Background

Antibiotics are substances that destroy microorganisms or inhibit their  growth; they have been used for 70 years to treat people who have  bacterial infections. In this report, the term antibiotic is used to refer to  any substance used to kill or inhibit microorganisms, also sometimes  referred to as an antimicrobial. Resistance to penicillin, 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 is becoming an increasingly serious public health problem  worldwide.

		Antibiotic-Resistant Bacteria Can Spread through a Number of Pathways

Bacteria acquire antibiotic resistance through mutation of their genetic  material or by acquiring genetic material that confers antibiotic resistance  from other bacteria. In addition, some bacteria developed resistance to  antibiotics naturally, long before the development of commercial  antibiotics. Once bacteria in an animal or human host develop resistance,  the resistant strain can spread from person to person, animal to animal,  or from animals to humans.
Antibiotic-resistant bacteria can spread from animals and cause disease  in humans through a number of pathways (see fig. 1). For example,  unsanitary conditions at slaughter plants and unsafe food handling  practices could allow these bacteria to survive on meat products and  reach a consumer. Resistant bacteria may also spread to fruits,  vegetables, and fish products through soil, well water, and water runoff  contaminated by fecal matter from animals harboring these bacteria. If the  bacteria are disease-causing, the consumer may develop an infection that  is resistant to antibiotics. However, not all bacteria cause illness in  humans. For example, there are hundreds of unique strains of  Escherichia coli (E. coli), the majority of which are not dangerous. Indeed,  while some strains of E. coli are dangerous to humans, many E. coli  bacteria strains are a normal component of human and animal digestive  systems.
The use of antibiotics in animals poses a potential human health risk, but  it is also an integral part of intensive animal production in which large  numbers of poultry, swine, and cattle are raised in confinement facilities.  Over time, food animal production has become more specialized and  shifted to larger, denser operations, known as concentrated animal  feeding operations. According to a 2009 USDA study, The Transformation  of U.S. Livestock Agriculture: Scale, Efficiency, and Risks, this shift has  led to greater efficiencies in agricultural productivity—meaning more meat  and dairy production for a given commitment of land, labor, and capital  resources—and lower wholesale and retail prices for meat and dairy  products. However, the study notes larger farms with higher  concentrations of animals may be more vulnerable to the rapid spread of  animal diseases, which producers may combat by using antibiotics. Some  producers elect to raise food animals without using antibiotics, in what are  known as alternative modes of production (see app. II for more  information about alternative modes of production).
Modern dairy production is diverse, ranging  from cows housed indoors year-round to  cows maintained on pasture nearly  year-round. In the United States, milk comes  primarily from black and white Holstein cows  genetically selected for milk production. Over  the years, the concentration of more cows on  fewer farms has been accompanied by  dramatic increases in production per cow,  arising from improved genetic selection,  feeds, health care, and management  techniques. Expansion to larger herd sizes  has also allowed producers to increase the  efficiency of production and capitalize on  economies of scale. When a cow is no longer  able to breed and produce milk, it is usually  sold to the market as beef. According to the  National Milk Producers’ Federation, dairy  producers use antibiotics to treat mastitis, an  inflammation of the udder, and other  diseases. Any milk produced during antibiotic  treatment, and for a specific withdrawal period  after treatment has ceased, must be  discarded in order to prevent antibiotic  residues in milk. This discarded milk imposes  an economic cost to dairy producers, so  producers generally avoid treating dairy cows  with antibiotics when possible. According to  the National Milk Producers’ Federation, dairy  producers do not use antibiotics for growth  promotion that are medically important in  human medicine.   Disease treatment: administered only to animals exhibiting clinical  signs of disease.   Disease control: administered to a group of animals when a proportion  of the animals in the group exhibit clinical signs of disease.   Disease prevention: administered to a group of animals, none of  which are exhibiting clinical signs of disease, in a situation where  disease is likely to occur if the drug is not administered.   Growth promotion: sometimes referred to as feed efficiency,  administered to growing, healthy animals to promote increased weight  gain. Such uses are typically administered continuously through the  feed or water on a herd- or flock-wide basis. Although such use is not  directed at any specifically identified disease, many animal producers  believe the use of antibiotics for growth promotion has the additional  benefit of preventing disease, and vice versa.
In recent years, both FDA and WHO have sought to identify antibiotics  that are used in both animals and people and that are important to treat  human infections, also known as medically important antibiotics.  Specifically, according to FDA, a medically important antibiotic is given  the highest ranking—critically important—if it is used to treat foodborne  illness and if it is one of only a few alternatives for treating serious human  disease. For example, the fluoroquinolone class of antibiotics is critically  important to human medicine because it is used to treat foodborne  illnesses caused by the bacteria Campylobacter (one of the most  common causes of diarrheal illness in the United States), and it is also  one of only a few alternatives for treating serious multidrug resistant  infections in humans. Some fluoroquinolones are also approved to treat  respiratory infections in cattle.

		Several Federal Agencies Have Responsibilities and Authorities Related to Animal Antibiotic Use

Two federal departments are primarily responsible for ensuring the safety  of the U.S. food supply, including the safe use of antibiotics in food  animals—HHS and USDA. Each department contains multiple agencies  that contribute to the national effort to assess, measure, and track  antibiotic use and resistance (see table 1). Both HHS and USDA officials  have stated that it is likely that the use of antibiotics in animal agriculture  leads to some cases of antibiotic resistance among humans and that  medically important antibiotics should be used judiciously in animals.
As mentioned, HHS and USDA agencies participate in the Interagency  Task Force on Antimicrobial Resistance, which developed a plan in 2001  to help federal agencies coordinate efforts related to antibiotic resistance.  The 2001 interagency plan contains 84 action items organized in four  focus areas: surveillance, prevention and control, research, and product  development. According to the 2001 interagency plan, public health  surveillance, which includes monitoring for antibiotic resistance, is the  ongoing and systematic collection, analysis, and interpretation of data for  use in the planning, implementation, and evaluation of public health  practice. Many of the plan’s action items focus on antibiotic use and  resistance in humans, and some action items address the use of  antibiotics in agriculture, including food animal production, and are  directly relevant to this report. For example, one action item in the  surveillance focus area states the agencies’ intentions to develop and  implement procedures for monitoring antibiotic use in agriculture, as well  as in human medicine. Another states that agencies will expand  surveillance for antibiotic-resistant bacteria in sick and healthy food  animals on farms and at slaughter plants, as well as in retail meat, such  as chicken, beef, and pork. The action plan also contains action items  related to research on alternatives to antibiotics and providing education  to producers and veterinarians about appropriate antibiotic use.
Since 2001, HHS and USDA have used the interagency task force to  coordinate their activities on antibiotic resistance. For example, each year  the task force produces an annual report listing activities completed in  that year related to the 2001 interagency plan. The task force recently  released a 2010 version of the interagency plan, which is still in draft form  but is expected to be finalized this year. The draft 2010 interagency plan  contains some new initiatives and also reformulates many of the action  items listed in the 2001 plan to be more action-oriented.

	Agency Data Are Limited and Restrict Efforts to Understand Antibiotic Resistance

The 2001 interagency plan discusses two types of data needed to  understand antibiotic resistance—data on the amount of antibiotics used  in food animals (“use data”) and data on the level of antibiotic resistance  in bacteria found in food animals and retail meat (“resistance data”).  Agencies have collected some data to track antibiotic use in animals, but  these data lack crucial details identified by the 2001 interagency plan as  essential for agencies to examine trends and understand the relationship  between use and resistance. To collect data on antibiotic resistance,  agencies have leveraged existing programs, but because these programs  were designed for other purposes, their sampling methods do not yield  data that are representative of antibiotic resistance in food animals and  retail meat across the United States. USDA also collected data on both  use and resistance in a pilot program that was discontinued.

		Agencies Collect Data on Use That Lack Crucial Details

The 2001 interagency plan set a “top priority” action item of monitoring  antibiotic use in veterinary medicine, including monitoring data regarding  species and purpose of use. The plan stated this information is essential  for interpreting trends and variations in rates of resistance, improving the  understanding of the relationship between antibiotic use and resistance,  and identifying interventions to prevent and control resistance. The task  force’s draft 2010 interagency plan reiterates the importance of  monitoring antibiotic use and sets a goal to better define, characterize,  and measure the impact of antibiotic use in animals.
Three federal efforts collect data about antibiotic use in food animals (see  table 2). One of these efforts, run by FDA, was created by Congress as a  reporting requirement for pharmaceutical companies to provide sales  data. The other two efforts are run by USDA agencies and collect on-farm  data on antibiotic use by incorporating questions into existing surveys of  food animal producers.
Since our 2004 report, FDA has begun to collect and publish data from  pharmaceutical companies on antibiotics sold for use in food animals, as  required by the Animal Drug User Fee Amendments of 2008 (ADUFA).  Under ADUFA, the sponsor of an animal antibiotic—generally a  pharmaceutical company—must report annually to FDA: (1) the amount  of each antibiotic sold by container size, strength, and dosage form; (2)  quantities distributed domestically and quantities exported; and (3) a  listing of the target animals and the approved ways each antibiotic can be  used (called indications). Section 105 of ADUFA also directs FDA to  publish annual summaries of these data. To fulfill this requirement, FDA  published the first of these reports on its public Web site in December  2010. (See app. III for examples of antibiotic sales data collected by  FDA.) However, to protect confidential business information, as required  by statute, FDA’s report summarizes the sales data by antibiotic class,  such as penicillin or tetracycline, rather than by specific drug and also  aggregates sales data for antibiotic classes with fewer than three distinct  sponsors.
In submitting the original ADUFA legislation for the House of  Representatives to consider, the House Committee on Energy and  Commerce stated that it expected these data to further FDA’s analysis of,  among other things, antibiotic resistance, but the data do not include  crucial details that would be needed to do so. Specifically, ADUFA does  not require FDA to collect information on the species in which antibiotics  are used and the purpose of their use. According to representatives of all  the producer and public health organizations we spoke with, because  FDA’s sales data lack information on the species in which the antibiotic is  used, these data do not allow the federal government to achieve the  antibiotic use monitoring action item in the 2001 interagency plan,  including interpreting trends and variations in rates of resistance,  improving the understanding of the relationship between antibiotic use  and resistance, and identifying interventions to prevent and control  resistance. For example, a representative of one public health  organization stated that species-specific data is needed to link antibiotic  use in animals with resistance in animals and food. Representatives of  most of the public health organizations also stated that the government  needs to collect data on the purpose of antibiotic use—that is if the  antibiotic is being given for disease treatment, disease control, disease  prevention, or growth promotion. Furthermore, representatives of some  public health organizations indicated that data on antibiotic use should be  integrated with information on antibiotic resistance to allow analysis of  how antibiotic use affects resistance. However, a representative of an  animal pharmaceutical organization stated that FDA should not attempt to  collect national-level antibiotic use data and should instead collect local  data to facilitate study of farm management practices in order to help  farmers better use antibiotics.
According to FDA officials, sales data can provide an overall picture of the  volume of antibiotics sold for use in animals. However, FDA faces several  challenges in collecting detailed antibiotic sales data from drug sponsors.  First, if an antibiotic is approved for use in multiple species, drug  sponsors may not be able to determine how much of their product is used  in a specific species. Second, if an antibiotic is approved for multiple  purposes, drug sponsors also may not be able to determine how much is  used for each purpose. Third, antibiotics may be stored in inventory or  expire before they are used, so the quantity sold and reported to the FDA  may not equal the quantity actually used in animals. FDA officials  acknowledged the limitation of their current sales data and noted that the  agency is exploring potential approaches to gather more detailed sales  data or other information on actual antibiotic use.
The United States is the world’s largest  producer of beef. The beef industry is roughly  divided into two production sectors: cow-calf  operations and cattle feeding. Beef cattle are  born in a cow-calf operation, where both cows  and calves are fed grass in a pasture  year-round. Once weaned, most cattle are  sent to feedlots, where they are fed grain for  about 140 days. The beef industry has  become increasingly concentrated. According  to USDA, feedlots with 1,000 or more head of  cattle comprise less than 5 percent of total  feedlots in the United States, but market 80 to  90 percent of fed cattle. Weaning, shipping,  and processing put stress on cattle and  compromise their immune systems. According  to the National Cattleman’s Beef Association,  beef producers use antibiotics to treat  common illnesses, including respiratory  disease, eye infections, intestinal disease,  anaplasmosis (a red blood cell parasite), and  foot infections. Some cattle producers also  use antibiotics for growth promotion.
Two USDA agencies collect data on antibiotic use from food animal  producers by incorporating questions into existing surveys. One of these  surveys, managed by APHIS, is the National Animal Health Monitoring  System (NAHMS), a periodic, national survey of producers that focuses  on animal health and management practices. APHIS staff collect  information from producers on how antibiotics are administered (e.g., in  water, feed, or injection), what antibiotics they prefer for various ailments,  and in what situations they would use an antibiotic. To collect this  information, APHIS staff visit farms multiple times over the course of 3 to  6 months and survey producers’ practices. Previous NAHMS surveys  have examined management practices for dairy cows, swine, feedlot  cattle, cow-calf operations, small broiler chicken flocks, and egg-laying  chicken flocks, among other species. APHIS officials told us that one of  NAHMS’ strengths is its national scope and that NAHMS can be used to  examine changes in animal management practices, including antibiotic  use practices, between NAHMS surveys. However, as we reported in  2004, NAHMS produces a snapshot of antibiotic use practices in a  particular species, but the data it collects cannot be used to monitor  trends in the amount of antibiotics used over time. According to APHIS  officials, these limitations remain today. For example, these officials said  that NAHMS is limited by long lag times (approximately 6 years) between  surveys of the same species, changes in methodology and survey  populations between studies, reliance on voluntary participation by food  animal producers, and collection of qualitative, rather than quantitative  information on antibiotic use.
Since our 2004 report, USDA’s ERS has begun to collect information on  antibiotic use through the Agricultural Resource Management Survey  (ARMS)—a survey of farms conducted since 1996—though these data  have limitations similar to those of NAHMS. ERS uses ARMS data to  study how production practices, including antibiotic use, affect financial  performance and whether specific production practices can substitute for  other production practices. For example, a January 2011 ERS study  found that broiler chicken producers who forgo subtherapeutic uses of  antibiotics (i.e., use in chickens that are not ill) tend to use distinctly  different production practices, such as testing flocks and feed for   pathogens, fully cleaning chicken houses between each flock, and  feeding chickens exclusively from vegetable sources. However, like  NAHMS, ARMS cannot be used to examine trends in antibiotic use over  time because ERS does not resurvey the same farms over time or  conduct annual surveys on specific commodities.
According to officials from agencies and some organizations, it is  challenging to collect detailed data on antibiotic use in animals from  producers for a variety of reasons. First, producers may not always  maintain records on antibiotic use. Second, producers who do collect  these data may be reluctant to provide them to the federal government  voluntarily. FDA is exploring its legal options for requiring producers to  report antibiotic use data to FDA. In addition, we observed during our site  visits that the types of use data producers collected varied widely. For  example, one producer used electronic systems to track all treatments by  individual animal, whereas others maintained paper records, and one  maintained no records. Also, some food animal species, such as broiler  chickens, are generally produced by integrated companies, which own  the chickens from birth through processing and contract with a grower to  raise them. These growers often receive feed as part of a contract and  may not know whether that feed contains antibiotics. For example, one  grower we visited did not know that his animals received antibiotics for  growth promotion, though the veterinarian from his integrated company  indicated that they did. Surveys, such as NAHMS and ARMS, that rely on  producers or growers to provide antibiotic use data may be particularly  limited by this lack of available data. Moreover, collecting data on-farm  from producers is expensive for the federal agencies involved due to the  large amount of personnel and time required.
Agencies also face challenges collecting antibiotic use data from other  sources. For example, use data gathered from veterinarians may be of  limited value because, according to FDA officials, many antibiotics can be  purchased without veterinary involvement. In cases where antibiotics do  require a prescription, the usefulness of records maintained by  veterinarians may vary. For example, one veterinary clinic we visited  maintained extensive paper records dating back 2 years, but because  they were not electronic, these records would be difficult to analyze. In  addition, a veterinary organization we spoke with stated that it would be  cumbersome for veterinarians to provide this information to an agency  because there is no centralized reporting mechanism, such as an  electronic database, for them to do so. According to an official from an  organization representing the animal feed industry, feed mills also  maintain records on antibiotics mixed into animal feed, including the  amount of antibiotic used and the type of feed the antibiotic went into.  Although feed mills do not intentionally track antibiotic use by species, the  official said that collectively, this information could be used to track  antibiotic use by species. However, FDA officials told us that collecting  use data from feed mills would require the development of a new  reporting mechanism for these data.

		Agencies Are Leveraging Existing Programs to Collect Resistance Data, but These Data Are Not Representative

In 2004, we reported that the federal government collects resistance data  through the National Antimicrobial Resistance Monitoring System  (NARMS), established in 1996. NARMS is an interagency effort that  monitors antibiotic resistance in certain bacteria under three programs:  the animal component, led by ARS, samples bacteria from food animals  at slaughter plants; the retail meat component, led by FDA, samples retail  meat purchased from grocery stores; and the human component, led by  CDC, samples bacteria from humans (see table 3). FDA serves as the  funding and coordinating agency. From fiscal years 2006 through 2010,  the NARMS budget remained constant at $6.7 million, with ARS, FDA,  and CDC receiving $1.4 million, $3.5 million, and $1.8 million,  respectively. NARMS received a funding increase in fiscal year 2011, to  $7.8 million.
The 2001 interagency plan contains an action item stating agencies will  design and implement a national antibiotic resistance surveillance plan.  Among other things, the 2001 interagency plan states that agencies will  expand and enhance coordination of surveillance for drug-resistant  bacteria in sick and healthy animals on farms, food animals at slaughter  plants, and retail meat. The plan also states that collecting data on  antibiotic resistance will help agencies detect resistance trends and  improve their understanding of the relationship between use and  resistance. The draft 2010 interagency plan also reiterates the importance  of resistance surveillance and includes several action items aimed at  strengthening, expanding, and coordinating surveillance systems for  antibiotic resistance. According to WHO’s Surveillance Standards for  Antimicrobial Resistance, which provides a framework to review existing  antibiotic resistance surveillance efforts, populations sampled for  surveillance purposes should normally be representative of the total  population—in this case, food animals and retail meat in the United  States. Additionally, WHO’s surveillance standards state that it is  important to understand the relationship of the population surveyed to the  wider population, meaning that agencies should understand how food  animals and retail meat surveyed in NARMS are similar to food animals  and retail meat throughout the United States.
The food animal component of NARMS, led by ARS, gathers bacteria  from food animal carcasses at slaughter plants and tests them for  antibiotic resistance, but because of a change in sampling method has  become less representative of food animals across the United States  since we reported in 2004. ARS receives these samples from an FSIS  regulatory program called the Hazard Analysis and Critical Control Points  (HACCP) verification testing program, which is designed to, among other  things, reduce the incidence of foodborne illness. FSIS inspectors work in  slaughter plants around the country, where they collect samples from  carcasses to test for foodborne pathogens, among other duties. When we  last reported on antibiotic resistance in 2004, HACCP verification testing  included two sampling programs—a nontargeted program, in which  inspectors sampled randomly selected plants, and a targeted program, in  which slaughter plants with a higher prevalence of bacteria causing  foodborne illness were more likely to be selected for additional sampling.  In 2006, FSIS eliminated the random sampling program, which FSIS  officials told us has allowed the agency to use its resources more  effectively. FSIS now conducts only targeted sampling of food animals in  its HACCP verification testing. This nonrandom sampling method means  the NARMS data obtained through HACCP are not representative of food  animals across the country and cannot be used for trend analysis  because bacteria tested by NARMS are now collected at greater rates  from slaughter plants that are not in compliance with food safety  standards. According to FDA officials, due to this sampling method, the  resulting data are skewed for NARMS purposes.
The NARMS retail meat component, led by FDA, collects samples of  meat sold in grocery stores and tests them for antibiotic-resistant  bacteria, but these samples may not be representative of retail meat  throughout the United States. The program began in 2002 and has since  expanded to collect retail meat samples from 11 states: the 10 participant  states in CDC’s FoodNet program, which conducts surveillance for  foodborne diseases, plus Pennsylvania, which volunteered to participate  in retail meat sampling (See table 3 for the types of bacteria tested). Due  to its nonrandom selection of states, FDA cannot determine the extent to  which NARMS retail meat samples are representative of the United  States. FDA collects bacteria from those states that volunteer to  participate in the program, so some regions of the country are not  represented in the NARMS retail meat program. According to the FDA  Science Advisory Board’s 2007 review of NARMS, this lack of a national  sampling strategy limits a broader interpretation of NARMS data.  According to FDA officials, FDA has not analyzed how representative  these samples are of the national retail meat supply in the United States  but officials believe that the samples provide useful data that serves as an  indicator for monitoring US retail meat.
FDA is aware of the sampling limitations in NARMS and has articulated a  strategic goal of making NARMS sampling more representative and  applicable to trend analysis in a draft 2011-2015 NARMS Strategic Plan,  which was released for public comment in January 2011. The comment  period closed in May 2011, and FDA is currently making changes to the  plan based on the submitted comments. The plan states that NARMS will  become more representative by, among other things, modifying its animal  sampling to overcome the biases resulting from the current reliance on  HACCP verification testing and improving the geographic representation  of retail meat testing, though FDA has not yet planned specific actions to  achieve this goal.
According to FDA officials, in light of increased funding for NARMS in  2011, they are exploring ways to improve NARMS sampling to make it  more representative. FDA hosted a public meeting in July 2011 to solicit  public comment on NARMS animal and retail meat sampling  improvements. At this meeting, ARS officials discussed two new on-farm  projects—one pilot project, in collaboration with FDA, plans to collect  samples from feedlot cattle, dairy cows, and poultry with the goal of  evaluating potential sampling sites within the food animal production  chain (e.g., on farms or in holding pens at slaughter plants). The second  project is in collaboration with Ohio State University and plans to use  industry personnel to collect samples from poultry and swine producers.  Both projects will test samples for antibiotic resistance through NARMS.  Some of the additional suggestions discussed during this meeting  included changing FSIS sampling to provide more representative data to  NARMS, discontinuing slaughter plant sampling altogether in favor of an  on-farm sampling program, and increasing the number of state  participants in the retail meat sampling program.
The NARMS human component, led by CDC, collects and tests bacteria  from health departments in all 50 states and the District of Columbia. We  reviewed the issue of antibiotic resistance and antibiotic use in humans in  2011. This review examined, among other things, the human component  of NARMS and concluded that CDC’s data is nationally-representative for  four of the five bacteria included in the program.
In our interviews, representatives of producer and public health  organizations identified several challenges associated with collecting data  on antibiotic resistance. First, according to representatives from most  public health organizations, ARS, FDA, and CDC are limited by available  funding. Sampling and testing bacteria can be expensive, and agencies  have to balance competing priorities when allocating resources. For  example, in the NARMS retail meat program, FDA could choose to  expand retail meat sampling geographically by adding new states to the  program, expand the number of bacteria tested, expand the number of  samples collected, or expand the types of meat sampled. Second,  according to representatives of several producer and public health  organizations, agencies may face challenges cooperating and reaching  consensus with one another. For example, NARMS reports do not include  interpretation of resistance trends across NARMS components.  Specifically, while NARMS issues annual Executive Reports that combine  data from all three components of NARMS (available on FDA’s Web site),  these reports do not provide interpretation of NARMS data. According to  FDA officials, it is difficult to develop consensus on interpretation for these  reports because agencies differ in their interpretations and preferred  presentations of NARMS data. Third, according to the FDA Science  Advisory Board’s 2007 review of NARMS, the lag between NARMS data  collection and report issuance can sometimes be excessive. For example,  as of August 2011, the latest NARMS Executive Report covered 2008  data. According to FDA and CDC officials, the process of testing bacteria,  analyzing and compiling data, and obtaining approval from agencies is  time-consuming and increases the lag time of NARMS reports.
In our interviews, representatives of public health organizations also  suggested that federal agencies collect additional types of resistance  data. First, representatives of several organizations suggested that  agencies expand the types of bacteria tested for antibiotic resistance.  FDA is aware of this suggestion and has considered whether to add to  the types of bacteria it tests. For example, recent studies have discussed  methicillin-resistant Staphylococcus aureus (MRSA) in retail meat. MRSA  is a type of bacteria that is resistant to several antibiotics, including  penicillin, and that can cause skin infections in humans and more severe  infections in health care settings. In response, FDA is conducting a pilot  study to collect data on the prevalence of MRSA in retail meat. However,  according to FDA officials, FDA is unlikely to include MRSA in its regular  NARMS testing because general consensus in the scientific community is  that food does not transmit community-acquired MRSA infections in  humans. Second, representatives of three public health organizations  suggested that federal agencies link resistance data with data on  outbreaks of foodborne illness in humans, which representatives of one  organization stated could help scientists document the link between  animal antibiotic use and resistant outbreaks of foodborne illness.  According to representatives of this organization, NARMS’ resistance  data are not currently linked to information about foodborne disease  outbreaks. According to CDC officials, CDC tests bacteria associated with  foodborne illness outbreaks in humans for antibiotic resistance, but does  not routinely publish these data.

		USDA Discontinued a Program That Collected Data on Both Use and Resistance

When we last reported on antibiotic resistance in 2004, APHIS, ARS, and  FSIS collected on-farm use and resistance data from 40 swine producers  through the pilot Collaboration in Animal Health and Food Safety  Epidemiology (CAHFSE), but this program faced challenges in collecting  data and was discontinued in 2006 due to lack of funding. By collecting  information from the same facilities over time, agencies could use  CAHFSE data to examine the relationship between antibiotic use and  resistance. However, according to officials at APHIS and ARS, collecting  quarterly on-farm data was burdensome and generated a large number of  bacterial samples, which were costly to test and store. Although the  agencies wanted to use CAHFSE to monitor antibiotic resistance  throughout the food production system, officials from all three agencies  told us that this “farm to fork” monitoring raised logistical challenges. For  example, FSIS officials examined the feasibility of monitoring resistance  data through the slaughter plant but discovered that slaughter plants were  reluctant to participate in the program due to fear of enforcement actions  and confidentiality concerns. According to APHIS officials, CAHFSE  released quarterly and annual data summaries, but it did not issue an  overall capping report or formal evaluation of the program.
CAHFSE was discontinued, but NAHMS continues to collect three types  of bacteria (Salmonella, Campylobacter, and E. coli) from a subset of  surveyed producers and sends them to ARS for antibiotic resistance  testing. However, as discussed earlier in this report, NAHMS data provide  a snapshot of a particular species but cannot be used to monitor trends.  Additionally, as discussed earlier in this report, ARS has started two on- farm projects to collect bacteria from food animals. In one of these  projects, which collects samples from poultry and swine, ARS partners  with integrated companies to collect a variety of samples from producers.  According to an ARS official, because personnel to collect samples were  responsible for the majority of costs in the CAHFSE program, using  industry personnel rather than ARS staff to collect on-farm samples can  significantly reduce the costs of on-farm sampling.
Although data on both use and resistance can be difficult to collect, other  countries have been successful in doing so. For example, the Canadian  government’s Canadian Integrated Program on Antimicrobial Resistance  Surveillance (CIPARS), created in 2002, provides an example of on-farm  collection of antibiotic use and resistance data. In addition to gathering  resistance data similar to NARMS, CIPARS also has an on-farm  component, which collects antibiotic use information annually from about  100 swine producers and integrates it with data from resistance testing on  fecal samples from the same farms. CIPARS addresses funding  limitations by restricting on-farm surveillance to swine, sampling annually  rather than quarterly, and collecting slaughter plant samples through  industry personnel. A CIPARS official stated that the program’s on-farm  data could be used to link antibiotic use and antibiotic resistance at the  herd level and help identify interventions to prevent antibiotic resistance.  CIPARS issues annual reports, which include interpretation of the data  such as discussions of trends over time. For example, the most recent  report, from 2007, noted an increase in the percentage of bacteria  resistant to several antibiotics in samples collected from pigs at slaughter  plants from 2003 to 2007.
Denmark also has a use and resistance data collection system, called the  Danish Integrated Antimicrobial Resistance Monitoring and Research  Program (DANMAP). Data collection covers antibiotic use in food animals  and humans, as well as antibiotic resistance in food animals, meat in  slaughter plants and at retail, and in humans. The objectives of DANMAP  are to monitor antibiotic use in food animals and humans; monitor  antibiotic resistance in bacteria from food animals, food of animal origin,  and humans; study associations between antibiotic use and resistance;  and identify routes of transmission and areas for further research studies.
According to DANMAP officials, Denmark achieves these goals by  gathering data on veterinary prescriptions, since all antibiotic use in  Denmark is via prescription-only. For veterinary prescriptions, these  officials told us Denmark gathers data on the medicine being prescribed,  the intended species and age group in which the prescription will be used,  the prescribed dose of the antibiotic, the prescribing veterinarian, and the  farm on which the prescription will be used. Further, DANMAP collects  information on antibiotic resistance in food animals, from healthy animals  at slaughter plants and from diagnostic laboratory submissions from sick  animals. Denmark also gathers both domestically produced and imported  retail meat samples from throughout the country to test for antibiotic  resistance. DANMAP officials noted that, in Denmark, the industry is  responsible for collecting and submitting bacterial samples from slaughter  plants for testing, according to a voluntary agreement, and that the  industry spends additional funds to do so. DANMAP issues annual  reports, which include interpretation of data on antibiotic use in animals  and humans, as well as data on antibiotic resistance in bacteria from food  animals, retail meat, and humans. Some DANMAP reports also include  more detailed analysis of particular areas of interest. For example, the  2009 DANMAP report examined E. coli resistant to penicillins in pigs,  retail meat, and humans and found that antibiotic use in both animals and  humans contributes to the development of penicillin-resistant E. Coli. See  appendix IV for more information on DANMAP.

	FDA Implemented a Process to Mitigate Resistance Risk for Newer Antibiotics but Faces Challenges with Older Antibiotics

FDA implemented a risk assessment process for antibiotic sponsors,  generally pharmaceutical companies, to mitigate the risk of resistance in  food animals to antibiotics approved since 2003. However, the majority of  antibiotics used in food animals were approved prior to 2003, and FDA  faces significant resource challenges in assessing and mitigating the risk  of older antibiotics. Instead, FDA has proposed a voluntary strategy to  mitigate this risk but has neither developed a plan nor collected the  “purpose of use” data necessary to measure the effectiveness of its  strategy.

		FDA Implemented a Risk Assessment Process to Mitigate Resistance Risk for New Antibiotics

FDA approves for sale, and regulates the manufacture and distribution of,  drugs used in veterinary medicine, including drugs given to food animals.  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, meaning 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 when new evidence  shows that it is not safe with regard to human health under the approved  conditions of use.
In 2003, FDA issued guidance recommending that antibiotic sponsors  include a risk assessment of any new antibiotics for use in food animals.  The guidance is known as Evaluating the Safety of Antimicrobial New  Animal Drugs with Regard to Their Microbiological Effects on Bacteria of  Human Health Concern, Guidance for Industry #152. Under this  framework, an antibiotic sponsor would assess three factors: the  probability that the resistant bacteria are present in the animal as a  consequence of the antibiotic use, the probability that humans would  ingest the bacteria in question, and the probability that human exposure  to resistant bacteria would result in an adverse health consequence. As  part of the third factor, the sponsor considers the importance of the  antibiotic to treating human illness, under the assumption that the  consequences of resistance are more serious for more important  antibiotics. The guidance provides a preliminary ranking of antibiotics  considered medically important to human medicine, with the highest  ranking assigned to antibiotics deemed “critically important” if it is (1)  used to treat foodborne illness and (2) one of only a few alternatives for  treating serious human disease. An antibiotic is considered highly  important if it meets one of these two criteria. By considering all three  factors, the sponsor estimates the overall risk of the antibiotic’s use in  food animals adversely affecting human health. Though this risk  assessment process is recommended by FDA, the antibiotic sponsor is  free to prove the safety of a drug in other ways and to consult with FDA to  decide if the approach is recommended for its animal antibiotic  application. FDA officials said that, in practice, the risk of antibiotic  resistance is considered as part of any new animal antibiotic approval.
According to FDA documents, this risk assessment process has been  effective at mitigating the risk of resistance posed by new antibiotics  because antibiotic sponsors usually consider the risk assessment process  in their product development, so the products ultimately submitted for  approval are intended to minimize resistance development.  Representatives of some producer, public health, and veterinary  organizations, as well as an animal pharmaceutical organization, told us  that they were generally satisfied with the risk assessment approach. For  example, a representative of an animal pharmaceutical organization  commented that the risk assessment process was helpful in that it  provided a clear road map for drug approvals. Representatives of a  veterinary organization said they were pleased that new antibiotics were  examined using a comprehensive, evidence-based approach to risk  assessment.
However, several organizations also raised concerns. For instance, a  representative of an animal pharmaceutical organization said that FDA’s  risk assessment process was an overly protective “blunt instrument,”  since FDA would likely not approve any antibiotic product designed for  use in feed to prevent or control disease in a herd or flock if the antibiotic  is critically important to human health. Representatives from this  pharmaceutical organization and a veterinary organization said that  FDA’s guidance makes it very difficult for antibiotic sponsors to gain  approval for new antibiotics for use in feed or water.
In addition, representatives of several public health organizations said  that flaws in the criteria FDA used to rank medically important antibiotics  may lead the agency to the inappropriate approval of animal antibiotics.  For example, they identified a class of antibiotics known as fourth- generation cephalosporins, which are an important treatment for  pneumonia in humans and one of the sole therapies for cancer patients  with certain complications from chemotherapy. However, since neither of  these are also foodborne diseases, under FDA criteria this antibiotic is not  ranked as critically important in treating human illness, which these  organizations said could lead to the approval of fourth-generation  cephalosporins for use in food animals and, eventually, increased  antibiotic resistance. FDA officials recently said they intend to revisit the  antibiotic rankings to reflect current information. However, FDA officials  noted that they believed the current ranking appropriately focused on  antibiotics used to treat foodborne illnesses in humans given that the  objective of the guidance was to examine the risk of antibiotic use in food  animals.

		FDA Faces Resource Challenges in Assessing the Risk of Older Antibiotics

According to FDA officials, the majority of antibiotics used in food animals  were approved prior to 2003. FDA faces significant challenges to  withdraw agency approval, either in whole or in part, of these antibiotics if  concerns arise about the safety of an antibiotic. If FDA initiates a  withdrawal action because of safety questions that have arisen after an  antibiotic’s approval, the agency has the initial burden of producing  evidence sufficient to raise serious questions about the safety of the drug.  Once FDA meets this initial burden of proof, the legal burden then shifts  to the antibiotic sponsor to demonstrate the safety of the drug. If, after a  hearing, the FDA Commissioner finds, based on the evidence produced,  that the antibiotic has not been shown to be safe, then the product  approval can be withdrawn.
FDA’s 5-year effort to withdraw approval for one antibiotic for use in  poultry illustrates the resource-intensive nature of meeting the legal  burden to withdraw an approved antibiotic. It is the only example of FDA  withdrawing an antibiotic’s approval for use in food animals because of  concerns about resistance. Specifically, Enrofloxacin, approved in  October 1996, is in the critically important fluoroquinolone class of  antibiotics, used to treat foodborne illnesses caused by the bacteria  Campylobacter, and it was used in poultry flocks via the water supply to  control mortality associated with E. coli and other organisms. In October  2000, based on evidence of increased fluoroquinolone resistance in  bacteria from animals and humans, FDA initiated a proceeding to  withdraw its approval for the use of two types of fluoroquinolones in  poultry. One pharmaceutical company voluntarily discontinued  production, but the manufacturer of enrofloxacin challenged the decision.  FDA officials told us that it took significant time and resources to gather  evidence for the case, even though they had good data showing a  correlation between the drug’s approval for use in poultry and increasing  resistance rates in humans. After an administrative law judge found that  enrofloxacin was not shown to be safe for use in poultry as previously  approved, the FDA’s Commissioner issued the final order withdrawing  approval for its use effective September 2005.
FDA officials said that from this case they learned that taking a case-by- case approach to withdrawing antibiotics due to concerns over resistance  was time-consuming and challenging. In our 2004 review of federal efforts  to address antibiotic resistance risk, we reported FDA was planning to  conduct similar risk assessments of other previously approved  antibiotics. FDA officials estimated, however, that the enrofloxacin  withdrawal cost FDA approximately $3.3 million, which they said was  significant. FDA officials told us that conducting individual postapproval  risk assessments for all of the antibiotics approved prior to 2003 would be  prohibitively resource intensive, and that pursuing this approach could  further delay progress on the issue.

		FDA Proposed a Voluntary Strategy for Older Antibiotics but Has No Plan to Assess Effectiveness

Instead of conducting risk assessments for individual antibiotics approved  prior to 2003, FDA in June 2010 proposed a strategy to promote the  “judicious use” of antibiotics in food animals. FDA proposed the strategy  in draft guidance titled The Judicious Use of Medically Important  Antimicrobial Drugs in Food-Producing Animals, draft Guidance for  Industry #209. FDA describes judicious uses as those appropriate and  necessary to maintain the health of the food animal. The draft guidance  includes two principles aimed at ensuring the judicious use of medically  important antibiotics. First, that antibiotic use is limited to uses necessary  for assuring animal health—such as to prevent, control, and treat  diseases. Second, that animal antibiotic use is undertaken with increased  veterinary oversight or consultation. To implement the first principle, FDA  is working with antibiotic sponsors to voluntarily phase out growth  promotion uses of their antibiotics. FDA officials told us they have met  with four of the approximately nine major antibiotic sponsors to discuss  withdrawing growth promotion uses from their antibiotics’ labels and that  they plan to engage with generic antibiotic manufacturers in the near  future. To implement the second principle of increasing veterinarian  oversight of antibiotic use, FDA officials told us that they would like to  work with antibiotic sponsors to voluntarily change the availability of  medically important antibiotics currently approved for use in feed from  over the counter to veterinary feed directive (VFD) status. The majority of  in-feed antibiotics are currently available over the counter, but VFD status  would instead require these antibiotics to be used with the professional  supervision of a licensed veterinarian. In March 2010, FDA issued an  advance notice of proposed rulemaking announcing its intention to  identify possible changes to improve its current rule on VFDs and seeking  public comments on how to do so. FDA officials told us that they received  approximately 80 comments by the end of the comment period in August  2010 from interested parties on how to improve the VFD rule, and were  taking them into consideration as they drafted the rule, which they hope to  publish in 2011. In April 2011, the American Veterinary Medicine  Association also formed a new committee to help FDA develop practical  means to increase veterinary oversight of antibiotic use.
Representatives of several producer organizations, veterinary  organizations, and an animal pharmaceutical organization expressed  concern that FDA’s focus on ending growth promotion uses would  adversely affect animal health. In particular, these representatives said  that some animal antibiotics approved for growth promotion may also  prevent disease, though they are not currently approved for that purpose.  FDA officials said that, in cases where pharmaceutical companies can  prove such claims, FDA would be willing to approve these antibiotics for  disease prevention. FDA officials emphasized, however, that they do not  want companies to relabel existing growth promotion antibiotics with new  disease prevention claims with no substantive change in the way  antibiotics are actually used on the farm. FDA officials told us they plan to  issue additional guidance for antibiotic sponsors to outline a specific  process for making changes in product labels.
Furthermore, representatives of several producer and veterinary  organizations we spoke with expressed concerns about FDA’s efforts to  increase veterinary oversight because there is shortage of large animal  veterinarians. As we reported in February 2009, there is a growing  shortage of veterinarians nationwide, particularly of veterinarians who  care for food animals, serve in rural communities, and have training in  public health. Additionally, representatives of veterinary organizations  said that the paperwork requirements under VFDs are onerous. In  particular, this is because VFDs require the veterinarian to deliver a copy  of the VFD to the feed producer directly for each VFD, and there are not  yet many systems for electronic distribution.
In addition, representatives of several public health organizations  expressed concern that FDA’s strategy will not change how antibiotics are  used for two reasons. First, because FDA is depending on voluntary  cooperation to remove growth promotion uses from antibiotic labels, there  is no guarantee that pharmaceutical companies will voluntarily agree to  relabel their antibiotics. To underline the seriousness of their concerns, in  May 2011, several public health organizations filed a suit to force FDA to  withdraw its approval for the growth promotion uses of two antibiotic  classes (penicillins and tetracyclines). Second, representatives of some  public health organizations noted that several medically important  antibiotics (six out of eight) currently approved by FDA for growth  promotion or feed efficiency are already approved for disease prevention  uses in some species (see table 4), which could negate the impact of  FDA’s strategy. Because disease prevention dosages often overlap with  growth promotion dosages, representatives of one of these organizations  said that food animal producers might simply alter the purpose for which  the antibiotics are used without altering their behavior on the farm. One  veterinarian told us that if FDA withdrew an antibiotic’s approval for  growth promotion, he could continue to give the antibiotic to the animals  under his care at higher doses for prevention of a disease commonly  found in this species. The veterinarian stated that there is an incentive to  do so because using an animal antibiotic can help the producers he  serves use less feed, resulting in cost savings. For example, the in-feed  antibiotic may cost approximately $1 per ton of feed, but it can save $2 to  $3 per ton of feed, making it an effective choice for the producer.
Although representatives of some producer and public health  organizations have raised doubts about the effectiveness of FDA’s  strategy, FDA does not have a plan to collect the data necessary to  understand the purpose for which antibiotics are being used or have a  plan to measure the effectiveness of its strategy to encourage more  judicious use of antibiotics in animals. FDA officials told us the agency will  consider this strategy to be successful when all the growth promotion  uses of medically important antibiotics are phased out. FDA officials were  unable to provide a timeline for phasing out growth promotion uses,  though they identified several next steps FDA intends to take, such as  finalizing the guidance document describing their voluntary strategy and  issuing additional guidance on its implementation, as well as proceeding  forward with the VFD rulemaking process. However, FDA officials stated  that the agency had no further plans to measure its progress. In addition,  FDA will still allow medically important antibiotics to be used for disease  prevention. However, because agency data on sales of antibiotics used in  food animals do not include the purpose for which the antibiotics are  used, it will be difficult for FDA to evaluate whether its strategy has  increased the judicious use of antibiotics or simply encouraged a shift in  the purpose of use—for instance, from growth promotion to disease  prevention—without lessening use. FDA officials told us the agency is  exploring approaches for obtaining additional information related to  antimicrobial drug use to enhance the antibiotic sales data that is  currently reported to FDA as required by ADUFA, but did not provide a  timeline for these efforts.

	Agencies Took Steps to Research Alternatives and Educate Users, but Progress Is Unclear

USDA and HHS agencies have taken some steps to research alternatives  to current antibiotic use practices and educate producers and  veterinarians on appropriate use of antibiotics but the extent of these  steps is unclear because neither USDA nor HHS has assessed the  progress toward fulfilling the related action items in the 2001 interagency  plan.

		USDA and HHS Have Conducted Research on Alternatives but Have Not Assessed Progress

An action item in the 2001 interagency plan states that federal agencies  will promote the development of alternatives to current antibiotic use,  including through research. According to the 2001 interagency plan, such  alternatives could include researching vaccines and management  practices that prevent illnesses or reduce the need for antibiotic use.  However, USDA has not tracked its activities in this area, and neither  USDA nor HHS has determined progress made toward this action item.
Since 2001, USDA agencies have undertaken some research related to  developing alternatives. However, according to agency officials they are  unable to provide a complete list of these activities because USDA’s  research database is not set up to track research at this level of detail.  Instead, research is categorized within the larger food safety research  portfolio. In addition, the agencies did not report any activities under this  action item in the annual reports published by the interagency task force.
Based on documents provided by USDA and research activities that  USDA reported to the interagency task force under other research action  items, we identified 22 projects the department funded since 2001 related  to alternatives to current antibiotic use practices, with total funding of at  least $10 million (see app. V). In addition, ARS officials emphasized that  the majority of research performed at ARS related to improving  agricultural practices can result in reduced antibiotic needs by producers.  Officials from both NIFA and ARS said that they had not assessed the  extent to which the research conducted helped achieve the action item in  the 2001 interagency plan. Indeed, conducting such an assessment  would be difficult without a complete list of relevant research activities.  NIFA officials told us that additional funding and resources would be  needed to conduct such an assessment, but they did not provide more  specific details on how many additional resources would be needed to do  so. Although an assessment of research activities on alternatives has not  been conducted, ARS officials nevertheless said the agency plans to  conduct more research on alternatives to antibiotics in the next 5 years.
Similar to USDA agencies, HHS agencies have conducted some research  on alternatives. Specifically, from 2001 through 2005, CDC and FDA  sponsored at least five research grants that included funding to research  alternatives and reduce resistant bacteria in food animals (see app. VI).  NIH has conducted research related to antibiotic resistance that may  have applications in both humans and in animals, but agency officials told  us that NIH considers human health issues its research priority. Like  USDA agencies, HHS agencies did not report any research activities  under the action item related to antibiotic alternatives to the interagency  task force. No HHS agency has sponsored any such research activities  since 2005. HHS officials told us this is because USDA may be the most  appropriate lead agency for undertaking alternatives research related to  food animals. USDA officials acknowledged that they have a role in  researching alternatives to antibiotics, although they said that it is also  important for HHS to be involved since FDA would likely be the regulatory  agency to approve any products resulting from such research. CDC and  FDA officials told us that their agencies have not performed any  assessments to determine whether their research activities have helped  the agency to fulfill this action item in the 2001 interagency plan.
Representatives of the national veterinary, producer, public health, and  animal pharmaceutical organizations that we spoke with told us that  greater federal efforts are needed to research alternatives to current  antibiotic use in animals. In addition, representatives from most of the  veterinary and several public health organizations we spoke with said that  the federal government should make greater efforts to coordinate with the  food animal industry about researching alternatives to current antibiotic  use. Specifically, most representatives from the producer and veterinary  organizations emphasized a need for the federal government to provide  funding and other resources to the food animal industry for research  projects looking at alternatives. For example, representatives from one  veterinary organization told us that several national producer and  veterinary organizations have goals of utilizing prevention as an  alternative to antibiotic use and said that the federal government could  help by conducting research on preventive measures such as vaccine  development.
The draft 2010 interagency plan includes an action item reiterating that  agencies will conduct research on alternatives to current antibiotic use  practices, yet USDA and HHS agencies have not evaluated their previous  research to determine the extent to which the action item in the 2001  interagency plan was achieved. Without an assessment of past research  efforts, agencies may be limited in their ability to identify gaps where  additional research is needed. In addition, the draft 2010 interagency plan  does not identify steps agencies intend to take to conduct research on  alternatives or time frames for taking these steps. In contrast, other action  items listed in the draft 2010 interagency plan under the surveillance,  prevention and control, and product development focus areas include  specific implementation steps illustrating how agencies plan to achieve  them. CDC officials told us that the interagency task force agreed not to  identify implementation steps until after the final version of the 2010  interagency plan is published, at which time the task force will publish its  plans for updating the 2010 interagency plan. In addition, ARS officials  said that the interagency task force requested agencies to identify  implementation steps that could be accomplished within the next 2 years,  and USDA was unable to determine such steps for alternatives research.  We have previously reported that evaluating performance allows  organizations to track the progress they are making toward their goals,  and it gives managers critical information on which to base decisions for  improving their programs. Tracking progress and making sound  decisions is particularly important in light of the fiscal pressures currently  facing the federal government.

		HHS and USDA Educated Users on Appropriate Use but Have Not Assessed Progress

An action item in the 2001 interagency plan states that federal agencies  will educate producers and veterinarians about appropriate antibiotic use.  Programs at both HHS and USDA have sought to educate users about  appropriate antibiotic use, but the impact of these efforts has not been  assessed. In addition, agricultural extension agents and national  associations also advise producers on appropriate antibiotic use. The  draft 2010 interagency plan no longer has an explicit action item related  to appropriate antibiotic use education. There is currently one education  activity on appropriate antibiotic use, and after the completion of this  effort, there are no plans to develop new education activities.
HHS agencies sponsored six programs to educate producers and  veterinarians about appropriate antibiotic use, the last of which ended in  2010 (see table 5). For example, from 2001 through 2010 CDC funded  “Get Smart: Know When Antibiotics Work on the Farm”—also called Get  Smart on the Farm—an outreach program that sponsored state-based  producer education activities to promote appropriate antibiotic use. CDC  officials told us that this was one of the first major education efforts to  bring together stakeholders from the public health, veterinary, and  agricultural communities to discuss the issue of appropriate antibiotic use.  Through the Get Smart on the Farm program, CDC hosted three national  animal health conferences designed to foster partnerships between these  stakeholders. These conferences included discussions of antibiotic use  and resistance in animals. Get Smart on the Farm also funded the  development of an online curriculum for veterinary students on antibiotic  resistance and appropriate use, which became available in December  2010. CDC officials told us that the agency is planning to take an advisory  rather than leadership role in future appropriate use education efforts  because they believe that FDA and USDA are the appropriate agencies  for leading such efforts. CDC reported that it spent approximately $1.7  million on Get Smart on the Farm activities from 2003 through 2010. Both  CDC and FDA officials said that the impact of their education activities  had not been assessed. HHS officials also said that they currently do not  have plans to develop new activities in the future.
USDA agencies also sponsored education programs addressing  appropriate antibiotic use in animals (see table 6). For example, from  2002 through 2005, USDA agencies worked with FDA to fund university- based programs that sought to educate producers on animal health  issues, including antibiotic resistance. From 2006 through 2010 USDA  agencies did not report any activities under this action item in the annual  reports published by the interagency task force. However, officials noted  that education on appropriate antibiotic use remains a priority and that  during these years USDA gave presentations at scientific meetings and  universities on this topic. USDA officials said the impact of these  education efforts was not assessed.
The one ongoing USDA appropriate antibiotic use education activity is an  APHIS-funded training module on antibiotic resistance currently under  development at a cost of $70,400. According to agency officials, the  module will be similar to CDC’s online curriculum for veterinary students.  It will be 1 of 19 continuing education modules for the National Veterinary  Accreditation Program, which is designed to train veterinarians to assist  the federal government with animal health and regulatory services. The  program requires participating veterinarians to periodically renew their  accreditations by completing continuing education modules online or at  conferences, and participants may elect which APHIS-approved modules  to take in order to fulfill their requirements. Since the APHIS module will  be similar to CDC’s online curriculum for veterinary students, APHIS  officials told us that they will look at CDC’s content to determine whether  or not to incorporate it into the APHIS-funded module. APHIS officials  also told us that they sought out representatives from NIFA, FDA, CDC,  the American Veterinary Medical Association, and academic institutions  to review the module’s content, and expect the training to be available for  veterinarians by June 2012. APHIS officials told us that the module on  appropriate antibiotic use is not within the National Veterinary  Accreditation Program’s traditional scope of work. More specifically,  APHIS officials are unsure how they would measure the impact of the  module because, unlike the other modules in the accreditation program, it  is not based on any APHIS regulatory information that can be tracked.  That said, officials told us providing antibiotic use education is beneficial  and will increase practitioners’ awareness in this area. After the  completion of the antibiotic use module, USDA officials said they have no  plans to develop new education activities.
Additional USDA-funded education activities on appropriate antibiotic use  may be conducted through local extension programs. Each U.S. state and  territory has a Cooperative Extension office at its land-grant university,  as well as a network of local or regional extension offices staffed by one  or more experts who provide research-based information to agricultural  producers, small business owners, youth, consumers, and others in local  communities. NIFA provides federal funding to the extension system,  though states and counties also contribute to the program. NIFA provides  program leadership and seeks to help the system identify and address  current agriculture-related issues. Two producers told us that extension  programs are a helpful source of information about animal health issues.  For example, they said that extension agents are very helpful in  disseminating information, though their impact may be difficult to  measure. In addition, they told us that when producers are successful  with a preventative practice suggested by an extension agent,  neighboring producers may notice and also make similar modifications,  creating a multiplier effect. Two current extension agents also told us they  have received inquiries from producers about antibiotic use, although  these questions are not necessarily framed as appropriate use. NIFA  officials told us that federally funded extension institutions submit an  annual plan of work and an annual accomplishment report that provides a  general overview of their yearly planned projects based on USDA  priorities, but these plans are broad in nature and often do not provide  details that allow NIFA to track efforts related to antibiotic use.
Representatives from most of the producer and veterinary organizations  that we spoke with said that industry-led efforts are responsible for most  of the progress made in educating producers and veterinarians in the last  10 years. For example, the National Cattlemen’s Beef Association,  National Milk Producers’ Federation, and National Pork Board have each  developed Quality Assurance programs that advise producers on their  views of proper antibiotic use during production. Representatives from  most of the organizations we spoke with said that the federal government  should have some type of role in educating producers and veterinarians  on appropriate antibiotic use, but many—including representatives from  all of the producer organizations—said that they believe that these  activities should be done in collaboration with industry. Representatives  from most of the veterinary and producer organizations also said the  federal government could improve collaboration with industry members  and groups, and representatives from one veterinary organization pointed  to previous federal education efforts to collect and disseminate  information about avian influenza as collaborative education efforts  federal agencies could model for appropriate use messages.  Representatives from this organization noted that such efforts included  the federal government and other industry stakeholders working together  and disseminating education messages to the public. They also  suggested that similar efforts between the federal government, producers,  and researchers could be used to educate the industry about appropriate  use of antibiotics in food animals.

	Regulation of Antibiotics in the EU and Denmark May Offer Lessons for the United States

Since 1995, the EU and Denmark have taken a variety of actions to  regulate antibiotic use in food animals and mitigate the risk such use may  pose to humans. Denmark is part of the EU and complies with EU policies  but has also taken some additional actions independently. Some of the  experiences in the EU and Denmark may be useful for U.S. government  officials and producers, though U.S. producers face different animal  health challenges and regulatory requirements than European producers.

		EU and Denmark Have Taken Action to Regulate Antibiotic Use in Food Animals

From 1995 to 2006, both the EU and Danish governments took a variety  of actions to regulate antibiotic use in food animals (see fig. 2). In 1995,  Denmark banned the use of avoparcin for growth promotion in food  animals, and an EU-wide ban followed in 1997. Avoparcin is similar to the  human medicine vancomycin, and some studies suggested that  avoparcin use in food animals could be contributing to vancomycin- resistant bacteria in humans. Both Denmark and the EU followed up  with bans on several additional growth promotion antibiotics, culminating  in a total ban on growth promotion antibiotics in 2000 and 2006,  respectively. Government and industry officials we spoke with in Denmark  emphasized that their bans on growth promotion antibiotics began as  voluntary industry efforts that were later implemented as regulations by  the government.
EU officials and both industry and government officials from Denmark  said the most important factor in the development of their policies was  sustained consumer interest in the issue of antibiotic use in food animals  and concerns that such use could cause resistance affecting humans. In  the face of these concerns, officials explained that EU policies were  developed based in part on the precautionary principle, which states that  where there are threats of serious or irreversible damage, lack of  scientific certainty should not postpone cost-effective measures to reduce  risks to humans. Danish industry officials added that, as new data and  knowledge arise, it is appropriate to reevaluate the measures taken to  reduce risks. We have previously reported that the EU made other food  safety decisions based on the precautionary principle, including decisions  about inspecting imports of live animal and animal products, such as  meat, milk, and fish.
According to Danish government officials, Denmark has implemented two  additional types of regulations regarding antibiotic use in food animals.  First, Denmark has increased government oversight of veterinarians and  producers. For example, in 1995, Denmark limited the amount that  veterinarians could profit on sales of antibiotics. Then, in 2005, Denmark  implemented policies requiring biannual audits of veterinarians who serve  the swine industry, which Danish government officials said uses about 80  percent of all food animal antibiotics in Denmark. Government officials  said these audits increase veterinarians’ awareness of their antibiotic  prescription patterns. In 2007 the audits were expanded to cover all food  animal veterinarians. Most recently, in 2010, Denmark developed a new  system—called the yellow card initiative—which sets regulatory limits on  antibiotic use based on the size of swine farms. Swine farms exceeding  their regulatory limit are subject to increased monitoring by government  officials, which they must pay for. Danish government officials explained  that the yellow card initiative is different from their past oversight efforts in  that it targets producers rather than veterinarians. Second, according to  Danish government officials, Denmark developed a policy to reduce  veterinary use of antibiotics classified as critically important to human  medicine by WHO, which like FDA, has a ranking of such antibiotics. For  example, in 2002 Denmark limited veterinary prescriptions of  fluoroquinolones to cases in which testing showed that no other antibiotic  would be effective at treating the disease. In addition, veterinarians  prescribing fluoroquinolones to food animals would need to notify  government regulatory officials.

		EU and Denmark Experiences Suggest Possible Lessons for the United States

U.S. producers face different animal health challenges and regulatory  requirements than producers in the EU and Denmark, making it difficult to  determine how effectively similar policies could be implemented in the  United States. Specifically, industry officials in Denmark explained that  several diseases that affect producers in the United States are no longer  active in Denmark. For example, broiler chicken producers in Denmark  spent many years improving their biosecurity and successfully eradicated  Salmonella, which can cause disease both in broiler chickens and in  humans, and Danish cattle producers do not have to worry about  brucellosis, which has not been seen in Denmark in decades. Similarly,  the regulatory environment in the EU differs from that in the United  States. For example, EU countries develop and implement policies using  the precautionary principle. In addition, the EU and Denmark both require  prescriptions for the use of most antibiotics in animals, but the United  States requires them in certain limited circumstances. Officials from HHS  and USDA said they are aware of other countries’ efforts to regulate  antibiotic use in food animals and participate in international conferences  and meetings addressing these issues. Based on the experiences in the  EU and Denmark, there are several lessons that may be useful for U.S.  government officials and producers.
According to Danish government officials, Denmark’s antibiotic use data  are detailed enough to allow the country to track trends in use and  monitor the effects of their policies. Specifically, data show that antibiotic  use in food animals declined from 1994 to 1999, but then it increased  modestly from 1999 to 2009, while remaining below 1994 levels (see   fig. 3). The decline coincides with the start of the changes to government  policies on growth promotion and veterinarian sales profits. Danish  industry and government officials noted some of the increase in antibiotic  use over the last decade may be in response to disease outbreaks on  swine farms. Danish government officials also mentioned, however, that  the government instituted the 2010 yellow card initiative to reverse the  recent increase in antibiotic use. According to these officials, antibiotic  use in pig production fell 25 percent from June 2010 to June 2011 in  response to the implementation of the yellow card initiative.
According to Danish officials, Danish data on antibiotic resistance in food  animals and retail meat show reductions in resistance after policy  changes in most instances. Specifically, Danish government officials have  tracked resistance to antibiotics banned for growth promotion among  Enterococcus bacteria since the mid-1990s. Enterococcus are commonly  found in the intestinal tract of humans and food animals, making them  relatively easy to track over time, though they rarely cause disease.  Officials said that the percentage of Enterococcus from food animals that  are resistant to antibiotics banned for growth promotion has decreased  since the bans were implemented. Officials also mentioned declines in  resistance among Campylobacter bacteria (which can cause foodborne  illness in humans) from food animals and retail meat. For example,  officials said that resistance to the critically important class of drugs called  macrolides has decreased in Campylobacter bacteria from swine.  However, Danish industry and government officials cautioned that the  association between antibiotic use and resistance is not straightforward.  For example, despite restrictions on veterinary use of the critically  important fluoroquinolone antibiotics since 2002, Danish resistance data  have not shown a decrease in fluoroquinolone-resistant bacteria from  food animals. Danish industry officials explained that restrictions on  fluoroquinolone use in swine were implemented before fluoroquinolone  resistance became pronounced in Denmark and that current rates of  fluoroquinolone-resistant Salmonella in Danish pork are lower than for  pork imported into Denmark.
Danish officials told us that Denmark’s resistance data have not shown a  decrease in antibiotic resistance in humans after implementation of the  various Danish policies, except for a few limited examples. Specifically,  officials said that the prevalence of vancomycin-resistant Enterococcus  faecium from humans has decreased since avoparcin was banned for use  in animals in 1995. Resistance has been tracked for other types of  bacteria and antibiotics, but similar declines have not been seen. Danish  government officials explained that, in addition to antibiotic use in food  animals, there are other important contributors to antibiotic resistance in  humans, including human antibiotic use, consumption of imported meat  (which may contain more antibiotic-resistant bacteria than Danish meat),  and acquisition of resistant bacteria while traveling. Danish officials told  us their data collection systems are not designed to gather information  about whether human deaths from antibiotic resistance have fallen after  the implementation of risk management policies. Officials mentioned a  challenge to this type of data collection is that “antibiotic resistance” is not  listed on death certificates as the cause of death; generally, as in the  United States, the cause of death would be listed as multiple organ  failure, making it difficult to identify deaths caused by antibiotic-resistant  infections.
Denmark has also tracked the prevalence of bacteria that cause human  foodborne illness on retail meat products, according to Danish industry  officials. Producer organizations in the United States have expressed  concerns that reductions in antibiotic use may lead to an increase in  foodborne pathogens on meat, but industry officials in Denmark said that  their data show no increase in the rates of these bacteria on meat  products. These officials said, however, that several changes to  management practices in slaughter plants may have helped ensure rates  of foodborne pathogens on meat remained low. For example, these  officials said Danish slaughter plants now use a flash-freezing  technique—called blast chilling—that freezes the outer layer of an animal  carcass, reducing the number of bacteria on the meat and even killing  most Campylobacter.
Danish producers and veterinary officials noted that the policies were  easier for poultry producers to implement than for swine producers.  Poultry producers had made changes to their production practices  throughout the 1990s to eradicate Salmonella from their flocks, and these  practices also helped maintain flock health without routine antibiotic use.  In contrast, swine producers faced difficulties weaning piglets without  antibiotics, reporting both an increase in mortality and a reduction in daily  weight gain shortly after the ban. However, Danish industry officials  explained that swine producers implemented multiple changes to  production practices that enabled them to comply with the ban. These  production practices included improved genetic selection, later weaning,  improved diet, increased space per piglet, and improved flooring. Industry  officials explained that such changes in production practices did have real  costs to the industry. For example, weaning piglets later increases the  time between litters and reduces the overall number of piglets produced  annually. Despite these additional costs, however, Danish industry  officials expressed pride in their ability to produce high-quality meat  products while ensuring that they do not contribute unduly to the problem  of antibiotic resistance.
EU officials told us that they rely on member states to collect data on  antibiotic use. As of September 2010, 10 countries in Europe collected  data on sales of antibiotics used in food animals, and 5 of these countries  collected species-specific data. In addition, 12 other countries have  recently started or planned to begin collecting antibiotic sales data.  Among countries that currently collect use data, these data are collected  using different methods, which complicates comparing them across  countries. EU officials identified several challenges to collecting  information about antibiotic use throughout the EU. Specifically,  identifying sources of detailed information about antibiotic use is difficult  because EU countries have different distribution systems for veterinary  medicines and therefore collect this information in varying ways. For  example, in Denmark, such data are collected from veterinary  pharmacies, but not all EU countries require animal antibiotics to be  dispensed through pharmacies. In addition, EU countries vary in the  extent to which veterinary prescriptions are monitored electronically,  making it difficult to track prescriptions consistently throughout the EU.
Despite these challenges, EU officials emphasized the importance of  gathering data on antibiotic use in food animals for two reasons. First,  they noted that tracking antibiotic use data allows governments to  evaluate the effects of their risk management policies. Second, they  mentioned that data on both antibiotic use and antibiotic resistance are  needed in order to fully understand how use in animals is related to  resistance in humans. Given the importance of collecting data, the EU  has begun a pilot project to collect comparable antibiotic use data  throughout the EU. The first phase will use a standard instrument to  collect, harmonize, and analyze data on sales of veterinary antibiotics  from countries that agree to participate. EU officials said that a report on  sales of veterinary medicines, covering nine European countries, will be  available in September 2011. EU officials said that subsequent phases  will include more detailed data about species and purpose of use. They  emphasized the importance of going beyond bulk sales data, noting that it  is necessary to report antibiotic use in the context of the number of  animals being treated or the pounds of meat produced, since it can allow  for comparisons between EU countries as well as comparisons to human  antibiotic use. EU officials said that the Danish system uses this type of  data collection, and that WHO is working on developing guidance for how  to create such data collection systems.
For resistance data, EU officials told us that the EU has been collecting  information from numerous member countries and working to improve the  comparability of the data between countries. In 2006, the EU produced its  first report for data gathered in 2004, collating information from 26  individual countries. However, EU officials said that resistance data  cannot currently be compared across countries or aggregated to provide  conclusions about the entire EU, though officials are in the process of  developing a report that will provide EU-wide information. Instead,  officials pointed to trends identified in particular member countries. For  example, officials noted a decrease in resistance in Enterococcus from  broiler chickens after avoparcin was banned for growth promotion uses in  Germany, the Netherlands, and Italy. Officials also mentioned similar  declines in resistance among Enterococcus from healthy humans in  Germany and the Netherlands.
Moreover, in addition to their data collection efforts on antibiotic use in  food animals and antibiotic resistance in humans, meat, and food  animals, the EU also conducts periodic baseline surveys to determine the  prevalence of particular drug-resistant bacteria throughout all countries in  the EU. EU officials said these baseline studies provide information that is  comparable across countries. EU officials explained that EU countries are  required to participate in these studies, which usually last 1 year and are  used to set reduction targets for regulatory programs or to develop risk  management measures. For example, in 2008 the EU conducted a  prevalence study of MRSA in swine herds. It determined that the  prevalence varied dramatically between member countries—it was found  in more than 50 percent of swine herds in Spain, but in eight other EU  countries there were no detections.
According to Danish government and industry officials we interviewed, the  Danish government does not conduct research on alternatives to  antibiotic use. Both industry and government officials agreed that it should  be government’s role to set regulatory policy and industry’s role to  conduct research on how to meet regulatory goals. The Danish  Agriculture and Food Council—an industry organization representing  producers of a variety of meat and agricultural products—has funded  several studies examining alternatives to growth promotion antibiotics.  For example, one such study examined the economics of five types of  products that had the potential to improve feed efficiency in swine without  leading to antibiotic resistance and found that few products were both  economical for farmers and successful in improving feed efficiency.
EU officials also reported that at the EU-level government does not  conduct a significant amount of research related to alternatives to  antibiotics. They noted, however, that the EU has been trying to  incentivize private industry to develop alternatives in other ways. For  example, EU officials have tried to spur pharmaceutical companies to  develop products to improve feed efficiency and growth by lengthening  patents on such products. EU officials said that this results in a reduction  in competition from generic manufacturers and has led to more than 300  applications for new feed additive products.

	Conclusions

Antibiotic resistance is a growing public health problem worldwide, and  any use of antibiotics—in humans or animals—can lead to the  development of resistance. In 2001, USDA and HHS agencies took steps  to coordinate their actions on surveillance, prevention and control of  resistance, research, and product development through the 2001  interagency plan. The surveillance focus area of this plan includes action  items related to improving efforts to monitor both antibiotic use in food  animals, as well as antibiotic resistance in food animals and in retail meat.  According to WHO, populations sampled for surveillance purposes should  normally be representative of the total population—in this case, food  animals and retail meat in the United States.
Since 2001, however, USDA and HHS agencies have made limited  progress in improving data collection on antibiotic use and resistance. For  example, although FDA has a new effort to collect data on antibiotics sold  for use in food animals, these data lack crucial details, such as the  species in which the antibiotics are used and the purpose for their use.  The 2001 interagency plan states such data are essential for interpreting  trends and variations in rates of resistance, improving the understanding  of the relationship between antibiotic use and resistance, and identifying  interventions to prevent and control resistance. In addition, two USDA  agencies collect data on antibiotic use from food animal producers, but  data from these surveys provide only a snapshot of antibiotic use  practices and cannot be used to examine trends. Collecting data on  antibiotic use in food animals can be challenging and costly, but without  an approach to collecting more detailed data, USDA and HHS cannot  track the effectiveness of policies they undertake to curb resistance.  Indeed, FDA currently does not have a plan to measure the effectiveness  of its voluntary strategy to reduce food animal use of antibiotics that are  medically important to humans. Although there are challenges to  collecting detailed data on antibiotic use, efforts are under way in the EU  to begin collecting such data.
For data on antibiotic resistance, HHS and USDA agencies have  leveraged existing programs to collect samples of bacteria, but the  resulting data are not representative of antibiotic resistance in food  animals and retail meat throughout the United States. According to the  2001 interagency plan, antibiotic resistance data will allow agencies to  detect resistance trends and improve their understanding of the  relationship between use and resistance. FDA is aware of the NARMS  sampling limitations and has included a strategic goal of making NARMS  sampling more representative and applicable to trend analysis in its draft  2011-2015 NARMS Strategic Plan. FDA officials mentioned several ways  that NARMS sampling could be improved, such as discontinuing  slaughter plant sampling in favor of an on-farm sampling program and  increasing the number of states participating in the retail meat program.
USDA and HHS have also undertaken some research related to  developing alternatives to current antibiotic use practices. However, the  extent of these research efforts is unclear, as neither USDA nor HHS has  assessed its research efforts to determine the progress made toward the  related action item in the 2001 interagency plan. In addition, officials from  most of the veterinary and several public health organizations we spoke  with said that the federal government should make greater efforts to  coordinate this research with the food animal industry. Without an  assessment of past research efforts and coordination with industry, USDA  and HHS may be limited in their ability to identify gaps where additional  research is needed. In addition, USDA and HHS managers may not have  the critical information they need to make decisions about future research  efforts. Focus on tracking progress and making sound decisions about  future research is particularly important in light of the fiscal pressures  currently facing the federal government. Nevertheless, the draft 2010  interagency plan includes an action item on researching alternatives, but  it does not identify steps the agencies intend to take to do so. Similarly,  USDA and HHS had sought to educate producers and veterinarians  about appropriate antibiotic use but did not assess their efforts. The one  remaining education activity, however, is a $70,400 USDA training  module on antibiotic resistance for veterinarians, which will be completed  in 2012, after which there are no plans to develop new education  activities.

	Recommendations for Executive Action

We are making the following three recommendations:    To track the effectiveness of policies to curb antibiotic resistance,  including FDA’s voluntary strategy designed to reduce antibiotic use in  food animals and to address action items in the surveillance focus  area of the 2001 interagency plan, we recommend the Secretaries of  Agriculture and Health and Human Services direct agencies to,  consistent with their existing authorities, (1) identify potential  approaches for collecting detailed data on antibiotic use in food  animals, including the species in which antibiotics are used and the  purpose for their use, as well as the costs, time frames, and potential  trade-offs associated with each approach; (2) collaborate with industry  to select the best approach; (3) seek any resources necessary to  implement the approach; and (4) use the data to assess the  effectiveness of policies to curb antibiotic resistance.   To enhance surveillance of antibiotic-resistant bacteria in food  animals, we recommend that the Secretaries of Agriculture and Health  and Human Services direct agencies to, consistent with their existing  authorities, modify NARMS sampling to make the data more  representative of antibiotic resistance in food animals and retail meat  throughout the United States.   To better focus future federal research efforts on alternatives to  current antibiotic use practices, we recommend that the Secretaries of  Agriculture and Health and Human Services direct agencies to (1)  assess previous research efforts on alternatives and identify gaps  where additional research is needed, in collaboration with the animal  production industry, and (2) specify steps in the draft 2010  interagency plan that agencies will take to fill those gaps.

	Agency Comments and Our Evaluation

We provided the Departments of Agriculture and Health and Human  Services a draft of this report for review and comment. Both departments  agreed with our recommendations and provided written comments on the  draft, which are summarized below and appear in their entirety in  appendixes VII and VIII, respectively, of this report. The departments also  provided technical comments, which we incorporated as appropriate.
In its comments, USDA agreed with our recommendations. In response to  our recommendation on collecting antibiotic use data, USDA noted that  the department has devised strategies to collect detailed information on  antibiotic use in food animals, as documented in “A USDA Plan to  Address Antimicrobial Resistance.” Our report discusses many of the  ongoing USDA activities described in the document, including NAHMS,  ARMS, and NARMS. In commenting on our recommendation to collect  more representative resistance data, USDA acknowledged that sampling  for antibiotic resistant bacteria in food animals is not currently conducted  on a nationally representative population, but also stated that NARMS  data can still be used to examine general trends. We continue to believe  that the nonrandom sampling method used for food animals in NARMS  results in data that are not representative of food animals across the  country and cannot be used for trend analysis. Moreover, as our report  states, the NARMS program has prioritized modifying animal sampling to  overcome its current biases, and both FDA and USDA have identified  efforts that could be used to improve NARMS food animal sampling. In its  letter, USDA identified several such efforts; we had included several of  these in the draft report, and we modified the final version to include the  remaining effort.
In its comments, HHS also agreed with our recommendations, but stated  that FDA has made substantial progress and taken an active and  deliberative role in addressing the controversial and complex issue of  antibiotic use in food animals. We acknowledge that FDA has taken many  actions, most of which are discussed in the report. However, as our report  states, since the 2001 interagency plan, USDA and HHS agencies have  made limited progress in improving data collection on antibiotic use and  resistance. Specifically, as we noted in our report, FDA’s data on sales of  antibiotics for animal use do not include information on the species in  which antibiotics are used or the purpose for their use, which, for  example, prevents agencies from interpreting trends and variations in  rates of resistance. Similarly, as our report states, data on antibiotic  resistance from food animals are not representative and cannot be used  for trend analysis—even though the 2001 interagency plan identified  detecting resistance trends as an important part of monitoring for  antibiotic resistance. In commenting on our recommendation regarding  antibiotic use data collection, FDA recognized that having more detailed  antibiotic use data would benefit its overall effort to assure the judicious  use of antibiotics. FDA also noted that it is exploring potential approaches  for obtaining more detailed information and that it plans to coordinate with  USDA in that effort. We modified our report to include this information. In  addition, regarding our findings on FDA’s resistance data from retail meat,  FDA stated that it does not believe samples need to be statistically  representative of the entire United States to serve as indicators of U.S.  retail meat. We modified our report to better reflect FDA’s position, but as  our report states, the FDA Science Advisory Board’s 2007 review of data  on antibiotic resistance in retail meat found that the lack of a national  sampling strategy limits a broader interpretation of NARMS data.
As agreed with your office, unless you publicly announce the contents of  this report earlier, we plan no further distribution until 30 days from the  report date. At that time, we will send copies to the appropriate  congressional committees, Secretaries of Agriculture and Health and  Human Services, and other interested parties. In addition, this report will  be available at no charge on the GAO Web site at http://www.gao.gov.
If you or your staff members have any questions about this report, please  contact me at (202) 512-3841 or shamesl@gao.gov. Contact points for  our Offices of Congressional Relations and Public Affairs may be found  on the last page of this report. GAO staff who made major contributions to  this report are listed in appendix IX.

Appendix I: Objectives, Scope, and Methodology

The objectives of our review were to determine (1) the extent to which  federal agencies have collected data on antibiotic use and resistance in  food animals; (2) the actions the Food and Drug Administration (FDA) has  taken to mitigate the risk of antibiotic resistance in humans as a result of  antibiotic use in food animals; (3) the extent to which federal agencies  have conducted research on alternatives to current antibiotic use  practices and educated producers and veterinarians about appropriate  antibiotic use; and (4) what actions the European Union (EU) and an EU  member country, Denmark, have taken to regulate antibiotic use in food  animals and what lessons, if any, have been learned.
To address the first three objectives of our study, we reviewed federal  laws, regulations, policies, and guidance; federal plans about antibiotic  resistance; agency documents related to data collection efforts on  antibiotic use and resistance; and documents from international  organizations and other countries related to surveillance of animal  antibiotic use and resistance. In particular, we reviewed the Food,  Conservation, and Energy Act of 2008 (2008 Farm Bill), as well as laws  related to FDA’s oversight of animal antibiotics, including the Federal  Food, Drug, and Cosmetic Act, the Animal Drug Availability Act of 1996,  the Animal Drug User Fee Act of 2003. We also reviewed regulations and  guidance implementing FDA’s authorities, including Evaluating the Safety  of Antimicrobial New Animal Drugs with Regard to Their Microbiological  Effects on Bacteria of Human Health Concern (Guidance for Industry  #152), and The Judicious Use of Medically Important Antimicrobial Drugs  in Food-Producing Animals (draft Guidance for Industry #209). In  addition, we reviewed the 2001 Interagency Public Health Action Plan to  Combat Antimicrobial Resistance, the draft 2010 Interagency Public  Health Action Plan to Combat Antimicrobial Resistance, and agencies’  annual updates of activities they completed related to these plans. We  also reviewed agency documents related to FDA’s sales data, the  National Animal Health Monitoring System (NAHMS), the Agricultural  Resource Management Survey (ARMS), the National Antimicrobial  Resistance Monitoring System (NARMS), and the now-defunct pilot  Collaboration on Animal Health and Food Safety Epidemiology  (CAHFSE). Internationally, we reviewed documents from surveillance  systems in Canada and Denmark, including reports about the Canadian  Integrated Program on Antimicrobial Resistance Surveillance (CIPARS)  and the Danish Antimicrobial Resistance Monitoring and Research  Programme (DANMAP). In addition, we reviewed the World Health  Organization’s guidance on developing surveillance systems for antibiotic  resistance related to food animal antibiotic use.
To discuss topics related to the first three objectives, we also conducted  interviews with officials at the Department of Health and Human Services’  (HHS) Centers for Disease Control and Prevention (CDC), FDA, and the  National Institutes of Health (NIH) and U.S. Department of Agriculture  (USDA) agency officials at the Animal and Plant Health Inspection  Service (APHIS), the Agricultural Research Service (ARS), the Economic  Research Service (ERS), the Food Safety and Inspection Service (FSIS),  and the National Institute of Food and Agriculture (NIFA). We also  interviewed an official representing CIPARS to discuss the program’s  efforts to monitor antibiotic use and resistance in animals across Canada,  the challenges it faces, and how the program may relate to current and  future data collection efforts in the United States.
We also conducted site visits with conventional and alternative (either  organic or antibiotic-free) producers of poultry, cattle, swine, and dairy  products in Delaware, Georgia, Iowa, Kansas, Minnesota, and Wisconsin  to obtain a better understanding of production practices and the types of  antibiotic use data available at the farm level. During these site visits, we  spoke with producers, veterinarians, academic researchers, and  extension agents involved with food animal production. We selected  these commodity groups because they represent the top four animal  products in the United States. We selected our site visit locations based  on the accessibility of production facilities of different sizes—we visited  both small and large facilities; including states that are among the largest  producers of each commodity in our scope of study; and proximity to  Washington, D.C., and the USDA NARMS laboratory in Georgia. These  sites were selected using a nonprobability sample and the findings from  those visits cannot be generalized to other producers.
Based on issues identified by reviewing documents and interviewing  federal, state, and local officials, we developed a questionnaire on the  use of antibiotics in animals and resistance. The questionnaire gathered  organizations’ perspectives on a range of topics including the extent to  which federal data collection programs support the action items identified  by federal agencies in the 2001 interagency plan; what actions, if any,  FDA or other federal agencies should take to implement the two  principles FDA outlined in draft Guidance for Industry #209 and how such  implementation may affect antibiotic use in food animals; and what role, if  any, the federal government should have in conducting research on  alternatives to current antibiotic use practices and educating producers  and veterinarians. We conducted a pretest of the questionnaire and made  appropriate changes based on the pretest.
In addition to developing the questionnaire, we identified 11 organizations  involved with the issue of antibiotic use in food animals and antibiotic  resistance. We selected these organizations because of their expertise in  topics surrounding antibiotic use in animals and resistance based on  whether they have been actively involved in this issue within the past 5  years, including through testimonies to Congress, in-depth public  discussions, or published research; and to provide representation across  producer organizations that represent the major commodities, in addition  to pharmaceutical and public health organizations. The selected  organizations are a nonprobability sample, and their responses are not  generalizable. The selected organizations were: National Cattleman’s  Beef Association, National Milk Producers’ Federation, National Pork  Producers Council, National Chicken Council, Animal Health Institute,  Alliance for the Prudent Use of Antibiotics, Center for Science in the  Public Interest, Infectious Diseases Society of America, Keep Antibiotics  Working, PEW Campaign on Human Health and Industrial Farming, and  Union of Concerned Scientists.
We administered the questionnaires through structured interviews with  representatives from the 11 national organizations, who spoke on behalf  of their members, either via phone or in-person. All 11 organizations  agreed to participate in these structured interviews. To identify trends in  responses, we qualitatively analyzed the open-ended responses from the  interviews to provide insight into organizations’ views on the issues  identified in the questionnaire.
We also conducted structured interviews with representatives from five  national veterinary organizations, who spoke on behalf of their members,  to discuss their views on federal research efforts on alternatives and  federal efforts to educate producers and veterinarians about appropriate  use. The questionnaire covered a range of topics including federal  progress in both of these areas since 2001 and actions the federal  government can take to improve future efforts in these areas. We  contacted five veterinary organizations to request their participation,  selecting these organizations to include the largest U.S. veterinary  organization—the American Veterinary Medical Association—as well as a  veterinary organization representing each of the major commodities in our  review—American Association of Avian Pathologists, American  Association of Bovine Practitioners, American Association of Swine  Veterinarians, and the Academy of Veterinary Consultants. We distributed  the questionnaire to the five organizations electronically and administered  the questionnaires through structured interviews with each organization  via phone or in person. All five veterinary organizations agreed to  participate in these structured interviews. To identify trends in responses,  we qualitatively analyzed the open-ended responses from the interviews  to provide insight into organizations’ views on the issues identified in the  questionnaire. Although we sought to include a variety of organizations  with perspectives about antibiotic use and resistance, the views of  organizations consulted should not be considered to represent all  perspectives about these issues and are not generalizable.
To describe actions the EU and Denmark have taken to regulate antibiotic  use in food animals and potential lessons that have been learned from  these actions, we reviewed documents, spoke with EU and Danish  government and industry officials, and visited producers. We selected the  EU and Denmark because they implemented bans on growth promotion  uses of antibiotics in 2006 and 2000, respectively, which allows for a  review of the effects of these policies in the years since. In addition,  Denmark’s experience with regulating antibiotic use has been well- documented in government-collected data that provide insight into the  effects of policy changes.
For the EU, we reviewed documents describing EU Commission  directives and regulations regarding antibiotic use in food animals, risk  assessments related to antibiotic use in food animals, surveillance reports  describing antibiotic resistance in the EU, and proposals for future data  collection efforts on antibiotic use. In addition, we spoke with officials from  the EU Directorates General for Health and Consumers, Agriculture and  Rural Development, and Research and Innovation. We also spoke with  an official from the European Food Safety Agency regarding their  surveillance reports describing antibiotic resistance in the EU. Finally, we  interviewed the following organizations that interact with the EU on behalf  of their members regarding animal antibiotic use: Federation of  Veterinarians of Europe, which represents veterinarians throughout the  EU, and the International Federation for Animal Health, which represents  pharmaceutical companies who manufacture animal health products. We  did not independently verify statements of EU law.
For Denmark, we reviewed documents describing Danish laws and  regulations regarding animal antibiotic use and government regulation of  veterinarians, surveillance reports describing antibiotic use and antibiotic  resistance in Denmark, and published studies examining Denmark’s  experience with regulating antibiotic use. In addition, we spoke with  officials at the Danish Veterinary and Food Administration and DANMAP.  We also spoke with officials at the Danish Agriculture and Food Council,  which represents producers in Denmark, to learn about how Danish  policies have affected producers. Finally, we conducted site visits and  interviewed Danish producers and veterinarians at a poultry and a swine  facility in Denmark to learn about current methods of production and how  these producers have implemented Danish policies. These sites were  selected based on convenience and the findings from those visits cannot  be generalized to other producers. We did not independently verify  statements of Danish law.
We conducted this performance audit from August 2010 to September  2011, in accordance with generally accepted government auditing  standards. Those standards require that we plan and perform the audit to  obtain sufficient, appropriate evidence to provide a reasonable basis for  our findings and conclusions based on our audit objectives. We believe  that the evidence obtained provides a reasonable basis for our findings  and conclusions based on our audit objectives.

Appendix II: Alternative Modes of Food Animal Production

Some producers raise animals using alternative modes of production.  One such alternative is organic production, for which USDA’s National  Organic Program (NOP) develops, implements, and administers national  standards. To comply with NOP standards, organically produced animals  cannot be treated with antibiotics. According to USDA, organic farming  has become one of the fastest-growing segments of U.S. agriculture, and  consumer demand for organically produced goods has shown double- digit growth for well over a decade, providing market incentives for U.S.  farmers across a broad range of commodities. According to recent  industry statistics, organic sales account for over 3 percent of total U.S.  food sales. Fruits and vegetables account for about 37 percent of U.S.  organic food sales, while dairy and food animals (including meat, fish, and  poultry) account for about 16 and 3 percent, respectively, of U.S. organic  food sales.
According to the Organic Trade Association, transitioning from  conventional to organic production can take several years, because  producers must adopt certain management practices to qualify for organic  certification. The NOP standards apply to animals used for meat, milk,  eggs, and other animal products represented as organically produced.  Some of the NOP livestock standards include the following:    Animals for slaughter must be raised under organic management from  the last third of gestation, or no later than the second day of life for  poultry.   Producers generally must provide a total feed ration composed of  agricultural products, but they may also provide allowed vitamin and  mineral supplements.   Traditional livestock have transition periods for converting to organic.
For example, producers may convert an entire distinct dairy herd to  organic production by providing 80 percent organically produced feed  for 9 months, followed by 3 months of 100 percent organically  produced feed. If the farm did not convert an entire distinct herd, new  animals added must be raised using organic methods for at least 1  year before the milk can be sold as organic.    Organically raised animals may not be given hormones to promote  growth, or antibiotics for any reason.   All organically raised animals must have access to the outdoors,  including access to pasture for ruminants, such as cattle. They may  be temporarily confined only for specified reasons, including reasons  of health, safety, the animal’s stage of production, or to protect soil or  water quality.   A USDA-approved certifier ensures that organic producers are  following all of the rules necessary to meet NOP standards, which  includes maintaining data that preserve the identity of all organically  managed animals and edible and nonedible animal products  produced on the operation.
One producer we visited told us that his farm began the transition from a  conventional farm in 1995 and became a grass-fed beef and certified  organic farm in 2006 (see fig. 4). This producer also said that the  transition experience was economically challenging. Specifically, during  this conversion the farm stopped bringing in outside animals and changed  confinement and feed practices. Through such changes, this producer  said that, overall, the animals are healthier and the farm has increased  marketing opportunities, which he feels outweighs the costs.
In addition to organic, there are other alternative modes of production. For  example, FSIS has a “raised without antibiotics” production label for red  meat and poultry. Before FSIS will approve such a label, producers must  provide the agency with sufficient documentation that demonstrates  animals were raised without antibiotics. Other commonly approved FSIS  poultry and meat production labels include “natural” and “free range,”  though these labels do not limit the use of antibiotics (see fig. 5).
Some conventional and alternative producers we visited told us that  animals produced without antibiotics typically grow at slower rates and  tend to weigh less at market, requiring producers to charge higher  premiums to cover these additional production costs. Producers raising  animals without antibiotics typically have to take greater preventative  measures, such as changes in husbandry practices, in order to reduce  chances of illness. These changes in husbandry practices may include  providing hay bedding for newly birthed calves and mother cows,  selecting and breeding animals with disease resistance, and allowing  greater access outdoors and space per animal. When animals do become  sick, alternative disease treatments depend on the animal and illness. For  example, cows may be treated with sea salt and a patch for pink eye and  splints for broken legs. Still, antibiotics may need to be used as a last  resort and, in such cases, these animals are sold to the conventional  market, creating an economic loss for the producer.

Appendix III: The Food and Drug Administration’s Antibiotic Sales Data

Tables 7 and 8 provide examples of the data collected by the Food and  Drug Administration as required by the Animal Drug User Fee  Amendments of 2008 (ADUFA).

Appendix IV: Structure of DANMAP

The objectives of the Danish Integrated Antimicrobial Resistance  Monitoring and Research Program (DANMAP) are to monitor the  consumption of antibiotics for food animals and humans; monitor the  occurrence of antibiotic resistance in bacteria from food animals, food of  animal origin, and humans; study associations between antibiotic use and  resistance; and identify routes of transmission and areas for further  research studies. Table 9 shows the types of data gathered about  antibiotic use and resistance in Denmark and the sources of these data.

Appendix V: ARS and NIFA Research Activities Related to Alternatives to Current Antibiotic Use Practices

	Agency ARS

Grantee(s)  (if applicable)
Project  year(s)

	Agency

Grantee(s)  (if applicable)
Project  year(s)

	Agency

Grantee(s)  (if applicable)
Project  year(s)
Researching methods and strategies  to reduce antibiotic resistance  transmission along the food chain  This figure is based on fiscal year 2010 funding levels, and is similar to funding for each year of the  project.
In 2010, NIFA was allocated up to $4 million to award two competitive grants related to antibiotic  resistance and use (awarded to Kansas State University and Washington State University). NIFA  expects to make decisions about similar grants for fiscal year 2011 in September, and to release  award announcements in fiscal year 2012.

Appendix VI: CDC and FDA Research Activities Related to Alternatives to Current Antibiotic Use Practices

	Agencies Grantees

Appendix VII: Comments from the Department of Agriculture

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

Appendix IX: GAO Contact and Staff Acknowledgments

	GAO Contact

	Staff Acknowledgments

In addition to the individual named above, Mary Denigan-Macauley,  Assistant Director; Kevin Bray; Antoine Clark; Julia Coulter; Cindy Gilbert;  Janice Poling; Katherine Raheb; Leigh Ann Sennette; Ben Shouse; and  Ashley Vaughan made key contributions to this report.

Related GAO Products

Antibiotic Resistance: Data Gaps Will Remain Despite HHS Taking Steps  to Improve Monitoring. GAO-11-406. Washington, D.C.: June 1, 2011.
Federal Food Safety Oversight: Food Safety Working Group Is a Positive  First Step but Governmentwide Planning Is Needed to Address  Fragmentation. GAO-11-289. Washington, D.C.: March 18, 2011.
High Risk Series: An Update. GAO-11-278. Washington, D.C.: February  2011.
Veterinarian Workforce: Actions are Needed to Ensure Sufficient Capacity  for Protecting Public and Animal Health. GAO-09-178. Washington, D.C.:  February 4, 2009.
Food Safety: Selected Countries’ Systems Can Offer Insights into  Ensuring Import Safety and Responding to Foodborne Illness.  GAO-08-794. Washington, D.C.: June 10, 2008.
Avian Influenza: USDA Has Taken Steps to Prepare for Outbreaks, but  Better Planning Could Improve Response. GAO-07-652. Washington,  D.C.: June 11, 2007.
Antibiotic Resistance: Federal Agencies Need to Better Focus Efforts to  Address Risk to Humans from Antibiotic Use in Animals. GAO-04-490.  Washington, D.C.: April 22, 2004.
Food Safety: The Agricultural Use of Antibiotics and Its Implications for  Human Health. GAO/RCED-99-74. Washington, D.C.: April 28, 1999.
Executive Guide: Effectively Implementing the Government Performance  and Results Act. GAO/GGD-96-118. Washington, D.C.: June 1996.

Summary:
Why GAO Did This Study

Antibiotics have saved millions of lives, but antibiotic use in food animals contributes to the emergence of resistant bacteria that may affect humans. The Departments of Health and Human Services (HHS) and Agriculture (USDA) are primarily responsible for ensuring food safety. GAO reviewed the issue in 2004 and recommended improved data collection and risk assessment. GAO was asked to examine the (1) extent to which agencies have collected data on antibiotic use and resistance in animals, (2) actions HHS's Food and Drug Administration (FDA) took to mitigate the risk of antibiotic resistance in humans as a result of use in animals, (3) extent to which agencies have researched alternatives to current use practices and educated producers and veterinarians about appropriate use, and (4) actions the European Union (EU) and an EU member country, Denmark, have taken to regulate use in animals and lessons that have been learned. GAO analyzed documents, interviewed officials from national organizations, and visited producers in five states and Denmark..

What GAO Found

HHS and USDA have collected some data on antibiotic use in food animals and on resistant bacteria in animals and retail meat. However, these data lack crucial details necessary to examine trends and understand the relationship between use and resistance. For example, since GAO's 2004 report, FDA began collecting data from drug companies on antibiotics sold for use in food animals, but the data do not show what species antibiotics are used in or the purpose of their use, such as for treating disease or improving animals' growth rates. Also, although USDA agencies continue to collect use data through existing surveys of producers, data from these surveys provide only a snapshot of antibiotic use practices. In addition, agencies' data on resistance are not representative of food animals and retail meat across the nation and, in some cases, because of a change in sampling method, have become less representative since GAO's 2004 report. Without detailed use data and representative resistance data, agencies cannot examine trends and understand the relationship between use and resistance. FDA implemented a process to mitigate the risk of new animal antibiotics leading to resistance in humans, which involves the assessment of factors such as the probability that antibiotic use in food animals would give rise to resistant bacteria in the animals, but it faces challenges mitigating risk from antibiotics approved before FDA issued guidance in 2003. FDA officials told GAO that conducting postapproval risk assessments for each of the antibiotics approved prior to 2003 would be prohibitively resource intensive, and that pursuing this approach could further delay progress. Instead, FDA proposed a voluntary strategy in 2010 that involves FDA working with drug companies to limit approved uses of antibiotics and increasing veterinary supervision of use. However, FDA does not collect the antibiotic use data, including the purpose of use, needed to measure the strategy's effectiveness. HHS and USDA have taken some steps to research alternatives to current antibiotic use practices and educate producers and veterinarians on appropriate use of antibiotics. However, the extent of these efforts is unclear because the agencies have not assessed their effectiveness. Without an assessment of past efforts, the agencies may be limited in their ability to identify gaps where additional research is needed. Except for one $70,400 USDA project, all other federal education programs have ended. Since 1995, the EU, including Denmark, banned the use of antibiotics to promote growth in animals, among other actions. Some of their experiences may offer lessons for the United States. For example, in Denmark, antibiotic use in animals initially decreased following a series of policy changes. The prevalence of resistant bacteria declined in food animals and retail meat in many instances, but a decline in humans has only occasionally been documented. Denmark's data on use and resistance helped officials track the effects of its policies and take action to reverse unwanted trends. The EU faces difficulty collecting data that can be compared across countries, but officials there said such data are needed to fully understand how use in animals may lead to resistance in humans.

What GAO Recommends

GAO recommends that HHS and USDA (1) identify and evaluate approaches to collecting detailed data on antibiotic use in animals and use these data to evaluate FDA's voluntary strategy, (2) collect more representative data on resistance, and (3) assess previous efforts on alternatives to identify where more research is needed. HHS and USDA agreed with GAO's recommendations.