Subtherapeutic antibiotic use in swine

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Commercial swine production CAFO hogs.jpg
Commercial swine production

Antibiotics are commonly used in commercial swine production in the United States and around the world. They are used for disease treatment, disease prevention and control, and growth promotion. When used for growth promoting purposes, antibiotics are given at low concentrations for long periods of time. [1] Low concentration of antibiotics, also referred to as subtherapeutic (STA), are given as feed and water additives which improve daily weight gain and feed efficiency through alterations in digestion and disease suppression. [2] Additionally, the use of STA in swine results in healthier animals and reduces the “microbial load” on meat resulting in an assumed decrease in potential Foodborne illness risk. [3] [4] [5] While the benefits of subtherapeutic antibiotic administration are well-documented, there is much concern and debate regarding the development of bacterial antibiotic resistance associated with their use.

Contents

This is a specific case of the more general practice of antibiotic use in livestock.

Amount and types of antibiotics used

Currently, there appears to be a lack of reliable data associated with the amount of antibiotics used in livestock production. [6] In 2001, the Union of Concerned Scientists (UCS) published that 24.6 million pounds of antibiotics are used annually for growth promotant purposes. This, they claimed, represented 70% of the antibiotics produced annually in the United States. [7] However, groups such as the Animal Health Institute have taken issue with this figure, accusing the UCS of using questionable methods and assumptions. [6] Listed in Table 1 are the specific types of antibiotics used in swine disease treatment, prevention and growth promotion and their importance in human medicine.

AntibioticUse in SwineImportance in Human Medicine
Sulfonamide
Growth
Not
Cephalosporin (3rd gen)
Disease treatment
Critical
Pencillins
Disease treatment, growth
High
Macrolides
Disease treatment, prevention, and growth
Critical
Tetracycline
Disease treatment, prevention, and growth
High
Lincosamide
Disease treatment
High
Pleuromutilin
Growth
Not
Polypeptide
Growth
Not
Carbadox
Growth
Not

Table 1- Commonly used antibiotics in swine production and their relative importance in human medicine. With regard to human medicine importance, FDA ranks antibiotics as “critically important” (“critical” in the above table), “highly important” (“high” in the table), or “important.” The ranking is based on five criteria from the most important (it is used in treating pathogens that cause foodborne disease) to the least important (there is difficulty in transmitting resistance across genera and species). [6] : 4 

Antibiotic resistance development

Bacterial antibiotic resistance is a process that can occur when bacteria are exposed to STA administration. When a population of bacteria that resides in a hog are exposed to a particular antibiotic for growth promotant purposes, the bacteria that are susceptible to the drug die while the organisms that are resistant will not be affected and will continue to replicate, resulting in a higher proportion of resistant organisms. [8] It has been shown that resistance to antibiotics develops in animals that are fed subtherapeutic doses of antibiotics for growth promoting purposes. [9] Certain bacteria that have the potential to cause human illness, such as Salmonella, that naturally reside in the swine gastrointestinal tracts are constantly exposed to antibiotics. With time, these bacteria become resistant to that class of antibiotics. There is great concern regarding the probability of subtherapeutic antibiotic use in swine causing treatment failures in human medicine. [6]

Resistance and the risk of treatment failure

There is concern that use of antibiotics in swine is leading to an increase in resistant bacteria. The reason for concern is that these resistant bacteria could lead to food-borne illness that is less responsive to treatment. Many proponents of the ban cite the “precautionary principle” of public health, which states if there is evidence of harm, the method in question should be avoided. [10] Risk assessment studies have explored the possibility of harm more objectively through causal pathways and model building. [1] These studies show a very small risk of failure of medical treatment due to resistant bacteria caused by the feeding of STA to livestock. For example, a stochastic risk assessment done in 2008 showed that the risk of consequences from an infection with drug resistant Campylobacteriosis was approximately 1 in 82 million. [3]

The general causal pathway depends on a number of variables and probabilities. First, the animal must be harboring resistant bacteria and the bacteria have a probability that they can survive from the animal to the dinner table at infectious doses. [11] Humans must then be exposed to these resistant bacteria by eating undercooked meat or coming into contact with them in the environment. Resistant bacteria and their genetic material that codes for resistance are not only found in food, but also the environment. For example, studies have found that resistant bacteria can leak from hog waste lagoons into ground water, creating an exposure through the public water supply. [12] Upon exposure, an individual must develop illness that is severe enough for them to seek medical attention. Factors such as age and immune system condition may influence disease susceptibility, which could impact the severity of disease. If the individual becomes ill and needs medical attention, a physician may prescribe an antibiotic. This pathway depends on the medical doctor’s ability to identify potential antibiotic resistance before prescribing treatment to a patient affected by food-borne illness. [1] [3] [4] [5] If the bacteria causing the illness is resistant to the drug the physician recommended, then the illness will not be improved by the medication. This could potentially lead to increased morbidity and mortality. [13]

European ban and legislation in the United States

In 1999, the European Union banned the use of subtherapeutic antibiotics in livestock. Data from Europe, particularly from Denmark, shows that the prevalence of bacteria resistant to particular antibiotics has decreased since the ban. [14] Some opponents of the use of subtherapeutic antibiotics in swine cite data and results from Europe to support a ban in the United States. They argue that since the ban in Europe, antibiotics resistance has decreased while the overall health of swine has remained the same. [10]

In 2003, the Food and Drug Administration of the USA released Guidance #152, which makes recommendations on how to best develop new animal drugs with regard to the potential impacts on human health. [15] In the summer of 2010, the FDA released Guidance #209, which suggests limited livestock use of antibiotics that are medically important to humans. [16] In 2009, Rep. Louise Slaughter introduced HR 1549, otherwise known as The Preservation of Antibiotics for Medical Treatment Act (PAMTA). Under this bill, medically important antibiotics would be phased out in livestock and other restrictions would be placed on antibiotic use in food-producing animals. [17] Some scientists argue that withdrawing antibiotic use will result in more diseased animals, which can result in an increased bacterial load on meat and an increased risk of food-borne illness. [1] Opponents of such a ban argue that the economic implications would be devastating in terms of higher food prices. One study found that the price of pork would increase five cents a pound. [18]

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Antimicrobial resistance</span> Resistance of microbes to drugs directed against them

Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance where the drugs are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR) and are sometimes referred to as superbugs. Although antimicrobial resistance is a naturally occurring process, it is often the result of improper usage of the drugs and management of the infections.

<i>Campylobacter</i> Genus of gram-negative bacteria

Campylobacter is a type of bacteria that can cause a diarrheal disease in people. Its name means "curved bacteria", as the germ typically appears in a comma or "s" shape. According to its scientific classification, it is a genus of gram-negative bacteria that is motile.

<span class="mw-page-title-main">Drug resistance</span> Pathogen resistance to medications

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant.

<i>Klebsiella pneumoniae</i> Species of bacterium

Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.

<span class="mw-page-title-main">Campylobacteriosis</span> Medical condition

Campylobacteriosis is among the most common infections caused by a bacterium in humans, often as a foodborne illness. It is caused by the Campylobacter bacterium, most commonly C. jejuni. It produces an inflammatory, sometimes bloody, diarrhea or dysentery syndrome, and usually cramps, fever and pain.

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

<span class="mw-page-title-main">Tetracycline antibiotics</span> Type of broad-spectrum antibiotic

Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named after their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloro, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.

<span class="mw-page-title-main">Medical microbiology</span> Branch of medical science

Medical microbiology, the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases. In addition, this field of science studies various clinical applications of microbes for the improvement of health. There are four kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.

Enterococcus faecium is a Gram-positive, gamma-hemolytic or non-hemolytic bacterium in the genus Enterococcus. It can be commensal in the gastrointestinal tract of humans and animals, but it may also be pathogenic, causing diseases such as neonatal meningitis or endocarditis.

<span class="mw-page-title-main">Antibiotic misuse</span>

Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse, refers to the misuse or overuse of antibiotics, with potentially serious effects on health. It is a contributing factor to the development of antibiotic resistance, including the creation of multidrug-resistant bacteria, informally called "super bugs": relatively harmless bacteria can develop resistance to multiple antibiotics and cause life-threatening infections.

<span class="mw-page-title-main">Animal Drug Availability Act 1996</span> US law

The Animal Drug Availability Act 1996 (ADAA) is a United States federal law. President Clinton signed the ADAA into law in October 1996. While still obligated to public health concerns, the Act intends more rapid drug approval and medicated feed approval to assist the animal health industry.

<span class="mw-page-title-main">Quinolone antibiotic</span> Class of antibacterial drugs, subgroup of quinolones

Quinolone antibiotics constitute a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as well as in animal husbandry, specifically poultry production.

<i>Staphylococcus hyicus</i> Species of bacterium

Staphylococcus hyicus is a Gram-positive, facultatively anaerobic bacterium in the genus Staphylococcus. It consists of clustered cocci and forms white circular colonies when grown on blood agar. S. hyicus is a known animal pathogen. It causes disease in poultry, cattle, horses, and pigs. Most notably, it is the agent that causes porcine exudative epidermitis, also known as greasy pig disease, in piglets. S. hyicus is generally considered to not be zoonotic, however it has been shown to be able to cause bacteremia and sepsis in humans.

Antimicrobials destroy bacteria, viruses, fungi, algae, and other microbes. The cells of bacteria (prokaryotes), such as salmonella, differ from those of higher-level organisms (eukaryotes), such as fish. Antibiotics are chemicals designed to either kill or inhibit the growth of pathogenic bacteria while exploiting the differences between prokaryotes and eukaryotes in order to make them relatively harmless in higher-level organisms. Antibiotics are constructed to act in one of three ways: by disrupting cell membranes of bacteria, by impeding DNA or protein synthesis, or by hampering the activity of certain enzymes unique to bacteria.

<span class="mw-page-title-main">Antibiotic use in livestock</span> Use of antibiotics for any purpose in the husbandry of livestock

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 group of animals when at least one is diagnosed with clinical infection (metaphylaxis), and preventative treatment (prophylaxis). Antibiotics are an important tool to treat animal as well as human disease, safeguard animal health and welfare, and support food safety. However, used irresponsibly, this may lead to antibiotic resistance which may impact human, animal and environmental health.

<span class="mw-page-title-main">One Health Model</span> Concept of interaction between all components of the global ecosystem determining its health

The concept of One Health is the unity of multiple practices that work together locally, nationally, and globally to help achieve optimal health for people, animals, and the environment. When the people, animals, and environment are put together they make up the One Health Triad .The One Health Triad shows how the health of people, animals, and the environment is linked to one another. With One Health being a worldwide concept, it makes it easier to advance health care in the 21st century. When this concept is used, and applied properly, it can help protect people, animals, and the environment in the present and future generations.

ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.

Antibiotic use in the United States poultry farming industry is the controversial prophylactic use of antibiotics in the country's poultry farming industry. It differs from the common practice in Europe, where antibiotics for growth promotion were disallowed in the 1950s.

References

  1. 1 2 3 4 Cox, L.A.; Popken (2010). "Assessing Potential Human Health Hazards and Benefits from Subtherapeutic Antibiotics in the United States: Tetracyclines as a Case Study". Risk Analysis. 30 (3): 432–458. Bibcode:2010RiskA..30..432C. doi:10.1111/j.1539-6924.2009.01340.x. PMID   20136749. S2CID   19486583.
  2. ↑ MacDonald, J.M.; McBride (January 2009). "The Transformation of U.S. livestock agriculture: Scale, efficiency, and risks". Economic Information Bulletin. No. (EIB-43). Archived from the original on 2012-06-29. Retrieved 2011-10-25.{{cite journal}}: |volume= has extra text (help)
  3. 1 2 3 Hurd, H.S.; Malladi (2008). "A stochastic assessment of the public health risks of the use of macrolide antibiotics in food animals". Risk Analysis. 28 (3): 695–710. Bibcode:2008RiskA..28..695H. doi:10.1111/j.1539-6924.2008.01054.x. PMID   18643826. S2CID   8201863.
  4. 1 2 Arsenault, J; et al. (2007). "Prevalence and risk factors for Salmonella and Campylobacter spp. carcass contamination in turkeys slaughtered in Quebec". Journal of Food Protection. 70 (6): 1350–1359. doi: 10.4315/0362-028X-70.6.1350 . PMID   17612063.
  5. 1 2 Singer, R.S.; et al. (2007). "Modeling the relationship between food animal health and human foodborne illness". Prev Vet Med. 79 (2–4): 186–203. doi:10.1016/j.prevetmed.2006.12.003. PMID   17270298.
  6. 1 2 3 4 Becker, Geoffrey (January 2010). "Antibiotic Use in Agriculture: Background and Legislation" (PDF). Congressional Research Service: 1–15.
  7. ↑ Union of Concerned Scientists (January 2001). "Hogging It: Estimates of Antimicrobial Abuse in Livestock".{{cite journal}}: Cite journal requires |journal= (help)
  8. ↑ CDC. "Antibiotic resistance 101" . Retrieved 2011-10-25.
  9. ↑ Mathew, A.; et al. (2007). "Antibiotic Resistance in Bacteria Associated with Food Animals: A United States Perspective of Livestock Production". Foodborne Pathogens and Disease. 4 (2): 115–133. doi:10.1089/fpd.2006.0066. PMID   17600481.
  10. 1 2 Marshall; Levy (Oct 2011). "Food Animals and Antimicrobials: Impacts on Human Health". Clinical Microbiology Reviews. 24 (4): 718–733. doi:10.1128/cmr.00002-11. PMC   3194830 . PMID   21976606.
  11. ↑ Snary, E.L.; et al. (2004). "Antimicrobial resistance: a microbial risk assessment perspective". Journal of Antimicrobial Chemotherapy . 53 (6): 906–917. doi: 10.1093/jac/dkh182 . PMID   15102745.
  12. ↑ Koike, S.; et al. (2007). "Monitoring and Source Tracking of Tetracycline Resistance Genes in Lagoons and Groundwater Adjacent to Swine Production Facilities over a 3-Year Period". Applied and Environmental Microbiology. 73 (15): 4813–23. Bibcode:2007ApEnM..73.4813K. doi:10.1128/aem.00665-07. PMC   1951052 . PMID   17545324.
  13. ↑ Witte, W. (2000). "Selective pressure by antibiotic use in livestock". International Journal of Antimicrobial Agents. 16 (1): 19–24. doi:10.1016/s0924-8579(00)00301-0. PMID   11137404.
  14. ↑ Aarestrup, F.M.; et al. (2010). "Changes in the use of antimicrobials and the effects on productivity of swine farms in Denmark". Am. J. Vet. Res. 71 (7): 726–733. doi: 10.2460/ajvr.71.7.726 . PMID   20594073. S2CID   38975663.
  15. ↑ Food and Drug Administration (October 2003). "Evaluating the safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern" (PDF). Guidance #152.{{cite journal}}: Cite journal requires |journal= (help)
  16. ↑ Food and Drug Administration. "The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals" (PDF). Food and Drug Administration . Retrieved 2011-11-15.
  17. ↑ Slaughter, Louise. "PAMTA" . Retrieved 2011-11-20.
  18. ↑ Hayes; et al. (2001). "Economic impact of a ban on the use of over the counter antibiotics in U.S. swine rations". International Food and Agribusiness Management Review. 4: 81–97. doi: 10.1016/s1096-7508(01)00071-4 .
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