Antibiotic Resistance: History, Impacts, and Approaches for Managing

Written by: Yuliya Velhan '25
Edited by: Elana Balch '22

​Antibiotics continue to be the most common drug class doctors prescribe. Not only do they kill  infectious diseases, but they also allow for procedures that would otherwise pose a tremendous risk for infection such as surgery, cancer treatments, and organ transplants. Antibiotics, however, were not “invented” by humans [1].

They are natural substances, often found in many microorganisms that reside in pristine environments( environments that have been accessed by humans for billions of years) . Since antibiotics existed long ago, we can infer that so did resistant organisms. Evidence shows that resistance has existed long before the effects of human antibiotic use. Recent sequencing of DNA found in 30,000-year-old permafrost detected genes that were resistant to antibiotics. In another case, bacteria sequenced from a cave that did not have any human or environmental contact for the past four million years showed resistance to 14 different types of antibiotics [1]. This evidence shows that resistance has existed long before the beginning of humans started using antibiotics for medical and healing purposes. 
The history of antibiotic resistance shows how much of an issue it could be today. If antibiotics existed before we applied it to our daily lives, what kinds of negative impacts and how significant would those impacts be if antibiotics are used worldwide in large quantities every day? So how were antibiotics discovered and how exactly did they make their way into our modern world? Alexander Fleming and Gerhard Domagk discovered penicillin in 1928. At the very beginning, however, they realized the dangers of it. Only after a few decades, the resistance already started to show as a strain of a bacteria, Staphylococcus aureus was able to develop a resistant strain and spread fast [2]. To stop this spread, other antibiotics, such as methicillin were discovered, followed by many others. This period of time where most of the known antibiotics were discovered became known as the “ Golden Age of Antibiotics”. While this way of controlling antibiotic resistance was effective at first, it was not a viable solution( there are only so many antibiotics to be discovered, and when we no longer have new ones, it will cause a spike of infections and deaths since the ones we had before are no longer effective) and only contributed to the problem in the long run [1]. 
When new antibiotics were no longer being discovered, bacteria would continue developing resistance and passing it on to future generations. When an antibiotic is first introduced to a bacterial population, the majority does not have resistance to it and immediately dies from the exposure. However, there will be a few bacteria that will be able to survive. While they will most likely not show in that organism they became resistant in (e.g., a human who is sick),  the resistant bacteria will replicate, passing on the resistant DNA to their offspring. Therefore, the next time the same antibiotic treatment is applied to the same population, it will no longer be as effective [2].Antibiotic use in medical and agricultural settings has caused more resistance to develop. As antibiotic usage continued increasing this phenomenon occurred more often, causing more and more bacteria populations to be resistant to certain antibiotics. 
So what are the solutions to this issue? While it may not be as profitable for pharmaceutical companies as it was in the “ Golden Age of Antibiotics” to work on the discovery of new antibiotics, it could reduce the potency of antibiotic resistance. With new antibiotics, we could not only learn from our past and use them more cautiously, but also reduce the use of the antibiotics that are already greatly impacted by resistance and prevent its further development. Additionally, since the most common places antibiotic resistance is detected are wastewater, agriculture, and hospitals, we could use screening techniques in these hotspots, which would allow us to identify new resistant genes and prevent their further development. For example, a technique that has already been used and proven effective is reusing already existing antibiotics in combinations [1]. Some organisms have proven to have collateral sensitivity, which means while they are resistant to one drug, they are still susceptible to the other. Using these drugs in combination with each other can prevent the development of further resistance. Not only does it prevent further evolutionary development of the mutation, but it also causes the bacteria to discard the resistant gene [1]. 
While it is important to develop new antibiotics and ways to combat and revert resistance, it is crucial that we closely oversee the further development of antibiotic resistance, especially in places we previously discussed as hotspots [1]. This would require regular testing for resistance of pathogens and microorganisms that cause disease, as well as the development of technology that would make testing( for resistance) on such a large scale possible.  

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References:

[1] Crofts TS, Gasparrini AJ, Dantas G. Next-generation approaches to understand and combat the antibiotic resistome [Internet]. Nature News. Nature Publishing Group; 2017 [cited 2021Oct10]. Available from: https://www.nature.com/articles/nrmicro.2017.28#Sec1

[2] Uchil RR, Singh Kohli G, Katekhaye VM, Swami OC. Strategies to combat antimicrobial resistance [Internet]. Journal of clinical and diagnostic research : JCDR. JCDR Research and Publications (P) Limited; 2014 [cited 2022Jan9]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149102/