Editing Antimicrobial resistance (section)

== Causes ==
AMR is driven largely by the [[Antibiotic misuse|misuse and overuse of antimicrobials]].<ref name="WHO10October2024" /> Yet, at the same time, many people around the world do not have access to essential antimicrobials.<ref name="WHO10October2024" /> This leads to microbes either evolving 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.<ref>{{cite web|url=http://cambridgemedicine.org/files/10-7244/cmj-2017-03-001/,%20http://cambridgemedicine.org/78-2/|title=Antimicrobial Resistance " Cambridge Medicine Journal|access-date=2020-02-27}} {{dead link|date=July 2023 |bot=InternetArchiveBot |fix-attempted=yes}}</ref> 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 led to antimicrobial resistance becoming increasingly more prevalent.<ref name="Holmes_2016">{{cite journal | vauthors = Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJ | title = Understanding the mechanisms and drivers of antimicrobial resistance | journal = Lancet | volume = 387 | issue = 10014 | pages = 176–87 | date = January 2016 | pmid = 26603922 | doi = 10.1016/S0140-6736(15)00473-0 | hdl-access = free | hdl = 10044/1/32225 | s2cid = 1944665 | url = http://pure-oai.bham.ac.uk/ws/files/25678970/Understanding_the_Mechanisms_and_Drivers_of_AMR_25_Aug_2015.docx | access-date = 5 December 2021 | archive-date = 14 April 2022 | archive-url = https://web.archive.org/web/20220414151453/http://pure-oai.bham.ac.uk/ws/files/25678970/Understanding_the_Mechanisms_and_Drivers_of_AMR_25_Aug_2015.docx | url-status = live}}</ref>

Although many microbes develop resistance to antibiotics over time through natural mutation, overprescribing and inappropriate prescription of antibiotics have accelerated the problem. It is possible that as many as 1 in 3 prescriptions written for antibiotics are unnecessary.<ref name="CDC_2016">{{cite web |date=2016-01-01 |title=CDC Newsroom |url=https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html |access-date=2023-02-28 |website=CDC |archive-date=9 March 2023 |archive-url=https://web.archive.org/web/20230309053532/https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html |url-status=live}}</ref> Every year, approximately 154 million prescriptions for antibiotics are written. Of these, up to 46 million are unnecessary or inappropriate for the condition that the patient has.<ref name="CDC_2016"/> Microbes may naturally develop resistance through genetic mutations that occur during cell division, and although random mutations are rare, many microbes reproduce frequently and rapidly, increasing the chances of members of the population acquiring a mutation that increases resistance.<ref name="Michael_2014">{{cite journal | vauthors = Michael CA, Dominey-Howes D, Labbate M | title = The antimicrobial resistance crisis: causes, consequences, and management | journal = Frontiers in Public Health | volume = 2 | pages = 145 | date = 2014 | pmid = 25279369 | pmc = 4165128 | doi = 10.3389/fpubh.2014.00145 | doi-access = free }}</ref> Many individuals stop taking antibiotics when they begin to feel better. When this occurs, it is possible that the microbes that are less susceptible to treatment still remain in the body.  If these microbes are able to continue to reproduce, this can lead to an infection by bacteria that are less susceptible or even resistant to an antibiotic.<ref name="Michael_2014"/>

=== Natural occurrence ===
[[File:Antibiotic Resistance Spread.jpg|thumb|A CDC infographic on how antibiotic resistance (a major type of antimicrobial resistance) happens and spreads]]
AMR is a naturally occurring process.<ref name="CDC About Antimicrobial Resistance"/> Antimicrobial resistance can evolve naturally due to continued exposure to antimicrobials. [[Natural selection]] means that organisms that are able to adapt to their environment, survive, and continue to produce offspring.<ref name="NS">{{cite web|url=https://evolution.berkeley.edu/evolibrary/article/evo_25|title=Natural selection|website=evolution.berkeley.edu|access-date=2020-03-10|archive-date=30 October 2019|archive-url=https://web.archive.org/web/20191030201404/https://evolution.berkeley.edu/evolibrary/article/evo_25|url-status=live}}</ref> As a result, the types of microorganisms that are able to survive over time with continued attack by certain antimicrobial agents will naturally become more prevalent in the environment, and those without this resistance will become obsolete.<ref name="Holmes_2016" />

Some contemporary antimicrobial resistances have also evolved naturally before the use of antimicrobials of human clinical uses. For instance, [[methicillin]]-resistance evolved as a pathogen of [[hedgehog]]s, possibly as a [[Coevolution|co-evolutionary]] adaptation of the pathogen to hedgehogs that are infected by a [[dermatophyte]] that naturally produces antibiotics.<ref name="MR">{{cite journal | vauthors = Larsen J, Raisen CL, Ba X, Sadgrove NJ, Padilla-González GF, Simmonds MS, Loncaric I, Kerschner H, Apfalter P, Hartl R, Deplano A, Vandendriessche S, Černá Bolfíková B, Hulva P, Arendrup MC, Hare RK, Barnadas C, Stegger M, Sieber RN, Skov RL, Petersen A, Angen Ø, Rasmussen SL, Espinosa-Gongora C, Aarestrup FM, Lindholm LJ, Nykäsenoja SM, Laurent F, Becker K, Walther B, Kehrenberg C, Cuny C, Layer F, Werner G, Witte W, Stamm I, Moroni P, Jørgensen HJ, de Lencastre H, Cercenado E, García-Garrote F, Börjesson S, Hæggman S, Perreten V, Teale CJ, Waller AS, Pichon B, Curran MD, Ellington MJ, Welch JJ, Peacock SJ, Seilly DJ, Morgan FJ, Parkhill J, Hadjirin NF, Lindsay JA, Holden MT, Edwards GF, Foster G, Paterson GK, Didelot X, Holmes MA, Harrison EM, Larsen AR | title = Emergence of methicillin resistance predates the clinical use of antibiotics | journal = Nature | volume = 602 | issue = 7895 | pages = 135–141 | date = February 2022 | pmid = 34987223 | pmc = 8810379 | doi = 10.1038/s41586-021-04265-w | bibcode = 2022Natur.602..135L}}</ref> Also, many [[Soil microbiology|soil fungi and bacteria]] are natural competitors and the original antibiotic [[penicillin]] discovered by [[Alexander Fleming]] rapidly lost clinical effectiveness in treating humans and, furthermore, none of the other natural penicillins (F, K, N, X, O, U1 or U6) are currently in clinical use.{{citation needed|date=April 2023}}

Antimicrobial resistance can be acquired from other microbes through swapping genes in a process termed [[horizontal gene transfer]]. This means that once a gene for resistance to an antibiotic appears in a microbial community, it can then spread to other microbes in the community, potentially moving from a non-disease causing microbe to a disease-causing microbe. This process is heavily driven by the [[natural selection]] processes that happen during antibiotic use or misuse.<ref>{{cite journal | vauthors = Crits-Christoph A, Hallowell HA, Koutouvalis K, Suez J | title = Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome | journal = Gut Microbes | volume = 14 | issue = 1 | pages = 2055944 | date = 2022-12-31 | pmid = 35332832 | pmc = 8959533 | doi = 10.1080/19490976.2022.2055944 }}</ref>

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, there is a speeding up of this natural process.<ref name="Ferri_2017">{{cite journal | vauthors = Ferri M, Ranucci E, Romagnoli P, Giaccone V | title = Antimicrobial resistance: A global emerging threat to public health systems | journal = Critical Reviews in Food Science and Nutrition | volume = 57 | issue = 13 | pages = 2857–2876 | date = September 2017 | pmid = 26464037 | doi = 10.1080/10408398.2015.1077192 | s2cid = 24549694 }}</ref>

=== Self-medication ===
In the vast majority of countries, antibiotics can only be prescribed by a doctor and supplied by a pharmacy.<ref>{{cite web |title=Global Database for Tracking Antimicrobial Resistance (AMR) Country Self- Assessment Survey (TrACSS) |url=http://amrcountryprogress.org/ |access-date=2023-03-28 |website=amrcountryprogress.org|archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115257/http://amrcountryprogress.org/ |url-status=live}}</ref> [[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 evolution of antimicrobial resistance.<ref name="Rather_2017">{{cite journal | vauthors = Rather IA, Kim BC, Bajpai VK, Park YH | title = Self-medication and antibiotic resistance: Crisis, current challenges, and prevention | journal = Saudi Journal of Biological Sciences | volume = 24 | issue = 4 | pages = 808–812 | date = May 2017 | pmid = 28490950 | pmc = 5415144 | doi = 10.1016/j.sjbs.2017.01.004}}</ref> Self-medication with antibiotics is an unsuitable way of using them but a common practice in resource-constrained countries. The practice exposes individuals to the risk of bacteria that have developed antimicrobial resistance.<ref name="nft1">{{cite journal | vauthors = Torres NF, Chibi B, Middleton LE, Solomon VP, Mashamba-Thompson TP | title = Evidence of factors influencing self-medication with antibiotics in low and middle-income countries: a systematic scoping review | journal = Public Health | volume = 168 | pages = 92–101 | date = March 2019 | pmid = 30716570 | doi = 10.1016/j.puhe.2018.11.018 | s2cid = 73434085}}</ref> Many people resort to this out of necessity, when access to a physician is unavailable, or when patients have a limited amount of time or money to see a doctor.<ref>{{cite journal | vauthors = Ayukekbong JA, Ntemgwa M, Atabe AN | title = The threat of antimicrobial resistance in developing countries: causes and control strategies | journal = Antimicrobial Resistance and Infection Control | volume = 6 | issue = 1 | pages = 47 | date = 2017-05-15 | pmid = 28515903 | pmc = 5433038 | doi = 10.1186/s13756-017-0208-x | doi-access = free}}</ref> This increased access makes it extremely easy to obtain antimicrobials. An example is India, where in the state of [[Punjab]] 73% of the population resorted to treating their minor health issues and chronic illnesses through self-medication.<ref name="Rather_2017" />

Self-medication is higher outside the hospital environment, and this is linked to higher use of antibiotics, with the majority of antibiotics being used in the community rather than hospitals. The prevalence of self-medication in [[Developing country|low- and middle-income countries]] (LMICs) ranges from 8.1% to 93%. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence self-medication in low- and middle-income countries.<ref name="nft1" /> Two significant issues with self-medication are the lack of knowledge of the public on, firstly, the dangerous effects of certain antimicrobials (for example [[ciprofloxacin]] which can cause [[Tendinopathy|tendonitis]], [[tendon rupture]] and [[aortic dissection]])<ref>{{cite journal | vauthors = Chen C, Patterson B, Simpson R, Li Y, Chen Z, Lv Q, Guo D, Li X, Fu W, Guo B | title = Do fluoroquinolones increase aortic aneurysm or dissection incidence and mortality? A systematic review and meta-analysis | journal = Frontiers in Cardiovascular Medicine | volume = 9 | pages = 949538 | date = 2022-08-09 | pmid = 36017083 | pmc = 9396038 | doi = 10.3389/fcvm.2022.949538 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shu Y, Zhang Q, He X, Liu Y, Wu P, Chen L | title = Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database | journal = Frontiers in Pharmacology | volume = 13 | pages = 990241 | date = 2022-09-06 | pmid = 36147351 | pmc = 9486157 | doi = 10.3389/fphar.2022.990241 | doi-access = free }}</ref> and, secondly, broad microbial resistance and when to seek medical care if the infection is not clearing. In order to determine the public's knowledge and preconceived notions on antibiotic resistance, a screening of 3,537 articles published in Europe, Asia, and North America was done. Of the 55,225 total people surveyed in the articles, 70% had heard of antibiotic resistance previously, but 88% of those people thought it referred to some type of physical change in the human body.<ref name="Rather_2017" />

=== Clinical misuse ===
{{see also|Antibiotic misuse}}
Clinical misuse by healthcare professionals is another contributor to increased antimicrobial resistance. Studies done in the US 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.<ref name="The antibiotic resistance crisis: p" /> In 2010 and 2011 about a third of antibiotic prescriptions in [[Patient#Outpatients and inpatients|outpatient settings]] in the United States were not necessary.<ref>{{cite journal |vauthors=Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, Lynfield R, Margolis DJ, May LS, Merenstein D, Metlay JP, Newland JG, Piccirillo JF, Roberts RM, Sanchez GV, Suda KJ, Thomas A, Woo TM, Zetts RM, Hicks LA |date=May 2016 |title=Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010–2011 |journal=JAMA |volume=315 |issue=17 |pages=1864–73 |doi=10.1001/jama.2016.4151 |pmid=27139059 |doi-access=free}}</ref> Another study in an intensive care unit in a major hospital in France has shown that 30% to 60% of prescribed antibiotics were unnecessary.<ref name="The antibiotic resistance crisis: p">{{cite journal | vauthors = Ventola CL | title = The antibiotic resistance crisis: part 1: causes and threats | journal = P & T | volume = 40 | issue = 4 | pages = 277–83 | date = April 2015 | pmid = 25859123 | pmc = 4378521 }}</ref> These inappropriate uses of antimicrobial agents promote the evolution of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance.<ref>{{cite journal | vauthors = Strachan CR, Davies J | title = The Whys and Wherefores of Antibiotic Resistance | journal = Cold Spring Harbor Perspectives in Medicine | volume = 7 | issue = 2 | pages = a025171 | date = February 2017 | pmid = 27793964 | pmc = 5287056 | doi = 10.1101/cshperspect.a025171 }}</ref>

According to research conducted in the US that 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.<ref>{{cite journal | vauthors = Harris A, Chandramohan S, Awali RA, Grewal M, Tillotson G, Chopra T | title = Physicians' attitude and knowledge regarding antibiotic use and resistance in ambulatory settings | journal = American Journal of Infection Control | volume = 47 | issue = 8 | pages = 864–868 | date = August 2019 | pmid = 30926215 | doi = 10.1016/j.ajic.2019.02.009 | s2cid = 88482220 }}</ref> This demonstrates that many 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 and prescribe antibiotics for both medical or legal reasons, even when clinical indications for use of these medications are not always confirmed. This can lead to unnecessary antimicrobial use, a pattern which may have worsened during the [[COVID-19]] pandemic.<ref name="Joshi">{{cite journal |vauthors=Joshi MP |title=Don't let Covid boost another killer |journal=Knowable Magazine |date=17 February 2021 |doi=10.1146/knowable-021621-1 |doi-access=free |url=https://knowablemagazine.org/article/health-disease/2021/antibiotic-resistance-covid |access-date=10 August 2022 |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022091845/https://knowablemagazine.org/article/health-disease/2021/antibiotic-resistance-covid |url-status=live }}</ref><ref>{{cite journal | vauthors = Rawson TM, Moore LS, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes A | title = Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing | journal = Clinical Infectious Diseases | volume = 71 | issue = 9 | pages = 2459–2468 | date = December 2020 | pmid = 32358954 | pmc = 7197596 | doi = 10.1093/cid/ciaa530 }}</ref>

Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.<ref>{{cite web|url=https://dailytargum.com//article/2021/02/rutgers-study-finds-antibiotic-overuse-is-caused-by-misconceptions-financial|title=Rutgers study finds antibiotic overuse is caused by misconceptions, financial incentives|vauthors=Barnes S|website=The Daily Targum|date=10 February 2021 |access-date=16 February 2021|archive-date=6 December 2021|archive-url=https://web.archive.org/web/20211206103329/https://dailytargum.com/article/2021/02/rutgers-study-finds-antibiotic-overuse-is-caused-by-misconceptions-financial|url-status=live}}</ref><ref>{{cite journal | vauthors = Blaser MJ, Melby MK, Lock M, Nichter M | title = Accounting for variation in and overuse of antibiotics among humans | journal = BioEssays | volume = 43 | issue = 2 | pages = e2000163 | date = February 2021 | pmid = 33410142 | doi = 10.1002/bies.202000163 | s2cid = 230811912 }}</ref>

Important to the conversation of antibiotic use is the [[Veterinary medicine|veterinary medical system]]. Veterinary oversight is required by law for all medically important antibiotics.<ref>{{Cite web |title=Antimicrobials {{!}} American Veterinary Medical Association |url=https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance |access-date=2024-04-24 |website=avma.org|archive-date=24 April 2024 |archive-url=https://web.archive.org/web/20240424183923/https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance |url-status=live }}</ref> Veterinarians use the [[Pharmacokinetics|Pharmacokinetic]]/pharmacodynamic model (PK/PD) approach to ensuring that the correct dose of the drug is delivered to the correct place at the correct timing.<ref>{{cite journal | vauthors = Caneschi A, Bardhi A, Barbarossa A, Zaghini A | title = The Use of Antibiotics and Antimicrobial Resistance in Veterinary Medicine, a Complex Phenomenon: A Narrative Review | journal = Antibiotics | volume = 12 | issue = 3 | pages = 487 | date = March 2023 | pmid = 36978354 | pmc = 10044628 | doi = 10.3390/antibiotics12030487 | doi-access = free }}</ref>

=== Pandemics, disinfectants and healthcare systems ===
Increased antibiotic use during the early waves of the COVID-19 pandemic may exacerbate this [[List of global issues|global health challenge]]<!--/threat/burden-->.<ref>{{cite news|title=Has COVID-19 made the superbug crisis worse?|url=https://globalnews.ca/news/8602057/has-covid-19-made-the-superbug-crisis-worse/|access-date=12 February 2022|work=Global News|archive-date=12 February 2022|archive-url=https://web.archive.org/web/20220212122151/https://globalnews.ca/news/8602057/has-covid-19-made-the-superbug-crisis-worse/|url-status=live}}</ref><ref>{{cite journal | vauthors = Lucien MA, Canarie MF, Kilgore PE, Jean-Denis G, Fénélon N, Pierre M, Cerpa M, Joseph GA, Maki G, Zervos MJ, Dely P, Boncy J, Sati H, Rio AD, Ramon-Pardo P | title = Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings | journal = International Journal of Infectious Diseases | volume = 104 | pages = 250–254 | date = March 2021 | pmid = 33434666 | pmc = 7796801 | doi = 10.1016/j.ijid.2020.12.087 }}</ref> Moreover, pandemic burdens on some healthcare systems may contribute to antibiotic-resistant infections.<ref>{{cite web |title=COVID-19 & Antibiotic Resistance |url=https://www.cdc.gov/drugresistance/covid19.html |website=Centers for Disease Control and Prevention |access-date=21 February 2022|date=18 November 2021 |archive-date=21 February 2022 |archive-url=https://web.archive.org/web/20220221120759/https://www.cdc.gov/drugresistance/covid19.html |url-status=live }}</ref> The use of [[disinfectant]]s such as alcohol-based hand sanitizers, and antiseptic hand wash may also have the potential to increase antimicrobial resistance.<ref>{{cite journal | vauthors = Lu J, Guo J | title = Disinfection spreads antimicrobial resistance | language = EN | journal = Science | volume = 371 | issue = 6528 | pages = 474 | date = January 2021 | pmid = 33510019 | doi = 10.1126/science.abg4380 | s2cid = 231730007 | bibcode = 2021Sci...371..474L | doi-access = free }}</ref> Extensive use of disinfectants can lead to mutations that induce antimicrobial resistance.<ref>{{cite journal | vauthors = Lobie TA, Roba AA, Booth JA, Kristiansen KI, Aseffa A, Skarstad K, Bjørås M | title = Antimicrobial resistance: A challenge awaiting the post-COVID-19 era | journal = International Journal of Infectious Diseases | volume = 111 | pages = 322–325 | date = October 2021 | pmid = 34508864 | pmc = 8425743 | doi = 10.1016/j.ijid.2021.09.003 | s2cid = 237444117}}</ref> On the other hand, "increased hand hygiene, decreased international travel, and decreased elective hospital procedures may have reduced AMR pathogen selection and spread in the short term" during the COVID-19 pandemic.<ref>{{cite journal |vauthors=Knight GM, Glover RE, McQuaid CF, Olaru ID, Gallandat K, Leclerc QJ, Fuller NM, Willcocks SJ, Hasan R, van Kleef E, Chandler CI |date=February 2021 |title=Antimicrobial resistance and COVID-19: Intersections and implications |journal=eLife |volume=10 |doi=10.7554/eLife.64139 |pmc=7886324 |pmid=33588991 |s2cid=231936902 |doi-access=free}}</ref> 

A 2024 [[United Nations]] High-Level Meeting on AMR has pledged to reduce deaths associated with bacterial AMR by 10% over the next six years.<ref name="WHO10October2024" /><ref>{{Cite web |date=2024-09-26 |title=World Leaders Approve Milestone Commitment To Reduce Deaths From Antibiotic Resistance By 10% By 2030 - Health Policy Watch |url=https://healthpolicy-watch.news/un-high-level-meeting-approves-milestone-commitment-to-reduce-deaths-from-antibiotic-resistance-10-by-2030/ |access-date=2024-09-28 |language=en-US}}</ref> In their first major declaration on the issue since 2016, global leaders also committed to raising $100 million to update and implement AMR action plans.<ref>{{Cite web |title=UN General Assembly High-Level Meeting on antimicrobial resistance 2024 |url=https://www.who.int/news-room/events/detail/2024/09/26/default-calendar/un-general-assembly-high-level-meeting-on-antimicrobial-resistance-2024 |access-date=2024-09-28 |website=www.who.int |language=en}}</ref> However, the final draft of the declaration omitted an earlier target to reduce antibiotic use in animals by 30% by 2030, due to opposition from meat-producing countries and the farming industry. Critics argue this omission is a major weakness, as livestock accounts for around 73% of global sales of antimicrobial agents, including [[antibiotic]]s, [[Antiviral drug|antivirals]], and [[antiparasitic]]s.<ref>{{Cite web |last=Held |first=Lisa |date=2024-09-25 |title=The US Weakens a UN Declaration on Antibiotic Resistance |url=https://civileats.com/2024/09/25/the-us-weakens-a-un-declaration-on-antibiotic-resistance/ |url-status=live |archive-url=https://web.archive.org/web/20241223075146/https://civileats.com/2024/09/25/the-us-weakens-a-un-declaration-on-antibiotic-resistance/ |archive-date=2024-12-23 |access-date=2025-05-18 |website=Civil Eats |language=en}}</ref><ref>{{Cite journal |last=Van Boeckel |first=Thomas P. |last2=Pires |first2=João |last3=Silvester |first3=Reshma |last4=Zhao |first4=Cheng |last5=Song |first5=Julia |last6=Criscuolo |first6=Nicola G. |last7=Gilbert |first7=Marius |last8=Bonhoeffer |first8=Sebastian |last9=Laxminarayan |first9=Ramanan |date=2019-09-20 |title=Global trends in antimicrobial resistance in animals in low- and middle-income countries |url=https://www.science.org/doi/10.1126/science.aaw1944 |url-status=live |journal=Science |volume=365 |issue=6459 |pages=eaaw1944 |doi=10.1126/science.aaw1944 |archive-url=https://web.archive.org/web/20250312224912/https://www.science.org/doi/10.1126/science.aaw1944 |archive-date=March 12, 2025}}</ref>

=== Environmental pollution ===
Considering the complex interactions between humans, animals and the environment, it is also important to consider the environmental aspects and contributors to antimicrobial resistance.<ref>{{cite journal | vauthors = Musoke D, Namata C, Lubega GB, Niyongabo F, Gonza J, Chidziwisano K, Nalinya S, Nuwematsiko R, Morse T | title = The role of Environmental Health in preventing antimicrobial resistance in low- and middle-income countries | journal = Environmental Health and Preventive Medicine | volume = 26 | issue = 1 | pages = 100 | date = October 2021 | pmid = 34610785 | pmc = 8493696 | doi = 10.1186/s12199-021-01023-2 | doi-access = free | bibcode = 2021EHPM...26..100M}}</ref> Although there are still some knowledge gaps in understanding the mechanisms and transmission pathways,<ref name="UC">{{cite journal | vauthors = Fletcher S | title = Understanding the contribution of environmental factors in the spread of antimicrobial resistance | journal = Environmental Health and Preventive Medicine | volume = 20 | issue = 4 | pages = 243–252 | date = July 2015 | pmid = 25921603 | pmc = 4491066 | doi = 10.1007/s12199-015-0468-0 | bibcode = 2015EHPM...20..243F}}</ref> environmental pollution is considered a significant contributor to antimicrobial resistance.<ref name="EA">{{cite journal | vauthors = Ahmad I, Malak HA, Abulreesh HH | title = Environmental antimicrobial resistance and its drivers: a potential threat to public health | journal = Journal of Global Antimicrobial Resistance | volume = 27 | pages = 101–111 | date = December 2021 | pmid = 34454098 | doi = 10.1016/j.jgar.2021.08.001 | doi-access = free}}</ref> Important contributing factors are through "antibiotic residues", "industrial effluents", " [[Agricultural pollution|agricultural runoffs]]", "heavy metals", "[[biocide]]s and [[pesticide]]s" and "sewage and wastewater" that create reservoirs for resistant genes and bacteria that facilitates the transfer of human pathogens.<ref name="UC" /><ref name="EA" /> Unused or expired antibiotics, if not disposed of properly, can enter water systems and soil.<ref name="EA" /> Discharge from pharmaceutical manufacturing and other industrial companies can also introduce antibiotics and other chemicals into the environment.<ref name="EA" /> These factors allow for creating selective pressure for resistant bacteria.<ref name="EA" /> Antibiotics used in livestock and [[aquaculture]] can contaminate soil and water, which promotes resistance in environmental microbes.<ref name="UC" /> Heavy metals such as [[zinc]], copper and [[Mercury (element)|mercury]], and also biocides and pesticides, can co- select for antibiotic resistance,<ref name="EA" /> enhancing their speed.<ref name="UC" /> Inadequate [[Wastewater treatment|treatment of sewage and wastewater]] allows resistant bacteria and genes to spread through water systems.<ref name="UC" />

=== Food production ===

==== Livestock ====
{{main|Antibiotic use in livestock#Antibiotic resistance}}
[[File:Ar-infographic-950px.jpg|thumb|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. With an ever-increasing human population, there is constant pressure to intensify productivity in many agricultural sectors, including the production of meat as a source of protein.<ref>{{cite journal | vauthors = Monger XC, Gilbert AA, Saucier L, Vincent AT | title = Antibiotic Resistance: From Pig to Meat | journal = Antibiotics | volume = 10 | issue = 10 | pages = 1209 | date = October 2021 | pmid = 34680790 | pmc = 8532907 | doi = 10.3390/antibiotics10101209 | doi-access = free }}</ref> Antibiotics are fed to livestock to act as growth supplements, and a preventive measure to decrease the likelihood of infections.<ref>{{cite web |vauthors=Torrella K |date=2023-01-08 |title=Big Meat just can't quit antibiotics |url=https://www.vox.com/future-perfect/2023/1/8/23542789/big-meat-antibiotics-resistance-fda |access-date=2023-01-23 |website=Vox|archive-date=23 January 2023 |archive-url=https://web.archive.org/web/20230123115850/https://www.vox.com/future-perfect/2023/1/8/23542789/big-meat-antibiotics-resistance-fda |url-status=live }}</ref>

Farmers typically use antibiotics in animal feed to improve growth rates and prevent infections. However, this is illogical as antibiotics are used to treat infections and not prevent infections. 80% of antibiotic use in the U.S. is for agricultural purposes and about 70% of these are medically important.<ref name="CA">{{cite journal | vauthors = Martin MJ, Thottathil SE, Newman TB | title = Antibiotics Overuse in Animal Agriculture: A Call to Action for Health Care Providers | journal = American Journal of Public Health | volume = 105 | issue = 12 | pages = 2409–2410 | date = December 2015 | pmid = 26469675 | pmc = 4638249 | doi = 10.2105/AJPH.2015.302870 }}</ref> Overusing antibiotics gives the bacteria time to adapt leaving higher doses or even stronger antibiotics needed to combat the infection. Though antibiotics for growth promotion were banned throughout the EU in 2006, 40 countries worldwide still use antibiotics to promote growth.<ref>{{cite web |title=Farm antibiotic use |url=https://www.saveourantibiotics.org/the-issue/antibiotic-overuse-in-livestock-farming/ |website=saveourantibiotics.org|access-date=21 March 2024 |archive-date=3 April 2024 |archive-url=https://web.archive.org/web/20240403061957/https://www.saveourantibiotics.org/the-issue/antibiotic-overuse-in-livestock-farming/ |url-status=live }}</ref>

This can result in the transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease. While the practice of using antibiotics as growth promoters does result in better yields and [[meat]] products, it is a major issue and needs to be decreased in order to prevent antimicrobial resistance.<ref>{{cite journal | vauthors = Tang KL, Caffrey NP, Nóbrega DB, Cork SC, Ronksley PE, Barkema HW, Polachek AJ, Ganshorn H, Sharma N, Kellner JD, Ghali WA | title = 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 | journal = The Lancet. Planetary Health | volume = 1 | issue = 8 | pages = e316–e327 | date = November 2017 | pmid = 29387833 | pmc = 5785333 | doi = 10.1016/S2542-5196(17)30141-9 }}</ref> Though the evidence linking antimicrobial usage in livestock to antimicrobial resistance is limited, the World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance strongly recommended the reduction of use of medically important antimicrobials in livestock. Additionally, the Advisory Group stated that such antimicrobials should be expressly prohibited for both growth promotion and disease prevention in food producing animals.<ref name="Innes" />

By mapping antimicrobial consumption in livestock globally, it was predicted that in 228 countries 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.<ref name="Ferri_2017" /> Several countries have restricted the use of antibiotics in livestock, including Canada, China, Japan, and the US. These restrictions are sometimes associated with a reduction of the [[prevalence]] of antimicrobial resistance in humans.<ref name="Innes">{{cite journal | vauthors = Innes GK, Randad PR, Korinek A, Davis MF, Price LB, So AD, Heaney CD | title = External Societal Costs of Antimicrobial Resistance in Humans Attributable to Antimicrobial Use in Livestock | journal = Annual Review of Public Health | volume = 41 | issue = 1 | pages = 141–157 | date = April 2020 | pmid = 31910712 | pmc = 7199423 | doi = 10.1146/annurev-publhealth-040218-043954 }}</ref>

In the United States the [[Veterinary Feed Directive]] went into practice in 2017 dictating that ''All medically important antibiotics to be used in feed or water for food animal species require a veterinary feed directive (VFD) or a prescription.''<ref>{{Cite web |title=Veterinary feed directive (VFD) basics {{!}} American Veterinary Medical Association |url=https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance/veterinary-feed-directive-basics |access-date=2024-04-24 |website=avma.org|archive-date=24 April 2024 |archive-url=https://web.archive.org/web/20240424183927/https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance/veterinary-feed-directive-basics |url-status=live }}</ref>

==== Pesticides ====
{{main|Pesticide resistance}}

Most [[pesticide]]s 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 evolving a tolerance against these antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the US [[United States Environmental Protection Agency|Environmental Protection Agency]] (EPA) and sold to market, showing the widespread use of these agents.<ref>{{cite web|url=https://www.epa.gov/pesticide-registration/what-are-antimicrobial-pesticides|title=What are Antimicrobial Pesticides?|last=US EPA|first=OCSPP|date=2013-03-15|website=US EPA|access-date=2020-02-28|archive-date=27 November 2022|archive-url=https://web.archive.org/web/20221127101423/https://www.epa.gov/pesticide-registration/what-are-antimicrobial-pesticides|url-status=live}}</ref> It is estimated that for every single meal a person consumes, 0.3&nbsp;g of pesticides is used, as 90% of all pesticide use is in 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.<ref>{{cite journal | vauthors = Ramakrishnan B, Venkateswarlu K, Sethunathan N, Megharaj M | title = Local applications but global implications: Can pesticides drive microorganisms to develop antimicrobial resistance? | journal = The Science of the Total Environment | volume = 654 | pages = 177–189 | date = March 2019 | pmid = 30445319 | doi = 10.1016/j.scitotenv.2018.11.041 | s2cid = 53568193 | bibcode = 2019ScTEn.654..177R }}</ref> In soil, air, and water these antimicrobial agents are able to spread, coming in contact with more microorganisms and leading to these microbes evolving mechanisms to tolerate and further resist pesticides. The use of antifungal [[azole]] pesticides that drive environmental azole resistance have been linked to azole resistance cases in the clinical setting.<ref>{{cite journal | vauthors = Rhodes J, Abdolrasouli A, Dunne K, Sewell TR, Zhang Y, Ballard E, Brackin AP, van Rhijn N, Chown H, Tsitsopoulou A, Posso RB, Chotirmall SH, McElvaney NG, Murphy PG, Talento AF, Renwick J, Dyer PS, Szekely A, Bowyer P, Bromley MJ, Johnson EM, Lewis White P, Warris A, Barton RC, Schelenz S, Rogers TR, Armstrong-James D, Fisher MC | title = Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment | journal = Nature Microbiology | volume = 7 | issue = 5 | pages = 663–674 | date = May 2022 | pmid = 35469019 | pmc = 9064804 | doi = 10.1038/s41564-022-01091-2}}</ref> The same issues confront the novel antifungal classes (e.g. [[orotomide]]s) which are again being used in both the clinic and agriculture.<ref name="Verweij_2022">{{cite journal | vauthors = Verweij PE, Arendrup MC, Alastruey-Izquierdo A, Gold JA, Lockhart SR, Chiller T, White PL | title = Dual use of antifungals in medicine and agriculture: How do we help prevent resistance developing in human pathogens? | journal = Drug Resistance Updates | volume = 65 | pages = 100885 | date = December 2022 | pmid = 36283187 | doi = 10.1016/j.drup.2022.100885 | pmc = 10693676 | s2cid = 253052170 | doi-access = free}}</ref>

=== Wild birds ===
Wildlife, including wild and [[Bird migration|migratory birds]], serve as a reservoir for zoonotic disease and antimicrobial-resistant organisms. Birds are a key link between the transmission of zoonotic diseases to human populations. By the same token, increased contact between wild birds and human populations (including domesticated animals), has increased the amount of anti-microbial resistance (AMR) to the bird population.<ref name="MP" /> The introduction of AMR to wild birds positively correlates with human pollution and increased human contact. Additionally, wild birds can participate in [[horizontal gene transfer]] with bacteria, leading to the transmission of antibiotic-resistant genes (ARG).<ref name="NS" />

For simplicity, wild bird populations can be divided into two major categories, wild sedentary birds and wild migrating birds. Wild sedentary bird exposure to AMR is through increased contact with densely populated areas, human waste, domestic animals, and domestic animal/livestock waste. Wild migrating birds interact with sedentary birds in different environments along their migration route. This increases the rate and diversity of AMR across varying ecosystems.<ref name="MP" />

Neglect of wildlife in the global discussions surrounding [[health security]] and AMR, creates large barriers to true AMR surveillance. The surveillance of anti-microbial resistant organisms in wild birds is a potential metric for the rate of AMR in the environment. This surveillance also allows for further investigation into the transmission routs between different ecosystems and human populations (including domesticated animals and livestock).<ref name="MP" /> Such information gathered from wild bird biomes, can help identify patterns of diseased transmission and better target interventions. These targeted interventions can inform the use of antimicrobial agents and reduce the persistence of multi-drug resistant organisms.<ref name="AR" /><ref name="MR" />

=== Gene transfer from ancient microorganisms ===
{{Main|Pathogenic microorganisms in frozen environments}}
[[File:Perron_2015_permafrost_antibiotic_resistances.png|thumb|Ancient bacteria found in the permafrost possess a remarkable range of genes which confer resistance to some of the most common antimicrobial classes (red). However, their capacity to resist is also generally lower than of modern bacteria from the same area (black).<ref name="Perron2015" />]]
[[Permafrost]] is a term used to refer to any ground that remained frozen for two years or more,  with the oldest known examples continuously frozen for around 700,000 years.<ref name="MIT2022">{{cite web |url=https://climate.mit.edu/explainers/permafrost |title=Permafrost | vauthors = McGee D, Gribkoff E |date=4 August 2022 |website=MIT Climate Portal |access-date=27 September 2023 |archive-date=27 September 2023 |archive-url=https://web.archive.org/web/20230927153347/https://climate.mit.edu/explainers/permafrost |url-status=live}}</ref> In the recent decades, permafrost has been rapidly thawing due to [[climate change]].<ref name="AR6_WG1_Chapter922">Fox-Kemper, B., H.T. Hewitt, C. Xiao, G. Aðalgeirsdóttir, S.S. Drijfhout, T.L. Edwards, N.R. Golledge, M. Hemer, R.E. Kopp, G.&nbsp; Krinner, A. Mix, D. Notz, S. Nowicki, I.S. Nurhati, L. Ruiz, J.-B. Sallée, A.B.A. Slangen, and Y. Yu, 2021: [https://www.ipcc.ch/report/ar6/wg1/downloads/report/IPCC_AR6_WGI_Chapter09.pdf Chapter 9: Ocean, Cryosphere and Sea Level Change] {{Webarchive|url=https://web.archive.org/web/20221024162651/https://www.ipcc.ch/report/ar6/wg1/downloads/report/IPCC_AR6_WGI_Chapter09.pdf |date=24 October 2022 }}. In [https://www.ipcc.ch/report/ar6/wg1/ Climate Change 2021: The Physical Science Basis. Contribution of Working Group I to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change]  [Masson-Delmotte, V., P. Zhai, A. Pirani, S.L.&nbsp; Connors, C. Péan, S. Berger, N. Caud, Y. Chen, L. Goldfarb, M.I. Gomis, M. Huang, K. Leitzell, E. Lonnoy, J.B.R. Matthews, T.K. Maycock, T. Waterfield, O. Yelekçi, R. Yu, and B. Zhou (eds.)]. Cambridge University Press, Cambridge, United Kingdom and New York, NY, USA, pp. 1211–1362, doi:10.1017/9781009157896.011.</ref>{{rp|1237}} The cold preserves any [[organic matter]] inside the permafrost, and it is possible for microorganisms to resume their life functions once it thaws. While some common [[pathogen]]s such as [[influenza]], [[smallpox]] or the bacteria associated with [[pneumonia]] have failed to survive intentional attempts to revive them,<ref name="Doucleff2020">{{cite web |url=https://www.npr.org/sections/goatsandsoda/2020/05/19/857992695/are-there-zombie-viruses-like-the-1918-flu-thawing-in-the-permafrost |title=Are There Zombie Viruses — Like The 1918 Flu — Thawing In The Permafrost? | vauthors = Michaeleen D |website=NPR.org |access-date=4 April 2023|archive-date=24 April 2023 |archive-url=https://web.archive.org/web/20230424072912/https://www.npr.org/sections/goatsandsoda/2020/05/19/857992695/are-there-zombie-viruses-like-the-1918-flu-thawing-in-the-permafrost |url-status=live }}</ref> more cold-adapted microorganisms such as [[anthrax]], or several ancient [[plant]] and [[amoeba]] viruses, have successfully survived prolonged thaw.<ref name="Doucleff2016">{{cite web|url=https://www.npr.org/sections/goatsandsoda/2016/08/03/488400947/anthrax-outbreak-in-russia-thought-to-be-result-of-thawing-permafrost|title=Anthrax Outbreak In Russia Thought To Be Result Of Thawing Permafrost|website=NPR.org |url-status=live|archive-url=https://web.archive.org/web/20160922013246/http://www.npr.org/sections/goatsandsoda/2016/08/03/488400947/anthrax-outbreak-in-russia-thought-to-be-result-of-thawing-permafrost|archive-date=2016-09-22|access-date=2016-09-24}}</ref><ref>{{cite journal | vauthors = Ng TF, Chen LF, Zhou Y, Shapiro B, Stiller M, Heintzman PD, Varsani A, Kondov NO, Wong W, Deng X, Andrews TD, Moorman BJ, Meulendyk T, MacKay G, Gilbertson RL, Delwart E | title = Preservation of viral genomes in 700-y-old caribou feces from a subarctic ice patch | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 47 | pages = 16842–16847 | date = November 2014 | pmid = 25349412 | pmc = 4250163 | doi = 10.1073/pnas.1410429111 | doi-access = free | bibcode = 2014PNAS..11116842N }}</ref><ref name="Legendre 2015 E5327–E5335">{{cite journal | vauthors = Legendre M, Lartigue A, Bertaux L, Jeudy S, Bartoli J, Lescot M, Alempic JM, Ramus C, Bruley C, Labadie K, Shmakova L, Rivkina E, Couté Y, Abergel C, Claverie JM | title = In-depth study of Mollivirus sibericum, a new 30,000-y-old giant virus infecting Acanthamoeba | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 38 | pages = E5327–E5335 | date = September 2015 | pmid = 26351664 | pmc = 4586845 | doi = 10.1073/pnas.1510795112 | doi-access = free | bibcode = 2015PNAS..112E5327L | jstor = 26465169 }}</ref><ref name="Alempic2023">{{cite journal | vauthors = Alempic JM, Lartigue A, Goncharov AE, Grosse G, Strauss J, Tikhonov AN, Fedorov AN, Poirot O, Legendre M, Santini S, Abergel C, Claverie JM | title = An Update on Eukaryotic Viruses Revived from Ancient Permafrost | journal = Viruses | volume = 15 | issue = 2 | page = 564 | date = February 2023 | pmid = 36851778 | pmc = 9958942 | doi = 10.3390/v15020564 | doi-access = free }}</ref><ref name="Alund2023">{{cite news |url=https://www.usatoday.com/story/news/health/2023/03/09/zombie-virus-frozen-permafrost-revived-after-50-000-years/11434218002/ |title=Scientists revive 'zombie virus' that was frozen for nearly 50,000 years | vauthors = Alund NN |date=9 March 2023 |website=[[USA Today]] |access-date=2023-04-23 |archive-date=2023-04-24 |archive-url=https://web.archive.org/web/20230424073604/https://www.usatoday.com/story/news/health/2023/03/09/zombie-virus-frozen-permafrost-revived-after-50-000-years/11434218002/ |url-status=live }}</ref>

Some scientists have argued that the inability of known [[disease causative agent|causative agent]]s of [[contagious disease]]s to survive being frozen and thawed makes this threat unlikely. Instead, there have been suggestions that when modern pathogenic bacteria interact with the ancient ones, they may, through [[horizontal gene transfer]], pick up [[genetic sequence]]s which are associated with  antimicrobial resistance, exacerbating an already difficult issue.<ref name="Sajjad2020">{{cite journal | vauthors = Sajjad W, Rafiq M, Din G, Hasan F, Iqbal A, Zada S, Ali B, Hayat M, Irfan M, Kang S | title = Resurrection of inactive microbes and resistome present in the natural frozen world: Reality or myth? | journal = The Science of the Total Environment | volume = 735 | pages = 139275 | date = September 2020 | pmid = 32480145 | doi = 10.1016/j.scitotenv.2020.139275 | s2cid = 219169932 | doi-access =  | bibcode = 2020ScTEn.73539275S }}</ref> Antibiotics to which permafrost bacteria have displayed at least some resistance include [[chloramphenicol]], [[streptomycin]], [[kanamycin]], [[gentamicin]], [[tetracycline]], [[spectinomycin]] and [[neomycin]].<ref name="Miner2021">{{cite journal | vauthors = Miner KR, D'Andrilli J, Mackelprang R, Edwards A, Malaska MJ, Waldrop MP, Miller CE |date=30 September 2021 |title=Emergent biogeochemical risks from Arctic permafrost degradation |journal=Nature Climate Change |volume=11 |issue=1 |pages=809–819 |doi=10.1038/s41558-021-01162-y |bibcode=2021NatCC..11..809M |s2cid=238234156 }}</ref> However, other studies show that resistance levels in ancient bacteria to modern antibiotics remain lower than in the contemporary bacteria from the [[active layer]] of thawed ground above them,<ref name="Perron2015">{{cite journal | vauthors = Perron GG, Whyte L, Turnbaugh PJ, Goordial J, Hanage WP, Dantas G, Desai MM | title = Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics | journal = PLOS ONE | volume = 10 | issue = 3 | pages = e0069533 | date = 25 March 2015 | pmid = 25807523 | pmc = 4373940 | doi = 10.1371/journal.pone.0069533 | doi-access = free | bibcode = 2015PLoSO..1069533P }}</ref> which may mean that this risk is "no greater" than from any other soil.<ref name="Wu2022">{{cite journal| vauthors = Wu R, Trubl G, Taş N, Jansson JK |date=15 April 2022|title=Permafrost as a potential pathogen reservoir|journal=One Earth |volume=5|issue=4|pages=351–360 |doi=10.1016/j.oneear.2022.03.010 |bibcode=2022OEart...5..351W |s2cid=248208195 |doi-access=free}}</ref>