antimicrobial resistance

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Antimicrobial resistance means a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism. A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe.{{cite web|url=https://www.cdc.gov/getsmart/antibiotic-use/antibiotic-resistance-faqs.html#antibiotic-resistance-concerns|title=CDC: Get Smart: Know When Antibiotics Work|publisher=Cdc.gov|access-date=12 June 2013|archive-url=https://web.archive.org/web/20150429180658/http://www.cdc.gov/getsmart/antibiotic-use/antibiotic-resistance-faqs.html#antibiotic-resistance-concerns|archive-date=29 April 2015|url-status=live|date=29 May 2018}} All types of microbes can develop drug resistance. Thus, there are antibiotic, antifungal, antiviral and antiparasitic resistance.

Antibiotic resistance is a subset of antimicrobial resistance. This more specific resistance is linked to bacteria and thus broken down into two further subsets, microbiological and clinical. Microbiological resistance is the most common and occurs from genes, mutated or inherited, that allow the bacteria to resist the mechanism to kill the microbe associated with certain antibiotics. Clinical resistance is shown through the failure of many therapeutic techniques where the bacteria that are normally susceptible to a treatment become resistant after surviving the outcome of the treatment. In both cases of acquired resistance, the bacteria can pass the genetic catalyst for resistance through horizontal gene transfer: conjugation, transduction, or transformation. This allows the resistance to spread across the same species of pathogen or even similar bacterial pathogens.{{cite journal| vauthors = MacGowan A, Macnaughton E |date=1 October 2017|title=Antibiotic resistance |journal=Medicine |volume=45 |issue=10 |pages=622–628 |doi=10.1016/j.mpmed.2017.07.006 }}

WHO report released April 2014 stated, "this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health."[https://www.who.int/mediacentre/news/releases/2014/amr-report/en/ "WHO's first global report on antibiotic resistance reveals serious, worldwide threat to public health"] {{Webarchive|url=https://web.archive.org/web/20140502044726/http://www.who.int/mediacentre/news/releases/2014/amr-report/en/ |date=2 May 2014}} Retrieved 2 May 2014.

Each year, nearly 5 million deaths are associated with AMR globally. In 2019, global deaths attributable to AMR numbered 1.27 million in 2019. That same year, AMR may have contributed to 5 million deaths and one in five people who died due to AMR were children under five years old.

In 2018, WHO considered antibiotic resistance to be one of the biggest threats to global health, food security and development.{{cite web|url=https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance|title=Antibiotic resistance|website=who.int|access-date=2020-03-16|archive-date=21 May 2021|archive-url=https://web.archive.org/web/20210521035847/https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance|url-status=live}} Deaths attributable to AMR vary by area:

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.{{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 | 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 }}{{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|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 }} In 2019 there were 133,000 deaths caused by AMR.{{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 | vauthors = Mestrovic T, Robles Aguilar G, Swetschinski LR, Ikuta KS, Gray AP, Davis Weaver N, Han C, Wool EE, Gershberg Hayoon A, Hay SI, Dolecek C, Sartorius B, Murray CJ, Addo IY, Ahinkorah BO, Ahmed A, Aldeyab MA, Allel K, Ancuceanu R, Anyasodor AE, Ausloos M, Barra F, Bhagavathula AS, Bhandari D, Bhaskar S, Cruz-Martins N, Dastiridou A, Dokova K, Dubljanin E, Durojaiye OC}}

AMR is driven largely by the misuse and overuse of antimicrobials. Yet, at the same time, many people around the world do not have access to essential antimicrobials. 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.{{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}} 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.{{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}}

Although many microbes develop resistance to antibiotics over time though 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.{{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}} 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. 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.{{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 }} 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.

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AMR is a naturally occurring process. 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.{{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}} 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.

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 hedgehogs, possibly as a co-evolutionary adaptation of the pathogen to hedgehogs that are infected by a dermatophyte that naturally produces antibiotics.{{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}} Also, many 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.{{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 }}

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.{{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 }}

In the vast majority of countries, antibiotics can only be prescribed by a doctor and supplied by a pharmacy.{{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}} 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.{{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}} 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.{{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}} 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.{{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}} 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.

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 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. 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 tendonitis, tendon rupture and aortic dissection){{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 }}{{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 }} 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.

{{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. In 2010 and 2011 about a third of antibiotic prescriptions in outpatient settings in the United States were not necessary.{{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}} Another study in an intensive care unit in a major hospital in France has shown that 30% to 60% of prescribed antibiotics were unnecessary.{{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 }} These inappropriate uses of antimicrobial agents promote the evolution of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance.{{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 }}

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.{{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 }} 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 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.{{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 }}{{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 }}

Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.{{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}}{{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 }}

Important to the conversation of antibiotic use is the veterinary medical system. Veterinary oversight is required by law for all medically important antibiotics.{{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 }} Veterinarians use the 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.{{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 }}

Increased antibiotic use during the early waves of the COVID-19 pandemic may exacerbate this global health challenge.{{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}}{{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 }} Moreover, pandemic burdens on some healthcare systems may contribute to antibiotic-resistant infections.{{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 }} 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.{{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 | title = Antimicrobial resistance and COVID-19: Intersections and implications | journal = eLife | volume = 10 | date = February 2021 | pmid = 33588991 | pmc = 7886324 | doi = 10.7554/eLife.64139 | s2cid = 231936902 | doi-access = free }} The use of disinfectants such as alcohol-based hand sanitizers, and antiseptic hand wash may also have the potential to increase antimicrobial resistance.{{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 }} Extensive use of disinfectants can lead to mutations that induce antimicrobial resistance.{{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}}

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.{{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}} 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.{{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}} 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 antibiotics, antivirals, and antiparasitics.

Considering the complex interactions between humans, animals and the environment, it is also important to consider the environmental aspects and contributors to antimicrobial resistance.{{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}} Although there are still some knowledge gaps in understanding the mechanisms and transmission pathways,{{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}} environmental pollution is considered a significant contributor to antimicrobial resistance.{{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}} Important contributing factors are through "antibiotic residues", "industrial effluents", " agricultural runoffs", "heavy metals", "biocides and pesticides" and "sewage and wastewater" that create reservoirs for resistant genes and bacteria that facilitates the transfer of human pathogens. Unused or expired antibiotics, if not disposed of properly, can enter water systems and soil. Discharge from pharmaceutical manufacturing and other industrial companies can also introduce antibiotics and other chemicals into the environment. These factors allow for creating selective pressure for resistant bacteria. Antibiotics used in livestock and aquaculture can contaminate soil and water, which promotes resistance in environmental microbes. Heavy metals such as zinc, copper and mercury, and also biocides and pesticides, can co- select for antibiotic resistance, enhancing their speed. Inadequate treatment of sewage and wastewater allows resistant bacteria and genes to spread through water systems.

{{main|Antibiotic use in livestock#Antibiotic resistance}}

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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.{{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 }} Antibiotics are fed to livestock to act as growth supplements, and a preventive measure to decrease the likelihood of infections.{{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 }}

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.{{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 }} 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.{{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 }}

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.{{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 }} 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.

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. 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.{{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 }}

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.{{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 }}

{{main|Pesticide resistance}}

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 evolving a tolerance against these antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the US Environmental Protection Agency (EPA) and sold to market, showing the widespread use of these agents.{{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}} 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 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.{{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 }} 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.{{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}} The same issues confront the novel antifungal classes (e.g. orotomides) which are again being used in both the clinic and agriculture.{{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}}

Wildlife, including wild and 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. 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).

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.

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). 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.

{{Main|Pathogenic microorganisms in frozen environments}}

File:Perron_2015_permafrost_antibiotic_resistances.png

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.{{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}} In the recent decades, permafrost has been rapidly thawing due to climate change.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.  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.  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.{{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 pathogens such as influenza, smallpox or the bacteria associated with pneumonia have failed to survive intentional attempts to revive them,{{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 }} more cold-adapted microorganisms such as anthrax, or several ancient plant and amoeba viruses, have successfully survived prolonged thaw.{{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}}{{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 }}{{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 }}{{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 }}{{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 }}

Some scientists have argued that the inability of known causative agents of contagious diseases 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 sequences which are associated with antimicrobial resistance, exacerbating an already difficult issue.{{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 }} Antibiotics to which permafrost bacteria have displayed at least some resistance include chloramphenicol, streptomycin, kanamycin, gentamicin, tetracycline, spectinomycin and neomycin.{{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 }} 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,{{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 }} which may mean that this risk is "no greater" than from any other soil.{{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}}

File:Antibioticresistance diagram.png

There have been increasing public calls for global collective action to address the threat, including a proposal for an international treaty on antimicrobial resistance. Further detail and attention is still needed in order to recognize and measure trends in resistance on the international level; the idea of a global tracking system has been suggested but implementation has yet to occur. A system of this nature would provide insight to areas of high resistance as well as information necessary for evaluating programs, introducing interventions and other changes made to fight or reverse antibiotic resistance.{{cite journal | vauthors = Rogers Van Katwyk S, Giubilini A, Kirchhelle C, Weldon I, Harrison M, McLean A, Savulescu J, Hoffman SJ | title = Exploring Models for an International Legal Agreement on the Global Antimicrobial Commons: Lessons from Climate Agreements | journal = Health Care Analysis | volume = 31 | issue = 1 | pages = 25–46 | date = March 2023 | pmid = 31965398 | pmc = 10042908 | doi = 10.1007/s10728-019-00389-3 }}{{cite journal | vauthors = Wilson LA, Van Katwyk SR, Weldon I, Hoffman SJ | title = A Global Pandemic Treaty Must Address Antimicrobial Resistance | journal = The Journal of Law, Medicine & Ethics | volume = 49 | issue = 4 | pages = 688–691 | date = 2021 | pmid = 35006051 | pmc = 8749967 | doi = 10.1017/jme.2021.94 }}

Delaying or minimizing the use of antibiotics for certain conditions may help safely reduce their use.{{cite journal | vauthors = Spurling GK, Dooley L, Clark J, Askew DA | title = Immediate versus delayed versus no antibiotics for respiratory infections | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 10 | pages = CD004417 | date = October 2023 | pmid = 37791590 | pmc = 10548498 | doi = 10.1002/14651858.CD004417.pub6 | collaboration = Cochrane Acute Respiratory Infections Group }} Antimicrobial treatment duration should be based on the infection and other health problems a person may have.{{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}} For many infections once a person has improved there is little evidence that stopping treatment causes more resistance. Some, therefore, feel that stopping early may be reasonable in some cases. Other infections, however, do require long courses regardless of whether a person feels better.

Delaying antibiotics for ailments such as a sore throat and otitis media may have no difference in the rate of complications compared with immediate antibiotics, for example. When treating respiratory tract infections, clinical judgement is required as to the appropriate treatment (delayed or immediate antibiotic use).

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.{{cite journal | vauthors = Abdelsalam Elshenawy R, Umaru N, Aslanpour Z | title = 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 | journal = Pharmaceuticals | volume = 17 | issue = 3 | pages = 339 | date = March 2024 | pmid = 38543125 | pmc = 10975983 | doi = 10.3390/ph17030339 | doi-access = free }}

There are multiple national and international monitoring programs for drug-resistant threats, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), extended spectrum beta-lactamase (ESBL) producing Enterobacterales, vancomycin-resistant Enterococcus (VRE), and multidrug-resistant Acinetobacter baumannii (MRAB).{{cite web|url=https://www.cdc.gov/drugresistance/biggest_threats.html|title=Biggest Threats – Antibiotic/Antimicrobial Resistance – CDC|website=cdc.gov|access-date=5 May 2016|archive-url=https://web.archive.org/web/20170912115220/https://www.cdc.gov/drugresistance/biggest_threats.html|archive-date=12 September 2017|url-status=live|date=10 September 2018}}

ResistanceOpen is an online global map of antimicrobial resistance developed by HealthMap which displays aggregated data on antimicrobial resistance from publicly available and user submitted data.{{cite web|url=http://www.healthmap.org/en/index.php|title=HealthMap Resistance|publisher=HealthMap.org Boston Children's Hospital|access-date=15 November 2017|archive-url=https://web.archive.org/web/20171115063743/http://www.healthmap.org/en/index.php|archive-date=15 November 2017|url-status=live}}{{cite news| vauthors = Scales D |title=Mapping Antibiotic Resistance: Know The Germs in Your Neighborhood|url=http://commonhealth.wbur.org/2015/12/antibiotic-resistance-data|newspaper=Commonhealth|publisher=National Public Radio|access-date=8 December 2015|archive-url=https://web.archive.org/web/20151208101609/http://commonhealth.wbur.org/2015/12/antibiotic-resistance-data|archive-date=8 December 2015|url-status=live}} The website can display data for a {{convert|25|mi}} radius from a location. Users may submit data from antibiograms for individual hospitals or laboratories. European data is from the EARS-Net (European Antimicrobial Resistance Surveillance Network), part of the ECDC. ResistanceMap is a website by the Center for Disease Dynamics, Economics & Policy and provides data on antimicrobial resistance on a global level.{{cite web|url=https://resistancemap.cddep.org/About.php|title=ResistanceMap|publisher=Center for Disease Dynamics, Economics & Policy|access-date=14 November 2017|archive-url=https://web.archive.org/web/20171114202902/https://resistancemap.cddep.org/About.php|archive-date=14 November 2017|url-status=live}}

The WHO's AMR global action plan also recommends antimicrobial resistance surveillance in animals.{{cite web |url= http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf |title= Global Action Plan on Antimicrobial Resistance | publisher = WHO |access-date=14 November 2017|archive-url= https://web.archive.org/web/20171031170522/http://www.wpro.who.int/entity/drug_resistance/resources/global_action_plan_eng.pdf |archive-date=31 October 2017|url-status=dead}} Initial steps in the EU for establishing the veterinary counterpart EARS-Vet (EARS-Net for veterinary medicine) have been made.{{cite journal | vauthors = Mader R, Damborg P, Amat JP, Bengtsson B, Bourély C, Broens EM, Busani L, Crespo-Robledo P, Filippitzi ME, Fitzgerald W, Kaspar H, Madero CM, Norström M, Nykäsenoja S, Pedersen K, Pokludova L, Urdahl AM, Vatopoulos A, Zafeiridis C, Madec JY | title = Building the European Antimicrobial Resistance Surveillance network in veterinary medicine (EARS-Vet) | journal = Euro Surveillance | volume = 26 | issue = 4 | date = January 2021 | pmid = 33509339 | pmc = 7848785 | doi = 10.2807/1560-7917.ES.2021.26.4.2001359 }} AMR data from pets in particular is scarce, but needed to support antibiotic stewardship in veterinary medicine.{{cite journal | vauthors = Feuer L, Frenzer SK, Merle R, Leistner R, Bäumer W, Bethe A, Lübke-Becker A, Klein B, Bartel A | title = Prevalence of MRSA in canine and feline clinical samples from one-third of veterinary practices in Germany from 2019-2021 | journal = The Journal of Antimicrobial Chemotherapy | volume = 79 | issue = 9 | pages = 2273–2280 | date = September 2024 | pmid = 39007221 | doi = 10.1093/jac/dkae225 }}

By comparison there is a lack of national and international monitoring programs for antifungal resistance.{{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 | 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 }}

{{Further|Antibiotic misuse}}

{{Further|Antimicrobial spectrum}}

Antimicrobial stewardship programmes appear useful in reducing rates of antimicrobial resistance.{{cite journal | vauthors = Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Döbele S, Tacconelli E | title = Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 9 | pages = 990–1001 | date = September 2017 | pmid = 28629876 | doi = 10.1016/S1473-3099(17)30325-0}} The antimicrobial stewardship program will also provide pharmacists with the knowledge to educate patients that antibiotics will not work for a virus for example.{{cite journal | vauthors = Gallagher JC, Justo JA, Chahine EB, Bookstaver PB, Scheetz M, Suda KJ, Fehrenbacher L, Klinker KP, MacDougall C | title = Preventing the Post-Antibiotic Era by Training Future Pharmacists as Antimicrobial Stewards | journal = American Journal of Pharmaceutical Education | volume = 82 | issue = 6 | pages = 6770 | date = August 2018 | pmid = 30181677 | pmc = 6116871 | doi = 10.5688/ajpe6770}}

Excessive antimicrobial use has become one of the top contributors to the evolution of antimicrobial resistance. Since the beginning of the antimicrobial era, antimicrobials have been used to treat a wide range of infectious diseases.{{cite journal | vauthors = Andersson DI, Hughes D | title = Persistence of antibiotic resistance in bacterial populations | journal = FEMS Microbiology Reviews | volume = 35 | issue = 5 | pages = 901–11 | date = September 2011 | pmid = 21707669 | doi = 10.1111/j.1574-6976.2011.00289.x | doi-access = free}} Overuse of antimicrobials has become the primary cause of rising levels of antimicrobial resistance. The main problem is that doctors are willing to prescribe antimicrobials to ill-informed individuals who believe that antimicrobials can cure nearly all illnesses, including viral infections like the common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both usually viral in origin) were given prescriptions for antibiotics.{{cite journal | vauthors = Gilberg K, Laouri M, Wade S, Isonaka S | title = Analysis of medication use patterns:apparent overuse of antibiotics and underuse of prescription drugs for asthma, depression, and CHF | journal = Journal of Managed Care Pharmacy | volume = 9 | issue = 3 | pages = 232–7 | year = 2003 | pmid = 14613466 | doi = 10.18553/jmcp.2003.9.3.232 | pmc = 10437266 | s2cid = 25457069}} These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria.{{cite journal | vauthors = Llor C, Bjerrum L | title = Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem | journal = Therapeutic Advances in Drug Safety | volume = 5 | issue = 6 | pages = 229–41 | date = December 2014 | pmid = 25436105 | pmc = 4232501 | doi = 10.1177/2042098614554919}} Using antimicrobials without prescription is another driving force leading to the overuse of antibiotics to self-treat diseases like the common cold, cough, fever, and dysentery resulting in an epidemic of antibiotic resistance in countries like Bangladesh, risking its spread around the globe.{{cite web|date=2021-07-18|title=Pandemic of Antibiotic Resistance Killing Children in Bangladesh|work=Science Trend|url=https://sciencetrend.ca/2021/07/antibiotic-resistance-killing-children/|access-date=2021-08-15|archive-date=29 November 2021|archive-url=https://web.archive.org/web/20211129044831/https://sciencetrend.ca/2021/07/antibiotic-resistance-killing-children/|url-status=dead}} Introducing strict antibiotic stewardship in the outpatient setting to reduce inappropriate prescribing of antibiotics may reduce the emerging bacterial resistance.{{cite journal | vauthors = Chisti MJ, Harris JB, Carroll RW, Shahunja KM, Shahid AS, Moschovis PP, Schenkel SR, Hasibur Rahman AS, Shahrin L, Faruk T, Kabir F, Ahmed D, Ahmed T | title = Antibiotic-Resistant Bacteremia in Young Children Hospitalized With Pneumonia in Bangladesh Is Associated With a High Mortality Rate | journal = Open Forum Infectious Diseases | volume = 8 | issue = 7 | pages = ofab260 | date = July 2021 | pmid = 34277885 | pmc = 8280371 | doi = 10.1093/ofid/ofab260}}

The WHO AWaRe (Access, Watch, Reserve) guidance and antibiotic book has been introduced to guide antibiotic choice for the 30 most common infections in adults and children to reduce inappropriate prescribing in primary care and hospitals. Narrow-spectrum antibiotics are preferred due to their lower resistance potential, and broad-spectrum antibiotics are only recommended for people with more severe symptoms. Some antibiotics are more likely to confer resistance, so are kept as reserve antibiotics in the AWaRe book.{{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}}

Various diagnostic strategies have been employed to prevent the overuse of antifungal therapy in the clinic, proving a safe alternative to empirical antifungal therapy, and thus underpinning antifungal stewardship schemes.{{cite journal | vauthors = Talento AF, Qualie M, Cottom L, Backx M, White PL | title = Lessons from an Educational Invasive Fungal Disease Conference on Hospital Antifungal Stewardship Practices across the UK and Ireland | journal = Journal of Fungi | volume = 7 | issue = 10 | pages = 801 | date = September 2021 | pmid = 34682223 | pmc = 8538376 | doi = 10.3390/jof7100801 | doi-access = free}}

Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials.{{cite journal | vauthors = Doron S, Davidson LE | title = Antimicrobial stewardship | journal = Mayo Clinic Proceedings | volume = 86 | issue = 11 | pages = 1113–23 | date = November 2011 | pmid = 22033257 | pmc = 3203003 | doi = 10.4065/mcp.2011.0358}} The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing the development of resistance. Stewardship interventions may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death.{{cite journal | vauthors = Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S | title = Interventions to improve antibiotic prescribing practices for hospital inpatients | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD003543 | date = February 2017 | issue = 2 | pmid = 28178770 | pmc = 6464541 | doi = 10.1002/14651858.cd003543.pub4}} Dispensing, to discharged in-house patients, the exact number of antibiotic pharmaceutical units necessary to complete an ongoing treatment can reduce antibiotic leftovers within the community as community pharmacies can have antibiotic package inefficiencies.{{Cite journal | vauthors = Costa T, Pimentel AC, Mota-Vieira L, Castanha AC |date=2021-05-01 |title=The benefits of a unit dose system in oral antibiotics dispensing: Azorean hospital pharmacists tackling the socioeconomic problem of leftovers in Portugal |url=https://link.springer.com/article/10.1007/s40267-021-00825-2 |journal=Drugs & Therapy Perspectives |language=en |volume=37 |issue=5 |pages=212–221 |doi=10.1007/s40267-021-00825-2 |issn=1179-1977}}

Given the volume of care provided in primary care (general practice), recent strategies have focused on reducing unnecessary antimicrobial prescribing in this setting. Simple interventions, such as written information explaining when taking antibiotics is not necessary, for example in common infections of the upper respiratory tract, have been shown to reduce antibiotic prescribing.{{cite journal | vauthors = O'Sullivan JW, Harvey RT, Glasziou PP, McCullough A | title = Written information for patients (or parents of child patients) to reduce the use of antibiotics for acute upper respiratory tract infections in primary care | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD011360 | date = November 2016 | issue = 11 | pmid = 27886368 | pmc = 6464519 | doi = 10.1002/14651858.CD011360.pub2}} Various tools are also available to help professionals decide if prescribing antimicrobials is necessary.

Parental expectations, driven by the worry for their children's health, can influence how often children are prescribed antibiotics. Parents often rely on their clinician for advice and reassurance. However a lack of plain language information and not having adequate time for consultation negatively impacts this relationship. In effect parents often rely on past experiences in their expectations rather than reassurance from the clinician. Adequate time for consultation and plain language information can help parents make informed decisions and avoid unnecessary antibiotic use.{{cite journal | vauthors = Bosley H, Henshall C, Appleton JV, Jackson D | title = A systematic review to explore influences on parental attitudes towards antibiotic prescribing in children | journal = Journal of Clinical Nursing | volume = 27 | issue = 5–6 | pages = 892–905 | date = March 2018 | pmid = 28906047 | doi = 10.1111/jocn.14073 | s2cid = 4336064 | url = https://radar.brookes.ac.uk/radar/file/935f9729-d7df-492d-92e9-4afe59a86772/1/fulltext.pdf | access-date = 6 May 2023 | archive-date = 14 October 2023 | archive-url = https://web.archive.org/web/20231014232802/https://radar.brookes.ac.uk/radar/file/935f9729-d7df-492d-92e9-4afe59a86772/1/fulltext.pdf | url-status = live }}

Parents play a critical role in reducing unnecessary antibiotic use, particularly during cold and flu season when children frequently experience respiratory illnesses. Many of these illnesses are caused by viruses, such as colds or the flu, which antibiotics cannot treat. Misusing antibiotics in these situations not only fails to benefit the child but also contributes to the emergence of antibiotic-resistant bacteria, posing a broader public health threat. To address parental concerns and reduce inappropriate prescribing, healthcare providers can offer plain-language explanations about the difference between bacterial and viral infections, alongside clear guidance on managing viral illnesses without antibiotics. Vaccinations also play a vital role in reducing the incidence of serious bacterial infections that may require antibiotic treatment, thereby helping to preserve the effectiveness of existing antibiotics. Schools further amplify the spread of infections due to close contact and shared surfaces, underscoring the importance of hygiene practices like regular handwashing, covering coughs, and staying home when unwell. These preventive measures not only reduce the need for antibiotics but also lower the overall risk of resistant bacteria spreading within communities.{{Cite web |title=Guidance for Safe and Healthy Journeys to School: During the COVID-19 Pandemic and Beyond (English) |url=https://www.corecommitments.unicef.org/kp/unicef-final-eng-safe-journeys-25-09-20.pdf?_gl=1*qjcyhq*_ga*MTA0ODEwOTAzNC4xNzM2NTYyNTU0*_ga_ZEPV2PX419*MTczNjU2MjU1NC4xLjEuMTczNjU2MjU3Ni4zOC4wLjA.*_gcl_au*Mzc3MDkxNjY0LjE3MzY1NjI1NTQ.*_ga_BCSVVE74RB*MTczNjU2MjU1NC4xLjEuMTczNjU2MjU3Ni4zOC4wLjA.*_ga_Q8DVG06WKT*MTczNjU2MjU1NC4xLjEuMTczNjU2MjU3Ni4wLjAuMA..*_ga_9ZKVYH4DTE*MTczNjU2MjU1NC4xLjEuMTczNjU2MjU3Ni4wLjAuMA..*_ga_P0DMSZ8KY6*MTczNjU2MjU1NC4xLjEuMTczNjU2MjU3OC4zNi4wLjA. |access-date=2025-01-11 |website=Humanitarian UNICEF |language=en}}

The prescriber should closely adhere to the five rights of drug administration: the right patient, the right drug, the right dose, the right route, and the right time.{{cite web|url=http://www.ihi.org/resources/pages/improvementstories/fiverightsofmedicationadministration.aspx|title=The Five Rights of Medication Administration|website=ihi.org|date=March 2007 |access-date=30 October 2015|archive-url=https://web.archive.org/web/20151024101457/http://www.ihi.org/resources/pages/improvementstories/fiverightsofmedicationadministration.aspx|archive-date=24 October 2015|url-status=live}} Microbiological samples should be taken for culture and sensitivity testing before treatment when indicated and treatment potentially changed based on the susceptibility report.{{cite web|url=https://www.cdc.gov/Features/AntibioticResistance/index.html|title=CDC Features – Mission Critical: Preventing Antibiotic Resistance|website=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}}{{cite journal | vauthors = Leekha S, Terrell CL, Edson RS | title = General principles of antimicrobial therapy | journal = Mayo Clinic Proceedings | volume = 86 | issue = 2 | pages = 156–67 | date = February 2011 | pmid = 21282489 | pmc = 3031442 | doi = 10.4065/mcp.2010.0639 | url = http://www.mayoclinicproceedings.org/article/S0025-6196(11)60140-7/pdf | access-date = 22 July 2015 | archive-date = 15 September 2019 | archive-url = https://web.archive.org/web/20190915154126/https://www.mayoclinicproceedings.org/article/S0025-6196(11)60140-7/pdf | url-status = live}}

Health workers and pharmacists can help tackle antibiotic resistance by: enhancing infection prevention and control; only prescribing and dispensing antibiotics when they are truly needed; prescribing and dispensing the right antibiotic(s) to treat the illness. A unit dose system implemented in community pharmacies can also reduce antibiotic leftovers at households.

People can help tackle resistance by using antibiotics only when infected with a bacterial infection and prescribed by a doctor; completing the full prescription even if the user is feeling better, never sharing antibiotics with others, or using leftover prescriptions. Taking antibiotics when not needed won't help the user, but instead give bacteria the option to adapt and leave the user with the side effects that come with the certain type of antibiotic.{{cite web |title=Are you using antibiotics wisely? |url=https://www.cdc.gov/antibiotic-use/do-and-dont.html |website=Centers for Disease Control and Prevention|date=3 January 2022 |access-date=21 March 2024 |archive-date=21 March 2024 |archive-url=https://web.archive.org/web/20240321051000/https://www.cdc.gov/antibiotic-use/do-and-dont.html |url-status=live}} The CDC recommends that you follow these behaviors so that you avoid these negative side effects and keep the community safe from spreading drug-resistant bacteria. Practicing basic bacterial infection prevention courses, such as hygiene, also helps to prevent the spread of antibiotic-resistant bacteria.{{Cite web|url=https://www.cedars-sinai.org/health-library/articles.html|title=Articles|website=Cedars-Sinai|access-date=23 March 2024|archive-date=30 May 2020|archive-url=https://web.archive.org/web/20200530132825/https://www.cedars-sinai.org/health-library/articles.html|url-status=dead}}

• The Netherlands has the lowest rate of antibiotic prescribing in the OECD, at a rate of 11.4 defined daily doses (DDD) per 1,000 people per day in 2011. The defined daily dose (DDD) is a statistical measure of drug consumption, defined by the World Health Organization (WHO).{{cite web |title=Defined Daily Dose (DDD) |url=https://www.who.int/tools/atc-ddd-toolkit/about-ddd |access-date=2023-03-28 |website=WHO|archive-date=10 May 2023 |archive-url=https://web.archive.org/web/20230510140020/https://www.who.int/tools/atc-ddd-toolkit/about-ddd |url-status=live }}
• Germany and Sweden also have lower prescribing rates, with Sweden's rate having been declining since 2007.
• Greece, France and Belgium have high prescribing rates for antibiotics of more than 28 DDD.{{cite web|url=http://www.qualitywatch.org.uk/indicator/antibiotic-prescribing#vis-ref_585|title=Indicator: Antibiotic prescribing|website=QualityWatch|publisher=Nuffield Trust & Health Foundation|access-date=16 July 2015|archive-url=https://web.archive.org/web/20150114213112/http://www.qualitywatch.org.uk/indicator/antibiotic-prescribing#vis-ref_585|archive-date=14 January 2015|url-status=live}}

Infectious disease control through improved water, sanitation and hygiene (WASH) infrastructure needs to be included in the antimicrobial resistance (AMR) agenda. The "Interagency Coordination Group on Antimicrobial Resistance" stated in 2018 that "the spread of pathogens through unsafe water results in a high burden of gastrointestinal disease, increasing even further the need for antibiotic treatment."IACG (2018) [https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_Optimize_use_of_antimicrobials_120718.pdf?ua=1 Reduce unintentional exposure and the need for antimicrobials, and optimize their use IACG Discussion Paper] {{Webarchive|url=https://web.archive.org/web/20210706080228/https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_Optimize_use_of_antimicrobials_120718.pdf?ua=1 |date=6 July 2021 }}, Interagency Coordination Group on Antimicrobial Resistance, [https://web.archive.org/web/20180726093245/http://www.who.int/antimicrobial-resistance/interagency-coordination-group/public-consultation-discussion-papers/en/ public consultation process] at WHO, Geneva, Switzerland This is particularly a problem in developing countries where the spread of infectious diseases caused by inadequate WASH standards is a major driver of antibiotic demand.{{cite web|url=https://amr-review.org/sites/default/files/LSE%20AMR%20Capstone.pdf|title=The Impact of Water and Sanitation on Diarrhoeal Disease Burden and Over-Consumption of Anitbiotics.| vauthors = Araya P |date=May 2016|access-date=12 November 2017|archive-url=https://web.archive.org/web/20171001195326/https://amr-review.org/sites/default/files/LSE%20AMR%20Capstone.pdf|archive-date=1 October 2017|url-status=live}} Growing usage of antibiotics together with persistent infectious disease levels have led to a dangerous cycle in which reliance on antimicrobials increases while the efficacy of drugs diminishes. The proper use of infrastructure for water, sanitation and hygiene (WASH) can result in a 47–72 percent decrease of diarrhea cases treated with antibiotics depending on the type of intervention and its effectiveness. A reduction of the diarrhea disease burden through improved infrastructure would result in large decreases in the number of diarrhea cases treated with antibiotics. This was estimated as ranging from 5 million in Brazil to up to 590 million in India by the year 2030. The strong link between increased consumption and resistance indicates that this will directly mitigate the accelerating spread of AMR. Sanitation and water for all by 2030 is Goal Number 6 of the Sustainable Development Goals.{{cite web |title=Goal 6: Ensure availability and sustainable management of water and sanitation for all |url=https://sdgs.un.org/goals/goal6 |access-date=2023-04-17 |website=United Nations Department of Economic and Social Affairs |archive-date=24 September 2020 |archive-url=https://archive.today/20200924190731/https://sdgs.un.org/goals/goal6 |url-status=live }}

An increase in hand washing compliance by hospital staff results in decreased rates of resistant organisms.{{cite journal | vauthors = Swoboda SM, Earsing K, Strauss K, Lane S, Lipsett PA | title = Electronic monitoring and voice prompts improve hand hygiene and decrease nosocomial infections in an intermediate care unit | journal = Critical Care Medicine | volume = 32 | issue = 2 | pages = 358–63 | date = February 2004 | pmid = 14758148 | doi = 10.1097/01.CCM.0000108866.48795.0F | s2cid = 9817602 }}{{subscription required}}

Water supply and sanitation infrastructure in health facilities offer significant co-benefits for combatting AMR, and investment should be increased. There is much room for improvement: WHO and UNICEF estimated in 2015 that globally 38% of health facilities did not have a source of water, nearly 19% had no toilets and 35% had no water and soap or alcohol-based hand rub for handwashing.WHO, UNICEF (2015). [https://www.susana.org/en/knowledge-hub/resources-and-publications/library/details/2374 Water, sanitation and hygiene in health care facilities – Status in low and middle income countries and way forward] {{Webarchive|url=https://web.archive.org/web/20180912092005/https://www.susana.org/en/knowledge-hub/resources-and-publications/library/details/2374 |date=12 September 2018 }}. World Health Organization (WHO), Geneva, Switzerland, {{ISBN|978 92 4 150847 6}}

Manufacturers of antimicrobials need to improve the treatment of their wastewater (by using industrial wastewater treatment processes) to reduce the release of residues into the environment.

{{Main|Antibiotic use in livestock#Antibiotic resistance}}It is established that the use of antibiotics in animal husbandry can give rise to AMR resistances in bacteria found in food animals to the antibiotics being administered (through injections or medicated feeds).{{cite journal |vauthors=Agga GE, Schmidt JW, Arthur TM |date=December 2016 |title=Effects of In-Feed Chlortetracycline Prophylaxis in Beef Cattle on Animal Health and Antimicrobial-Resistant Escherichia coli |journal=Applied and Environmental Microbiology |volume=82 |issue=24 |pages=7197–7204 |bibcode=2016ApEnM..82.7197A |doi=10.1128/AEM.01928-16 |pmc=5118930 |pmid=27736789}} For this reason only antimicrobials that are deemed "not-clinically relevant" are used in these practices.

Unlike resistance to antibacterials, antifungal resistance can be driven by arable farming, currently there is no regulation on the use of similar antifungal classes in agriculture and the clinic.

Recent studies have shown that the prophylactic use of "non-priority" or "non-clinically relevant" antimicrobials in feeds can potentially, under certain conditions, lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics.{{cite journal |vauthors=Brown EE, Cooper A, Carrillo C, Blais B |date=2019 |title=Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds |journal=Frontiers in Microbiology|volume=10 |pages=456 |doi=10.3389/fmicb.2019.00456 |pmc=6414793 |pmid=30894847 |doi-access=free}} The possibility for co-selection of AMR resistances in the food chain pipeline may have far-reaching implications for human health.{{cite journal |vauthors=Marshall BM, Levy SB |date=October 2011 |title=Food animals and antimicrobials: impacts on human health |journal=Clinical Microbiology Reviews |volume=24 |issue=4 |pages=718–33 |doi=10.1128/CMR.00002-11 |pmc=3194830 |pmid=21976606}}

In 1997, European Union health ministers voted to ban avoparcin and four additional antibiotics used to promote animal growth in 1999.{{cite journal | vauthors = Casewell M, Friis C, Marco E, McMullin P, Phillips I | title = The European ban on growth-promoting antibiotics and emerging consequences for human and animal health | journal = The Journal of Antimicrobial Chemotherapy | volume = 52 | issue = 2 | pages = 159–61 | date = August 2003 | pmid = 12837737 | doi = 10.1093/jac/dkg313 | doi-access = free }} In 2006 a ban on the use of antibiotics in European feed, with the exception of two antibiotics in poultry feeds, became effective.{{cite journal | vauthors = Castanon JI | title = History of the use of antibiotic as growth promoters in European poultry feeds | journal = Poultry Science | volume = 86 | issue = 11 | pages = 2466–71 | date = November 2007 | pmid = 17954599 | doi = 10.3382/ps.2007-00249 | doi-access = free }}{{subscription required}} In Scandinavia, there is evidence that the ban has led to a lower prevalence of antibiotic resistance in (nonhazardous) animal bacterial populations.{{cite journal | vauthors = Bengtsson B, Wierup M | title = Antimicrobial resistance in Scandinavia after ban of antimicrobial growth promoters | journal = Animal Biotechnology | volume = 17 | issue = 2 | pages = 147–56 | year = 2006 | pmid = 17127526 | doi = 10.1080/10495390600956920 | s2cid = 34602891 }}{{subscription required}} As of 2004, several European countries established a decline of antimicrobial resistance in humans through limiting the use of antimicrobials in agriculture and food industries without jeopardizing animal health or economic cost.{{cite journal | vauthors = Angulo FJ, Baker NL, Olsen SJ, Anderson A, Barrett TJ | title = Antimicrobial use in agriculture: controlling the transfer of antimicrobial resistance to humans | journal = Seminars in Pediatric Infectious Diseases | volume = 15 | issue = 2 | pages = 78–85 | date = April 2004 | pmid = 15185190 | doi = 10.1053/j.spid.2004.01.010 }}

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.{{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}} About 80% of antibiotic use in the U.S. is for agriculture purposes, and about 70% of these are medically important. This gives reason for concern about the antibiotic resistance crisis in the U.S. and more reason to monitor it. The FDA first determined in 1977 that there is evidence of emergence of antibiotic-resistant bacterial strains in livestock. The long-established practice of permitting OTC sales of antibiotics (including penicillin and other drugs) to lay animal owners for administration to their own animals nonetheless continued in all states.

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.{{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 }} Fluroquinolones have been banned from extra-label use in food animals in the USA since 2007.{{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|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 }} However, they remain widely used in companion and exotic animals.{{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 }}

At the 79th United Nations General Assembly High-Level Meeting on AMR on 26 September 2024, world leaders approved a political declaration committing to a clear set of targets and actions, including reducing the estimated 4.95 million human deaths associated with bacterial AMR annually by 10% by 2030.

The increasing interconnectedness of the world and the fact that new classes of antibiotics have not been developed and approved for more than 25 years highlight the extent to which antimicrobial resistance is a global health challenge.{{cite web|url=https://www.rand.org/randeurope/research/health/focus-on-antimicrobial-resistance.html|title=RAND Europe Focus on Antimicrobial Resistance (AMR)|website=rand.org|access-date=23 April 2018|archive-url=https://web.archive.org/web/20180421004546/https://www.rand.org/randeurope/research/health/focus-on-antimicrobial-resistance.html|archive-date=21 April 2018|url-status=live}} A global action plan to tackle the growing problem of resistance to antibiotics and other antimicrobial medicines was endorsed at the Sixty-eighth World Health Assembly in May 2015. One of the key objectives of the plan is to improve awareness and understanding of antimicrobial resistance through effective communication, education and training. This global action plan developed by the World Health Organization was created to combat the issue of antimicrobial resistance and was guided by the advice of countries and key stakeholders. The WHO's global action plan is composed of five key objectives that can be targeted through different means, and represents countries coming together to solve a major problem that can have future health consequences. These objectives are as follows:

• improve awareness and understanding of antimicrobial resistance through effective communication, education and training.
• strengthen the knowledge and evidence base through surveillance and research.
• reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures.
• optimize the use of antimicrobial medicines in human and animal health.
• develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines and other interventions.

Steps towards progress

• React based in Sweden has produced informative material on AMR for the general public.{{cite web|url=https://www.reactgroup.org/antibiotic-resistance/the-threat/|title=React|access-date=16 November 2017|archive-url=https://web.archive.org/web/20171116185129/https://www.reactgroup.org/antibiotic-resistance/the-threat/|archive-date=16 November 2017|url-status=live}}
• Videos are being produced for the general public to generate interest and awareness.{{cite web|url=https://www.youtube.com/watch?v=LX6XHvFdzeY| archive-url=https://ghostarchive.org/varchive/youtube/20211111/LX6XHvFdzeY| archive-date=2021-11-11 | url-status=live|title=Antibiotic Resistance: the silent tsunami (youtube video)|date=6 March 2017|website=ReActTube|access-date=17 November 2017}}{{cbignore}}{{cite web|url=https://www.youtube.com/watch?time_continue=1&v=xZbcwi7SfZE|title=The Antibiotic Apocalypse Explained|date=16 March 2016|website=Kurzgesagt – In a Nutshell|access-date=17 November 2017|archive-date=20 March 2021|archive-url=https://web.archive.org/web/20210320182755/https://www.youtube.com/watch?time_continue=1&v=xZbcwi7SfZE|url-status=live}}
• The Irish Department of Health published a National Action Plan on Antimicrobial Resistance in October 2017.{{cite web|date=October 2017|title=Ireland's National Action Plan on Antimicrobial Resistance 2017 – 2020|url=https://www.lenus.ie/handle/10147/622661|via=Lenus (Irish Health Repository)|access-date=11 January 2019|archive-date=10 August 2022|archive-url=https://web.archive.org/web/20220810172114/https://www.lenus.ie/handle/10147/622661|url-status=live}} The Strategy for the Control of Antimicrobial Resistance in Ireland (SARI), Iaunched in 2001 developed Guidelines for Antimicrobial Stewardship in Hospitals in Ireland{{cite book|url=https://www.lenus.ie/handle/10147/303394|title=Guidelines for antimicrobial stewardship in hospitals in Ireland|author=SARI Hospital Antimicrobial Stewardship Working Group|publisher=HSE Health Protection Surveillance Centre (HPSC)|year=2009|isbn=978-0-9551236-7-2|location=Dublin|access-date=11 January 2019|archive-date=5 December 2021|archive-url=https://web.archive.org/web/20211205203416/https://www.lenus.ie/handle/10147/303394|url-status=live}} in conjunction with the Health Protection Surveillance Centre, these were published in 2009. Following their publication a public information campaign 'Action on Antibiotics{{cite web|url=https://www.hse.ie/eng/health/hl/hcaiamr/antibiotics/antibiotics.html|archive-url=https://web.archive.org/web/20180528134226/https://www.hse.ie/eng/health/hl/hcaiamr/antibiotics/antibiotics.html|url-status=dead|archive-date=28 May 2018|title=Taking antibiotics for colds and flu? There's no point|website=HSE.ie|access-date=11 January 2019}}' was launched to highlight the need for a change in antibiotic prescribing. Despite this, antibiotic prescribing remains high with variance in adherence to guidelines.{{cite journal | vauthors = Murphy M, Bradley CP, Byrne S | title = Antibiotic prescribing in primary care, adherence to guidelines and unnecessary prescribing—an Irish perspective | journal = BMC Family Practice | volume = 13 | pages = 43 | date = May 2012 | issue = 1 | pmid = 22640399 | pmc = 3430589 | doi = 10.1186/1471-2296-13-43 | doi-access = free }}
• The United Kingdom published a 20-year vision for antimicrobial resistance that sets out the goal of containing and controlling AMR by 2040.{{cite web |title=UK 20-year vision for antimicrobial resistance |url=https://www.gov.uk/government/publications/uk-20-year-vision-for-antimicrobial-resistance |access-date=2023-03-28 |website=GOV.UK|archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115249/https://www.gov.uk/government/publications/uk-20-year-vision-for-antimicrobial-resistance |url-status=live }} The vision is supplemented by a 5-year action plan running from 2019 to 2024, building on the previous action plan (2013–2018).{{cite web |title=UK 5-year action plan for antimicrobial resistance 2019 to 2024 |url=https://www.gov.uk/government/publications/uk-5-year-action-plan-for-antimicrobial-resistance-2019-to-2024 |access-date=2023-03-28 |website=GOV.UK|archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115251/https://www.gov.uk/government/publications/uk-5-year-action-plan-for-antimicrobial-resistance-2019-to-2024 |url-status=live }}
• The World Health Organization has published the 2024 Bacterial Priority Pathogens List which covers 15 families of antibiotic-resistant bacterial pathogens. Notable among these are gram-negative bacteria resistant to last-resort antibiotics, drug-resistant mycobacterium tuberculosis, and other high-burden resistant pathogens such as Salmonella, Shigella, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Staphylococcus aureus. The inclusion of these pathogens in the list underscores their global impact in terms of burden, as well as issues related to transmissibility, treatability, and prevention options. It also reflects the R&D pipeline of new treatments and emerging resistance trends.{{Cite web |title=WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance |url=https://www.who.int/publications-detail-redirect/9789240093461 |access-date=2024-05-20 |website=who.int|archive-date=20 May 2024 |archive-url=https://web.archive.org/web/20240520211731/https://www.who.int/publications-detail-redirect/9789240093461 |url-status=live }}

The World Health Organization has promoted the first World Antibiotic Awareness Week running from 16 to 22 November 2015. The aim of the week is to increase global awareness of antibiotic resistance. It also wants to promote the correct usage of antibiotics across all fields in order to prevent further instances of antibiotic resistance.{{cite web|url=https://www.who.int/mediacentre/events/2015/world-antibiotic-awareness-week/event/en/|title=World Antibiotic Awareness Week|website=World Health Organization|access-date=20 November 2015|archive-url=https://web.archive.org/web/20151120222039/http://www.who.int/mediacentre/events/2015/world-antibiotic-awareness-week/event/en/|archive-date=20 November 2015|url-status=dead}}

World Antibiotic Awareness Week has been held every November since 2015. For 2017, the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO) and the World Organisation for Animal Health (OIE) are together calling for responsible use of antibiotics in humans and animals to reduce the emergence of antibiotic resistance.{{cite web|url=https://www.who.int/campaigns/world-antibiotic-awareness-week/2017/launch-event/en/|title=World Antibiotic Awareness Week|website=WHO|access-date=14 November 2017|archive-url=https://web.archive.org/web/20171113074006/http://www.who.int/campaigns/world-antibiotic-awareness-week/2017/launch-event/en/|archive-date=13 November 2017|url-status=dead}}

United Nations

In 2016 the Secretary-General of the United Nations convened the Interagency Coordination Group (IACG) on Antimicrobial Resistance.{{cite web|url=https://www.who.int/antimicrobial-resistance/interagency-coordination-group/en/|archive-url=https://web.archive.org/web/20170320110535/http://www.who.int/antimicrobial-resistance/interagency-coordination-group/en/|url-status=dead|archive-date=20 March 2017|title=WHO {{!}} UN Interagency Coordination Group (IACG) on Antimicrobial Resistance|website=WHO|access-date=7 August 2019}} The IACG worked with international organizations and experts in human, animal, and plant health to create a plan to fight antimicrobial resistance. Their report released in April 2019 highlights the seriousness of antimicrobial resistance and the threat it poses to world health. It suggests five recommendations for member states to follow in order to tackle this increasing threat. The IACG recommendations are as follows:{{cite report |url=https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdf |title=No Time to Wait: Securing the Future from Drug-Resistant Infections |last=Interagency Coordination Group (IACG) |date=April 2019 |access-date=2023-04-19 |archive-date=19 April 2023 |archive-url=https://web.archive.org/web/20230419181246/https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdf |url-status=live }}

• Accelerate progress in countries
• Innovate to secure the future
• Collaborate for more effective action
• Invest for a sustainable response
• Strengthen accountability and global governance

The One Health approach recognizes that human, animal, and environmental health are interconnected in the development and spread of antimicrobial resistance (AMR).{{cite web |title=Global action plan on antimicrobial resistance |url=https://www.who.int/publications/i/item/9789241509763 |publisher=World Health Organization |access-date=15 May 2023 |date=2021}} Key strategies include:

• Monitoring antibiotic use and resistance trends across human medicine, agriculture, and environmental sectors.{{cite web |title=One Health and Antimicrobial Resistance |url=https://www.cdc.gov/onehealth/basics/antimicrobial-resistance.html |publisher=CDC |access-date=15 May 2023 |date=2023}}
• For example, 73% of the world's antibiotics are used in livestock, often for non-therapeutic purposes like growth promotion.{{cite web |title=Stop using antibiotics in healthy animals to prevent the spread of antibiotic resistance |url=https://www.who.int/news/item/07-11-2017-stop-using-antibiotics-in-healthy-animals-to-prevent-the-spread-of-antibiotic-resistance |publisher=World Health Organization |access-date=15 May 2023 |date=2017}}

• Banning non-therapeutic antibiotics in agriculture (e.g., European Union's 2006 growth promoter ban).{{cite report |title=Tracking progress on food and agriculture-related SDG indicators |url=http://www.fao.org/sdg-progress-report/en/ |publisher=Food and Agriculture Organization |date=2020 |access-date=15 May 2023}}
• Incentivizing development of new antibiotics and alternatives (e.g., vaccines, bacteriophages).{{cite web |title=OIE Annual Report on Antimicrobial Agents Intended for Use in Animals |url=https://www.woah.org/en/document/oie-annual-report-on-antimicrobial-agents-intended-for-use-in-animals/ |publisher=World Organisation for Animal Health |date=2022 |access-date=15 May 2023}}

• Reducing pharmaceutical waste in water systems and soil through improved waste management.{{cite journal |last1=Berendonk |first1=T.U. |title=Environmental antimicrobial resistance and its drivers: A potential threat to public health |journal=The Lancet Infectious Diseases |date=2022 |volume=22 |issue=7 |pages=e217–e228 |doi=10.1002/ijop.12869 |pmid=35753343}}
• Addressing resistance genes in wastewater from hospitals, farms, and drug manufacturing sites.{{cite report |title=National Action Plan for Combating Antibiotic-Resistant Bacteria |url=https://www.cdc.gov/drugresistance/pdf/national-action-plan-2020-2025.pdf |publisher=U.S. Government |date=2020 |access-date=15 May 2023}}

{{Further|List of antibiotic resistant bacteria}}File:mecA Resistance.svg, which are essential for bacterial life, by permanently binding to their active sites. MRSA, however, expresses a PBP that does not allow the antibiotic into its active site.|alt=Diagram depicting antibiotic resistance through alteration of the antibiotic's target site]]

The five main mechanisms by which bacteria exhibit resistance to antibiotics are:

1. Drug inactivation or modification: for example, enzymatic deactivation of penicillin G in some penicillin-resistant bacteria through the production of β-lactamases. Drugs may also be chemically modified through the addition of functional groups by transferase enzymes; for example, acetylation, phosphorylation, or adenylation are common resistance mechanisms to aminoglycosides. Acetylation is the most widely used mechanism and can affect a number of drug classes.{{cite journal | vauthors = Reygaert WC | title = An overview of the antimicrobial resistance mechanisms of bacteria | journal = AIMS Microbiology | volume = 4 | issue = 3 | pages = 482–501 | date = 2018 | pmid = 31294229 | pmc = 6604941 | doi = 10.3934/microbiol.2018.3.482 }}{{cite book | vauthors = Baylay AJ, Piddock LJ, Webber MA |title=Bacterial Resistance to Antibiotics – from Molecules to Man |chapter=Molecular Mechanisms of Antibiotic Resistance – Part I |date=14 March 2019 |pages=1–26 |publisher=Wiley |doi=10.1002/9781119593522.ch1|isbn=978-1-119-94077-7 |s2cid=202806156 }}{{rp|6–8}}
2. Alteration of target- or binding site: for example, alteration of PBP—the binding target site of penicillins—in MRSA and other penicillin-resistant bacteria. Another protective mechanism found among bacterial species is ribosomal protection proteins. These proteins protect the bacterial cell from antibiotics that target the cell's ribosomes to inhibit protein synthesis. The mechanism involves the binding of the ribosomal protection proteins to the ribosomes of the bacterial cell, which in turn changes its conformational shape. This allows the ribosomes to continue synthesizing proteins essential to the cell while preventing antibiotics from binding to the ribosome to inhibit protein synthesis.{{cite journal | vauthors = Connell SR, Tracz DM, Nierhaus KH, Taylor DE | title = Ribosomal protection proteins and their mechanism of tetracycline resistance | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 12 | pages = 3675–81 | date = December 2003 | pmid = 14638464 | pmc = 296194 | doi = 10.1128/AAC.47.12.3675-3681.2003 }}
3. Alteration of metabolic pathway: for example, some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides, instead, like mammalian cells, they turn to using preformed folic acid.{{cite journal | vauthors = Henry RJ | title = The Mode of Action of Sulfonamides | journal = Bacteriological Reviews | volume = 7 | issue = 4 | pages = 175–262 | date = December 1943 | pmid = 16350088 | pmc = 440870 | doi = 10.1128/MMBR.7.4.175-262.1943 }}
4. Reduced drug accumulation: by decreasing drug permeability or increasing active efflux (pumping out) of the drugs across the cell surface.{{cite journal | vauthors = Li XZ, Nikaido H | title = Efflux-mediated drug resistance in bacteria: an update | journal = Drugs | volume = 69 | issue = 12 | pages = 1555–623 | date = August 2009 | pmid = 19678712 | pmc = 2847397 | doi = 10.2165/11317030-000000000-00000 }} These multidrug efflux pumps within the cellular membrane of certain bacterial species are used to pump antibiotics out of the cell before they are able to do any damage. They are often activated by a specific substrate associated with an antibiotic,{{cite journal | vauthors = Aminov RI, Mackie RI | title = Evolution and ecology of antibiotic resistance genes | journal = FEMS Microbiology Letters | volume = 271 | issue = 2 | pages = 147–61 | date = June 2007 | pmid = 17490428 | doi = 10.1111/j.1574-6968.2007.00757.x | doi-access = free }} as in fluoroquinolone resistance.{{cite journal | vauthors = Morita Y, Kodama K, Shiota S, Mine T, Kataoka A, Mizushima T, Tsuchiya T | title = NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Escherichia coli | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 7 | pages = 1778–82 | date = July 1998 | pmid = 9661020 | pmc = 105682 | doi = 10.1128/AAC.42.7.1778 }}
5. Ribosome splitting and recycling: for example, drug-mediated stalling of the ribosome by lincomycin and erythromycin unstalled by a heat shock protein found in Listeria monocytogenes, which is a homologue of HflX from other bacteria. Liberation of the ribosome from the drug allows further translation and consequent resistance to the drug.{{cite journal | vauthors = Duval M, Dar D, Carvalho F, Rocha EP, Sorek R, Cossart P | title = HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 52 | pages = 13359–13364 | date = December 2018 | pmid = 30545912 | pmc = 6310831 | doi = 10.1073/pnas.1810555115 | bibcode = 2018PNAS..11513359D | doi-access = free }}

File:Antibiotic resistance mechanisms.jpg

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.{{cite journal | vauthors = Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, Han C, Bisignano C, Rao P, Wool E, Johnson SC, Browne AJ, Chipeta MG, Fell F, Hackett S, Haines-Woodhouse G, Kashef Hamadani BH, Kumaran EA, McManigal B, Achalapong S, Agarwal R, Akech S, Albertson S, Amuasi J, Andrews J, Aravkin A, Ashley E, Babin FX, Bailey F, Baker S | collaboration = Antimicrobial Resistance Collaborators | title = Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis | language = English | journal = Lancet | volume = 399 | issue = 10325 | pages = 629–655 | date = February 2022 | pmid = 35065702 | pmc = 8841637 | doi = 10.1016/S0140-6736(21)02724-0 | s2cid = 246077406 }}

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.{{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}}

In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug's effectiveness.{{cite journal | vauthors = Robicsek A, Jacoby GA, Hooper DC | title = The worldwide emergence of plasmid-mediated quinolone resistance | journal = The Lancet. Infectious Diseases | volume = 6 | issue = 10 | pages = 629–40 | date = October 2006 | pmid = 17008172 | doi = 10.1016/S1473-3099(06)70599-0 }}

Some bacteria are naturally resistant to certain antibiotics; for example, gram-negative bacteria are resistant to most β-lactam antibiotics due to the presence of β-lactamase. Antibiotic resistance can also be acquired as a result of either genetic mutation or horizontal gene transfer.{{cite journal|vauthors=Ochiai K, Yamanaka T, Kimura K, Sawada O, O|year=1959|title=Inheritance of drug resistance (and its transfer) between Shigella strains and Between Shigella and E.coli strains|journal=Hihon Iji Shimpor|language=ja|volume=34|page=1861}} Although mutations are rare, with spontaneous mutations in the pathogen genome occurring at a rate of about 1 in 10⁵ to 1 in 10⁸ per chromosomal replication,{{cite book |vauthors=Watford S, Warrington SJ |chapter=Bacterial DNA Mutations |date=2018 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK459274/ |title=StatPearls |publisher=StatPearls Publishing |pmid=29083710 |access-date=21 January 2019 |archive-date=8 March 2021 |archive-url=https://web.archive.org/web/20210308150820/https://www.ncbi.nlm.nih.gov/books/NBK459274/ |url-status=live }} the fact that bacteria reproduce at a high rate allows for the effect to be significant. Given that lifespans and production of new generations can be on a timescale of mere hours, a new (de novo) mutation in a parent cell can quickly become an inherited mutation of widespread prevalence, resulting in the microevolution of a fully resistant colony. However, chromosomal mutations also confer a cost of fitness. For example, a ribosomal mutation may protect a bacterial cell by changing the binding site of an antibiotic but may result in slower growth rate.{{cite journal | vauthors = Levin BR, Perrot V, Walker N | title = Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria | journal = Genetics | volume = 154 | issue = 3 | pages = 985–97 | date = March 2000 | doi = 10.1093/genetics/154.3.985 | pmid = 10757748 | pmc = 1460977 | url = http://www.genetics.org/cgi/pmidlookup?view=long&pmid=10757748 | access-date = 4 March 2017 | archive-date = 18 January 2023 | archive-url = https://web.archive.org/web/20230118003230/https://academic.oup.com/genetics | url-status = live }} Moreover, some adaptive mutations can propagate not only through inheritance but also through horizontal gene transfer. The most common mechanism of horizontal gene transfer is the transferring of plasmids carrying antibiotic resistance genes between bacteria of the same or different species via conjugation. However, bacteria can also acquire resistance through transformation, as in Streptococcus pneumoniae uptaking of naked fragments of extracellular DNA that contain antibiotic resistance genes to streptomycin,{{cite journal | vauthors = Hotchkiss RD | title = Transfer of penicillin resistance in pneumococci by the desoxyribonucleate derived from resistant cultures | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 16 | pages = 457–61 | date = 1951 | pmid = 14942755 | doi = 10.1101/SQB.1951.016.01.032 }} through transduction, as in the bacteriophage-mediated transfer of tetracycline resistance genes between strains of S. pyogenes,{{cite journal | vauthors = Ubukata K, Konno M, Fujii R | title = Transduction of drug resistance to tetracycline, chloramphenicol, macrolides, lincomycin and clindamycin with phages induced from Streptococcus pyogenes | journal = The Journal of Antibiotics | volume = 28 | issue = 9 | pages = 681–8 | date = September 1975 | pmid = 1102514 | doi = 10.7164/antibiotics.28.681 | doi-access = free }} or through gene transfer agents, which are particles produced by the host cell that resemble bacteriophage structures and are capable of transferring DNA.{{cite journal | vauthors = von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LB, Savelkoul PH, Wolffs PF | title = Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer | journal = Frontiers in Microbiology | volume = 7 | pages = 173 | date = 19 February 2016 | pmid = 26925045 | pmc = 4759269 | doi = 10.3389/fmicb.2016.00173 | doi-access = free }}

Antibiotic resistance can be introduced artificially into a microorganism through laboratory protocols, sometimes used as a selectable marker to examine the mechanisms of gene transfer or to identify individuals that absorbed a piece of DNA that included the resistance gene and another gene of interest.{{cite journal | vauthors = Chan CX, Beiko RG, Ragan MA | title = Lateral transfer of genes and gene fragments in Staphylococcus extends beyond mobile elements | journal = Journal of Bacteriology | volume = 193 | issue = 15 | pages = 3964–77 | date = August 2011 | pmid = 21622749 | pmc = 3147504 | doi = 10.1128/JB.01524-10 }}

Recent findings show no necessity of large populations of bacteria for the appearance of antibiotic resistance. Small populations of Escherichia coli in an antibiotic gradient can become resistant. Any heterogeneous environment with respect to nutrient and antibiotic gradients may facilitate antibiotic resistance in small bacterial populations. Researchers hypothesize that the mechanism of resistance evolution is based on four SNP mutations in the genome of E. coli produced by the gradient of antibiotic.{{cite journal | vauthors = Johansen TB, Scheffer L, Jensen VK, Bohlin J, Feruglio SL | title = Whole-genome sequencing and antimicrobial resistance in Brucella melitensis from a Norwegian perspective | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 8538 | date = June 2018 | pmid = 29867163 | pmc = 5986768 | doi = 10.1038/s41598-018-26906-3 | bibcode = 2018NatSR...8.8538J }}

In one study, which has implications for space microbiology, a non-pathogenic strain E. coli MG1655 was exposed to trace levels of the broad spectrum antibiotic chloramphenicol, under simulated microgravity (LSMMG, or Low Shear Modeled Microgravity) over 1000 generations. The adapted strain acquired resistance to not only chloramphenicol, but also cross-resistance to other antibiotics;{{cite journal | vauthors = Tirumalai MR, Karouia F, Tran Q, Stepanov VG, Bruce RJ, Ott M, Pierson DL, Fox GE| title = Evaluation of acquired antibiotic resistance in Escherichia coli exposed to long-term low-shear modeled microgravity and background antibiotic exposure| journal = mBio | volume =10 |issue= e02637-18| date = January 2019 | pmid = 30647159 | pmc = 6336426 | doi = 10.1128/mBio.02637-18}} this was in contrast to the observation on the same strain, which was adapted to over 1000 generations under LSMMG, but without any antibiotic exposure; the strain in this case did not acquire any such resistance.{{cite journal | vauthors = Tirumalai MR, Karouia F, Tran Q, Stepanov VG, Bruce RJ, Ott M, Pierson DL, Fox GE| title = The adaptation of Escherichia coli cells grown in simulated microgravity for an extended period is both phenotypic and genomic.| journal = npj Microgravity | volume =3 |issue= 15| date = May 2017 | page = 15| pmid = 28649637 | pmc = 5460176 | doi = 10.1038/s41526-017-0020-1}} Thus, irrespective of where they are used, the use of an antibiotic would likely result in persistent resistance to that antibiotic, as well as cross-resistance to other antimicrobials.

In recent years, the emergence and spread of β-lactamases called carbapenemases has become a major health crisis.{{cite journal | vauthors = Ghaith DM, Mohamed ZK, Farahat MG, Aboulkasem Shahin W, Mohamed HO | title = Colonization of intestinal microbiota with carbapenemase-producing Enterobacteriaceae in paediatric intensive care units in Cairo, Egypt | journal = Arab Journal of Gastroenterology | volume = 20 | issue = 1 | pages = 19–22 | date = March 2019 | pmid = 30733176 | doi = 10.1016/j.ajg.2019.01.002 | s2cid = 73444389 | url = https://zenodo.org/record/6349599 | access-date = 30 May 2022 | archive-date = 27 November 2022 | archive-url = https://web.archive.org/web/20221127085649/https://zenodo.org/record/6349599 | url-status = live }}{{cite journal | vauthors = Diene SM, Rolain JM | title = Carbapenemase genes and genetic platforms in Gram-negative bacilli: Enterobacteriaceae, Pseudomonas and Acinetobacter species | journal = Clinical Microbiology and Infection | volume = 20 | issue = 9 | pages = 831–8 | date = September 2014 | pmid = 24766097 | doi = 10.1111/1469-0691.12655 | doi-access = free }} One such carbapenemase is New Delhi metallo-beta-lactamase 1 (NDM-1),{{cite journal | vauthors = Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N | title = Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study | journal = The Lancet. Infectious Diseases | volume = 10 | issue = 9 | pages = 597–602 | date = September 2010 | pmid = 20705517 | pmc = 2933358 | doi = 10.1016/S1473-3099(10)70143-2 }} an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. The most common bacteria that make this enzyme are gram-negative such as E. coli and Klebsiella pneumoniae, but the gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer.{{cite journal | vauthors = Hudson CM, Bent ZW, Meagher RJ, Williams KP | title = Resistance determinants and mobile genetic elements of an NDM-1-encoding Klebsiella pneumoniae strain | journal = PLOS ONE | volume = 9 | issue = 6 | pages = e99209 | date = 7 June 2014 | pmid = 24905728 | pmc = 4048246 | doi = 10.1371/journal.pone.0099209 | bibcode = 2014PLoSO...999209H | doi-access = free }}

Specific antiviral drugs are used to treat some viral infections. These drugs prevent viruses from reproducing by inhibiting essential stages of the virus's replication cycle in infected cells. Antivirals are used to treat HIV, hepatitis B, hepatitis C, influenza, herpes viruses including varicella zoster virus, cytomegalovirus and Epstein–Barr virus. With each virus, some strains have become resistant to the administered drugs.{{cite journal | vauthors = Lou Z, Sun Y, Rao Z | title = Current progress in antiviral strategies | journal = Trends in Pharmacological Sciences | volume = 35 | issue = 2 | pages = 86–102 | date = February 2014 | pmid = 24439476 | pmc = 7112804 | doi = 10.1016/j.tips.2013.11.006 }}

Antiviral drugs typically target key components of viral reproduction; for example, oseltamivir targets influenza neuraminidase, while guanosine analogs inhibit viral DNA polymerase. Resistance to antivirals is thus acquired through mutations in the genes that encode the protein targets of the drugs.

Resistance to HIV antivirals is problematic, and even multi-drug resistant strains have evolved.{{cite journal | vauthors = Pennings PS | title = HIV Drug Resistance: Problems and Perspectives | journal = Infectious Disease Reports | volume = 5 | issue = Suppl 1 | pages = e5 | date = June 2013 | pmid = 24470969 | pmc = 3892620 | doi = 10.4081/idr.2013.s1.e5 }} One source of resistance is that many current HIV drugs, including NRTIs and NNRTIs, target reverse transcriptase; however, HIV-1 reverse transcriptase is highly error prone and thus mutations conferring resistance arise rapidly.{{cite journal | vauthors = Das K, Arnold E | title = HIV-1 reverse transcriptase and antiviral drug resistance. Part 1 | journal = Current Opinion in Virology | volume = 3 | issue = 2 | pages = 111–8 | date = April 2013 | pmid = 23602471 | pmc = 4097814 | doi = 10.1016/j.coviro.2013.03.012 }} Resistant strains of the HIV virus emerge rapidly if only one antiviral drug is used.{{cite journal | vauthors = Ton Q, Frenkel L | title = HIV drug resistance in mothers and infants following use of antiretrovirals to prevent mother-to-child transmission | journal = Current HIV Research | volume = 11 | issue = 2 | pages = 126–36 | date = March 2013 | pmid = 23432488 | doi = 10.2174/1570162x11311020005 }} Using three or more drugs together, termed combination therapy, has helped to control this problem, but new drugs are needed because of the continuing emergence of drug-resistant HIV strains.{{cite journal | vauthors = Ebrahim O, Mazanderani AH | title = Recent developments in hiv treatment and their dissemination in poor countries | journal = Infectious Disease Reports | volume = 5 | issue = Suppl 1 | pages = e2 | date = June 2013 | pmid = 24470966 | pmc = 3892621 | doi = 10.4081/idr.2013.s1.e2 }}

Infections by fungi are a cause of high morbidity and mortality in immunocompromised persons, such as those with HIV/AIDS, tuberculosis or receiving chemotherapy.{{cite journal | vauthors = Xie JL, Polvi EJ, Shekhar-Guturja T, Cowen LE | title = Elucidating drug resistance in human fungal pathogens | journal = Future Microbiology | volume = 9 | issue = 4 | pages = 523–42 | year = 2014 | pmid = 24810351 | doi = 10.2217/fmb.14.18 }} The fungi Candida, Cryptococcus neoformans and Aspergillus fumigatus cause most of these infections and antifungal resistance occurs in all of them.{{cite journal | vauthors = Srinivasan A, Lopez-Ribot JL, Ramasubramanian AK | title = Overcoming antifungal resistance | journal = Drug Discovery Today: Technologies | volume = 11 | pages = 65–71 | date = March 2014 | pmid = 24847655 | pmc = 4031462 | doi = 10.1016/j.ddtec.2014.02.005 }} Multidrug resistance in fungi is increasing because of the widespread use of antifungal drugs to treat infections in immunocompromised individuals and the use of some agricultural antifungals.{{cite journal | vauthors = Costa C, Dias PJ, Sá-Correia I, Teixeira MC | title = MFS multidrug transporters in pathogenic fungi: do they have real clinical impact? | journal = Frontiers in Physiology | volume = 5 | pages = 197 | date = 2014 | pmid = 24904431 | pmc = 4035561 | doi = 10.3389/fphys.2014.00197 | doi-access = free }} Antifungal resistant disease is associated with increased mortality.

Some fungi (e.g. Candida krusei and fluconazole) exhibit intrinsic resistance to certain antifungal drugs or classes, whereas some species develop antifungal resistance to external pressures. Antifungal resistance is a One Health concern, driven by multiple extrinsic factors, including extensive fungicidal use, overuse of clinical antifungals, environmental change and host factors.

In the USA fluconazole-resistant Candida species and azole resistance in Aspergillus fumigatus have been highlighted as a growing threat.

More than 20 species of Candida can cause candidiasis infection, the most common of which is Candida albicans. Candida yeasts normally inhabit the skin and mucous membranes without causing infection. However, overgrowth of Candida can lead to candidiasis. Some Candida species (e.g. Candida glabrata) are becoming resistant to first-line and second-line antifungal agents such as echinocandins and azoles.

The emergence of Candida auris as a potential human pathogen that sometimes exhibits multi-class antifungal drug resistance is concerning and has been associated with several outbreaks globally. The WHO has released a priority fungal pathogen list, including pathogens with antifungal resistance.{{cite book |url=https://www.who.int/publications/i/item/9789240060241 |title=WHO fungal priority pathogens list to guide research, development and public health action |date=25 October 2022 |publisher=World Health Organization |editor=World Health Organization |isbn=978-92-4-006024-1 |language=En |access-date=27 October 2022 |archive-url=https://web.archive.org/web/20221026235331/https://www.who.int/publications/i/item/9789240060241 |archive-date=26 October 2022 |url-status=live}}

The identification of antifungal resistance is undermined by limited classical diagnosis of infection, where a culture is lacking, preventing susceptibility testing. National and international surveillance schemes for fungal disease and antifungal resistance are limited, hampering the understanding of the disease burden and associated resistance. The application of molecular testing to identify genetic markers associating with resistance may improve the identification of antifungal resistance, but the diversity of mutations associated with resistance is increasing across the fungal species causing infection. In addition, a number of resistance mechanisms depend on up-regulation of selected genes (for instance reflux pumps) rather than defined mutations that are amenable to molecular detection.

Due to the limited number of antifungals in clinical use and the increasing global incidence of antifungal resistance, using the existing antifungals in combination might be beneficial in some cases but further research is needed. Similarly, other approaches that might help to combat the emergence of antifungal resistance could rely on the development of host-directed therapies such as immunotherapy or vaccines.

The protozoan parasites that cause the diseases malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis are important human pathogens.{{cite journal | vauthors = Andrews KT, Fisher G, Skinner-Adams TS | title = Drug repurposing and human parasitic protozoan diseases | journal = International Journal for Parasitology: Drugs and Drug Resistance | volume = 4 | issue = 2 | pages = 95–111 | date = August 2014 | pmid = 25057459 | pmc = 4095053 | doi = 10.1016/j.ijpddr.2014.02.002 }}

Malarial parasites that are resistant to the drugs that are currently available to infections are common and this has led to increased efforts to develop new drugs.{{cite journal | vauthors = Visser BJ, van Vugt M, Grobusch MP | title = Malaria: an update on current chemotherapy | journal = Expert Opinion on Pharmacotherapy | volume = 15 | issue = 15 | pages = 2219–54 | date = October 2014 | pmid = 25110058 | doi = 10.1517/14656566.2014.944499 | s2cid = 34991324 }} Resistance to recently developed drugs such as artemisinin has also been reported. The problem of drug resistance in malaria has driven efforts to develop vaccines.{{cite journal | vauthors = Chia WN, Goh YS, Rénia L | title = Novel approaches to identify protective malaria vaccine candidates | journal = Frontiers in Microbiology | volume = 5 | pages = 586 | year = 2014 | pmid = 25452745 | pmc = 4233905 | doi = 10.3389/fmicb.2014.00586 | doi-access = free }}

Trypanosomes are parasitic protozoa that cause African trypanosomiasis and Chagas disease (American trypanosomiasis).{{cite journal | vauthors = Franco JR, Simarro PP, Diarra A, Jannin JG | title = Epidemiology of human African trypanosomiasis | journal = Clinical Epidemiology | volume = 6 | pages = 257–75 | year = 2014 | pmid = 25125985 | pmc = 4130665 | doi = 10.2147/CLEP.S39728 | doi-access = free }}{{cite journal | vauthors = Herrera L | title = Trypanosoma cruzi, the Causal Agent of Chagas Disease: Boundaries between Wild and Domestic Cycles in Venezuela | journal = Frontiers in Public Health | volume = 2 | pages = 259 | date = 2014 | pmid = 25506587 | pmc = 4246568 | doi = 10.3389/fpubh.2014.00259 | doi-access = free }} There are no vaccines to prevent these infections so drugs such as pentamidine and suramin, benznidazole and nifurtimox are used to treat infections. These drugs are effective but infections caused by resistant parasites have been reported.

Leishmaniasis is caused by protozoa and is an important public health problem worldwide, especially in sub-tropical and tropical countries. Drug resistance has "become a major concern".{{cite journal | vauthors = Mansueto P, Seidita A, Vitale G, Cascio A | title = Leishmaniasis in travelers: a literature review | journal = Travel Medicine and Infectious Disease | volume = 12 | issue = 6 Pt A | pages = 563–81 | year = 2014 | pmid = 25287721 | doi = 10.1016/j.tmaid.2014.09.007 | url = https://iris.unipa.it/bitstream/10447/101959/4/Travel%20Medicine%20and%20Infectious%20Disease%202014%2012%20563-581.pdf | hdl = 10447/101959 | hdl-access = free | access-date = 23 October 2017 | archive-date = 12 October 2022 | archive-url = https://web.archive.org/web/20221012000116/https://iris.unipa.it/bitstream/10447/101959/4/Travel%20Medicine%20and%20Infectious%20Disease%202014%2012%20563-581.pdf | url-status = live }}

File:The global resistome based on sewage-based monitoring.webp

File:Gene-sharing network between bacterial genera.webp

In 2022, genomic epidemiologists reported results from a global survey of antimicrobial resistance via genomic wastewater-based epidemiology, finding large regional variations, providing maps, and suggesting resistance genes are also passed on between microbial species that are not closely related.{{cite news |title=Antibiotika-Resistenzen verbreiten sich offenbar anders als gedacht |url=https://www.deutschlandfunknova.de/nachrichten/bakterien-antibiotika-resistenzen-verbreiten-sich-offenbar-anders-als-gedacht |access-date=17 January 2023 |work=Deutschlandfunk Nova |language=de |archive-date=17 January 2023 |archive-url=https://web.archive.org/web/20230117125129/https://www.deutschlandfunknova.de/nachrichten/bakterien-antibiotika-resistenzen-verbreiten-sich-offenbar-anders-als-gedacht |url-status=live }}{{cite journal | vauthors = Munk P, Brinch C, Møller FD, Petersen TN, Hendriksen RS, Seyfarth AM, Kjeldgaard JS, Svendsen CA, van Bunnik B, Berglund F, Larsson DG, Koopmans M, Woolhouse M, Aarestrup FM | title = Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance | journal = Nature Communications | volume = 13 | issue = 1 | pages = 7251 | date = December 2022 | pmid = 36456547 | pmc = 9715550 | doi = 10.1038/s41467-022-34312-7 | doi-access = free | bibcode = 2022NatCo..13.7251M }} The WHO provides the Global Antimicrobial Resistance and Use Surveillance System (GLASS) reports which summarize annual (e.g. 2020's) data on international AMR, also including an interactive dashboard.{{cite news |title=Superbugs on the rise: WHO report signals increase in antibiotic resistance |url=https://medicalxpress.com/news/2022-12-superbugs-antibiotic-resistance.html |access-date=18 January 2023 |work=World Health Organization via medicalxpress.com|archive-date=2 February 2023 |archive-url=https://web.archive.org/web/20230202015448/https://medicalxpress.com/news/2022-12-superbugs-antibiotic-resistance.html |url-status=live }}{{cite web |title=Global antimicrobial resistance and use surveillance system (GLASS) report: 2022 |url=https://www.who.int/publications/i/item/9789240062702 |website=who.int |access-date=18 January 2023|archive-date=21 January 2023 |archive-url=https://web.archive.org/web/20230121073827/https://www.who.int/publications/i/item/9789240062702 |url-status=live }}

Public Health England reported that the total number of antibiotic resistant infections in England rose by 9% from 55,812 in 2017 to 60,788 in 2018, but antibiotic consumption had fallen by 9% from 20.0 to 18.2 defined daily doses per 1,000 inhabitants per day between 2014 and 2018.{{cite news |date=31 October 2019 |title=Patients contracted 165 antibiotic resistant infections each day in 2018, says PHE |publisher=Pharmaceutical Journal |url=https://www.pharmaceutical-journal.com/20207273.article |access-date=11 December 2019 |archive-date=26 July 2020 |archive-url=https://web.archive.org/web/20200726070017/https://www.pharmaceutical-journal.com/20207273.article |url-status=dead }}

The Centers for Disease Control and Prevention reported that more than 2.8 million cases of antibiotic resistance have been reported. However, in 2019 overall deaths from antibiotic-resistant infections decreased by 18% and deaths in hospitals decreased by 30%.{{cite web |date=2022-07-06 |title=National Infection & Death Estimates for AR |url=https://www.cdc.gov/drugresistance/national-estimates.html |access-date=2023-08-03 |website=Centers for Disease Control and Prevention|archive-date=3 August 2023 |archive-url=https://web.archive.org/web/20230803195914/https://www.cdc.gov/drugresistance/national-estimates.html |url-status=live }}

The COVID pandemic caused a reversal of much of the progress made on attenuating the effects of antibiotic resistance, resulting in more antibiotic use, more resistant infections, and less data on preventive action.{{cite web |date=2022-08-11 |title=COVID-19 & Antibiotic Resistance |url=https://www.cdc.gov/drugresistance/covid19.html |access-date=2023-08-03 |website=Centers for Disease Control and Prevention|archive-date=21 February 2022 |archive-url=https://web.archive.org/web/20220221120759/https://www.cdc.gov/drugresistance/covid19.html |url-status=live }} Hospital-onset infections and deaths both increased by 15% in 2020, and significantly higher rates of infections were reported for 4 out of 6 types of healthcare associated infections.{{cite web |date=2022 |title=2022 SPECIAL REPORT: COVID-19 U.S. IMPACT ON ANTIMICROBIAL RESISTANCE |url=https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf |access-date=3 August 2023 |website=Centers for Disease Control and Prevention |page=7 |archive-date=26 August 2023 |archive-url=https://web.archive.org/web/20230826095614/https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf |url-status=live }}

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.{{cite journal | vauthors = Aminov RI | title = A brief history of the antibiotic era: lessons learned and challenges for the future| journal = Frontiers in Microbiology | volume = 1 | pages = 134 | date = 2010 | pmid = 21687759 | pmc = 3109405 | doi = 10.3389/fmicb.2010.00134 | doi-access = free }} 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{{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 }} shown over time and the continued misuse and overuse of antibiotics in treatment.{{cite book|title=Antimicrobial resistance : global report on surveillance| publisher = World Health Organization|isbn=978-92-4-156474-8|location=Geneva, Switzerland|oclc=880847527 |year=2014}}

Already in 1940, in their letter to the editor of Nature journal, Abraham and Chain identified the enzyme penicillinase as responsible for the deactivation of penicillin in penicillin-resistant bacteria. This discovery was the first step in understanding the mechanisms of microbial resistance to β-lactam antibiotics.{{cite journal |last1=Abraham |first1=E. P. |last2=Chain |first2=E. |title=An Enzyme from Bacteria able to Destroy Penicillin |journal=Nature |volume=146 |pages=837 |year=1940 |issue=3713 |doi=10.1038/146837a0}} 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."{{cite book | veditors = Amábile-Cuevas CF | title = Antimicrobial resistance in bacteria. | publisher = Horizon Scientific Press | date = 2007 }}{{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}} 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.{{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}} 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.

Since the mid-1980s pharmaceutical companies have invested in medications for cancer or chronic disease that have greater potential to make money and have "de-emphasized or dropped development of antibiotics". On 20 January 2016 at the World Economic Forum in Davos, Switzerland, more than "80 pharmaceutical and diagnostic companies" from around the world called for "transformational commercial models" at a global level to spur research and development on antibiotics and on the "enhanced use of diagnostic tests that can rapidly identify the infecting organism".{{cite news | url=https://www.nytimes.com/2016/01/21/business/to-fight-superbugs-drug-makers-call-for-incentives-to-develop-antibiotics.html | title=To Fight 'Superbugs,' Drug Makers Call for Incentives to Develop Antibiotics | newspaper=New York Times |date=20 January 2016 | access-date=24 January 2016 | vauthors = Pollack A | series=Davos 2016 Special Report | location=Davos, Switzerland | archive-url=https://web.archive.org/web/20180424142407/https://www.nytimes.com/2016/01/21/business/to-fight-superbugs-drug-makers-call-for-incentives-to-develop-antibiotics.html?smid=tw-share | archive-date=24 April 2018 | url-status=live }} A number of countries are considering or implementing delinked payment models for new antimicrobials whereby payment is based on value rather than volume of drug sales. This offers the opportunity to pay for valuable new drugs even if they are reserved for use in relatively rare drug resistant infections.{{cite journal | vauthors = Leonard C, Crabb N, Glover D, Cooper S, Bouvy J, Wobbe M, Perkins M | title = Can the UK 'Netflix' Payment Model Boost the Antibacterial Pipeline? | journal = Applied Health Economics and Health Policy | volume = 21 | issue = 3 | pages = 365–372 | date = May 2023 | pmid = 36646872 | pmc = 9842493 | doi = 10.1007/s40258-022-00786-1 }}

Some global health scholars have argued that a global, legal framework is needed to prevent and control antimicrobial resistance.{{cite journal | vauthors = Behdinan A, Hoffman SJ, Pearcey M | title = Some Global Policies for Antibiotic Resistance Depend on Legally Binding and Enforceable Commitments | journal = The Journal of Law, Medicine & Ethics | volume = 43 | issue = 2 Suppl 3 | pages = 68–73 | year = 2015 | pmid = 26243246 | doi = 10.1111/jlme.12277 | s2cid = 7415203 }}{{cite journal | vauthors = Hoffman SJ, Outterson K | title = What Will It Take to Address the Global Threat of Antibiotic Resistance? | journal = The Journal of Law, Medicine & Ethics | volume = 43 | issue = 2 | pages = 363–8 | year = 2015 | pmid = 26242959 | doi = 10.1111/jlme.12253 | s2cid = 41987305 | url = https://scholarship.law.bu.edu/cgi/viewcontent.cgi?article=1007&context=faculty_scholarship | access-date = 11 November 2019 | archive-date = 12 October 2022 | archive-url = https://web.archive.org/web/20221012000131/https://scholarship.law.bu.edu/cgi/viewcontent.cgi?article=1007&context=faculty_scholarship | url-status = live }}{{cite journal | vauthors = Hoffman SJ, Outterson K, Røttingen JA, Cars O, Clift C, Rizvi Z, Rotberg F, Tomson G, Zorzet A | title = An international legal framework to address antimicrobial resistance | journal = Bulletin of the World Health Organization | volume = 93 | issue = 2 | pages = 66 | date = February 2015 | pmid = 25883395 | pmc = 4339972 | doi = 10.2471/BLT.15.152710 }}{{cite journal | vauthors = Rizvi Z, Hoffman SJ | title = Effective Global Action on Antibiotic Resistance Requires Careful Consideration of Convening Forums | journal = The Journal of Law, Medicine & Ethics | volume = 43 | issue = 2 Suppl 3 | pages = 74–8 | year = 2015 | pmid = 26243247 | doi = 10.1111/jlme.12278 | s2cid = 24223063 }} For instance, binding global policies could be used to create antimicrobial use standards, regulate antibiotic marketing, and strengthen global surveillance systems. Ensuring compliance of involved parties is a challenge. Global antimicrobial resistance policies could take lessons from the environmental sector by adopting strategies that have made international environmental agreements successful in the past such as: sanctions for non-compliance, assistance for implementation, majority vote decision-making rules, an independent scientific panel, and specific commitments.{{cite journal | vauthors=Andresen S, Hoffman SJ | year=2015 | title=Much Can Be Learned about Addressing Antibiotic Resistance from Multilateral Environmental Agreements | journal=Journal of Law, Medicine & Ethics | volume=43 | issue=2| pages=46–52 }}

{{update section|date=October 2023}}

For the United States 2016 budget, U.S. president Barack Obama proposed to nearly double the amount of federal funding to "combat and prevent" antibiotic resistance to more than $1.2 billion.[https://obamawhitehouse.archives.gov/the-press-office/2015/01/27/fact-sheet-president-s-2016-budget-proposes-historic-investment-combat-a President's 2016 Budget Proposes Historic Investment to Combat Antibiotic-Resistant Bacteria to Protect Public Health] {{Webarchive|url=https://web.archive.org/web/20170122010901/https://obamawhitehouse.archives.gov/the-press-office/2015/01/27/fact-sheet-president-s-2016-budget-proposes-historic-investment-combat-a |date=22 January 2017 }} The White House, Office of the Press Secretary, 27 January 2015 Many international funding agencies like USAID, DFID, SIDA and Gates Foundation have pledged money for developing strategies to counter antimicrobial resistance.{{citation needed|date=April 2023}}

On 27 March 2015, the White House released a comprehensive plan to address the increasing need for agencies to combat the rise of antibiotic-resistant bacteria. The Task Force for Combating Antibiotic-Resistant Bacteria developed The National Action Plan for Combating Antibiotic-Resistant Bacteria with the intent of providing a roadmap to guide the US in the antibiotic resistance challenge and with hopes of saving many lives. This plan outlines steps taken by the Federal government over the next five years needed in order to prevent and contain outbreaks of antibiotic-resistant infections; maintain the efficacy of antibiotics already on the market; and to help to develop future diagnostics, antibiotics, and vaccines.{{cite web|url=https://obamawhitehouse.archives.gov/the-press-office/2015/03/27/fact-sheet-obama-administration-releases-national-action-plan-combat-ant|title=FACT SHEET: Obama Administration Releases National Action Plan to Combat Antibiotic-Resistant Bacteria|access-date=30 October 2015|archive-url=https://web.archive.org/web/20170121155651/https://obamawhitehouse.archives.gov/the-press-office/2015/03/27/fact-sheet-obama-administration-releases-national-action-plan-combat-ant|archive-date=21 January 2017|url-status=live|via=National Archives|work=whitehouse.gov|date=27 March 2015}}

The Action Plan was developed around five goals with focuses on strengthening health care, public health veterinary medicine, agriculture, food safety and research, and manufacturing. These goals, as listed by the White House, are as follows:

• Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections
• Strengthen National One-Health Surveillance Efforts to Combat Resistance
• Advance Development and use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria
• Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines
• Improve International Collaboration and Capacities for Antibiotic Resistance Prevention, Surveillance, Control and Antibiotic Research and Development

The following are goals set to meet by 2020:

• Establishment of antimicrobial programs within acute care hospital settings
• Reduction of inappropriate antibiotic prescription and use by at least 50% in outpatient settings and 20% inpatient settings
• Establishment of State Antibiotic Resistance (AR) Prevention Programs in all 50 states
• Elimination of the use of medically important antibiotics for growth promotion in food-producing animals.

Current Status of AMR in the U.S.

As of 2023, antimicrobial resistance (AMR) remains a significant public health threat in the United States. According to the Centers for Disease Control and Prevention's 2023 Report on Antibiotic Resistance Threats, over 2.8 million antibiotic-resistant infections occur in the U.S. each year, leading to at least 35,000 deaths annually.{{cite web | title=Antibiotic Resistance Threats in the United States, 2023 | publisher=Centers for Disease Control and Prevention | url=https://www.cdc.gov/antimicrobial-resistance/data-research/threats/update-2022.html | access-date=October 20, 2023}} Among the most concerning resistant pathogens are Carbapenem-resistant Enterobacteriaceae (CRE), Methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile (C. diff), all of which continue to be responsible for severe healthcare-associated infections (HAIs).

The COVID-19 pandemic led to a significant disruption in healthcare, with an increase in the use of antibiotics during the treatment of viral infections. This rise in antibiotic prescribing, coupled with overwhelmed healthcare systems, contributed to a resurgence in AMR during the pandemic years. A 2021 CDC report identified a sharp increase in HAIs caused by resistant pathogens in COVID-19 patients, a trend that has persisted into 2023.{{cite journal | title=The Impact of the COVID-19 Pandemic on Antimicrobial Resistance and Management of Bloodstream Infections | journal= Pathogens| year=2023 | volume=21 | issue=6 | pages= e22–e25 | doi= 10.3390/pathogens12060780| doi-access= free| pmid= 37375470| pmc= 10302285| vauthors = Petrakis V, Panopoulou M, Rafailidis P, Lemonakis N, Lazaridis G, Terzi I, Papazoglou D, Panagopoulos P}} Recent data suggest that although antibiotic use has decreased since the pandemic, some resistant pathogens remain prevalent in healthcare settings.

The CDC has also expanded its Get Ahead of Sepsis campaign in 2023, focusing on raising awareness of AMR's role in sepsis and promoting the judicious use of antibiotics in both healthcare and community settings.{{cite web | title=Get Ahead of Sepsis | publisher=Centers for Disease Control and Prevention | url=https://www.cdc.gov/sepsis/get-ahead-of-sepsis/index.html | access-date=October 20, 2023}} This initiative has reached millions through social media, healthcare facilities, and public health outreach, aiming to educate the public on the importance of preventing infections and reducing antibiotic misuse.

According to World Health Organization, policymakers can help tackle resistance by strengthening resistance-tracking and laboratory capacity and by regulating and promoting the appropriate use of medicines. Policymakers and industry can help tackle resistance by: fostering innovation and research and development of new tools; and promoting cooperation and information sharing among all stakeholders.

The U.S. government continues to prioritize AMR mitigation through policy and legislation. In 2023, the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) 2023-2028 was released, outlining strategic objectives for reducing antibiotic-resistant infections, advancing infection prevention, and accelerating research on new antibiotics.{{cite web | title=National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) 2023-2028 | publisher=The White House | url=https://www.hhs.gov/sites/default/files/carb-national-action-plan-2020-2025.pdf/ | access-date=October 20, 2023}} The plan also emphasizes the importance of improving antibiotic stewardship across healthcare, agriculture, and veterinary settings.

Furthermore, the PASTEUR Act (Pioneering Antimicrobial Subscriptions to End Upsurging Resistance) has gained momentum in Congress. If passed, the bill would create a subscription-based payment model to incentivize the development of new antimicrobial drugs, while supporting antimicrobial stewardship programs to reduce the misuse of existing antibiotics.{{cite web | title=PASTEUR Act of 2023 | date=28 October 2021 | publisher=United States Congress | url=https://www.congress.gov/bill/117th-congress/house-bill/965/ | access-date=October 20, 2023}} This legislation is considered a critical step toward addressing the economic barriers to developing new antimicrobials.

Measuring the costs and benefits of strategies to combat AMR is difficult and policies may only have effects in the distant future. In other infectious diseases this problem has been addressed by using mathematical models. More research is needed to understand how AMR develops and spreads so that mathematical modelling can be used to anticipate the likely effects of different policies.{{cite journal | vauthors = Knight GM, Davies NG, Colijn C, Coll F, Donker T, Gifford DR, Glover RE, Jit M, Klemm E, Lehtinen S, Lindsay JA, Lipsitch M, Llewelyn MJ, Mateus AL, Robotham JV, Sharland M, Stekel D, Yakob L, Atkins KE | title = Mathematical modelling for antibiotic resistance control policy: do we know enough? | journal = BMC Infectious Diseases | volume = 19 | issue = 1 | pages = 1011 | date = November 2019 | pmid = 31783803 | pmc = 6884858 | doi = 10.1186/s12879-019-4630-y | doi-access = free }}

File:Antibiotic sensitivity test.jpg: Thin paper discs containing an antibiotic have been placed on an agar plate growing bacteria. Bacteria are not able to grow around antibiotics to which they are sensitive.]]

Distinguishing infections requiring antibiotics from self-limiting ones is clinically challenging. In order to guide appropriate use of antibiotics and prevent the evolution and spread of antimicrobial resistance, diagnostic tests that provide clinicians with timely, actionable results are needed.

Acute febrile illness is a common reason for seeking medical care worldwide and a major cause of morbidity and mortality. In areas with decreasing malaria incidence, many febrile patients are inappropriately treated for malaria, and in the absence of a simple diagnostic test to identify alternative causes of fever, clinicians presume that a non-malarial febrile illness is most likely a bacterial infection, leading to inappropriate use of antibiotics. Multiple studies have shown that the use of malaria rapid diagnostic tests without reliable tools to distinguish other fever causes has resulted in increased antibiotic use.{{cite journal |vauthors=Hopkins H, Bruxvoort KJ, Cairns ME, Chandler CI, Leurent B, Ansah EK, Baiden F, Baltzell KA, Björkman A, Burchett HE, Clarke SE, DiLiberto DD, Elfving K, Goodman C, Hansen KS, Kachur SP, Lal S, Lalloo DG, Leslie T, Magnussen P, Jefferies LM, Mårtensson A, Mayan I, Mbonye AK, Msellem MI, Onwujekwe OE, Owusu-Agyei S, Reyburn H, Rowland MW, Shakely D, Vestergaard LS, Webster J, Wiseman VL, Yeung S, Schellenberg D, Staedke SG, Whitty CJ |date=March 2017 |title=Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings |journal=BMJ |volume=356 |pages=j1054 |doi=10.1136/bmj.j1054 |pmc=5370398 |pmid=28356302}}

Antimicrobial susceptibility testing (AST) can facilitate a precision medicine approach to treatment by helping clinicians to prescribe more effective and targeted antimicrobial therapy.{{cite news |date=20 November 2018 |title=Diagnostics Are Helping Counter Antimicrobial Resistance, But More Work Is Needed |work=MDDI Online |url=https://www.mddionline.com/diagnostics-are-helping-counter-antimicrobial-resistance-more-work-needed |access-date=2 December 2018 |archive-date=2 December 2018 |archive-url=https://web.archive.org/web/20181202202615/https://www.mddionline.com/diagnostics-are-helping-counter-antimicrobial-resistance-more-work-needed |url-status=dead }} At the same time with traditional phenotypic AST it can take 12 to 48 hours to obtain a result due to the time taken for organisms to grow on/in culture media.{{cite journal |vauthors=van Belkum A, Bachmann TT, Lüdke G, Lisby JG, Kahlmeter G, Mohess A, Becker K, Hays JP, Woodford N, Mitsakakis K, Moran-Gilad J, Vila J, Peter H, Rex JH, Dunne WM |date=January 2019 |title=Developmental roadmap for antimicrobial susceptibility testing systems |journal=Nature Reviews. Microbiology |volume=17 |issue=1 |pages=51–62 |doi=10.1038/s41579-018-0098-9 |pmc=7138758 |pmid=30333569 |doi-access=free |hdl=2445/132505}} Rapid testing, possible from molecular diagnostics innovations, is defined as "being feasible within an 8-h working shift". There are several commercial Food and Drug Administration-approved assays available which can detect AMR genes from a variety of specimen types. Progress has been slow due to a range of reasons including cost and regulation.{{cite journal |vauthors= |date=October 2018 |title=Progress on antibiotic resistance |journal=Nature |volume=562 |issue=7727 |pages=307 |bibcode=2018Natur.562Q.307. |doi=10.1038/d41586-018-07031-7 |pmid=30333595 |doi-access=free}} Genotypic AMR characterisation methods are, however, being increasingly used in combination with machine learning algorithms in research to help better predict phenotypic AMR from organism genotype.{{cite journal |vauthors=Kim JI, Maguire F, Tsang KK, Gouliouris T, Peacock SJ, McAllister TA, McArthur AG, Beiko RG |date=September 2022 |title=Machine Learning for Antimicrobial Resistance Prediction: Current Practice, Limitations, and Clinical Perspective |journal=Clinical Microbiology Reviews |volume=35 |issue=3 |pages=e0017921 |doi=10.1128/cmr.00179-21 |pmc=9491192 |pmid=35612324 }}{{cite journal |vauthors=Banerjee R, Patel R |date=February 2023 |title=Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions |journal=JAC-antimicrobial Resistance |volume=5 |issue=1 |pages=dlad018 |doi=10.1093/jacamr/dlad018 |pmc=9937039 |pmid=36816746}}

Optical techniques such as phase contrast microscopy in combination with single-cell analysis are another powerful method to monitor bacterial growth. In 2017, scientists from Uppsala University in Sweden published a method{{cite journal |vauthors=Baltekin Ö, Boucharin A, Tano E, Andersson DI, Elf J |date=August 2017 |title=Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=114 |issue=34 |pages=9170–9175 |bibcode=2017PNAS..114.9170B |doi=10.1073/pnas.1708558114 |pmc=5576829 |pmid=28790187 |doi-access=free}} that applies principles of microfluidics and cell tracking, to monitor bacterial response to antibiotics in less than 30 minutes overall manipulation time. This invention was awarded the 8M£ Longitude Prize on AMR in 2024. Recently, this platform has been advanced by coupling microfluidic chip with optical tweezing{{cite journal |vauthors=Luro S, Potvin-Trottier L, Okumus B, Paulsson J |date=January 2020 |title=Isolating live cells after high-throughput, long-term, time-lapse microscopy |journal=Nature Methods |volume=17 |issue=1 |pages=93–100 |doi=10.1038/s41592-019-0620-7 |pmc=7525750 |pmid=31768062}} in order to isolate bacteria with altered phenotype directly from the analytical matrix.

Rapid diagnostic methods have also been trialled as antimicrobial stewardship interventions to influence the healthcare drivers of AMR. Serum procalcitonin measurement has been shown to reduce mortality rate, antimicrobial consumption and antimicrobial-related side-effects in patients with respiratory infections, but impact on AMR has not yet been demonstrated.{{cite journal |vauthors=Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, Bhatnagar N, Annane D, Reinhart K, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Lima SS, Maravić-Stojković V, Verduri A, Cao B, Shehabi Y, Beishuizen A, Jensen JS, Corti C, Van Oers JA, Falsey AR, de Jong E, Oliveira CF, Beghe B, Briel M, Mueller B |date=October 2017 |title=Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections |journal=The Cochrane Database of Systematic Reviews |volume=10 |issue=10 |pages=CD007498 |doi=10.1002/14651858.CD007498.pub3 |pmc=6485408 |pmid=29025194 |collaboration=Cochrane Acute Respiratory Infections Group}} Similarly, point of care serum testing of the inflammatory biomarker C-reactive protein has been shown to influence antimicrobial prescribing rates in this patient cohort, but further research is required to demonstrate an effect on rates of AMR.{{cite journal |vauthors=Smedemark SA, Aabenhus R, Llor C, Fournaise A, Olsen O, Jørgensen KJ |date=October 2022 |title=Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=10 |pages=CD010130 |doi=10.1002/14651858.CD010130.pub3 |pmc=9575154 |pmid=36250577 |collaboration=Cochrane Acute Respiratory Infections Group}} Clinical investigation to rule out bacterial infections are often done for patients with pediatric acute respiratory infections. Currently it is unclear if rapid viral testing affects antibiotic use in children.{{cite journal |vauthors=Doan Q, Enarson P, Kissoon N, Klassen TP, Johnson DW |date=September 2014 |title=Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department |journal=The Cochrane Database of Systematic Reviews |volume=2014 |issue=9 |pages=CD006452 |doi=10.1002/14651858.CD006452.pub4 |pmc=6718218 |pmid=25222468}}

Vaccines are an essential part of the response to reduce AMR as they prevent infections, reduce the use and overuse of antimicrobials, and slow the emergence and spread of drug-resistant pathogens.

Microorganisms usually do not develop resistance to vaccines because vaccines reduce the spread of the infection and target the pathogen in multiple ways in the same host and possibly in different ways between different hosts. Furthermore, if the use of vaccines increases, there is evidence that antibiotic resistant strains of pathogens will decrease; the need for antibiotics will naturally decrease as vaccines prevent infection before it occurs.{{cite journal | vauthors = Mishra RP, Oviedo-Orta E, Prachi P, Rappuoli R, Bagnoli F | title = Vaccines and antibiotic resistance | journal = Current Opinion in Microbiology | volume = 15 | issue = 5 | pages = 596–602 | date = October 2012 | pmid = 22981392 | doi = 10.1016/j.mib.2012.08.002}} A 2024 report by WHO finds that vaccines against 24 pathogens could reduce the number of antibiotics needed by 22% or 2.5 billion defined daily doses globally every year. If vaccines could be rolled out against all the evaluated pathogens, they could save a third of the hospital costs associated with AMR. Vaccinated people have fewer infections and are protected against potential complications from secondary infections that may need antimicrobial medicines or require admission to hospital. However, there are well documented cases of vaccine resistance, although these are usually much less of a problem than antimicrobial resistance.{{cite journal | vauthors = Kennedy DA, Read AF | title = Why does drug resistance readily evolve but vaccine resistance does not? | journal = Proceedings. Biological Sciences | volume = 284 | issue = 1851 | pages = 20162562 | date = March 2017 | pmid = 28356449 | pmc = 5378080 | doi = 10.1098/rspb.2016.2562 }}{{cite journal | vauthors = Kennedy DA, Read AF | title = Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 51 | pages = 12878–12886 | date = December 2018 | pmid = 30559199 | pmc = 6304978 | doi = 10.1073/pnas.1717159115 | bibcode = 2018PNAS..11512878K | doi-access = free }}

While theoretically promising, antistaphylococcal vaccines have shown limited efficacy, because of immunological variation between Staphylococcus species, and the limited duration of effectiveness of the antibodies produced. Development and testing of more effective vaccines is underway.{{cite web|url=http://www.homesteadschools.com/nursing/courses/Immunity/Chapter05.html|title=Immunity, Infectious Diseases, and Pandemics—What You Can Do|publisher=HomesteadSchools.com|access-date=12 June 2013|archive-url=https://web.archive.org/web/20131203005320/http://www.homesteadschools.com/nursing/courses/Immunity/Chapter05.html|archive-date=3 December 2013|url-status=live}}

Two registrational trials have evaluated vaccine candidates in active immunization strategies against S. aureus infection. In a phase II trial, a bivalent vaccine of capsular proteins 5 & 8 was tested in 1804 hemodialysis patients with a primary fistula or synthetic graft vascular access. After 40 weeks following vaccination a protective effect was seen against S. aureus bacteremia, but not at 54 weeks following vaccination.{{cite journal | vauthors = Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, Yeoh H, Law D, Robbins JB, Schneerson R, Muenz L, Fuller S, Johnson J, Fireman B, Alcorn H, Naso R | title = Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis | journal = The New England Journal of Medicine | volume = 346 | issue = 7 | pages = 491–6 | date = February 2002 | pmid = 11844850 | doi = 10.1056/NEJMoa011297 | doi-access = free }} Based on these results, a second trial was conducted which failed to show efficacy.{{cite journal | vauthors = Fowler VG, Proctor RA | title = Where does a Staphylococcus aureus vaccine stand? | journal = Clinical Microbiology and Infection | volume = 20 | issue = 5 | pages = 66–75 | date = May 2014 | pmid = 24476315 | pmc = 4067250 | doi = 10.1111/1469-0691.12570 }}

Merck tested V710, a vaccine targeting IsdB, in a blinded randomized trial in patients undergoing median sternotomy. The trial was terminated after a higher rate of multiorgan system failure–related deaths was found in the V710 recipients. Vaccine recipients who developed S. aureus infection were five times more likely to die than control recipients who developed S. aureus infection.{{cite journal | vauthors = McNeely TB, Shah NA, Fridman A, Joshi A, Hartzel JS, Keshari RS, Lupu F, DiNubile MJ | title = Mortality among recipients of the Merck V710 Staphylococcus aureus vaccine after postoperative S. aureus infections: an analysis of possible contributing host factors | journal = Human Vaccines & Immunotherapeutics | volume = 10 | issue = 12 | pages = 3513–6 | date = 2014 | pmid = 25483690 | pmc = 4514053 | doi = 10.4161/hv.34407 }}

Numerous investigators have suggested that a multiple-antigen vaccine would be more effective, but a lack of biomarkers defining human protective immunity keep these proposals in the logical, but strictly hypothetical arena.

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.{{cite journal | vauthors = Lu RM, Hwang YC, Liu IJ, Lee CC, Tsai HZ, Li HJ, Wu HC | title = Development of therapeutic antibodies for the treatment of diseases | journal = Journal of Biomedical Science | volume = 27 | issue = 1 | pages = 1 | date = January 2020 | pmid = 31894001 | pmc = 6939334 | doi = 10.1186/s12929-019-0592-z | doi-access = free }}{{cite journal | vauthors = Singh G, Rana A | title = Decoding antimicrobial resistance: unraveling molecular mechanisms and targeted strategies | journal = Archives of Microbiology | volume = 206 | issue = 6 | pages = 280 | date = May 2024 | pmid = 38805035 | doi = 10.1007/s00203-024-03998-2 | bibcode = 2024ArMic.206..280S }} Innovative strategies include DSTA4637S, an antibody-antibiotic conjugate, and MEDI13902, a bispecific antibody targeting Pseudomonas aeruginosa components.

Alternating therapy is a proposed method in which two or three antibiotics are taken in a rotation versus taking just one antibiotic such that bacteria resistant to one antibiotic are killed when the next antibiotic is taken. Studies have found that this method reduces the rate at which antibiotic resistant bacteria emerge in vitro relative to a single drug for the entire duration.{{cite journal | vauthors = Kim S, Lieberman TD, Kishony R | title = Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 40 | pages = 14494–9 | date = October 2014 | pmid = 25246554 | pmc = 4210010 | doi = 10.1073/pnas.1409800111 | bibcode = 2014PNAS..11114494K | doi-access = free }}

Studies have found that bacteria that evolve antibiotic resistance towards one group of antibiotic may become more sensitive to others.{{cite journal | vauthors = Pál C, Papp B, Lázár V | title = Collateral sensitivity of antibiotic-resistant microbes | journal = Trends in Microbiology | volume = 23 | issue = 7 | pages = 401–7 | date = July 2015 | pmid = 25818802 | pmc = 5958998 | doi = 10.1016/j.tim.2015.02.009 }} This phenomenon can be used to select against resistant bacteria using an approach termed collateral sensitivity cycling, which has recently been found to be relevant in developing treatment strategies for chronic infections caused by Pseudomonas aeruginosa.{{cite journal | vauthors = Imamovic L, Ellabaan MM, Dantas Machado AM, Citterio L, Wulff T, Molin S, Krogh Johansen H, Sommer MO | title = Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections | journal = Cell | volume = 172 | issue = 1–2 | pages = 121–134.e14 | date = January 2018 | pmid = 29307490 | pmc = 5766827 | doi = 10.1016/j.cell.2017.12.012 }} Despite its promise, large-scale clinical and experimental studies revealed limited evidence of susceptibility to antibiotic cycling across various pathogens.{{cite journal | vauthors = Beckley AM, Wright ES | title = Identification of antibiotic pairs that evade concurrent resistance via a retrospective analysis of antimicrobial susceptibility test results | language = English | journal = The Lancet. Microbe | volume = 2 | issue = 10 | pages = e545–e554 | date = October 2021 | pmid = 34632433 | pmc = 8496867 | doi = 10.1016/S2666-5247(21)00118-X }}{{cite journal| vauthors = Ma Y, Chua SL |date=2021-11-15|title=No collateral antibiotic sensitivity by alternating antibiotic pairs |journal=The Lancet Microbe|volume=3|issue=1 |pages=e7|language=English|doi=10.1016/S2666-5247(21)00270-6|pmid=35544116 |s2cid=244147577|issn=2666-5247|doi-access=free}}

Since the discovery of antibiotics, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics, but in the 2000s there has been concern that development has slowed enough that seriously ill people may run out of treatment options.{{cite journal | vauthors = Liu J, Bedell TA, West JG, Sorensen EJ | title = Design and Synthesis of Molecular Scaffolds with Anti-infective Activity | journal = Tetrahedron | volume = 72 | issue = 25 | pages = 3579–3592 | date = June 2016 | pmid = 27284210 | pmc = 4894353 | doi = 10.1016/j.tet.2016.01.044 }}{{cite web |url= https://www.wp.dh.gov.uk/publications/files/2013/03/CMO-Annual-Report-Volume-2-20111.pdf |title=Annual Report of the Chief Medical Officer - Infections and the rise of antimicrobial resistance|date=2011|publisher=UK NHS|archive-url=https://web.archive.org/web/20131030190650/http://media.dh.gov.uk/network/357/files/2013/03/CMO-Annual-Report-Volume-2-20111.pdf|archive-date=30 October 2013|url-status=dead}} Another concern is that practitioners may become reluctant to perform routine surgeries because of the increased risk of harmful infection.{{cite news|url=https://www.npr.org/blogs/health/2013/06/04/188380562/obama-administration-seeks-to-loosen-antibiotic-approvals|title=Obama Administration Seeks To Ease Approvals For Antibiotics|newspaper=NPR.org|date=4 June 2013|publisher=NPR|access-date=7 August 2016|archive-url=https://web.archive.org/web/20150313042023/http://www.npr.org/blogs/health/2013/06/04/188380562/obama-administration-seeks-to-loosen-antibiotic-approvals|archive-date=13 March 2015|url-status=live}} Backup treatments can have serious side-effects; for example, antibiotics like aminoglycosides (such as amikacin, gentamicin, kanamycin, streptomycin, etc.) used for the treatment of drug-resistant tuberculosis and cystic fibrosis can cause respiratory disorders, deafness and kidney failure.{{cite journal | vauthors = Prayle A, Watson A, Fortnum H, Smyth A | title = Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis | journal = Thorax | volume = 65 | issue = 7 | pages = 654–658 | date = July 2010 | pmid = 20627927 | pmc = 2921289 | doi = 10.1136/thx.2009.131532 }}{{cite journal | vauthors = Alene KA, Wangdi K, Colquhoun S, Chani K, Islam T, Rahevar K, Morishita F, Byrne A, Clark J, Viney K | title = Tuberculosis related disability: a systematic review and meta-analysis | journal = BMC Medicine | volume = 19 | issue = 1 | pages = 203 | date = September 2021 | pmid = 34496845 | pmc = 8426113 | doi = 10.1186/s12916-021-02063-9 | doi-access = free}}

The potential crisis at hand is the result of a marked decrease in industry research and development.{{cite news|url=https://www.bbc.co.uk/news/health-21737844|title=BBC News – Antibiotics resistance 'as big a risk as terrorism' – medical chief| vauthors = Walsh F |publisher=Bbc.co.uk|access-date=12 March 2013|archive-url=https://web.archive.org/web/20180808002730/https://www.bbc.co.uk/news/health-21737844|archive-date=8 August 2018|url-status=live|work=BBC News|date=11 March 2013}}{{cite journal | vauthors = Berida T, Adekunle Y, Dada-Adegbola H, Kdimy A, Roy S, Sarker S | title = Plant antibacterials: The challenges and opportunities | journal = Heliyon | volume = 10 | issue = 10 | pages = e31145 | date = May 2024 | pmid = 38803958 | pmc = 11128932 | doi = 10.1016/j.heliyon.2024.e31145 | doi-access = free | bibcode = 2024Heliy..1031145B}} Poor financial investment in antibiotic research has exacerbated the situation.{{cite web | url=http://therealnews.com/t2/index.php?option=com_content&task=view&id=31&Itemid=74&jumival=11872 | title=Why Are Antibiotics Becoming Useless All Over the World? | vauthors = Khor M | author-link=Martin Khor |date=18 May 2014 | publisher=The Real News | access-date=18 May 2014 | archive-url=https://web.archive.org/web/20140518173348/http://therealnews.com/t2/index.php?option=com_content&task=view&id=31&Itemid=74&jumival=11872 | archive-date=18 May 2014 | url-status=live}} The pharmaceutical industry has little incentive to invest in antibiotics because of the high risk and because the potential financial returns are less likely to cover the cost of development than for other pharmaceuticals.{{cite news |title=Antibiotic Resistance: Why Aren't Drug Companies Developing New Medicines to Stop Superbugs?| vauthors = Nordrum A | website=International Business Times|year=2015}} In 2011, Pfizer, one of the last major pharmaceutical companies developing new antibiotics, shut down its primary research effort, citing poor shareholder returns relative to drugs for chronic illnesses.{{cite web|url=http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/24708|title=Pfizer Moves May Dim Prospect for New Antibiotics| vauthors = Gever J |date=4 February 2011|publisher=MedPage Today|access-date=12 March 2013 |archive-url=https://web.archive.org/web/20131214004508/http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/24708 |archive-date=14 December 2013|url-status=live}} However, small and medium-sized pharmaceutical companies are still active in antibiotic drug research. In particular, apart from classical synthetic chemistry methodologies, researchers have developed a combinatorial synthetic biology platform on single cell level in a high-throughput screening manner to diversify novel lanthipeptides.{{cite journal | vauthors = Schmitt S, Montalbán-López M, Peterhoff D, Deng J, Wagner R, Held M, Kuipers OP, Panke S | title = Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale | journal = Nature Chemical Biology | volume = 15 | issue = 5 | pages = 437–443 | date = May 2019 | pmid = 30936500 | doi = 10.1038/s41589-019-0250-5 | s2cid = 91188986 | url = https://pure.rug.nl/ws/files/82569070/Brl_k_et_al_2019_Journal_of_Animal_Ecology.pdf | access-date = 12 April 2023 | archive-date = 18 April 2023 | archive-url = https://web.archive.org/web/20230418031100/https://pure.rug.nl/ws/files/82569070/Brl_k_et_al_2019_Journal_of_Animal_Ecology.pdf | url-status = live }}

In the 5–10 years since 2010, there has been a significant change in the ways new antimicrobial agents are discovered and developed – principally via the formation of public-private funding initiatives. These include CARB-X,{{cite web |title=Overview |url=https://carb-x.org/about/overview/ |access-date=2023-03-28 |website=Carb-X|archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115249/https://carb-x.org/about/overview/ |url-status=live }} which focuses on nonclinical and early phase development of novel antibiotics, vaccines, rapid diagnostics; Novel Gram Negative Antibiotic (GNA-NOW),{{cite journal |title=Novel Gram Negative Antibiotic Now |url=https://cordis.europa.eu/project/id/853979 |access-date=28 March 2023 |website=CORDIS |doi=10.3030/853979 |archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115251/https://cordis.europa.eu/project/id/853979 |url-status=live }} which is part of the EU's Innovative Medicines Initiative; and Replenishing and Enabling the Pipeline for Anti-infective Resistance Impact Fund (REPAIR).{{cite web |title=About |url=https://www.repair-impact-fund.com/about/ |access-date=2023-03-28 |website=REPAIR Impact Fund|archive-date=23 January 2019 |archive-url=https://web.archive.org/web/20190123223739/https://www.repair-impact-fund.com/about/ |url-status=live }} Later stage clinical development is supported by the AMR Action Fund, which in turn is supported by multiple investors with the aim of developing 2–4 new antimicrobial agents by 2030. The delivery of these trials is facilitated by national and international networks supported by the Clinical Research Network of the National Institute for Health and Care Research (NIHR), European Clinical Research Alliance in Infectious Diseases (ECRAID) and the recently formed ADVANCE-ID, which is a clinical research network based in Asia.{{cite web |title=ADVANcing Clinical Evidence in Infectious Diseases (ADVANCE-ID) |url=https://sph.nus.edu.sg/2022/11/advancing-clinical-evidence-in-infectious-diseases-advance-id/ |access-date=2023-03-28 |website=sph.nus.edu.sg |archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115252/https://sph.nus.edu.sg/2022/11/advancing-clinical-evidence-in-infectious-diseases-advance-id/ |url-status=live }} The Global Antibiotic Research and Development Partnership (GARDP) is generating new evidence for global AMR threats such as neonatal sepsis, treatment of serious bacterial infections and sexually transmitted infections as well as addressing global access to new and strategically important antibacterial drugs.{{cite web |date=2022-09-27 |title=About GARDP |url=https://gardp.org/about-gardp/ |access-date=2023-03-28 |website=GARDP|archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115300/https://gardp.org/about-gardp/ |url-status=live }}

The discovery and development of new antimicrobial agents has been facilitated by regulatory advances, which have been principally led by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). These processes are increasingly aligned although important differences remain and drug developers must prepare separate documents. New development pathways have been developed to help with the approval of new antimicrobial agents that address unmet needs such as the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD). These new pathways are required because of difficulties in conducting large definitive phase III clinical trials in a timely way.

Some of the economic impediments to the development of new antimicrobial agents have been addressed by innovative reimbursement schemes that delink payment of antimicrobials from volume-based sales. In the UK, a market entry reward scheme has been pioneered by the National Institute for Clinical Excellence (NICE) whereby an annual subscription fee is paid for use of strategically valuable antimicrobial agents – cefiderocol and ceftazidime-aviabactam are the first agents to be used in this manner and the scheme is potential blueprint for comparable programs in other countries.

The available classes of antifungal drugs are still limited but as of 2021 novel classes of antifungals are being developed and are undergoing various stages of clinical trials to assess performance.{{cite journal | vauthors = Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely OA, Krause R, Lass-Flörl C, Prattes J, Spec A, Thompson GR, Wiederhold N, Jenks JD | title = The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin | journal = Drugs | volume = 81 | issue = 15 | pages = 1703–1729 | date = October 2021 | pmid = 34626339 | pmc = 8501344 | doi = 10.1007/s40265-021-01611-0}}

Scientists have started using advanced computational approaches with supercomputers for the development of new antibiotic derivatives to deal with antimicrobial resistance.{{cite news |title=Antibiotic resistance outwitted by supercomputers |url=https://medicalxpress.com/news/2021-11-antibiotic-resistance-outwitted-supercomputers.html |access-date=13 December 2021 |work=University of Portsmouth|archive-date=13 December 2021 |archive-url=https://web.archive.org/web/20211213175124/https://medicalxpress.com/news/2021-11-antibiotic-resistance-outwitted-supercomputers.html |url-status=live}}{{cite journal | vauthors = König G, Sokkar P, Pryk N, Heinrich S, Möller D, Cimicata G, Matzov D, Dietze P, Thiel W, Bashan A, Bandow JE, Zuegg J, Yonath A, Schulz F, Sanchez-Garcia E | title = Rational prioritization strategy allows the design of macrolide derivatives that overcome antibiotic resistance | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 118 | issue = 46 | pages = e2113632118 | date = November 2021 | pmid = 34750269 | pmc = 8609559 | doi = 10.1073/pnas.2113632118 | bibcode = 2021PNAS..11813632K | doi-access = free}}

Using antibiotic-free alternatives in bone infection treatment may help decrease the use of antibiotics and thus antimicrobial resistance. The bone regeneration material bioactive glass S53P4 has shown to effectively inhibit the bacterial growth of up to 50 clinically relevant bacteria including MRSA and MRSE.{{cite journal | vauthors = Leppäranta O, Vaahtio M, Peltola T, Zhang D, Hupa L, Hupa M, Ylänen H, Salonen JI, Viljanen MK, Eerola E | title = Antibacterial effect of bioactive glasses on clinically important anaerobic bacteria in vitro | journal = Journal of Materials Science. Materials in Medicine | volume = 19 | issue = 2 | pages = 547–51 | date = February 2008 | pmid = 17619981 | doi = 10.1007/s10856-007-3018-5 | s2cid = 21444777 }}{{cite journal | vauthors = Munukka E, Leppäranta O, Korkeamäki M, Vaahtio M, Peltola T, Zhang D, Hupa L, Ylänen H, Salonen JI, Viljanen MK, Eerola E | title = Bactericidal effects of bioactive glasses on clinically important aerobic bacteria | journal = Journal of Materials Science. Materials in Medicine | volume = 19 | issue = 1 | pages = 27–32 | date = January 2008 | pmid = 17569007 | doi = 10.1007/s10856-007-3143-1 | s2cid = 39643380 }}{{cite journal | vauthors = Drago L, De Vecchi E, Bortolin M, Toscano M, Mattina R, Romanò CL | title = Antimicrobial activity and resistance selection of different bioglass S53P4 formulations against multidrug resistant strains | journal = Future Microbiology | volume = 10 | issue = 8 | pages = 1293–9 | date = August 2015 | pmid = 26228640 | doi = 10.2217/FMB.15.57 }}

During the last decades, copper and silver nanomaterials have demonstrated appealing features for the development of a new family of antimicrobial agents.{{cite journal | vauthors = Ermini ML, Voliani V | title = Antimicrobial Nano-Agents: The Copper Age | journal = ACS Nano | volume = 15 | issue = 4 | pages = 6008–6029 | date = April 2021 | pmid = 33792292 | pmc = 8155324 | doi = 10.1021/acsnano.0c10756 | doi-access = free }} Nanoparticles (1–100 nm) show unique properties and promise as antimicrobial agents against resistant bacteria. Silver (AgNPs) and gold nanoparticles (AuNPs) are extensively studied, disrupting bacterial cell membranes and interfering with protein synthesis. Zinc oxide (ZnO NPs), copper (CuNPs), and silica (SiNPs) nanoparticles also exhibit antimicrobial properties. However, high synthesis costs, potential toxicity, and instability pose challenges. To overcome these, biological synthesis methods and combination therapies with other antimicrobials are explored. Enhanced biocompatibility and targeting are also under investigation to improve efficacy.

Similar to the situation in malaria therapy, where successful treatments based on ancient recipes have been found,{{cite web |title=Medieval medical books could hold the recipe for new antibiotics |date=18 April 2017 |vauthors=Connelly E |work=The Conversation |url=https://theconversation.com/medieval-medical-books-could-hold-the-recipe-for-new-antibiotics-74490 |access-date=20 December 2019 |archive-date=25 December 2022 |archive-url=https://web.archive.org/web/20221225165030/http://theconversation.com/medieval-medical-books-could-hold-the-recipe-for-new-antibiotics-74490 |url-status=live }} there has already been some success in finding and testing ancient drugs and other treatments that are effective against AMR bacteria.{{cite web |url=https://www.nottingham.ac.uk/news/pressreleases/2015/march/ancientbiotics---a-medieval-remedy-for-modern-day-superbugs.aspx |title=AncientBiotics – a medieval remedy for modern day superbugs? |publisher=University of Nottingham |date=30 March 2015 |type=Press release |access-date=13 August 2019 |archive-date=21 October 2022 |archive-url=https://web.archive.org/web/20221021185808/https://www.nottingham.ac.uk/news/pressreleases/2015/march/ancientbiotics---a-medieval-remedy-for-modern-day-superbugs.aspx |url-status=live }}

One of the key tools identified by the WHO and others for the fight against rising antimicrobial resistance is improved surveillance of the spread and movement of AMR genes through different communities and regions. Recent advances in high-throughput DNA sequencing as a result of the Human Genome Project have resulted in the ability to determine the individual microbial genes in a sample.{{cite journal | vauthors = Kim DW, Cha CJ | title = Antibiotic resistome from the One-Health perspective: understanding and controlling antimicrobial resistance transmission | journal = Experimental & Molecular Medicine | volume = 53 | issue = 3 | pages = 301–309 | date = March 2021 | pmid = 33642573 | pmc = 8080597 | doi = 10.1038/s12276-021-00569-z }} Along with the availability of databases of known antimicrobial resistance genes, such as the Comprehensive Antimicrobial Resistance Database (CARD){{cite journal | vauthors = Alcock BP, Huynh W, Chalil R, Smith KW, Raphenya AR, Wlodarski MA, Edalatmand A, Petkau A, Syed SA, Tsang KK, Baker SJ, Dave M, McCarthy MC, Mukiri KM, Nasir JA, Golbon B, Imtiaz H, Jiang X, Kaur K, Kwong M, Liang ZC, Niu KC, Shan P, Yang JY, Gray KL, Hoad GR, Jia B, Bhando T, Carfrae LA, Farha MA, French S, Gordzevich R, Rachwalski K, Tu MM, Bordeleau E, Dooley D, Griffiths E, Zubyk HL, Brown ED, Maguire F, Beiko RG, Hsiao WW, Brinkman FS, Van Domselaar G, McArthur AG | title = CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database | journal = Nucleic Acids Research | volume = 51 | issue = D1 | pages = D690–D699 | date = January 2023 | pmid = 36263822 | pmc = 9825576 | doi = 10.1093/nar/gkac920 }}{{cite web |title=The Comprehensive Antibiotic Resistance Database |url=https://card.mcmaster.ca/ |access-date=2023-03-28 |website=card.mcmaster.ca |archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115250/https://card.mcmaster.ca/ |url-status=live }} and ResFinder,{{cite journal | vauthors = Florensa AF, Kaas RS, Clausen PT, Aytan-Aktug D, Aarestrup FM | title = ResFinder – an open online resource for identification of antimicrobial resistance genes in next-generation sequencing data and prediction of phenotypes from genotypes | journal = Microbial Genomics | volume = 8 | issue = 1 | date = January 2022 | pmid = 35072601 | pmc = 8914360 | doi = 10.1099/mgen.0.000748 | doi-access = free }}{{cite web |title=ResFinder 4.1 |url=https://cge.food.dtu.dk/services/ResFinder/ |access-date=2023-03-28 |website=cge.food.dtu.dk |archive-date=28 March 2023 |archive-url=https://web.archive.org/web/20230328115302/https://cge.food.dtu.dk/services/ResFinder/ |url-status=live }} this allows the identification of all the antimicrobial resistance genes within the sample – the so-called "resistome". In doing so, a profile of these genes within a community or environment can be determined, providing insights into how antimicrobial resistance is spreading through a population and allowing for the identification of resistance that is of concern.

{{Main|Phage therapy}}

Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections.{{cite web|url=https://www.cbsnews.com/news/silent-killers-fantastic-phages/|title=Silent Killers: Fantastic Phages?|website=CBS News|date=19 September 2002 |access-date=14 November 2017|archive-url=https://web.archive.org/web/20130210183045/http://www.cbsnews.com/stories/2002/09/19/48hours/main522596.shtml|archive-date=10 February 2013|url-status=live}} Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture.{{cite book | chapter-url=https://www.caister.com/highveld/virology/phage.html | vauthors=McAuliffe O, Ross RP, Fitzgerald GF | chapter=The New Phage Biology: From Genomics to Applications" (introduction) | veditors=McGrath S, van Sinderen D | title=Bacteriophage: Genetics and Molecular Biology | publisher=Caister Academic Press | isbn=978-1-904455-14-1 | year=2007 | access-date=11 August 2021 | archive-date=26 November 2020 | archive-url=https://web.archive.org/web/20201126231811/https://www.caister.com/highveld/virology/phage.html | url-status=live}}

Phage therapy relies on the use of naturally occurring bacteriophages to infect and lyse bacteria at the site of infection in a host. Due to current advances in genetics and biotechnology these bacteriophages can possibly be manufactured to treat specific infections.{{cite journal | vauthors = Lin DM, Koskella B, Lin HC | title = Phage therapy: An alternative to antibiotics in the age of multi-drug resistance | journal = World Journal of Gastrointestinal Pharmacology and Therapeutics | volume = 8 | issue = 3 | pages = 162–173 | date = August 2017 | pmid = 28828194 | pmc = 5547374 | doi = 10.4292/wjgpt.v8.i3.162 | doi-access = free}} Phages can be bioengineered to target multidrug-resistant bacterial infections, and their use involves the added benefit of preventing the elimination of beneficial bacteria in the human body. Phages destroy bacterial cell walls and membrane through the use of lytic proteins which kill bacteria by making many holes from the inside out.{{cite journal | vauthors = Salmond GP, Fineran PC | title = A century of the phage: past, present and future | journal = Nature Reviews. Microbiology | volume = 13 | issue = 12 | pages = 777–86 | date = December 2015 | pmid = 26548913 | doi = 10.1038/nrmicro3564 | s2cid = 8635034}} Bacteriophages can even possess the ability to digest the biofilm that many bacteria develop that protect them from antibiotics in order to effectively infect and kill bacteria. Bioengineering can play a role in creating successful bacteriophages.

Understanding the mutual interactions and evolutions of bacterial and phage populations in the environment of a human or animal body is essential for rational phage therapy.{{cite journal | vauthors = Letarov AV, Golomidova AK, Tarasyan KK | title = Ecological basis for rational phage therapy | journal = Acta Naturae | volume = 2 | issue = 1 | pages = 60–72 | date = April 2010 | pmid = 22649629 | pmc = 3347537 | doi = 10.32607/20758251-2010-2-1-60-71 }}

Bacteriophagics are used against antibiotic resistant bacteria in Georgia (George Eliava Institute) and in one institute in Wrocław, Poland.{{cite journal | vauthors = Parfitt T | title = Georgia: an unlikely stronghold for bacteriophage therapy | journal = Lancet | volume = 365 | issue = 9478 | pages = 2166–7 | date = June 2005 | pmid = 15986542 | doi = 10.1016/S0140-6736(05)66759-1 | s2cid = 28089251 }}{{cite journal | vauthors = Golkar Z, Bagasra O, Pace DG | title = Bacteriophage therapy: a potential solution for the antibiotic resistance crisis | journal = Journal of Infection in Developing Countries | volume = 8 | issue = 2 | pages = 129–36 | date = February 2014 | pmid = 24518621 | doi = 10.3855/jidc.3573 | doi-access = free }} Bacteriophage cocktails are common drugs sold over the counter in pharmacies in eastern countries.{{cite journal | vauthors = McCallin S, Alam Sarker S, Barretto C, Sultana S, Berger B, Huq S, Krause L, Bibiloni R, Schmitt B, Reuteler G, Brüssow H | title = Safety analysis of a Russian phage cocktail: from metagenomic analysis to oral application in healthy human subjects | journal = Virology | volume = 443 | issue = 2 | pages = 187–96 | date = September 2013 | pmid = 23755967 | doi = 10.1016/j.virol.2013.05.022 | doi-access = free }}{{cite journal | vauthors = Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM | title = Phage treatment of human infections | journal = Bacteriophage | volume = 1 | issue = 2 | pages = 66–85 | date = March 2011 | pmid = 22334863 | pmc = 3278644 | doi = 10.4161/bact.1.2.15845 }} In Belgium, four patients with severe musculoskeletal infections received bacteriophage therapy with concomitant antibiotics. After a single course of phage therapy, no recurrence of infection occurred and no severe side-effects related to the therapy were detected.{{cite journal | vauthors = Onsea J, Soentjens P, Djebara S, Merabishvili M, Depypere M, Spriet I, De Munter P, Debaveye Y, Nijs S, Vanderschot P, Wagemans J, Pirnay JP, Lavigne R, Metsemakers WJ | title = Bacteriophage Application for Difficult-to-treat Musculoskeletal Infections: Development of a Standardized Multidisciplinary Treatment Protocol | journal = Viruses | volume = 11 | issue = 10 | page = 891 | date = September 2019 | pmid = 31548497 | pmc = 6832313 | doi = 10.3390/v11100891 | doi-access = free }}

{{collist|colwidth=30em|

• {{annotated link|Alliance for the Prudent Use of Antibiotics}}
• {{annotated link|Anthelmintic resistance}}
• {{annotated link|Antimicrobial resistance in Australia}}
• {{annotated link|Broad-spectrum antibiotic}}
• {{annotated link|Colonisation resistance}}
• {{annotated link|Drug of last resort}}
• {{annotated link|Genetic engineering}}
• {{annotated link|Beta-lactamase#KPC (K. pneumoniae carbapenemase) (class A)|(KPC) antibacterial resistance gene}}
• {{annotated link|Multidrug-resistant Gram-negative bacteria}}
• {{annotated link|Multidrug-resistant tuberculosis}}
• {{annotated link|New Delhi metallo-beta-lactamase 1}}
• {{annotated link|Persister cells}}
• {{annotated link|Resistance-nodulation-cell division superfamily}} (RND)
• {{annotated link|Resistome}}

}}

{{reflist}}

{{refbegin}}

• {{cite web|url=http://evolution.berkeley.edu/evolibrary/article/mutations_07|trans-title=Mutations are random|title=Understanding Evolution|publisher=University of California Museum of Paleontology|veditors=Caldwell R, Lindberg D|year=2011|access-date=15 August 2011|archive-date=8 February 2012|archive-url=https://web.archive.org/web/20120208025322/http://evolution.berkeley.edu/evolibrary/article/mutations_07|url-status=live}}
• {{cite book| veditors = Reynolds LA, Tansey EM |title=Superbugs and superdrugs : a history of MRSA : the transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 11 July 2006|date=2008|publisher=Wellcome Trust Centre for the History of Medicine at UCL|location=London|isbn=978-0-85484-114-1}}
• {{cite book | date = 2018 | doi = 10.1787/9789264307599-en | title = Stemming the Superbug Tide: Just A Few Dollars More | series = OECD Health Policy Studies | publisher = OECD Publishing | location = Paris | isbn = 978-92-64-30758-2 | s2cid = 239804815 }}

{{refend}}

{{refbegin}}

• {{cite journal | vauthors = Arias CA, Murray BE | title = Antibiotic-resistant bugs in the 21st century – a clinical super-challenge | journal = The New England Journal of Medicine | volume = 360 | issue = 5 | pages = 439–443 | date = January 2009 | pmid = 19179312 | doi = 10.1056/NEJMp0804651 | s2cid = 205104375 | doi-access = free}}
• {{cite journal | title=Special Issue: Ethics and Antimicrobial Resistance | journal=Bioethics | volume=365 | issue=33 | year=2019 | url=https://onlinelibrary.wiley.com/toc/14678519/2019/33/7 | access-date=22 January 2020 | archive-date=9 March 2022 | archive-url=https://web.archive.org/web/20220309010759/https://onlinelibrary.wiley.com/toc/14678519/2019/33/7 | url-status=live}}
• {{cite journal | vauthors = Goossens H, Ferech M, Vander Stichele R, Elseviers M | title = Outpatient antibiotic use in Europe and association with resistance: a cross-national database study |journal = Lancet | volume = 365 | issue = 9459 | pages = 579–587 | year = 2005 | pmid = 15708101 | doi = 10.1016/S0140-6736(05)17907-0 |series = Group Esac Project | others = Esac Project | s2cid = 23782228}}
• {{cite journal | vauthors = Hawkey PM, Jones AM |title=The changing epidemiology of resistance | journal = The Journal of Antimicrobial Chemotherapy | volume = 64 |issue=Suppl 1 | pages = i3–10 | date = September 2009 | pmid = 19675017 | doi = 10.1093/jac/dkp256 | url = https://academic.oup.com/jac/article-pdf/64/suppl_1/i3/2249203/dkp256.pdf | doi-access = free | access-date = 20 April 2018 | archive-date = 17 February 2024 |archive-url=https://web.archive.org/web/20240217013307/https://academic.oup.com/jac/article/64/suppl_1/i3/750430 | url-status = live}}
• {{cite journal | vauthors = Soulsby EJ | title = Resistance to antimicrobials in humans and animals | journal = BMJ | volume = 331 | issue = 7527 | pages = 1219–1220 | date = November 2005 | pmid = 16308360 | pmc = 1289307 | doi = 10.1136/bmj.331.7527.1219 }}
• {{cite web |url=http://www.csiro.au/solutions/Alternatives-to-antibodies.html|title=Alternatives to Antibiotics Reduce Animal Disease|publisher=CSIRO|date=9 January 2006|access-date=26 April 2009|archive-date=5 June 2011|archive-url=https://web.archive.org/web/20110605082838/http://www.csiro.au/solutions/Alternatives-to-antibodies.html|url-status=live}}
• {{cite AV media |vauthors=Cooke P, Rees-Roberts D |year=2017 |title=CATCH |url=http://www.catchshortfilm.com/ |access-date=23 February 2017 |archive-date=9 March 2022 |archive-url=https://web.archive.org/web/20220309061945/http://www.catchshortfilm.com/ |url-status=live}} 16-minute film about a post-antibiotic world. Review: {{cite journal | vauthors = Sansom C |title=Media Watch: An intimate family story in a world without antibiotics |journal=Lancet Infect Dis |volume=17 |issue=3 |pages=274 |date=March 2017 |doi=10.1016/S1473-3099(17)30067-1}}

{{refend}}

File:Why won’t antibiotics cure us anymore.webm) on antibiotic resistance]]

• {{cite journal|author=Bancroft, EA|title=Antimicrobial resistance: it's not just for hospitals|journal=JAMA|volume=298|issue=15|pages=1803–1804|date=October 2007|doi=10.1001/jama.298.15.1803|pmid=17940239|pmc=2536104}}
• {{cite journal|author=Larson, E|title=Community factors in the development of antibiotic resistance|journal=Annual Review of Public Health|volume=28|pages=435–447|year=2007|issue=1 |pmid=17094768|doi=10.1146/annurev.publhealth.28.021406.144020|doi-access=free}}

{{Commons category|Antimicrobial resistance}}

{{offline|med}}

• {{wikiquote-inline}}
• [https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance WHO fact sheet on antimicrobial resistance]
• [https://pharmaxchange.info/2011/02/animation-of-antimicrobial-resistance/ Animation of Antibiotic Resistance] {{Webarchive|url=https://web.archive.org/web/20220928132102/https://pharmaxchange.info/2011/02/animation-of-antimicrobial-resistance/ |date=28 September 2022 }}
• [https://www.unep.org/resources/superbugs/environmental-action Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance] UNEP, 2023.
• [https://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf CDC Guideline "Management of Multidrug-Resistant Organisms in Healthcare Settings, 2006"]

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