health.

[57] Subtherapeutic drugs are typically used to enhance growth rates or 
improve feed efficiency. 

[58] Categories of drugs identified in Guidance for Industry #152 as 
critically important for human health include third-generation 
cephalosporins, fluoroquinolones, macrolides, and trimethoprim/
sulfamethoxazole.

[59] By law, the Secretary of HHS can also determine that there is an 
imminent hazard from an animal drug. In such cases, the authority to 
market the drug could be immediately suspended pending challenges from 
the manufacturer. 21 U.S.C. 360b(e)(2000).

[60] In addition, the Animal Health Institute--a trade association 
representing veterinary pharmaceutical manufacturers--publishes yearly 
information on the total quantity of animal antibiotics sold by its 
members. The Animal Health Institute's members account for about 85 
percent of animal drug sales in the United States. Its reports present 
the data by antibiotic class and groups certain classes together. The 
data include amounts sold for both livestock and pets and are not 
separated by species. 

[61] According to Animal Health Institute officials, many manufacturers 
sell antibiotics to wholesale distributors or feed mills and cannot 
provide the details on the end use of their products. In addition, 
certain antibiotics are authorized for use in multiple species and for 
multiple purposes. 

[62] With regard to trade in meat, the key U.S. trading partners on 
which we obtained information were the EU, Australia, Canada, China, 
Denmark, Hong Kong, Japan, Mexico, New Zealand, Russia, and South 
Korea; the key U.S. competitors were the EU, Australia, Brazil, Canada, 
and Denmark. We did not independently verify the information in foreign 
government documents, which included laws and regulations. 

[63] China, Hong Kong, and Mexico allow the use of antibiotics for 
growth promotion. We did not obtain information on whether these 
include antibiotics from classes important in human medicine.

[64] The EU will still allow the use of coccidiostat and histomonostat 
drugs as feed additives for growth promotion. These drugs control 
parasites, and many coccidiostat and histomonostat drugs are not used 
in humans.

[65] The United States has not started a risk assessment for any 
antibiotic in this class.

[66] Australia, Brazil, China, Hong Kong, Japan, Mexico, Russia, and 
South Korea permit the sale of some antibiotics over the counter. We 
did not obtain more detailed information on which antibiotics these 
countries allow to be sold in this manner. 

[67] Information obtained in the course of this study identified only 
Ukraine as having import requirements banning fresh or frozen poultry 
products that were treated with antibiotics for growth promotion. 
However, Ukraine is not a significant market for U.S. poultry.

[68] Antibiotic residues in meat may occur when antibiotics are 
improperly used. Traces of the antibiotic can remain in the meat 
tissue, which may affect human health when the meat is consumed.

[69] U.S. Department of Agriculture, Economic Research Service, 
International Trade and Food Safety: Economic Theory and Case Studies 
(Washington, D.C.: 2003).

[70] Report of the Advisory Committee on Animal Uses of Antimicrobials 
and Impact on Resistance and Human Health. Uses of Antimicrobials in 
Food Animals in Canada: Impact on Resistance and Human Health. A 
special report prepared at the request of the Veterinary Drugs 
Directorate, Health Canada. June 2002.

[71] Food and Agriculture Organization of the United Nations, Office 
International des Epizooties, and World Health Organization. Joint FAO/
OIE/WHO Expert Workshop on Non-Human Antimicrobial Usage and 
Antimicrobial Resistance: Scientific Assessment. December 2003.

[72] To the extent information was available, we obtained information 
on policies to regulate antibiotic use, quantities of antibiotics sold, 
and systems to monitor antibiotic use in animals and antibiotic 
resistance associated with this use.

[73] Although Denmark is an EU member, we included it in addition to 
the EU because it is a major U.S. competitor in pork exports.

[74] To identify these countries, we used USDA's Foreign Agricultural 
Service data on (1) countries' trade of beef, pork, and poultry with 
the United States and (2) countries' worldwide exports of these 
products. We selected those countries whose share of imports or exports 
of a product was at least 10 percent. In addition, we included China 
because it is a major importer of poultry although it does not trade 
extensively with the United States.

[75] 21 C.F.R. parts 520, 522, and 558 (2003).

[76] H.D. Chapman, Z.B. Johnson, "Use of Antibiotics and Roxarsone in 
Broiler Chickens in the USA: Analysis for the Years 1995 to 2000," 
Poultry Science, 81: 356-364, (2002).

[77] M. Mellon, C. Benbrook, and K.L. Benbrook, "Hogging It! Estimates 
of Antimicrobial Abuse in Livestock," Union of Concerned Scientists, 
January 2001.

[78] The WHO study described in this appendix also has estimated a cost 
of $1.04 per animal; however, the study was done to estimate economic 
impacts on the Danish swine market. (See World Health Organization, 
Impacts of Antimicrobial Growth Promoter Termination in Denmark, 
Department of Communicable Diseases, Prevention and Eradication and 
Collaborating Centre for Antimicrobial Resistance in Foodborne 
Pathogens, 2003.)

[79] Ramanan Laxminarayan, "Fighting Antibiotic Resistance: Can 
Economic Incentives Play a Role?" Resources, Spring 2001, Issue 143.

[80] Phelps (1989) estimated that the annual economic costs of drug 
resistance range from a best-case scenario of $100 million to a worst-
case scenario of $30 billion, with the wide range of estimates 
accounted for by different assumptions about the economic value of a 
human life. Also, a study done by the Office of Technology Assessment 
in 1995 estimated that the cost of antibiotic resistance for six 
different strains of antibiotic bacteria reached about $1.3 billion in 
1992 dollars. 

[81] E.H. Elbasha, "Deadweight Loss of Bacterial Resistance Due to 
Overtreatment," Health Economics, 2003, 12(2): 125-138.

[82] World Health Organization, Impacts of Antimicrobial Growth 
Promoter Termination in Denmark, Department of Communicable Diseases, 
Prevention and Eradication and Collaborating Centre for Antimicrobial 
Resistance in Foodborne Pathogens, 2003.

[83] L.B. Jacobsen and H.G. Jensen, "Sector and Economy Wide Effects of 
Terminating the Use of Antimicrobial Growth Promoters in Denmark," In: 
International Invitational Symposium; Beyond Antimicrobial Growth 
Promoters in Food Animal Production, November 6-7, 2002 (subsequently 
revised, 2003), Foulum, Denmark. 

[84] Dermot J. Hayes and Helen H. Jensen, "Lessons from the Danish Ban 
on Feed-Grade Antibiotics," Briefing Paper 03-BP 41, Center for 
Agricultural and Rural Development, Iowa State University, Ames, Iowa, 
June 2003. 

[85] While the United States and Denmark are both leading pork 
exporters, their market structures are different. In Denmark, unlike in 
the United States, farmer cooperatives dominate production, processing, 
and distribution systems.

[86] Sort-loss costs represent discounts or penalties for increased 
weight variability for marketing swine that are either too light or too 
heavy. The Swedish experience indicated that removal of antibiotics in 
feed increased this variability at marketing. However, because they 
were able to influence the packers to accept more light weight pigs, 
Swedish producers actually did not have a problem with sort loss. 

[87] Gay Y. Miller, Kenneth A. Algozin, Paul E. McNamara, and Eric J. 
Bush, "Productivity and Economic Effects of Antibiotics Used for Growth 
Promotion in U.S. Pork Production," Journal of Agricultural and Applied 
Economics, 35,3(December 2003): 469-482. 

[88] The National Animal Health Monitoring System (NAHMS) is a program 
operated by veterinary and animal science professionals at USDA's 
Center for Animal Health Monitoring. A primary function of this branch 
of USDA is to make periodic surveys and assessments of animal health 
management practices on commercial livestock farms across the United 
States.

[89] Gay Y. Miller, Xuanli Liu, Paul E. McNamara, and Eric J. Bush, 
"Producer Incentives for Antibiotic Use in U.S. Pork Production," paper 
prepared for presentation at the American Agricultural Economics 
Association Annual Meeting, Montreal, Canada, July 2003.

[90] Each scenario in the model estimates profit for a 1,020-head barn 
of swine. A swine producer, however, could have many such barns in his/
her operation.

[91] B. Wade Brorsen, Terry Lehenbauer, Dasheng Ji, and Joe Conner, 
"Economic Impacts of Banning Subtherapeutic Use of Antibiotics in Swine 
Production," Journal of Agricultural and Applied Economics, 34,3 
(December 2002): 489-500; and M.K. Wohlgenant "Distribution of Gains 
from Research and Promotion in Multi-Stage Production Systems: The Case 
of the U.S. Beef and Pork Industries," American Journal of Agricultural 
Economics 75 (1993): 642-651.

[92] Kenneth H. Mathews, Jr., "Economic Effects of a Ban Against 
Antimicrobial Drugs Used in U.S. Beef Production," Journal of 
Agricultural and Applied Economics, 34, 3 (December 2002): 513-530. 

[93] All estimates for this study are in 1984 dollars.

[94] Dermot J. Hayes, Helen H. Jensen, Lennart Backstrom, and Jay 
Fabiosa, "Economic Impact of a Ban on the Use of Over-the-Counter 
Antibiotics, " Staff Report 99-SR 90, Center for Agricultural and Rural 
Development, Iowa State University, Ames, Iowa, December 1999.

[95] National Research Council, "Costs of Eliminating Subtherapeutic 
Use of Antibiotics," Chapter 7, in The Use of Drugs in Food Animals: 
Benefits and Risk, National Academy Press, Washington, D.C., 1999, 179-
187. Although the precise definition is the subject of some debate, 
subtherapeutic use refers to antibiotic use in animal production to 
improve animal performance, such as enhanced growth rates or improved 
feed efficiency, whereas therapeutic use refers to antibiotics used to 
treat specific health problems.

[96] The NRC cites Colemon Natural Beef of Colorado, a company that 
raises its beef without antibiotic treatments or exogenous growth 
promoters, as an example of such a company. 

[97] Cross-resistance refers to the transmission of antibiotic-
resistant determinants between bacterial species or genera and does not 
refer to transmission of antibiotic-resistant organisms between animals 
and humans.

[98] In January 2001, the task force issued A Public Health Action Plan 
to Combat Antimicrobial Resistance (Part I Domestic Issues).

[99] In September 1999, the committee released The use of antibiotics 
in food-producing animals: antibiotic-resistant bacteria in animals and 
humans.

[100] The EU will still allow the use of coccidiostat and histomonostat 
drugs as feed additives for growth promotion. These drugs control 
parasites and many coccidiostat and histomonostat drugs are not used in 
humans.

[101] In July 1999, the expert panel released Antibiotic Resistance and 
In-Feed Use of Antibiotics in New Zealand.

[102] NAHMS did not specify the purpose of this use, but included the 
possible purposes of disease treatment, disease prevention, and growth 
promotion.

[103] H.D. Chapman and Z.B. Johnson, "Use of Antibiotics and Roxarsone 
in Broiler Chickens in the USA: Analysis for the Years 1995-2000." 
Poultry Science, vol. 81 (2002).

[104] A production unit in most cases represents a broiler complex 
comprising a group of farms, in a common geographical area, that is 
served by a single feed mill. 

GAO's Mission: 

The General Accounting Office, the investigative arm of Congress, 
exists to support Congress in meeting its constitutional 
responsibilities and to help improve the performance and accountability 
of the federal government for the American people. GAO examines the use 
of public funds; evaluates federal programs and policies; and provides 
analyses, recommendations, and other assistance to help Congress make 
informed oversight, policy, and funding decisions. GAO's commitment to 
good government is reflected in its core values of accountability, 
integrity, and reliability.

Obtaining Copies of GAO Reports and Testimony: 

The fastest and easiest way to obtain copies of GAO documents at no 
cost is through the Internet. GAO's Web site ( www.gao.gov ) contains 
abstracts and full-text files of current reports and testimony and an 
expanding archive of older products. The Web site features a search 
engine to help you locate documents using key words and phrases. You 
can print these documents in their entirety, including charts and other 
graphics.

Each day, GAO issues a list of newly released reports, testimony, and 
correspondence. GAO posts this list, known as "Today's Reports," on its 
Web site daily. The list contains links to the full-text document 
files. To have GAO e-mail this list to you every afternoon, go to 
www.gao.gov and select "Subscribe to e-mail alerts" under the "Order 
GAO Products" heading.

Order by Mail or Phone: 

The first copy of each printed report is free. Additional copies are $2 
each. A check or money order should be made out to the Superintendent 
of Documents. GAO also accepts VISA and Mastercard. Orders for 100 or 
more copies mailed to a single address are discounted 25 percent. 
Orders should be sent to: 

U.S. General Accounting Office

441 G Street NW,

Room LM Washington,

D.C. 20548: 

To order by Phone: 

Voice: (202) 512-6000: 

TDD: (202) 512-2537: 

Fax: (202) 512-6061: 

To Report Fraud, Waste, and Abuse in Federal Programs: 

Contact: 

Web site: www.gao.gov/fraudnet/fraudnet.htm E-mail: fraudnet@gao.gov

Automated answering system: (800) 424-5454 or (202) 512-7470: 

Public Affairs: 

Jeff Nelligan, managing director, NelliganJ@gao.gov (202) 512-4800 U.S.

General Accounting Office, 441 G Street NW, Room 7149 Washington, D.C.

20548: