2019 Mizzou Advantage Writing Contest: 1st Place

Antibiotic Use in the Agricultural Industry and the Rise in Resistant Strains

Bacterial resistance to antibiotics has become a controversial issue over the years, ultimately leading to regulations on their use in the agricultural industry. Improper management of antibiotic utilization can result in the development of resistant strains. Furthermore, in the present day, there has been a transfer of these resistant strains to not only animals, but humans as well, leading to concern in society. The government has even implemented legislation limiting antibiotic use. Despite these cons, they do provide benefits for the industry. These include: prevention and treatment against bacteria, improved gastrointestinal function, increased growth in livestock, and a decrease in environmental pollutants (Allen et al., 2013). There are many advantages and disadvantages with using antibiotics, but it is up to the user to implement management plans, specifically in tune with their administration, to prevent resistance from occurring.

Antibiotics are commonly used across all livestock and poultry operations. According to the United States Department of Agriculture, there are only 39 registered antibiotics for use in cattle, swine, and poultry (Durso and Cook, 2014). They contain a broad spectrum of uses but two categories take precedence: disease treatment and improvement of gastrointestinal function. Treated diseases include those that are pathogenic or parasitic in nature (Hao et al., 2014). Pathogenic diseases originate from bacterial or viral infections. Parasitic diseases are caused by a parasite, which are organisms that need a host to survive. As an example, Macrolides and Benzimidazoles effectively control nematodes, parasitic worms, in domestic animals (Hao et al., 2014). On the other hand, antibiotics provide improved gastrointestinal function. These enhancements include better intestinal morphology resulting in more efficient digestion and absorption, increased colonization of intestinal bacteria, inhibition of pathogenic bacteria growth, and superior immune function (Hao et al., 2014). With the enhancement of these factors, animals are able to grow faster due to more efficient nutrient utilization and being more disease-resistant.  Antibiotics are powerful tools for livestock or poultry operations in the agriculture industry and can easily be administrated.

Applying Antibiotics to Animals

General application of antibiotics can be done in two ways, as feed additives or injections (Hao et al., 2014). If the feed additive route were to be taken, the antibiotics could be formulated into the feed itself. The animal will then ingest the feed and internalize the antibiotic within its digestive tract. On the other hand, the injectable method involves a subcutaneous injection. This type of injection involves the applicator injecting the antibiotic within the fatty layer between the skin and muscular tissue. The antibiotic is then absorbed through the neighboring tissues. Either method is suitable, yet some antibiotics are easier to administrate with injection or vice versa. Regardless of the method of administrating the antibiotic, the producer needs to determine the necessary dosage.

There are two types of dosages, either a therapeutic or a nontherapeutic dose (Allen et al., 2013). A therapeutic dose is directed at treating and preventing a disease (Allen et al., 2013). A nontherapeutic dose is given for performance enhancement and is composed of a smaller amount of antibiotic in comparison (Allen et al., 2013). Performance enhancement refers to attributes such as faster growth rates or increased feed efficiency (Centner et al., 2016).  In the last few years, the nontherapeutic dose was banned from the industry, which is still in effect today.

Government Antibiotic Legislation

In 2015, during the Obama administration, the National Action Plan for Combating Antibiotic-Resistant Bacteria was created to reform antibiotic use and to help prevent resistant strains from developing in agriculture (Centner, 2016). This movement sought to limit therapeutic doses as well as completely eliminate any forms of nontherapeutic doses (Centner, 2016). As previously stated, not only was there a complete removal of nontherapeutic doses, but the FDA stepped in and further intensified the restrictions. The FDA enacted Veterinarian Feed Directives (Centner, 2016).

These regulations contained two principal statutes. The first principal stated, “the use of medically important antimicrobial drugs in food-producing animals should be limited to those uses that are considered necessary for assuring animal health” (Centner, 2016). The second principal mandated that any antimicrobial use must have veterinarian oversight or consultation (Centner, 2016). With both of these laws in effect, producers are now restricted when it comes to purchasing and applying any antibiotics to their livestock or poultry. In reality, it is a warranted restriction. Antibiotics may be the number one treatment for controlling microorganisms, but they can end up cultivating hard-to-manage resistant strains.

Antibiotic Resistance, Transmission, and Sources

Recently in society, individuals have been arguing that animal antibiotic resistance has caused the development of “super bugs” in human health. This claim is inconclusive. According to research done by the Department of Epidemiology at Harvard University, any of the resistant bacteria resulting from animal use is already in the external environment due to continuous mutation in response to its own surroundings (Chang et al., 2014). Some antibiotics have contributed to this development, but it has been minuscule in nature.

Antibiotic resistance is defined as the ability of a bacterial cell to survive and grow despite being exposed to an antibiotic. (Luby et al., 2016). Resistance takes time and continuous exposure of the same antibiotic to develop. Basically, the bacteria has essentially mutated over generations to the point that its mutation has allowed itself to survive a specific antibiotic treatment.  Once established, the resistant bacterium has the ability to take part in horizontal transmission (Luby et al., 2016). Which refers to the fact that the bacterium can pass its resistant genes to neighboring bacteria, producing more resistant bacteria (Luby et al., 2016).

Transmission can occur in two different ways, through direct effects or indirect effects. Direct effects are those that can be linked to contact with antibiotic resistant bacteria from food animals (Landers et al., 2012). These examples include events such as eating contaminated meat, exposure to contaminated animal feed from either livestock or pets, or handling and preparing the contaminated meat. Indirect effects are those that result from contact with resistant bacteria that have been spread to various components of the ecosystem around an individual (Landers et al., 2012). This exposure could be due to the soil, wind, or water. A major contributor to the environmental inoculation of resistant bacteria is manure (Heuer et al., 2011).

Environmental Transmission

Application of manure to the soil and leakage from lagoons are the two main pathways that resistant bacteria can use to contaminate the environment (Heuer et al., 2011). Over time, if the same antibiotics are continuously fed to a group of animals, a higher amount of resistant bacteria accumulation will occur in the feces (Heuer et al., 2011). The feces will be stored and then utilized as fertilizer within the industry. Storage options range from open pits, closed pits, to lagoons, depending on management as well as farm type. Especially within lagoons, leaching can occur from the manure source. A lagoon is a small man-made pond used to hold animal feces. The Department of Animal Sciences at the University of Illinois at Urbana Champaign conducted a study on leaching within swine lagoons and found that over a three-year period, resistant bacteria had developed in localized areas surrounding the lagoons with a genetic match of 99.8% identity (Heuer et al., 2011). This localization can soon spread and infiltrate the groundwater (Heuer et al., 2011).  Once the groundwater is contaminated, it is only a matter of time until it will contaminate the neighboring streams, lakes and rivers. This concept holds true for both open pits and closed pits

Application of the manure as fertilizer can have the same effects with leaching as with lagoons and pits. Fertilizer application involves spreading the manure in a solid, liquid, or slurry form over a plot of land. The only difference is that the producer spreads the feces, instead of the feces leaching out on its own. The Department of Biological Sciences in the United Kingdom conducted a two-year study on slurry application within a swine facility (Heuer et al., 2011). They concluded that three sulfonamide-resistant bacteria strains developed due to the manure application (Heuer et al., 2011). Whether a farm wants to apply or store their manure, they must consider the contents present in their manure. Proper storage, management, and application of manure is crucial in preventing resistant bacterial populations from growing. Regularly testing the contents of livestock manure, as well as the soil in which they reside, is always a prudent course of action. This will help minimize these indirect effects. An individual can not gauge resistance without scientifically testing for it.

There are many different lab tests that can be done to determine resistance, but the most common is molecular testing through DNA. The molecular testing is focusing in on searching for any resistant genes present in the DNA sequence (Luby et al., 2016). The test involves an extraction of the target organism and microscopic visualization (Luby et al., 2016). Specifically for feces, there are fecal analyzers that use fluorescence (Stanton et al., 2013). A sample of feces would be gathered and depending the fluorescence attained, would determine if there were resistant bacterial strains present (Stanton et al., 2013). The prices for each of these tests can have a broad range, depending on the type of test, the company issuing the test, and how extensive the producer wants to be. With the testing and proper management in check, a farming operation can better ensure the control of resistance in their livestock and or poultry. However, with the immense challenge of controlling the risk for resistance, many producers are leaning toward alternatives for antibiotics.

Antibiotic Alternatives

The industry has many alternatives available in the market, yet their effectiveness can be questioned. The main alternatives consist of prebiotics, probiotics, vaccines, bacteriophages, and bacteriocins. Prebiotics are non-living microbial stimulants (Hume et al., 2011). They are described as selectively-fermented components of feed that alter the gut micro biota to benefit the host’s health, such as out-competing harmful pathogens or the stimulation of health-promoting metabolites (Allen et al., 2013).

In contrast, probiotics are living cells which act analogous to prebiotics. Traits are crucial in the selection of a probiotic strain. Desired characteristics of probiotics include being nonpathogenic, resistant to stomach acids and bile, having the potential to colonize the host, production of nutrients, being free of antibiotic resistance genes or having reduced gene transfer functions, and antagonistic to pathogens (Allen et al., 2013).  Fundamentally speaking, the strain must be able to grow in the gut, prevent pathogenic bacteria growth, and not become resistant in the process. Recently researchers have tested products with formulations of both pre and probiotics. The combination is known as synbiotics. This proposes combining prebiotics and probiotics together to achieve improved gut health (Allen at el., 2013). Unfortunately, the findings are juvenile and still require further testing.

Another alternative are vaccines. These can be administrated yearly and have long-lasting effects. They eliminate clinical infections which could in turn reduce the use of therapeutic antibiotics (Allen et al., 2013). The problem with vaccines is that they target specific bacteria, so it takes several different injections to make sure all of the desired strains would be eliminated (Allen et al., 2013). This costs the producer additional money and jeopardizes the welfare of the animal due to the strenuous process. Unless the pharmaceutical industry comes up with several combination vaccines, the application of vaccines could seem excessive as well as expensive for the producer.

Bacteriophages could also be a solution. These are viruses that attack specific bacteria or a narrow group of bacteria (Allen et al., 2013). The only problem with this method is that there is some risk and more management required post-application. Factors that make them most effective are bacteria accessibility, a high concentration of target bacteria, timing the administration in tune with the start of the bacterial infection, as well as making sure that the bacteriophage is neutralized after inoculation (Allen et al., 2013). This has potential for specific animal cases, but treating an entire operation this way may be inefficient. The producer would have to take extra steps each and every time for antimicrobial prevention. Another alternative working hand-in-hand with bacteriophages are bacteriocins. They are specialized proteins selected to kill specific bacteria. They disrupt the bacterium’s membranes, resulting in cell death (Hume et al., 2011). The problem with this product is that not all bacterium are affected by bacteriocins, therefore intensive screening is necessary (Hume et al., 2011).

Difficulties With Alternatives to Antibiotics

With all of these specificities and different modes of action, these alternatives may have difficulty acting upon the gastrointestinal tract as effectively as antibiotics. The difficulty lies with the complexity of the gut. The gastrointestinal tract has an intricate alignment of epithelial cells that separate the microbiota, pathogens, and unfavorable environmental conditions from the host, which create the main site of absorption (Allen et al., 2013).  Here the microbiota compete with intestinal pathogens for nutrients and binding sites that are used to influence the immune system (Allen et al., 2013). Any alternative must be able to effectively commingle with this complex system and keep the homeostatic balance between healthy microbiota and proper immune function (Allen et al., 2013). With all of these moving parts, it can be very difficult to develop any completely effective alternatives.

Recommendations for Operating as an Agricultural Producer

With few effective alternatives available on the market, producers in the agricultural industry need to understand that the reality of antibiotic resistance is unavoidable. Consequently, they need to have a well-designed operation plan to effectively combat it. When utilizing antibiotics, there must be a rotation schedule in place. For example, if a herd of cattle is set on using Neomycin to treat E. coli one month, then there must be a replacement antibiotic that can be rotated in the following month. In accordance with animal waste, manure management must be well-structured. When utilizing different storage methods, there needs to be an emphasis on containment. The goal here is to have no chance for runoff or leaching, which could result in soil or groundwater contamination. Limiting any forms of indirect transmission is key. When applying the manure to the land, farmers should implement plot rotations so that no portion of land ever gets oversaturated with manure. This will minimize resistant bacterial strain development. Frequently testing soil and manure for any resistant strains is also important. If confident in the product, utilize alternatives when possible to help ease the antibiotic pressure. A producer could potentially combine certain products to attain desired results by using synbiotics or utilizing vaccines along side with pre or probiotics.

Following these conditions should result in both low production of resistant bacteria and enhanced maintenance of an efficient operation. Incorporating these actions could result in a more complex production scheme, but the producer does not have to pick the most extensive methods to achieve this business model. Variations can exist within this recommended model so long as resistance is minimized at all levels of production. This encompasses the antibiotics used in production, the animals grown for product, and the manure produced from them. Resistance is a rapidly increasing crisis across the agricultural industry. Producers need to take heed and act before it is too late.

 

Biography photo of Alex Sommerfeldt

My name is Alexander Sommerfeldt and I am an animal science major with a pre-vet emphasis. I am from Chicago, Illinois and lived the entirety of my life there till I went off to college. I have always had an interest in animals my whole life and have been working as a veterinarian technician for over three years. I hope to make it into the vet school this coming fall. Animals have always been my passion and I couldn’t see life without them.

Reference List

Allen, H. K., Levine, U. Y., Looft, T., Bandrick, M., and Casey, T. A. 2013. Treatment, promotion, commotion: antibiotic alternatives in food-producing animals. Sci Drct, 21(3), 114-119.

Centner, t. J. 2016.Recent government regulations in the United States seek to ensure the effectiveness of antibiotics by limiting their agricultural use. Sci Drct, 94, 1-7.

Durso, L. M., & Cook, K. L. 2014. Impacts of antibiotic use in agriculture: what are the benefits and risks? Sci Drct, 19, 37-44.

Hao, H., Cheng, G., Iqbal, Z., Ai, X., Hussain, H., Huang, L., and Dai, M. 2014. Benefits and risks of antimicrobial use in food-producing animals. Frontiers in Microbiology.

Heuer, H., Schmitt, H., and Smalla, K. 2011. Antibiotic resistance gene spread due to manure application on agricultural fields. Sci Drct, 14(3), 236-243.

Hume, M. E. 2011. Historic perspective: Prebiotics, probiotics, and other alternatives to antibiotics. Oxford Academic, 90(11), 2663-2669.

Landers, T. F., Cohen, B., and Wittum, T. E. 2012. A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential. Sage Journals127(1), 4-22.

Luby, E., Ibekwe, M. A., Zilles, J., and Pruden, A. 2016. Molecular Methods for Assessment of Antibiotic Resistance in Agricultural Ecosystems: Prospects and Challenges. Alliance of Crop, Soil, and Environmental Science Societies, 45(2), 441-453.

Stanton, T. B. 2013. A call for antibiotic alternatives research. Sci Drct21(3), 111-113.