Epidemics have historically ravaged the human population since its early existence, but are they a problem of the past? Will we ever have another Scarlet Fever, Spanish Flu, or Black Plague? In 1928, Alexander Fleming discovered the antibiotic, penicillin, the first highly marketed, mass-produced antibiotic. By the early 1940’s, when it was commercially produced, Penicillin was bringing more order to the disarrayed world of illnesses. At the time, demand for more drugs increased, and with 12 new antibiotics being churned out a year [4], widespread disease was deemed to be under control from the public viewpoint. However, even after years of scientific development, the chance for an epidemic still exists.

The Counting Toll


     
Despite our advances, 2 million Americans are infected by drug resistant “superbugs,” and more than 23,000 of them die per year [2]. Fleming warned of drug-resistant bacteria after observing that many microbes were withstanding penicillin. Sustained applications of new drugs have resulted in multidrug resistant bacterium, such as Methicillin-resistant Staphylococcus aureus (MRSA). Methicillin used to be the primary method of treating Staphylococcus aureus but is now ineffective against MRSA. This resilience has had far reaching consequences. The Centers for Disease Control (CDC) found that between 2000 and 2008, cases of sepsis, a life-threatening condition caused by infection, rose from 621,000 to 1,141,000, and deaths rose from 154,000 to 207,0001. Additionally, officials discovered a sample human E. coli with the mcr-1 gene for resistance to colistin5, a last resort pharmaceutical used in the event that no other drug is effective. Economist Jim O’Neill projects that by 2050, an estimated ten million people will die annually due to resistant bacteria. The estimated GDP lost to resistant disease will be $100 trillion [6]. The impacts of antibiotic inefficacy could mean a possible throwback to the microbial dark ages, where a thorn prick can kill you and a hip transplant is no longer worth the risk.

Understanding the Problem


     
Before taking the proper steps to remediate the situation, we must understand the cause. The continued exposure of bacteria to intense and diverse antibiotics has wiped any susceptible microbes, naturally selecting those with the favorable mutations to survive and thrive without competition. These new strains force scientists to move to a new drug, continuing the cycle. In addition to developing resistance through natural selection, bacteria have the ability to transmit resistance through the use of plasmids, loops of self-replicating DNA in bacterial cytosol that carry potentially useful genes. Once resistance develops, the plasmid, can swap between bacteria of the same and of other species through conjugation, in which the bacterial cell membranes are connected through a pilus and the plasmid is replicated and horizontally transferred. However, the ability to resist an antibiotic requires resources; in order for a bacterium to produce a molecule or an enzyme for defense, it must allocate resources away from another important cell function. With no exposure to antibiotics, these bacteria are ecologically less fit and naturally are surpassed by others of their kind. Resistant bacteria would be scarce in nature, however, the introduction of large doses of antibiotics exerts an ecological stress that now favors resistant strains. Antibiotics create a naturally selective system that necessitates these survival systems that did not exist under typical conditions.

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​     If the presence of an antibiotic is what causes resistance, one solution is to reduce the use of antibiotics. Society favors the extensive use of antibiotics. For instance, forty million people receive antibiotics every year while only thirteen million have bacterial infections that can actually benefit from these pharmaceuticals. Accurate and economical diagnosis of patients can drastically reduce the overuse of antibiotics. In addition, agriculture employs the widespread use of antibiotics to supplement the growth of animals. In America, 70% of the medically useful antibiotics are used in the growth and treatment of livestock, these drugs are used as dietary or growth supplements to make up for poor farming practices [6]. Similarly, colistin is widely used in Chinese livestock [5]. The continued usage of these drugs provide more avenues for microbes to gain resistance and transfer the gene and the resistance through food or contaminated soil. As bacterial resistance continues to spread, treatment options become more limited. Simple operations and small infections can become life-threatening. Doctors find themselves relying on colistin despite its unideal nature. It is a half-century-old drug that poses health concerns to the kidney, but with fewer viable options, physicians have no choice. Perhaps soon, even colistin will lose its efficacy.


     Having recognized several sources of the problem, why hasn’t anything been done? With so few tools at hand, why not make more antibiotics? After Penicillin, there was a flood of pharmaceuticals hitting the market. Scientists were developing antibiotics from the dirt in their backyard. The thought of running out of more new drugs was inconceivable. However, having harvested all the low hanging fruits from the 50’s to 70’s, antibiotic production has sputtered to a crawl. For example, the newest antibiotic discovery, as of 2016, is teixobactin. If approved (a process of 5 years), it will be the first antibiotic produced since 1987 [4].

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     Antibiotic production suffers from decreased availability of natural sources, as well as decreased funding. Drug investment has stagnated since the 70’s as large pharmaceutical companies dropped their antibiotic programs. Why? The average expenditure per pharmaceutical is $2.5 billion and because only 1-2% of pharmaceuticals ever reach the market, companies must make many billions of dollars in profit for every successful drug they can pass [7]. Pfizer, a pharmaceutical giant, was historically a leader in antibiotic development, manufacturing penicillin for troops during World War II. With the advent of resistant bacteria, it ended up closing antibiotic research in 2011 [7]. This decision was made for financial reasons. The profits earned by creating expensive drugs for chronic diseases that last a patient’s lifetime disproportionately overshadowed the profits earned by acute diseases because “the customers stick around longer” [1]. For instance, the cholesterol-lowering drug Lipitor earned $13 billion per year for Pfizer, a profit that cheaper, temporary pills cannot compete with [4]. This brings us to a point, posed by Matt Cooper, a medicinal chemist at the University of Queensland: “We also need to think long and hard about antibiotic drug pricing and whether it’s ethically acceptable to pay so much for life-extending drugs but still expect to pay peanuts for life-saving antibiotics” [4]. Obviously, the threat of bacterial resistance isn’t solely attributed to the production of new antibiotics. However, the practices of large pharmaceutical corporations exhibit an apparent, “mismatch between value to society and value to capitalist economics” [4].


​     How about antibiotics in agriculture? Despite the FDA’s acknowledgement of the growing resistant trend and the role agricultural antibiotics play, the FDA has only implemented a policy of voluntary restrictions. Current efforts in Congress include Pass the Preservation of Antibiotics for Medical Treatment Act (PAMTA), which would, regulate the amount and types of antibiotics that can be used in agriculture to prevent routine use of antibiotics where they are unnecessary [8]. However, there have been several gauntlets that have created a 1% change for bill approval. For one, there are few means of documenting the use of antibiotics in the U.S. for researchers to verify results that would support the bill. Second, if a bill involves agriculture, it is very difficult to pass the legislation. When bills pertaining agriculture arise, “agriculture and pharmaceutical industries have extended their well-funded lobbying arms to push back” in order to protect their interests. To give one example, “Pfizer has filed more than 20 lobbying briefs against antibiotics legislation and has spent nearly $900,000 lobbying against PAMTA alone.” It’s obvious that once again, pharmaceutical giants are prioritizing monetary gains over public health.

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Moving Forward


     The looming problem of superbugs is one that can be avoided. The discovery of new antibiotics must once again be prioritized. For one, Congress has passed the Generating Antibiotic Incentives Now (GAIN) act, signed by Obama, which creates a drug development task force, extends patent exclusivity for 5 additional years, extends FDA fast track and increases FDA trial guidance [7]. Additionally, the economist O’Neill comes back with a few proposed solutions. He suggests a market-entry reward, payments for corporations who develop a new antibiotic, and global innovation fund for early stage research, which could provide the economic stimulus to tip research back to the antibiotic arena [6]. More important, however, is a decreased usage of antibiotics. By exposing microbes to less ecological stress, their development of resistance is immensely diminished. We need expansion in the diagnostic sector to enable doctors to accurately determine what type of disease they are dealing with so they can make an effective treatment procedure. Antibiotics do not need to be used in cases of non-bacterial diseases. There are obvious avenues where antibiotics are unnecessary. While antibiotic regulation is being stifled in Congress, ultimately regulation falls to the hands of the consumers. Choosing antibiotic-free meat in the store, and using antibacterial soaps sparingly are some ways of not only preventing antibiotic resistance, but also promoting personal health [9]. Through active education of the risks of resistance, sponsoring of antibiotic research, and reduced usage of our current antibiotics – we can restrict the spread of microbe resistance before it begins to restrict the ways in which we live.



References 

1. “Antibiotic Resistance, The Grim Prospect.” (2016, May 21). Economist. Retrieved from http://www. economist.com/news/briefing/21699115-evolution-pathogens-making-many- medical-problemsworse-time-take-drug-resistance 2. Deutschmann, Jennifer. (2016, Sept. 8). The Inquisitr News. Retrieved from http://www.inquisitr. com/3492396/what-is-a-superbug-antibiotic-resistant-bacteria/
3. Kupferschmidt, Kai. (2016). Resistance Fighters, Science, Vol. 352 (6287), 758-761.
4. Mohammadi, Dara. (2015, July 19). The Gaurdian. Retrieved from https://www.theguardian.com/ science/2015/jul/19/antibiotics-new-research-end-of-drug-resistant-superbugs
5. Sun, Lena H., and Brad Dennis. (2016, May 27). Washington Post. Retrieved from https://www. washingtonpost.com/news/to-your-health/wp/2016/05/26/the-superbug-that-doctors-havebeen-dreading-just-reached-the-u-s/
6. Yong, Ed. (2016, May 19). The Atlantic. Retrieved from http://www.theatlantic.com/science/archive/2016/05/the-ten-part-plan-to-avert-our-post-antibiotic-apocalypse/483360/
7. Krans, Brian. (2014, June 22). Healthline. Retrieved from http://www.healthline.com/health/antibiotics/why-pipeline-running-dry
8. Krans, Brain. (2014, June 22). Healthline. Retrieved from http://www.healthline.com/health/ antibiotics/politics-pork-and-poultry-why-legislation-has-not-passed
9. Krans, Brain. (2014, June 22). Healthline. Retrieved from http://www.healthline.com/health/ antibiotics/how-you-can-help-prevent-resistance