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Added information on the potential of nanoparticles and antibodies as antimicrobial agents against resistant bacteria. Briefly mentioned various nanoparticles including silver, gold, zinc oxide, copper, and silica. Highlighted innovative antibody strategies such as monoclonal antibodies, DSTA4637S, and MEDI13902, and their mechanisms. |
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{{Short description|Resistance of microbes to drugs directed against them}}
{{cs1 config|mode=cs1|name-list-style=vanc}}|display-authors=6
{{Use dmy dates|date=January 2020}}
{{longlead|date=June 2024}}
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'''Antibiotic resistance''' is a major subset of AMR, that applies specifically to [[bacteria]] that become resistant to [[antibiotic]]s.<ref name="WHO2014" /> Resistance in bacteria can arise naturally by [[genetic mutation]], or by one species acquiring resistance from another.<ref>{{cite web |title=General Background: About Antibiotic Resistance |url=http://www.tufts.edu/med/apua/about_issue/about_antibioticres.shtml |url-status=dead |archive-url=https://web.archive.org/web/20151023035356/http://www.tufts.edu/med/apua/about_issue/about_antibioticres.shtml |archive-date=23 October 2015 |access-date=30 October 2015 |website=www.tufts.edu}}</ref> Resistance can appear spontaneously because of random mutations, but also arises through spreading of resistant genes through [[horizontal gene transfer]]. However, extended use of antibiotics appears to encourage selection for mutations which can render antibiotics ineffective.<ref>{{cite journal | vauthors = Dabour R, Meirson T, Samson AO | title = Global antibiotic resistance is mostly periodic | journal = Journal of Global Antimicrobial Resistance | volume = 7 | pages = 132–134 | date = December 2016 | pmid = 27788414 | doi = 10.1016/j.jgar.2016.09.003 }}</ref> '''Antifungal resistance''' is a subset of AMR, that specifically applies to fungi that have become resistant to antifungals. Resistance to antifungals can arise naturally, for example by genetic mutation or through [[aneuploidy]]. Extended use of antifungals leads to development of antifungal resistance through various mechanisms.<ref name=":11">{{cite journal | vauthors = Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, Bromley M, Brüggemann R, Garber G, Cornely OA, Gurr SJ, Harrison TS, Kuijper E, Rhodes J, Sheppard DC, Warris A, White PL, Xu J, Zwaan B, Verweij PE | display-authors = 6 | title = Tackling the emerging threat of antifungal resistance to human health | journal = Nature Reviews. Microbiology | volume = 20 | issue = 9 | pages = 557–571 | date = September 2022 | pmid = 35352028 | pmc = 8962932 | doi = 10.1038/s41579-022-00720-1 }}</ref>
Clinical conditions due to infections caused by microbes containing AMR cause millions of deaths each year.<ref>{{cite journal | title = Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019 | journal = Lancet | volume = 400 | issue = 10369 | pages = 2221–2248 | date = December 2022 | pmid = 36423648 | pmc = 9763654 | doi = 10.1016/S0140-6736(22)02185-7 |
The prevention of [[antibiotic misuse]], which can lead to antibiotic resistance, includes taking antibiotics only when prescribed.<ref name="About Antimicrobial Resistance">{{cite web|url=https://www.cdc.gov/drugresistance/about.html|title=About Antimicrobial Resistance|website=www.cdc.gov|access-date=30 October 2015|archive-url=https://web.archive.org/web/20171001044758/https://www.cdc.gov/drugresistance/about.html|archive-date=1 October 2017|url-status=live|date=10 September 2018}}</ref><ref name="Swedish">{{cite book|title=Swedish work on containment of antibiotic resistance – Tools, methods and experiences|publisher=Public Health Agency of Sweden|year=2014|isbn=978-91-7603-011-0|url=http://www.folkhalsomyndigheten.se/pagefiles/17351/Swedish-work-on-containment-of-antibiotic-resistance.pdf|location=Stockholm|pages=16–17, 121–128|access-date=23 July 2015|archive-url=https://web.archive.org/web/20150723081110/http://www.folkhalsomyndigheten.se/pagefiles/17351/Swedish-work-on-containment-of-antibiotic-resistance.pdf|archive-date=23 July 2015|url-status=live|df=dmy-all}}</ref> [[Narrow-spectrum antibiotic]]s are preferred over [[broad-spectrum antibiotic]]s when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance, as well as side effects.<ref name="NPS2013">{{cite web|title=Duration of antibiotic therapy and resistance|url=http://www.nps.org.au/publications/health-professional/health-news-evidence/2013/duration-of-antibiotic-therapy|website=NPS Medicinewise|publisher=National Prescribing Service Limited trading, Australia|access-date=22 July 2015|date=13 June 2013|archive-url=https://web.archive.org/web/20150723074759/http://www.nps.org.au/publications/health-professional/health-news-evidence/2013/duration-of-antibiotic-therapy|archive-date=23 July 2015|url-status=dead|df=dmy-all}}</ref><ref>{{cite journal | vauthors = Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, Barkman D, Odeniyi F, Conaboy K, Bell L, Zaoutis TE, Fiks AG | display-authors = 6 | title = Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections | journal = JAMA | volume = 318 | issue = 23 | pages = 2325–2336 | date = December 2017 | pmid = 29260224 | pmc = 5820700 | doi = 10.1001/jama.2017.18715 }}</ref><ref name=":13">{{cite book |url=https://www.who.int/publications/i/item/9789240062382 |title=The WHO AWaRe (Access, Watch, Reserve) antibiotic book |publisher=[[World Health Organization]] (WHO) |year=2022 |isbn=978-92-4-006238-2 |location=Geneva |access-date=28 March 2023 |archive-date=13 August 2023 |archive-url=https://web.archive.org/web/20230813134739/https://www.who.int/publications/i/item/9789240062382 |url-status=live }}</ref> For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper [[sanitation]] and [[hygiene]], including [[handwashing]] and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.<ref name="CDC Mission">{{cite web|url=https://www.cdc.gov/Features/AntibioticResistance/index.html|title=CDC Features – Mission Critical: Preventing Antibiotic Resistance|website=www.cdc.gov|access-date=22 July 2015|archive-url=https://web.archive.org/web/20171108202412/https://www.cdc.gov/features/antibioticresistance/index.html|archive-date=8 November 2017|url-status=live|date=4 April 2018}}</ref>
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Antimicrobial resistance is increasing globally due to increased prescription and dispensing of antibiotic drugs in [[developing countries]].<ref>{{cite news|url=https://www.theguardian.com/science/2018/mar/26/calls-to-rein-in-antibiotic-use-after-study-shows-65-increase-worldwide|title=Calls to rein in antibiotic use after study shows 65% increase worldwide| vauthors = Sample I |date=26 March 2018|journal=The Guardian|access-date=28 March 2018|archive-url=https://web.archive.org/web/20180408063812/https://www.theguardian.com/science/2018/mar/26/calls-to-rein-in-antibiotic-use-after-study-shows-65-increase-worldwide|archive-date=8 April 2018|url-status=live}}</ref> Estimates are that 700,000 to several million deaths result per year and continues to pose a major public health threat worldwide.<ref name="Dramé_2020">{{cite journal | vauthors = Dramé O, Leclair D, Parmley EJ, Deckert A, Ouattara B, Daignault D, Ravel A | title = Antimicrobial Resistance of ''Campylobacter'' in Broiler Chicken Along the Food Chain in Canada | journal = Foodborne Pathogens and Disease | volume = 17 | issue = 8 | pages = 512–520 | date = August 2020 | pmid = 32130036 | pmc = 7415884 | doi = 10.1089/fpd.2019.2752 }}</ref><ref name="WHO 2014">{{cite web|url=https://www.who.int/drugresistance/documents/surveillancereport/en/ |title=Antimicrobial resistance: global report on surveillance 2014|author=WHO|date=April 2014|work=WHO|access-date=9 May 2015|archive-url= https://web.archive.org/web/20150515101620/http://www.who.int/drugresistance/documents/surveillancereport/en/ |archive-date=15 May 2015|url-status=dead}}</ref><ref name="AMR2016">{{cite web|url=https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf|title=Tackling drug-resistant infections globally: final report and recommendations | vauthors = O'Neill J |date=May 2016|website=amr-review.org/|access-date=10 November 2017|archive-url= https://web.archive.org/web/20171114170946/https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf |archive-date=14 November 2017|url-status=live}}</ref> Each year in the [[United States]], at least 2.8 million people become infected with bacteria that are resistant to antibiotics and at least 35,000 people die and US$55 billion is spent on increased health care costs and lost productivity.<ref>{{cite journal | vauthors = Dadgostar P | title = Antimicrobial Resistance: Implications and Costs | language = English | journal = Infection and Drug Resistance | volume = 12 | pages = 3903–3910 | date = 2019-12-20 | pmid = 31908502 | pmc = 6929930 | doi = 10.2147/IDR.S234610 | doi-access = free }}</ref><ref>{{cite web |title=The biggest antibiotic-resistant threats in the U.S. |url=https://www.cdc.gov/drugresistance/biggest-threats.html |website=Centers for Disease Control and Prevention |access-date=15 November 2019 |language=en-us |date=6 November 2019 |archive-date=6 November 2019 |archive-url=https://web.archive.org/web/20191106224431/https://www.cdc.gov/drugresistance/biggest-threats.html |url-status=live }}</ref> According to [[World Health Organization]] (WHO) estimates, 350 million deaths could be caused by AMR by 2050.<ref>{{cite news|vauthors=Chanel S, Doherty B|date=2020-09-10|title='Superbugs' a far greater risk than Covid in Pacific, scientist warns|language=en-GB|work=The Guardian|url=https://www.theguardian.com/world/2020/sep/10/superbugs-a-far-greater-risk-than-covid-in-pacific-scientist-warns|access-date=2020-09-14|issn=0261-3077|archive-date=5 December 2022|archive-url=https://web.archive.org/web/20221205165241/https://www.theguardian.com/world/2020/sep/10/superbugs-a-far-greater-risk-than-covid-in-pacific-scientist-warns|url-status=live}}</ref> By then, the yearly death toll will be 10 million, according to a [[United Nations]] report.<ref>{{cite web|vauthors=Samuel S|date=2019-05-07|title=Our antibiotics are becoming useless|url=https://www.vox.com/future-perfect/2019/5/7/18535480/drug-resistance-antibiotics-un-report|access-date=2021-01-28|website=Vox|language=en|archive-date=11 May 2021|archive-url=https://web.archive.org/web/20210511162852/https://www.vox.com/future-perfect/2019/5/7/18535480/drug-resistance-antibiotics-un-report|url-status=live}}</ref>
There are public calls for global collective action to address the threat that include proposals for [[international treaty|international treaties]] on antimicrobial resistance.<ref name="Hoffman" /> The [[Disease burden|burden]] of worldwide antibiotic resistance is not completely identified, but [[Developing country|low-and middle- income countries]] with weaker healthcare systems are more affected, with mortality being the highest in [[sub-Saharan Africa]].<ref name=":
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The [[European Centre for Disease Prevention and Control]] calculated that in 2015 there were 671,689 infections in the EU and European Economic Area caused by antibiotic-resistant bacteria, resulting in 33,110 deaths. Most were acquired in healthcare settings.<ref>{{cite journal | vauthors = Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, Colomb-Cotinat M, Kretzschmar ME, Devleesschauwer B, Cecchini M, Ouakrim DA, Oliveira TC, Struelens MJ, Suetens C, Monnet DL | display-authors = 6 | title = Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis | journal = The Lancet. Infectious Diseases | volume = 19 | issue = 1 | pages = 56–66 | date = January 2019 | pmid = 30409683 | pmc = 6300481 | doi = 10.1016/S1473-3099(18)30605-4 }}</ref><ref>{{cite web |title=Antibiotic-resistant bacteria responsible for over 33,000 deaths in Europe in 2015, study finds |url=https://pharmaceutical-journal.com/article/news/antibiotic-resistant-bacteria-responsible-for-over-33000-deaths-in-europe-in-2015-study-finds |access-date=2023-03-28 |website=The Pharmaceutical Journal |date=7 November 2018 |language=en-US |archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328155238/https://pharmaceutical-journal.com/article/news/antibiotic-resistant-bacteria-responsible-for-over-33000-deaths-in-europe-in-2015-study-finds |url-status=live }}</ref> In 2019 there were 133,000 deaths caused by AMR.<ref>{{cite journal | title = The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis | journal = The Lancet. Public Health | volume = 7 | issue = 11 | pages = e897–e913 | date = November 2022 | pmid = 36244350 | pmc = 9630253 | doi = 10.1016/S2468-2667(22)00225-0 | hdl = 10023/26218 |
== Causes ==
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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|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 medical system. Veterinary oversight is required by law for all medically important antibiotics.
=== Pandemics, disinfectants and healthcare systems ===
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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 |language=en |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>{{cite journal |
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 | display-authors = 6 | 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" />
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{{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 |
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 |
==Prevention==
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===Duration of antimicrobials===
Delaying or minimizing the use of antibiotics for certain conditions may help safely reduce their use.<ref name=":15">{{cite journal |
Delaying antibiotics for ailments such as a sore throat and otitis media may have not different in the rate of complications compared with immediate antibiotics, for example.<ref name=":15" /> When treating respiratory tract infections, clinical judgement is required as to the appropriate treatment (delayed or immediate antibiotic use).<ref name=":15" />
The study, "Shorter and Longer Antibiotic Durations for Respiratory Infections: To Fight Antimicrobial Resistance—A Retrospective Cross-Sectional Study in a Secondary Care Setting in the UK," highlights the urgency of reevaluating antibiotic treatment durations amidst the global challenge of antimicrobial resistance (AMR). It investigates the effectiveness of shorter versus longer antibiotic regimens for respiratory tract infections (RTIs) in a UK secondary care setting, emphasizing the need for evidence-based prescribing practices to optimize patient outcomes and combat AMR. <ref>{{cite journal | vauthors = Abdelsalam Elshenawy R, Umaru N, Aslanpour Z | title = Shorter and Longer Antibiotic Durations for Respiratory Infections: To Fight Antimicrobial
===Monitoring and mapping===
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===== United States =====
The [[United States Department of Agriculture]] (USDA) and the [[Food and Drug Administration]] (FDA) collect data on antibiotic use in humans and in a more limited fashion in animals.<ref name="gao">{{cite web|url=http://www.gao.gov/assets/330/323097.html|title=GAO-11-801, Antibiotic Resistance: Agencies Have Made Limited Progress Addressing Antibiotic Use in Animals|publisher=gao.gov|access-date=25 January 2014|archive-url=https://web.archive.org/web/20131105120254/http://www.gao.gov/assets/330/323097.html|archive-date=5 November 2013|url-status=live}}</ref> About 80% of antibiotic use in the U.S. is for agriculture purposes, and about 70% of these are medically important.<ref>{{cite journal |
In 2000, the FDA announced their intention to revoke approval of [[fluoroquinolone]] use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone-resistant ''[[Campylobacter]]'' infections in humans. Legal challenges from the food animal and pharmaceutical industries delayed the final decision to do so until 2006.<ref name="Nelson-2007">{{cite journal | vauthors = Nelson JM, Chiller TM, Powers JH, Angulo FJ | title = Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story | journal = Clinical Infectious Diseases | volume = 44 | issue = 7 | pages = 977–80 | date = April 2007 | pmid = 17342653 | doi = 10.1086/512369 | doi-access = free }}</ref> Fluroquinolones have been banned from extra-label use in food animals in the USA since 2007.<ref>{{cite journal |date=2022-04-29 |title=Extralabel Use and Antimicrobials |url=https://www.fda.gov/animal-veterinary/antimicrobial-resistance/extralabel-use-and-antimicrobials |journal=FDA |language=en |access-date=19 April 2023 |archive-date=19 April 2023 |archive-url=https://web.archive.org/web/20230419181246/https://www.fda.gov/animal-veterinary/antimicrobial-resistance/extralabel-use-and-antimicrobials |url-status=live }}</ref> However, they remain widely used in companion and exotic animals.<ref>{{cite journal | vauthors = Pallo-Zimmerman LM, Byron JK, Graves TK | title = Fluoroquinolones: then and now | journal = Compendium | volume = 32 | issue = 7 | pages = E1-9; quiz E9 | date = July 2010 | pmid = 20957609 | url = https://vetfolio-vetstreet.s3.amazonaws.com/1a/a3a710678c11e0a3340050568d17ce/file/PV0710_zimmerman_CE.pdf | access-date = 19 April 2023 | archive-date = 21 June 2023 | archive-url = https://web.archive.org/web/20230621165809/https://vetfolio-vetstreet.s3.amazonaws.com/1a/a3a710678c11e0a3340050568d17ce/file/PV0710_zimmerman_CE.pdf | url-status = live }}</ref>
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There are several different types of germs that have developed a resistance over time.
The six pathogens causing most deaths associated with resistance are ''Escherichia coli'', ''Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii'', and ''Pseudomonas aeruginosa''. They were responsible for 929,000 deaths attributable to resistance and 3.57 million deaths associated with resistance in 2019.<ref name=":8">{{cite journal | vauthors = Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar
Penicillinase-producing ''Neisseria gonorrhoeae'' developed a resistance to penicillin in 1976. Another example is Azithromycin-resistant ''Neisseria gonorrhoeae'', which developed a resistance to azithromycin in 2011.<ref>{{cite web|title=About Antibiotic Resistance|url=https://www.cdc.gov/drugresistance/about.html|website=CDC|date=13 March 2020|access-date=8 September 2017|archive-date=1 October 2017|archive-url=https://web.archive.org/web/20171001044758/https://www.cdc.gov/drugresistance/about.html|url-status=live}}</ref>
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== History ==
The 1950s to 1970s represented the golden age of antibiotic discovery, where countless new classes of antibiotics were discovered to treat previously incurable diseases such as tuberculosis and syphilis.<ref>{{cite journal | vauthors = Aminov RI | title = A brief history of the antibiotic era: lessons learned and challenges for the future | language = en | journal = Frontiers in Microbiology | volume = 1 | pages = 134 | date = 2010 | pmid = 21687759 | pmc = 3109405 | doi = 10.3389/fmicb.2010.00134 | doi-access = free }}</ref> However, since that time the discovery of new classes of antibiotics has been almost nonexistent, and represents a situation that is especially problematic considering the resiliency of bacteria<ref>{{cite journal | vauthors = Carvalho G, Forestier C, Mathias JD | title = Antibiotic resilience: a necessary concept to complement antibiotic resistance? | journal = Proceedings. Biological Sciences | volume = 286 | issue = 1916 | pages = 20192408 | date = December 2019 | pmid = 31795866 | pmc = 6939251 | doi = 10.1098/rspb.2019.2408 }}</ref> shown over time and the continued misuse and overuse of antibiotics in treatment.<ref name="worldcat.org">{{cite book|title=Antimicrobial resistance : global report on surveillance|
The phenomenon of antimicrobial resistance caused by overuse of antibiotics was predicted as early as 1945 by [[Alexander Fleming]] who said "The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant."<ref>{{cite book | veditors = Amábile-Cuevas CF | title = Antimicrobial resistance in bacteria. | publisher = Horizon Scientific Press | date = 2007 }}</ref><ref>{{Citation|url=https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture/|contribution-url=https://www.nobelprize.org/uploads/2018/06/fleming-lecture.pdf|contribution=Penicillin|title=Nobel Lecture| vauthors = Fleming A |date=11 December 1945|access-date=9 August 2020|archive-url= https://web.archive.org/web/20180331001640/https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf |archive-date= 31 March 2018|url-status=live}}</ref> Without the creation of new and stronger antibiotics an era where common infections and minor injuries can kill, and where complex procedures such as surgery and chemotherapy become too risky, is a very real possibility.<ref>{{cite web|url=https://www.who.int/antimicrobial-resistance/publications/global-action-plan/en/|title=WHO {{!}} Global action plan on antimicrobial resistance|website=WHO|access-date=23 April 2018|archive-url=https://web.archive.org/web/20180418062254/http://www.who.int/antimicrobial-resistance/publications/global-action-plan/en/|archive-date=18 April 2018|url-status=dead}}</ref> Antimicrobial resistance can lead to epidemics of enormous proportions if preventive actions are not taken. In this day and age current antimicrobial resistance leads to longer hospital stays, higher medical costs, and increased mortality.<ref name="worldcat.org"/>
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===Antibody therapy===
Antibodies are promising against antimicrobial resistance. Monoclonal antibodies (mAbs) target bacterial virulence factors, aiding in bacterial destruction through various mechanisms. Three FDA-approved antibodies target ''B. anthracis'' and ''C. difficile'' toxins.<ref>{{
===Alternating therapy===
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