Antibiotic use in livestock

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Antibiotic use in livestock is the use of antibiotics for any purpose in the husbandry of livestock, which includes treatment when ill (therapeutic), treatment of a batch of animals when at least one is diagnosed as ill (metaphylaxis, similar to the way bacterial meningitis is treated in children), and preventative treatment (prophylaxis). The use of subtherapeutic doses in animal feed and water[1] to promote growth and improve feed efficiency is discouraged by the FDA as part of their Veterinary Feed Directive, which seeks voluntary compliance from drug manufacturers to re-label their antibiotics.[2][3] The practice has been banned in Europe since 2006.[4]

In 2013, the CDC finalized and released a report detailing antibiotic resistance and classified the top 18 resistant bacterium as either being urgent, serious or concerning threats. Of those organisms, three (C. diff, carbapanem-resistant enterobacteriaceae, and Neisseria gonorrhoeae) have been classified as urgent threats and require more monitoring and prevention. In the US alone, more than 2 million people are diagnosed with antibiotic resistant infections and over 23,000 die per year due to resistant infections.[5]

Given the concerns about antibiotic use for feed conversion, research into alternatives is ongoing.

History

In 1910 in the United States, a meat shortage resulted in protests and boycotts.[6][7] After this and other shortages, the public demanded government research into stabilization of food supplies.[6] Since the 1900s, livestock production on United States farms has had to rear larger quantities of animals over a short period of time to meet new consumer demands. Factory farming originated in the late 19th century when advances in technology and science allowed for mass production of livestock. Global agriculture production doubled four times within 1820 and 1975, feeding one billion in 1800 and up to 6.5 billion in 2002.[8][page needed] The increase in animal densities brought the threat of disease, necessitating greater disease control. In 1950, a group of United States scientists found that adding antibiotics to animal feed increases the growth rate of livestock.[6][9] American Cyanamid published research establishing the practice.[6]

By 2001, this practice had grown so much that a report by the Union of Concerned Scientists found that nearly 90% of the total use of antimicrobials in the United States was for non-therapeutic purposes in agricultural production.[10]

Growth stimulation

Certain antibiotics, when given in low, sub-therapeutic doses, are known to improve feed conversion efficiency (more output, such as muscle or milk, for a given amount of feed) and may promote greater growth, most likely by affecting gut flora.[11] The drugs listed below are used to increase feed conversion ratio and weight gain. Some drugs listed below are ionophores, which are not antibiotics and do not pose any potential risk to human health.

Antibiotic Growth Promoters used in Livestock Production
Drug Class Livestock
Bacitracin Peptide Beef cattle, chickens, swine, and turkeys; promotes egg production in chickens[12][13]
Bambermycin Beef cattle, chickens, swine, and turkeys.[12][13]
Carbadox Swine[12]
Laidlomycin Beef cattle[12]
Lasalocid Ionophore Beef cattle[12][13]
Lincomycin Chickens and swine[12]
Monensin Ionophore Beef cattle and sheep; promotes milk production in dairy cows[12][13]
Neomycin/ oxytetracyclinee Beef cattle, chickens, swine, and turkeys[12]
Penicillin Chickens, swine, and turkeys[12]
Roxarsone Chickens and turkeys[12]
Salinomycin Ionophore
Tylosin Chickens and swine[12]
Virginiamycin Peptide Beef cattle, chickens, swine, turkeys[12][13]

Concentrated animal feeding operations

Concentrated animal feeding operations (CAFO) refer to large, often multi-species, farming operations which lead to close animal housing quarters, rampant infections and disease, among many other malaises.[14]

These animals are sedentary due to the lack of space in the cramped cages. They often catch disease due to the packed rooms and ease of transmission among the manure, blood and bodily fluids. The current justification for these conditions is the belief that due to the animals not roaming, they save energy, and therefore better digest their food; this energy is reserved for growth of the animals.[15]

Organic beef comes from cattle who have not been fed antibiotics.

Manure

The large amounts of manure produced in cattle livestock populations are a problem for many CAFOs. Dependent on size of the operation, there can be 2,800 to 1.6 million tons of manure produced per year.[16] Annually, the livestock population in the United States produces 3 to 20 times more manure than people. However, many operations lack ultimate sewage treatment.[14]

The manure produced from concentrated populations of animals can be diseased and have negatives impact on the environment itself. Livestock manure can be tainted by blood, pathogens such as E. coli, antibiotics, growth hormones, chemical additives, etc. Some of this manure can be treated and used as fertilizer by liquefying and spraying it, but larger operations often revert to storing it until it can be disposed of properly.[14] Manure is also trucked off site, stored in containers, or held in holding ponds. There can be problems associated with storing manure;[14] manure can have detrimental effects on the surrounding area due to leaking containers or holding ponds. This, known as manure leaching, can lead to manure run-off affecting the ground or soil water by percolation or direct contamination.[17]

Groundwater contamination

When manure run-off or percolation enters a water system, the infecting agents thrive in that environment.[17] Previous studies have shown private well water in Idaho found high levels of veterinary antibiotics as well as additive chemicals. The surrounding areas of concentrated animal feeding operations are at particular risk for groundwater or soil water sources of contamination.[16] When manure enters a water source, either underground or above ground, whatever pathogens inhabiting the manure enters the water as well. All the agents inside the manure can contaminate a water source. Pathogens survive longer in groundwater than surface water due to lower temperatures and protection from the sun and other harsher elements. Additionally, this water will not be treated until far later in the process, allowing bacterial colonies to grow.[14]

Groundwater is one of the larger sources of water that humans are supplied from. As of 2010, 53% of people in the United States relied on groundwater as their primary source of drinking water. Groundwater also gradually leads to surface waters, such as rivers and streams.[14] Water as a contaminant is a major source of outbreak in human populations – the areas around concentrated animal feeding operations are typically at a higher risk of exposure to antibiotic resistant bacteria strains and subsequent outbreaks.[16]

Antibiotic usage

The living conditions of animal feeding operations leads to a shotgun approach at targeting a sick population of livestock. Due to denser amounts of animals in smaller spaces, illness spreading and affecting a few animals can signal a precursor that more animals in an area will be infected by pathogens. In the United States, 80% of all antibiotics are given as feed additives.[18] The antibiotics given to treat all the animals in dense area are not specific to each animal's illness and use a general approach to dosing. This leads to the antibiotics not being fully metabolized by the animals.[19] This has been tested by levels of antibiotics still present in the manure of these animals.

Vectors

A vector, in this context, is an organism that transmits disease to another organism. Insects such as flies and mosquitoes have high amounts of breeding grounds and nests of eggs around manure waste, allowing rapid reproduction and fresh vectors for potential disease. Typically with dense populations of livestock, transmission of disease from one animal to another can be on account of insects, such as flies, mosquitoes or ticks, spreading blood from one animal to another.[20][failed verification] This can be particularly dangerous for sick animals spreading diseases to healthier animals, promoting general malaise in a concentrated area. Additionally, the animals can be infected from other animals' manure making contact with their food; fecal-oral transmission are one of the largest sources for pathogen transmission.[14] Within concentrated animal farming operations, there is no mandatory testing of novel viruses, only reporting known illnesses to the World Organization for Animal Health. Thus, certain mutations or recombinant bacteria strains, which are more efficient in translation to human to human events, can be unnoticed.

Additionally, insect beds around manure pools or containers are a particular threat for contamination. These insects feed and reproduce in the runoff of treated manure, so they can acquire resistant strains of bacteria from blood and the manure of livestock treated with antibiotics. Since most manure holding ponds are on or near the sites of the operations, the insects are not far from livestock populations.[14] These insects are also particularly dangerous because they can spread bacteria or other pathogens to humans by infecting human food. This is prevalent when treated manure is used as fertilizers of liquefied for spraying and as a result of the unsanitary handling of meat in kitchens.[17]

Regulatory context

The use of drugs in food animals is regulated in nearly all countries. Historically, this has been to prevent alteration or contamination of meat, milk, eggs and other products with toxins that are harmful to humans. Treating a sick animal with drugs may lead to some of those drugs remaining in the animal when it is slaughtered or milked. Scientific experiments provide data that shows how long a drug is present in the body of an animal and what the animal's body does to the drug. Of particular concern are drugs that may be passed into milk or eggs. By the use of 'drug withdrawal periods' before slaughter or the use of milk or eggs from treated animals, veterinarians and animal owners ensure that the meat, milk and eggs is free of contamination.

These restrictions include not only poisons or drugs (such as penicillin) which may result in allergic reactions but also contaminants which may cause cancer. It is illegal in the US to administer drugs or feed substances to animals if they have been shown to cause cancer.

One of the main restrictions is the amount that is administered to animals in the industry. These drugs should be administered to healthy livestock at a low concentration of 200 g per ton of feed. The amount distributed is also altered throughout the lifespan of livestock in order to meet specific growth needs.[21]

Legality of the use of specific drugs in animal medicine varies according to location.

Just as in human medicine, some drugs are available over the counter and others are restricted to use only on the prescription of a veterinary physician. In the US, the Food and Drug Administration (FDA) requires specific labels on all drugs, giving directions on the use of the drug. For animals, this includes the species, dose, reason for giving the drug (indication) and the required withdrawal period, if any. Federal law requires laypersons to use drugs only in the manner listed. Veterinarians who have examined an animal or a herd of animals may issue a replacement label, giving new directions, based on their medical knowledge, unless it is a feed-grade antibiotic (is administered through the feed or water) in which case the veterinarian cannot issue directions different than the label.[22] It is illegal in the US for any layperson to administer any drug to a food animal in a way not specific to the drug label. Over-the-counter drugs which may be used by laypersons include anti-parasite drugs (including fly sprays) and antimicrobials. These drugs can be applied as sprays, creams, injections, oral pills or fluids, or as a feed additive, depending on the drug and the label.

In December 2013, the FDA updated its regulations to try to begin reducing use of antibiotics for growth enhancement.[23] Significant lobbying comes from all directions, from those against tighter regulation to those who complain it doesn't go far enough.[24]

Currently few policies, regulations and laws exist that promote limitation of antibiotic use on factory farms. In addition, few policies are being created that call for this decrease in antibiotic use. However, numerous state senators and members of congress showed support for the Preventing Antibiotic Resistance Act of 2015 (PARA) and the Preservation of Antibiotics for Medical Treatment Act of 2013 (PAMTA). These acts proposed amendments be made to the Federal Food, Drug and Cosmetic Act which would limit and preserve the use of antibiotics for medically necessary situations. Both of these bills died in Congress in 2015.[25]

In 2015, the FDA approved a new Veterinary Feed Directive (VFD), which is an updated rule that give instructions to pharmaceutical companies, veterinarians, and producers about how to administer necessary drugs through the animal's feed and water. This new rule followed through on the FDA's commitment to phase out the use of antibiotics for growth promotion and increased feed conversion.[26] It is now illegal to use any antimicrobial that is medically important to humans for anything other than treatment, control, and prevention of disease. Furthermore, even then, producers now have to have a licensed veterinarian sign a legal form - much like a prescription - for producers to purchase, store, or administer these products. This document gives specific instructions about the animals to be fed, the dates when they will be fed, and the concentration. Violating a VFD is now a violation of federal law. This is a major step toward reducing antibiotic resistance in both animals and humans. The new VFD took effect on January 1, 2017.[22][3][2]

FDA and risk assessment

When it comes to quantifying the risks towards humans from antibiotic usage in live stock, there are several barriers to identifying direct causation. The topic itself covers everything from epidemiology, ecology, and molecular biology.[27] Many models for risk assessment rely on the Impact Fraction, or the etiologic fraction, which is a specific link in an ecologic chain between animal antibiotic usage and epidemiological outbreaks.[28] For example, tracking an epidemiological outbreak must incorporate the ecology of the source, the molecular biology of the organisms themselves, and then show correlation to an event.[28]

The Food and Drug Administration categorizes potential antibiotic usage and negative effects in the human population in 3 tiers. These tiers categorize the likelihood that bacteria acquire resistance to antibiotics before ending up in food and subsequently result in adverse effects to human health as: low, medium or high probabilities.[28] These categorizations determine the impact, or risk, of antibiotic resistance residing in human intestinal flora with calculation for an acceptable level of risk to human health.[28]

In general, the work towards risk assessment models are very unfinished and often contradictory. These incongruities mostly result in hard to pinpoint generalities about usage and risk for adverse health effects. In the past 40 years of research on indirect effects of antibiotic usage, it is becoming harder to disprove the problem is directly linked to antibiotic usage. However, arguments still arise about the proportion of resistant infections that are caused by antibiotics used in livestock. Additionally, the research to better understand the molecular level of how bacteria spreads from livestock to human needs to be more concrete and unidirectional. In essence, resistance is difficult to predict and varies dependent on strain of bacteria and populations of people.

Regulation

The Food and Drug Administration allows four uses for antibiotics in livestock populations: Disease treatments, disease prevention, disease control, and growth promotion.[29] Disease treatment differs from disease prevention in terms of when the antibiotics are used. Treatments are administered after bacterial infection has affected a group of animals. Prevention is prophylactic usage, or administered before there is an infection. This would be prevalent in a group of healthy animals not near or in the general vicinity of infected animals. Disease control is the targeting of animals in or near a group with a few infected animals.[30] Growth promotion is beginning to be largely banned by countries or, in some cases, large meat suppliers choose to purchase livestock grown without antibiotics.[31] The reasons why antibiotics increase growth efficiency are generally agreed to be due to modifications to the rumen flora microenvironment and the molecular biology of the intestinal bacteria.[32]

The Food and Drug Administration estimates 80% of antibiotics, or 15.4 million kilograms of antimicrobial agents, in the United States are used on livestock. The rest is allocated for usage in the medical field.[18]

Administering drugs

Drugs can be administered to animals in a variety of means, just as with humans. Among these are topical (on the skin), by injection (including intravenous, subcutaneous, subcutaneous implants, intramuscular and intraperitoneal), orally and by inhalation.[33] Oral drugs can be in pill or liquid form, and can be given by mixing the drug with both feed or drinking water.[33] The type of administration can differ depending on the drug you're giving, and the specific case of the animal. Illness, severity of illness, selected drug, age and or condition of the animal, species of the animal, type of housing and many other factors come into play when deciding how to administer the drug.[33] For animals that are not regularly fed a concentrated feed or which can be handled repeatedly, a slow-release medication might be the more appropriate depending on the severity of the issue. For animals that are fed regularly (rather than grazing freely) or that can not be easily handled, the most appropriate means of administering the drug may be to include the drug in feed or water, although this is not as common, because you will be administering the drug to all animals that come in contact with the sources. This eliminates the stress of daily (or more frequent) handling of animals, which can cause stress on the animal. Poultry are most commonly medicated in this fashion, as they are easily stressed to the point of dying.

The timely administration of drugs is key to preventing animal suffering and economic loss to the farmer. Infected animals can spread the disease to the healthy animals, causing the whole herd to become ill. A variety of techniques are used to monitor animals for illness so that they can be treated appropriately. Stress reduction, adequate nutrition, shelter, and quarantine of incoming stock are all important factors to promote growth and reduce illness and the need for active treatment, although some vaccinations are essential for disease prevention.[33] The age and status of an animal is also important in determining correct treatment – a young animal or pregnant animal is at greater risk and are treated more aggressively than an older animals. Specifically in calves, at weaning (the period in which they begin to separate from their mothers) generates stress and makes them more susceptible to catching an infection like pneumonia or diseases like blackleg. Antibiotics are commonly administered in the calves' feed along with by injection in some cases during this time to fight the possibility and arrise of stress-induced infections.[33] Feed antibiotics are also used to prevent illnesses in calves caused by liver abscesses that develop during their last stages of growth.[33]

Use by country

European Union

The European Union (EU) in 1999 implemented an antibiotic resistance monitoring program and phase out plan for all antibiotic use by 2006.[34] Although the European Union banned the use of antibiotics as growth agents from 2006,[35] its use has not changed much until recently[citation needed]. In Germany, 1,734 tons of antimicrobial agents were used for animals in 2011 compared with 800 tons for humans[citation needed]. On the other hand, Sweden banned their use in 1986 and Denmark started cutting down drastically in 1994, so that its use is now 60% less.[36] In the Netherlands, the use of antibiotics to treat diseases increased after the ban on its use for growth purposes in 2006.[37] In 2011, the EU voted to ban the prophylactic use of antibiotics, alarmed at signs that the overuse of antibiotics is blunting their use for humans.[38]

United States

In 2011, a total of 13.6 million kilograms of antimicrobials were sold for use in food-producing animals in the United States,[39] which represents 80% of all antibiotics sold or distributed in the United States.[40] Of the antibiotics given to animals from 2009 through 2013, just above 60% distributed for food animal use are "medically-important" drugs, that are also used in humans.[39] The rest are drug classes like ionophores which are not used in human medicine.[41] Due to concerns about the overuse of antibiotics in food-producing animals, the U.S. Food & Drug Administration has implemented new industry guidelines that will restrict the use of medically-important drugs to uses "that are considered necessary for assuring animal health" and will require veterinary oversight.[42] The food animal and veterinary pharmaceutical industries will need to phase out medically important antimicrobial use by January 1, 2017.[43]

Eighty percent of antibiotics sold in the United States are used on livestock. The majority of these antibiotics are given to animals that are otherwise healthy. Rather, it is normal practice to mix antibiotics with fodder to promote healthier living conditions and to encourage animal growth.[44] The use of antibiotics in animals is to a large degree involved in the emergence of antibiotic-resistant microorganisms.[45] Antibiotics are used in food with the intention of not only preventing, controlling, and treating diseases, but also to promote growth.[46] Antibiotic use in animals can be classified into therapeutic, prophylactic, metaphylactic, and growth promotion uses of antibiotics.[47] All four patterns select for bacterial resistance, since antibiotic resistance is a natural evolutionary process, but the non-therapeutic uses expose larger number of animals, and therefore of bacteria, for more extended periods, and at lower doses. They therefore greatly increase the cross-section for the evolution of resistance.

The origins of antibiotic-resistant Staphylococcus aureus (CAFO: concentrated animal feeding operations)

[48] Since the last third of the 20th century, antibiotics have been used extensively in animal husbandry. In 2013, 80% of antibiotics used in the US were used in animals and only 20% in humans; in 1997 half were used in humans and half in animals.[49] Some antibiotics are not used and not considered significant for use in humans, because they either lack efficacy or purpose in humans, such as ionophores in ruminants,[50] or because the drug has gone out of use in humans. Others are used in both animals and humans, including penicillin and some forms of tetracycline.[51] Historically, regulation of antibiotic use in food animals has been limited to limiting drug residues in meat, egg, and milk products, rather than by direct concern over the development of antibiotic resistance. This mirrors the primary concerns in human medicine, where, in general, researchers and doctors were more concerned about effective but non-toxic doses of drugs rather than antibiotic resistance.

In 2001, the Union of Concerned Scientists estimated that greater than 70% of the antibiotics used in the U.S. are given to food animals (for example, chickens, pigs, and cattle), in the absence of disease.[49][52] The amounts given are termed "sub-therapeutic", i.e., insufficient to combat disease. Despite no diagnosis of disease, the administration of these drugs result in decreased mortality and morbidity and increased growth in the animals so treated. It is theorized that sub-therapeutic dosages kills some, but not all, of the bacterial organisms in the animal – likely leaving those that are naturally antibiotic-resistant.[53] Studies have shown, however, that, in essence, the overall population levels of bacteria are unchanged; only the mix of bacteria is affected.[citation needed] The actual mechanism by which sub-therapeutic antibiotic feed additives serve as growth promoters is thus unclear. Some people have speculated that animals and fowl may have sub-clinical infections, which would be cured by low levels of antibiotics in feed, thereby allowing the creatures to thrive. No convincing evidence has been advanced for this theory, and the bacterial load in an animal is essentially unchanged by use of antibiotic feed additives. The mechanism of growth promotion is therefore probably something other than "killing off the bad bugs".

Antibiotics are used in U.S. animal feed to promote animal productivity.[54][55] In particular, poultry feed and drinking water is a common route of administration of drugs, because of higher overall costs when drugs are administered by handling animals individually.

In research studies, occasional animal-to-human spread of antibiotic-resistant organisms has been demonstrated. Resistant bacteria can be transmitted from animals to humans in three ways: by consuming animal products (milk, meat, eggs, etc.), from close or direct contact with animals or other humans, or through the environment.[56] In the first pathway, food preservation methods can help eliminate, decrease, or prevent the growth of bacteria in some food classes. Evidence for the transfer of macrolide-resistant microorganisms from animals to humans has been scant,[citation needed] and most evidence shows that pathogens of concern in human populations originated in humans and are maintained there, with rare cases of transference to humans.[57][58]

China

China produces and consumes the most antibiotics of all countries.[59] Antibiotic use has been measured by checking the water near factory farms in China[60][61] as well as through animal dung.[62] It was calculated that 38.5 million kg (or 84.9 million lbs) of antibiotics were used in China's swine and poultry production in 2012.[63] The abuse of antibiotics caused severe pollution of soil and surface water in Northern China.[64]

India

In 2012 India manufactured about a third of the total amount of antibiotics in the world.[65]

Brazil

Brazil is the world's largest exporter of beef and the government regulates antibiotic use in the cattle production industry.[66]

Concerns about antibiotic resistance

More recently, there has been increased concern about the use of anti-microbials in animals (including pets, livestock, and companion animals) contributing to the rise in antibiotic resistant infections in humans. The use of antimicrobials has been linked to the rise of resistance in every drug and species where it has been studied, including humans and livestock. However, the role of antibiotic use in food animals – in contrast to the use of antibiotics in humans – in the rise of resistant infections in humans is in dispute. The use of antimicrobials in various forms is widespread throughout animal industry, and is an essential part in preventing animals from suffering from disease and economic loss to farmers. It is linked by some activist groups to the animal welfare concern, large scale commercial agriculture, international food trade, agricultural protectionist laws, environmental protection (including climate change) and other topics, which make the aims of some groups on both sides of the debate difficult to untangle.

Around 70% of all antibiotics administered are used for livestock. Some drugs are used in livestock feed to prevent illnesses and or increase growth rates, but others are used as injection to treat illnesses to prevent death. The use of antibiotics in livestock can be harmful to humans because it can create an antibiotic resistant bacteria in humans that can be transferred through several different ways such as: raw meats, consumption of meats, as well as ingestion through airborne bacteria. Waste from food-producing animals can also contain antibiotic-resistant bacteria and is sometimes stored in lagoons. This waste is often sprayed as fertilizer and can thus contaminate crops and water with the antibiotic-resistant bacteria.[67] Although antibiotic use in livestock can be harmful to humans, most see it as a necessary evil to prevent disease and death in out livestock. Antibiotic resistance makes humans resistant to certain types of drugs for different diseases, as well as makes it harder for them to fight off infections.[68]

The World Health Organization has published a list of Critically Important Antimicrobials for Human Medicine with the intent that it be used "as a reference to help formulate and prioritize risk assessment and risk management strategies for containing antimicrobial resistance due to human and non-human antimicrobial use."[69]

Effects in humans

The effects of antibiotic usage in livestock transferring to humans has been well documented for over 40 years.[18] It was first documented in 1976, where a study followed a novel antibiotic being used in livestock. The bacteria in animals and workers were regularly followed to record translational effects. The findings revealed that within 2 weeks, the bacteria found in the guts of animals fed antibiotics were resistant to the new antibiotic.[70] Additionally, the resistant bacteria had spread to farm's laborers within 6 months. The bacteria in the stool of the laborers were tested and contained more than 80% resistance to the initial antibiotic given to the livestock.[19] Since the primary study, there have been many well documented events showing that antibiotic usage in livestock results in direct influence of antibiotic resistance in humans.

Major bacterial infections in humans can be traced back to livestock. The family of bacteria, Enterobacteriaceae, include many opportunistic pathogens.[70] These bacteria are commonly found in livestock and commercial meats. These include Escherichia coli, Klebsiella and Staphylococcus aureus. Representing urinary and digestive tract infections, skin infections and bloodstream infections- they account for a significant portion of antibiotic resistant bacterial infections.[70]

These resistant strains of bacteria are easily transmitted between one farm animal to another, between humans, and between animals and humans. Besides being a threat to health in essence, they also carry genetic information that can lead to other bacteria spreading and gaining resistant traits in humans, or acting as a vector for desirable plasmids.[18] Thus, not only is there a direct threats of infection from them, but also the implication that other bacteria in a person can acquire the mutant traits of antibiotics resistance.

Positions of advocates for restricting antibiotic use

The practice of using antibiotics for growth stimulation is problematic for these reasons:

  • it is the largest use of antimicrobials worldwide[71]
  • subtherapeutic use of antibiotics results in bacterial resistance[71]
  • every important class of antibiotics are being used in this way, making every class less effective[71]
  • the bacteria being changed harm humans[71]

Donald Kennedy, former director of the United States Food and Drug Administration, has said "There's no question that routinely administering non-therapeutic doses of antibiotics to food animals contributes to antibiotic resistance."[72] David Aaron Kessler, another former director of the FDA, said that "We have more than enough scientific evidence to justify curbing the rampant use of antibiotics for livestock, yet the food and drug industries are not only fighting proposed legislation to reduce these practices, they also oppose collecting the data."[73]

In 2013 the United States Centers for Disease Control and Prevention (CDC) published a white paper discussing antibiotic resistance threats in the US and calling for "improved use of antibiotics" among other measures to contain the threat to human health. The CDC asked leaders in agriculture, healthcare, and other disciplines to work together to combat the issue of increasing antibiotic resistance.[74]

Some scientists have said that "all therapeutic antimicrobial agents should be available only by prescription for human and veterinary use."[75]

The Pew Charitable Trusts have stated that "hundreds of scientific studies conducted over four decades demonstrate that feeding low doses of antibiotics to livestock breeds antibiotic-resistant superbugs that can infect people. The FDA, the U.S. Department of Agriculture and the Centers for Disease Control and Prevention all testified before Congress that there is a definitive link between the routine, non-therapeutic use of antibiotics in food animal production and the challenge of antibiotic resistance in humans."[76]

Moderate positions

The World Organisation for Animal Health has acknowledged the need to protect antibiotics but argued against a total ban on antibiotic use in animal production.[77]

Positions of advocates for status quo

In 2011 the National Pork Producers Council, an American trade association, has said "Not only is there no scientific study linking antibiotic use in food animals to antibiotic resistance in humans, as the U.S. pork industry has continually pointed out, but there isn't even adequate data to conduct a study."[78] The statement contradicts scientific consensus,[79] and was issued in response to a United States Government Accountability Office report that asserts "antibiotic use in food animals contributes to the emergence of resistant bacteria that may affect humans".[80]

The National Pork Board, a Government-owned corporation of the United States, has said that "the vast majority of producers use (antibiotics) appropriately."[81]

Effects of restricting antibiotic use

When government regulation restricts use of antibiotics the negative economic impact is not often considered.[82]

Regulation of antibiotics in livestock production would affect the business models of corporations including Tyson Foods, Cargill, and Hormel.[83]

Difficulties with determining relevant facts

It is difficult to set up a comprehensive surveillance system for measuring rates of change in antibiotic resistance.[84] The US Government Accountability Office published a report in 2011 stating that government and commercial agencies had not been collecting sufficient data to make a decision about best practices.[85]

Currently there is no regulatory agency in the United States that systematically collects detailed data on antibiotic use in humans and animals. It is not clear which antibiotics are prescribed for which purpose and at what time. Furthermore, the world has no surveillance infrastructure to monitor emerging antibiotic resistance threats. Because of these issues, it is difficult to quantify antibiotic resistance, to regulate antibiotic prescribing practices, and to detect and respond to rising threats.[74]

Specific resistance that has been identified and human impact

There have been many studies that document antibiotic resistant bacteria in livestock, though the impact of the different bacteria in humans is still undergoing research. At this time, the most well-documented impact on humans is foodborne gastrointestinal illness. In most cases, these illnesses are mild and do not require antibiotics; though if the infectious bacteria is drug-resistant, research has shown that these bacteria have increased virulence (ability to cause disease), leading to prolonged illness. Furthermore, in approximately 10% of cases, the disease becomes severe, requiring more advanced treatments. These treatments can take the form of intravenous antibiotics, supportive care for blood infections, and hospital stays, leading to higher costs and greater morbidity with a trend toward higher mortality. Severe disease with this outcome is more common with drug-resistant bacteria.[74][86] Though all people are susceptible, populations shown to be at higher risk for severe disease include children, the elderly, and those with chronic disease.[74][87][88]

Over the past 20 years, the most common drug-resistant foodborne bacteria in industrialized countries have been non-typhoidal salmonella and campylobacter. Research has consistently shown the main contributing factors are bacteria sourced in livestock.[86] One example of this was a 1998 outbreak of multidrug-resistant salmonella in Denmark linked back to two Danish swine herds.[87] Coupled with the discovery of this link, there have been improved monitoring systems that have helped to quantify the impact. In the United States, it is estimated that there are approximately 400,000 cases and over 35,000 hospitalizations per year attributable to increasing resistant strains of salmonella and campylobacter. In terms of financial impact in the US, the treatment of non-typhoidal salmonella infections alone is now estimated to cost $365 million per year.[74][89] In light of this, in its inaugural 2013 report on antibiotic resistance threats in the United States, the CDC identified resistant non-typhoidal salmonella and campylobacter as "serious threats" and called for improved surveillance and intervention in food production moving forward.[74]

There are other bacteria as well, where research is evolving and revealing that bacterial resistance acquired through use in livestock may be contributing to disease in humans. Examples of these include Enterococcus, E. coli 0157 and Staphylococcus Aureus. In the case of foodborne illness from E.coli, though it is still not typically treated with antibiotics because of associated risk of renal failure, increasing rates of antibiotic resistant infections have been correlated with increasing virulence of the bacteria.[89][90] In the case of enterococcus and staphylococcus aureus, resistant forms of both of these bacteria have resulted in greatly increasing morbidity and mortality in the US.[74] At this point, there have been studies, though a limited number, that definitively link antibiotic use in food production to these resistance patterns in humans and further research will help to further characterize this relationship.[88][91][92]

Mechanisms for transfer to humans

Humans can be exposed to antibiotic-resistant bacteria by ingesting them through the food supply. Dairy products, ground beef and poultry are the most common foods harboring these pathogens.[93] There is evidence that a large proportion of resistant E. coli isolates causing blood stream infections in people are from livestock produced as food.[94]

When manure from antibiotic-fed swine is used as fertilizer elsewhere, the manure may be contaminated with bacteria which can infect humans.[95]

Studies have also shown that direct contact with livestock can lead to the spread of antibiotic-resistant bacteria from animals to humans.,[96][97]

Antibiotic resistant bacteria can spread to humans through a variety of routes including: soil and groundwater, direct contamination of farm workers, insect vectors, and infecting meat during the butchering process.[18] From the livestock to worker perspective, this puts entire communities of people at risk of acquiring antibiotic resistant bacteria. Articles such as clothes or materials can indirectly and unintentionally aid the transmission of these resistant strains of bacteria to larger human populations.

Sampling of retail meats such as turkey, chicken, pork and beef consistently show high levels of Enterobacteriaceae. Rates of resistant bacteria in these meats are high as well. Sources on contaminated meat put humans at direct risk by handling the meat or ingesting it before it is completely cooked.[70] In these instances, we are ingesting the living bacteria as well. Ingesting contaminated meat sources, as mentioned above, account for 20% of antibiotic resistant infections in humans.

Action and advocacy by country

Legislation and activism worldwide have aimed at restricting antibiotic use in livestock.

European Union

On 1 January 2006 the European Union banned the non-medicinal use of antibiotics in livestock production.[98]

United States

During 2007, two federal bills (S. 549[99] and H.R. 962[100]) aimed at phasing out "nontherapeutic" antibiotics in U.S. food animal production. The Senate bill, introduced by Sen. Edward "Ted" Kennedy, died. The House bill, introduced by Rep. Louise Slaughter, died after being referred to Committee.

In March 2012, the United States District Court for the Southern District of New York, ruling in an action brought by the Natural Resources Defense Council and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock that violated FDA regulations.[101] On April 11, 2012 the FDA announced a voluntary program to phase out unsupervised use of drugs as feed additives and convert approved over-the-counter uses for antibiotics to prescription use only, requiring veterinarian supervision of their use and a prescription.[102][103] In December 2013, the FDA announced the commencement of these steps to phase out the use of antibiotics for the purposes of promoting livestock growth.[49][104] Some grocery stores have policies about voluntarily not selling meat produced by using antibiotics to stimulate growth. In 2012 in the United States advocacy organization Consumers Union organized a petition asking the store Trader Joe's to discontinue the sale of meat produced with antibiotics.[105]

The U.S. Animal Drug User Fee Act was passed by Congress in 2008 and requires that drug manufacturers report all sales of antibiotics into the food animal production industry.[106][107]

Some proposed legislation in the US has failed to be adopted.[108] The Animal Drug and Animal Generic Drug User Fee Reauthorization Act of 2013 proposes other regulation.

In the United States the danger of emergence of antibiotic-resistant bacterial strains due to wide use of antibiotics to promote weight gain in livestock was determined by the United States Food and Drug Administration in 1977, but nothing effective was done to prevent the practice. In March, 2012 the United States District Court for the Southern District of New York, ruling in an action brought by the Natural Resources Defense Council and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock which violated FDA regulations.[101] On 11 April 2012 the FDA announced a program to phase out unsupervised use of drugs as feed additives and, on a voluntary basis, convert approved uses for antibiotics to therapeutic use only, requiring veterinarian supervision of their use and a prescription.[102]

In response to consumer concerns about the use of antibiotics in poultry, in 2007, Perdue removed all human antibiotics from its feed and launched the Harvestland brand, under which it sold products that met the requirements for an "antibiotic-free" label. By 2014, Perdue had also phased out ionophores (antibiotics used in animals to lower production costs by promoting growth, and preventing disease) from its hatchery and began using the "antibiotic free" labels on its Harvestland, Simply Smart and Perfect Portions products.[109] By 2015, 52% of the company's chickens were raised without the use of any type of antibiotics.[110]

In 1970 the FDA started recommending that antibiotic use in livestock be limited but set no actual regulations governing this recommendation.[1] Further, in 2004 the Government Accountability Office (GAO) heavily critiqued the FDA for not collecting enough information and data on antibiotic use in factory farms. From this the GAO concluded that the FDA does not have enough information to create effective policy changes regarding antibiotic use. In response to this the FDA insisted that more research was being conducted and voluntary efforts within the industry would solve the problem of antibiotic resistance.[111]

Growing U.S. consumer concern about using antibiotics in animal feed has led to greater availability of "antibiotic-free" animal products. For example, chicken producer Perdue removed all human antibiotics from its feed and launched products labeled “antibiotic free” under the Harvestland brand in 2007. Consumer response was positive, and in 2014 Perdue also phased out ionophores from its hatchery and began using the “antibiotic free” labels on its Harvestland, Simply Smart, and Perfect Portions products.[109]

China

In 2012, U.S. News & World Report described the Chinese government's regulation of antibiotics in livestock production as "weak".[112]

India

In 2011 the Indian government proposed a "National policy for containment of antimicrobial resistance".[113] Other policies set schedules for requiring that food producing animals not be given antibiotics for a certain amount of time before their food goes to market.[114][115] A study released by Centre for Science and Environment (CSE) on 30 July 2014 found antibiotic residues in chicken. This study claims that Indians are developing resistance to antibiotics – and hence falling prey to a host of otherwise curable ailments. Some of this resistance might be due to large-scale unregulated use of antibiotics in the poultry industry. CSE finds that India has not set any limits for antibiotic residues in chicken and says that India will have to implement a comprehensive set of regulations including banning of antibiotic use as growth promoters in the poultry industry. Not doing this will put lives of people at risk.[116]

Brazil

Antibiotic resistant bacteria have been found in Brazilian cattle.[117]

South Korea

In 1998 some researchers reported use in livestock production was a factor in the high prevalence of antibiotic resistant bacteria in Korea.[118] In 2007 The Korea Times noted that Korea has relatively high usage of antibiotics in livestock production.[119] In 2011 the Korean government banned the use of antibiotics as growth promoters in livestock.[120]

New Zealand

In 1999 the New Zealand government issued a statement that they would not then ban the use of antibiotics in livestock production.[121] In 2007 ABC Online reported on antibiotic use in chicken production in New Zealand.[122]

Research into alternatives

Increasing concern due to the emergence of antibiotic resistant bacteria has led researchers to look for alternatives to using antibiotics in livestock.[123]

Probiotics, cultures of a single bacteria strain or mixture of different strains, are being studied in livestock as a production enhancer.[124]

Prebiotics are non-digestible carbohydrates. The carbohydrates are mainly made up of oligosaccharides which are short chains of monosaccharides. The two most commonly studied prebiotics are fructooligosaccharides (FOS) and mannanoligosaccharides (MOS). FOS has been studied for use in chicken feed. MOS works as a competitive binding site, as bacteria bind to it rather than the intestine and are carried out.[125]

Bacteriophages are able to infect most bacteria and are easily found in most environments colonized by bacteria, and have been studied as well.[123]

In another study it was found that using probiotics, competitive exclusion, enzymes, immunomodulators and organic acids prevents the spread of bacteria and can all be used in place of antibiotics.[126] Another research team was able to use bacteriocins, antimicrobial peptides and bacteriophages in the control of bacterial infections.[127] While further research is needed in this field, alternative methods have been identified in effectively controlling bacterial infections in animals. All of the alternative methods listed pose no known threat to human health and all can lead the elimination of antibiotics in factory farms. With further research it is highly likely that a cost effective and health effective alternative could and will be found.

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External links

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