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Causes

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Antimicrobial resistance is mainly caused by the overuse of antimicrobials. This leads to microbes either developing a defense against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication.[1]  While antimicrobial resistance does occur naturally over time, the use of antimicrobial agents in a variety of settings both within the healthcare industry and outside of has lead to antimicrobial resistance becoming increasingly more prevalent.[2]

Natural occurrence

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A CDC infographic on how antibiotic resistance (a major type of antimicrobial resistance) happens and spreads.

Antimicrobial resistance is something that will develop naturally. It is an evolutionary response to continued exposure of antimicrobials. As explained by Darwin's theory of natural selection, organisms that are able to adapt better to their environment will be the ones that survive and continue to produce offspring.[3] As a result, the types of microorganisms that are able to survive overtime with continued attack by certain antimicrobial agents will naturally become more prevalent in the environment, and antimicrobials without this resistance will become obsolete.[2] Over time most of the strains of bacteria and infections present will be the type resistant to the antimicrobial agent being used to treat them, making this agent now ineffective to defeat most microbes. With the increased use of antimicrobial agents becoming much more common, it is speeding up this natural process.[4]

Self medication

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Self medication by consumers is defined as “the taking of medicines on one's own initiative or on another person's suggestion, who is not a certified medical professional”, and it has been identified as one of the primary reasons for the development of antimicrobial resistance.[5] In an effort to manage their own illness, patients take the advice of false media sources, friends, and family causing them to take antimicrobials unnecessarily or in excess. Many people resort to this out of necessity, when they have a limited amount of money to see a doctor, or in many developing countries a poorly developed economy and lack of doctors are the cause of self-medication.  In these developing countries, governments resort to allowing the sale of antimicrobials as over the counter medications so people can have access to them without having to find or pay to see a medical professional.[6] This increased access makes it extremely easy to obtain antimicrobials without the advice of a physician, and as a result many antimicrobials are taken incorrectly leading to resistant microbial strains. One major example of a place that faces these challenges is India, where in a state called Punjab 73% of the population resorted to treating their minor health issues and chronic illnesses through self-medication.[5]

The major issue with self-medication is the lack of knowledge of the public on the dangerous effects of antimicrobial resistance, and how they can contributing to it through mistreating or misdiagnosing themselves.  In order to determine the public's knowledge and preconceived notions on antibiotic resistance, a major type of antimicrobial resistance, a screening of 3537 articles published in Europe, Asia, and North America was done.  Of the 55,225 total people surveyed, 70% had heard of antibiotic resistance previously, but 88% of those people thought it referred to some type of physical change in the body.[5]  With so many people around the world with the ability to self-medicate using antibiotics, and a vast majority unaware of what antimicrobial resistance is, it makes the increase of antimicrobial resistance much more likely.

Clinical misuse

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Clinical misuse by healthcare professionals is another cause leading to increased antimicrobial resistance. Studies done by the CDC show that the indication for treatment of antibiotics, choice of the agent used, and the duration of therapy was incorrect in up to 50% of the cases studied.  In another study done in an intensive care unit in a major hospital in France, it was shown that 30% to 60% of prescribed antibiotics were unnecessary.[7] These inappropriate uses of antimicrobial agents promote the development of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance. In a study done by the American Journal of Infection Control aimed to evaluate physicians’ attitudes and knowledge on antimicrobial resistance in ambulatory settings, only 63% of those surveyed reported antibiotic resistance as a problem in their local practices, while 23% reported the aggressive prescription of antibiotics as necessary to avoid failing to provide adequate care.[8]  This demonstrates how a majority of doctors underestimate the impact that their own prescribing habits have on antimicrobial resistance as a whole. It also confirms that some physicians may be overly cautious when it comes to prescribing antibiotics for both medical or legal reasons, even when indication for use for these medications is not always confirmed, leading to unnecessary antimicrobial use.

Food production

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Livestock

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A CDC infographic on how antibiotic resistance spreads through farm animals.

The antimicrobial resistance crisis also extends to the food industry, specifically with food producing animals.  Antibiotics are fed to livestock to act as growth supplements, and a preventative measure to decrease the likelihood of infections.  This results in the transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease.  While this practice does result in better yields and meat products, it is a major issue in terms of preventing antimicrobial resistance.[9] The American Center for Science in the Public Interest linked a total of 35 food borne outbreaks from 1973 through 2009 where bacterial resistance to antibiotics was implicated, showing how this overuse in the food industry has and will continue to threaten public health.  Not only are 80% of antibiotics sold in the United States used on animals, but 90% of those antibiotics are excreted in the urine and stool of livestock.[4] Those antibiotics also end up in fertilizer used for food, groundwater, and surface runoff, all of which could not only lead to the spread of antibiotic resistant bacteria, but also serious environmental consequences. This isn’t just a problem in the United States, but a global emerging threat.  In a study published by the National Academy of Sciences mapping antimicrobial consumption in livestock globally, it was predicted that in the 228 countries studied, there would be a total 67% increase in consumption of antibiotics by livestock by 2030. In some countries such as Brazil, Russia, India, China, and South Africa it is predicted that a 99% increase will occur.[4] This shows how serious the misuse of antimicrobials specifically antibiotics in livestock is, and why it can in many ways lead to antimicrobial resistance.

Pesticides

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Most pesticides protect crops against insects and plants, but in some cases antimicrobial pesticides are used to protect against various microorganisms such as bacteria, viruses, fungi, algae, and protozoa. The overuse of many pesticides in an effort to have a higher yield of crops has resulted in many of these microbes developing a tolerance against antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the EPA and sold to market, showing the widespread use of these agents.[10] It is estimated that for every single meal a person consumes, 0.3 g of pesticides is used, as 90% of all pesticide use is used on agriculture. A majority of these products are used to help defend against the spread of infectious diseases, and hopefully protect public health. But out of the large amount of pesticides used, it is also estimated that less than 0.1% of those antimicrobial agents, actually reach their targets. That leaves over 99% of all pesticides used available to contaminate other resources.[11] In soil, air, and water these antimicrobial agents are able to spread, coming in contact with more microorganisms and leading to these microbes developing mechanisms to tolerate and further resist pesticides.

  1. ^ "Antimicrobial Resistance » Cambridge Medicine Journal". Retrieved 2020-02-27.
  2. ^ a b Holmes, Alison H; Moore, Luke S P; Sundsfjord, Arnfinn; Steinbakk, Martin; Regmi, Sadie; Karkey, Abhilasha; Guerin, Philippe J; Piddock, Laura J V (2016-01-09). "Understanding the mechanisms and drivers of antimicrobial resistance". The Lancet. 387 (10014): 176–187. doi:10.1016/S0140-6736(15)00473-0. ISSN 0140-6736.
  3. ^ "Natural selection". evolution.berkeley.edu. Retrieved 2020-03-10.
  4. ^ a b c Maurizio Ferri, Elena Ranucci, Paola Romagnoli & Valerio Giaccone (2017) Antimicrobial resistance: A global emerging threat to public health systems, Critical Reviews in Food Science and Nutrition, 57:13, 2857-2876, DOI: 10.1080/10408398.2015.1077192
  5. ^ a b c Rather, Irfan A.; Kim, Byung-Chun; Bajpai, Vivek K.; Park, Yong-Ha (2017-05-01). "Self-medication and antibiotic resistance: Crisis, current challenges, and prevention". Saudi Journal of Biological Sciences. 24 (4): 808–812. doi:10.1016/j.sjbs.2017.01.004. ISSN 1319-562X.
  6. ^ Ayukekbong, James A.; Ntemgwa, Michel; Atabe, Andrew N. (2017-05-15). "The threat of antimicrobial resistance in developing countries: causes and control strategies". Antimicrobial Resistance & Infection Control. 6 (1): 47. doi:10.1186/s13756-017-0208-x. ISSN 2047-2994. PMC 5433038. PMID 28515903.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ Ventola, C. Lee (2015-4). "The Antibiotic Resistance Crisis". Pharmacy and Therapeutics. 40 (4): 277–283. ISSN 1052-1372. PMC 4378521. PMID 25859123. {{cite journal}}: Check date values in: |date= (help)
  8. ^ Harris, Amanda; Chandramohan, Suganya; Awali, Reda A.; Grewal, Mehr; Tillotson, Glenn; Chopra, Teena (2019-08-01). "Physicians' attitude and knowledge regarding antibiotic use and resistance in ambulatory settings". American Journal of Infection Control. 47 (8): 864–868. doi:10.1016/j.ajic.2019.02.009. ISSN 0196-6553.
  9. ^ Tang, Karen L; Caffrey, Niamh P; Nóbrega, Diego B; Cork, Susan C; Ronksley, Paul E; Barkema, Herman W; Polachek, Alicia J; Ganshorn, Heather; Sharma, Nishan; Kellner, James D; Ghali, William A (2017-11-01). "Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis". The Lancet Planetary Health. 1 (8): e316–e327. doi:10.1016/S2542-5196(17)30141-9. ISSN 2542-5196.
  10. ^ US EPA, OCSPP (2013-03-15). "What are Antimicrobial Pesticides?". US EPA. Retrieved 2020-02-28.
  11. ^ Ramakrishnan, Balasubramanian; Venkateswarlu, Kadiyala; Sethunathan, Nambrattil; Megharaj, Mallavarapu (2019-03-01). "Local applications but global implications: Can pesticides drive microorganisms to develop antimicrobial resistance?". Science of The Total Environment. 654: 177–189. doi:10.1016/j.scitotenv.2018.11.041. ISSN 0048-9697.