The Rise of Antibiotic Resistance

Abstract
The discovery of antibiotics was one of the most groundbreaking innovations of medicine. This healthcare staple, responsible for treating diseases that once were incurable, is now becoming less and less effective due to antibiotic resistance. The bacteria responsible can become resistant to this medicine by genetic mutation through reproduction or from other bacteria via transformation, transduction, or conjugation. It is important to understand the methods in which antibiotic resistance occurs to formulate a plan of attack on this healthcare crisis. The largest population of antibiotic users in the U.S. is livestock, as medication is given preventatively and in large quantities so as to protect the herd. Knowing this, efforts are being made to combat it. As of now the two primary strategies to alleviate this pressing matter are to either create new antibiotics to outrun the swift mutations of the bacteria or to lessen the amount of antibiotics consumed which would pause or slow the rate of antibiotic resistance. Both of these approaches come with disadvantages, however these efforts are employed for lack of a better alternative. It is evident that we are on the brink of a pharmaceutical crisis both nationally and globally and more exploration is needed to gain control of antibiotic resistance.

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The Rise of Antibiotic Resistance
Penicillin, the first true antibiotic, was discovered in 1928 (McKinley, 2012). The introduction of antibiotics was ground-breaking. Infections that would have normally been fatal became curable. While this profound discovery would undoubtedly change the world of medicine and science as well as save millions of individuals, it would not come without consequence. Mother nature has taken its course and now resistance to antibiotics is rising to dangerously high levels in all parts of the world. This puts the achievements of modern medicine at risk. Understanding how antibiotics work as well as what the leading causes of resistance are is crucial in finding effective solutions to this global health crisis.
Antibiotics work by killing or slowing the growth of bacteria. When antibiotics are used and reused over time, bacteria evolve to overcome the antibiotics. This resistance is called antibiotic resistance (Van Hoey, 2017). This can happen two ways; by genetic mutation, or by acquiring resistance from another bacterium. Genetic mutations are rare spontaneous changes in the bacteria’s genetic nucleotide sequence. The mutations and resistance spread among people as the bacterial disease is spread (Van Hoey, 2017). Bacterial resistance develops because of changes to enzymes, target sites, or cell-wall components (Van Hoey, 2017). Different mutations can yield different kinds of resistance. Perhaps one mutation would enable the bacteria to produce enzymes that deactivate the antibiotic while other mutations may close the entry port that allows the antibiotic into the cell. The possibilities are vast. Bacteria can also acquire antibiotic resistance genes from other bacteria in several ways. Horizontal transmission can occur via three mechanisms: transformation, when bacteria scavenge resistance genes from dead bacterial cells and integrate them into their own genomes; transduction, when resistance genes are transferred by bacteriophages; or conjugation, when genes are transferred between bacterial cells through tubes called pilli (Gautam & Morten, 2014). Bacteria also reproduce asexually through binary fission and can accumulate mutations during this replication. This is referred to as vertical transmission. Regardless, antibiotic resistance genes can be passed on in all of these methods.
Antibiotic resistance is a global health issue. A growing list of infections such as pneumonia, tuberculosis, blood poisoning, gonorrhea, and foodborne diseases are becoming harder, and sometimes impossible, to treat as antibiotics become less effective. With the spontaneous and varied nature of bacteria acquiring antibiotic resistance, finding a way to overcome this worsening crisis has proven to be a challenge. One method of thinking is to simply create new antibiotics to fight infection. This creates an endless cat and mouse cycle between evolution and medicine. Insert sentence on the difficulty of coming out with new antibiotics. Another method of slowing or preventing the progression of antibiotic resistance is to use antibiotics sparingly. However, if too little antibiotic is used on an individual, the most susceptible bacteria are killed off, leaving a hardy group of survivors that grow and multiple into resistant strains (Schmidt, 2002). Not only is this ineffective in terms of treating patients long-term, but it creates ‘super’ strains of bacteria. Thus, it is important to use antibiotics at dose levels intended to kill as many as possible, if not all of the bacteria present that are causing infection.
Usually when the term antibiotics is brought up, a clinic or hospital comes to mind. However, as much as 70% of the antibiotics produced in the United States today are for use in food animals (Schmidt, 2002). Likewise, in many countries antibiotic use in livestock outweighs human consumption. Antibiotics in food animals allow farmers to grow the animals quicker and they provide a cheaper alternative to keeping them healthy. Furthermore, antibiotics in livestock are given in mass quantities vs. treating just the infected organism. A farmer might treat and entire flock or herd because he believes there is a threat of disease even in the absence of sick animals (Schmidt, 2002). Because of the large quantity of antibiotics given annually to livestock, this is often viewed as the primary driver for the rise of antibiotic resistance. This not only affects the livestock as they die from new strains of disease and don’t have functional antibiotics to help, but also humans, and in more ways than one. Firstly, this issue originates in livestock, which means if the livestock population decreases it can put a strain on one of the world’s most relied upon food sources. It can also create issues for the livestock industry and farmers that rely upon these animals for their livelihood and sustainability. Most concerningly, antibiotic resistance may spread from animals to humans and vice versa; directly by the spread of the resistant bacteria or indirectly by the spread of resistance genes from animal bacteria to human bacteria. According to the World Health Organization’s Global Action Plan on Antimicrobial Resistance, food is one of the possible vehicles for transmission of resistant bacteria from animals to human beings and human consumption of food carrying antibiotic resistant bacteria has led to acquisition of antibiotic-resistant infections (Giubilini, A. et. Al., 2017). Moreover, from 2010 to 2030, the global use of antibiotics in agriculture is predicted to increase by 67%, in part due to expanding demand for livestock products in various countries (Giubilini, A. et. Al., 2017). We must act immediately to put systems in place to properly control the use of such valuable and increasingly scarce drugs.
Recognizing that livestock play a huge role in the war on antibiotic resistance, some countries have taken a proactive approach. In the 1990’s Denmark initiated the ban of antibiotic use for promoting growth in livestock (McKinley, 2012). The World Health Organization found that Denmark’s ban on antibiotics did not harm the farmer’s income or increase animals’ health risk (McKinley, 2012). The ban is not as clear cut as it may seem however in terms of generalizability. The challenge that presents itself with this solution is surveillance. It has been estimated that the total annual consumption of antibiotics in animal agriculture ranges from around 63,000 tons to around 240,000 tons although estimates vary considerably because of lack of adequate surveillance and data collection, particularly in developing countries (Giubilini, A. et. Al., 2017). In order to know truly how many antibiotics farmers are using on their livestock, a surveillance system to monitor them would need to be put in place. This could prove to be difficult to implement on a global scale. Furthermore, it is unclear if verification of illness or documentation is needed for farmers to administer antibiotics as opposed to just breaking the ban and administering antibiotics for growth anyway as well as the repercussions for doing so.
Other theories have evolved on how best to handle this problem including limiting meat consumption and taxing antibiotics. Some believe that introducing a tax on agricultural products produced with the aid of antibiotics is preferable to an outright ban on antibiotic use in animal farming, because they claim (contradictory to Denmark’s outcome) that producers would probably not be able to afford the cost of transitioning immediately to an antibiotic-free system of meat production; however, revenue generated by taxation could be used to fund this transition (Giubilini, A. et. Al., 2017). Taxing antibiotics also would make antibiotics more expensive so as to deter farmers and veterinarians from using them other than when absolutely necessary. This method would also generate money to be invested back into research for new antibiotics.
While the road to the eradication of antibiotic resistance may not be linear, there are many different methods and avenues available for exploration. Perhaps there is no one cure-all solution; rather, a combination of these efforts may be needed.  Nevertheless, it is evident that this crisis is rising. A solution to antibiotic resistance is pertinent to protect the advancements of modern medicine and more importantly, the lives of individuals now and future generations.
References

Van Hoey, N. (2017). “Antibiotic Resistance”. Salem Press Encyclopedia of Health.
Schmidt, C. (2002). Antibiotic Resistance in Livestock: More at Stake than Steak. Environmental Health Perspectives vol 110 number 7.
Gautum D. & Morten S. (2014). How to Fight Back Against Antibiotic Resistance. American Scientist 102.
McKinley, L. (2012). Denmark’s Precautionary Approach to Antibiotic Resistance. Penn Bioethics Journal. Vol 8 Issue 2, p7-8.
Giubilini, A. et. Al. (2017). Taxing Meat: Taking Responsibility for One’s Contribution to Antibiotic Resistance. Journal of Agricultural & Environmental Ethics. 30:179–198