Antimicrobial resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials (drugs used to treat infections).[2] All classes of microbes can evolve resistance where the drugs are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR) and are sometimes referred to as superbugs.[3] Although antimicrobial resistance is a naturally occurring process, it is often the result of improper usage of the drugs and management of the infections.[4][5]
Antibiotic resistance is a major subset of AMR, that applies specifically to bacteria that become resistant to antibiotics.[2] Resistance in bacteria can arise naturally by genetic mutation, or by one species acquiring resistance from another.[6] Resistance can appear spontaneously because of random mutations, but also arises through spreading of resistant genes through horizontal gene transfer. However, extended use of antibiotics appears to encourage selection for mutations which can render antibiotics ineffective.[7] Antifungal resistance is a subset of AMR, that specifically applies to fungi that have become resistant to antifungals. Resistance to antifungals can arise naturally, for example by genetic mutation or through aneuploidy. Extended use of antifungals leads to development of antifungal resistance through various mechanisms.[8]
Clinical conditions due to infections caused by microbes containing AMR cause millions of deaths each year.[9] In 2019 there were around 1.27 million deaths globally caused by bacterial AMR.[10] Infections caused by resistant microbes are more difficult to treat, requiring higher doses of antimicrobial drugs, more expensive antibiotics, or alternative medications which may prove more toxic. These approaches may also cost more.[4][5]
The prevention of antibiotic misuse, which can lead to antibiotic resistance, includes taking antibiotics only when prescribed.[11][12] Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance, as well as side effects.[13][14][15] For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper sanitation and hygiene, including handwashing and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.[16]
Rising drug resistance is caused mainly by use of antimicrobials in humans and other animals, and spread of resistant strains between the two.[11] Growing resistance has also been linked to releasing inadequately treated effluents from the pharmaceutical industry, especially in countries where bulk drugs are manufactured.[17] Antibiotics increase selective pressure in bacterial populations, killing vulnerable bacteria; this increases the percentage of resistant bacteria which continue growing. Even at very low levels of antibiotic, resistant bacteria can have a growth advantage and grow faster than vulnerable bacteria.[18] Similarly, the use of antifungals in agriculture increases selective pressure in fungal populations which triggers the emergence of antifungal resistance.[8] As resistance to antimicrobials becomes more common there is greater need for alternative treatments. Calls for new antimicrobial therapies have been issued, but there is very little development of new drugs which would lead to an improved research process.[19]
Antimicrobial resistance is increasing globally due to increased prescription and dispensing of antibiotic drugs in developing countries.[20] Estimates are that 700,000 to several million deaths result per year and continues to pose a major public health threat worldwide.[21][22][23] Each year in the United States, at least 2.8 million people become infected with bacteria that are resistant to antibiotics and at least 35,000 people die and US$55 billion is spent on increased health care costs and lost productivity.[24][25] According to World Health Organization (WHO) estimates, 350 million deaths could be caused by AMR by 2050.[26] By then, the yearly death toll will be 10 million, according to a United Nations report.[27]
There are public calls for global collective action to address the threat that include proposals for international treaties on antimicrobial resistance.[28] The burden of worldwide antibiotic resistance is not completely identified, but low-and middle- income countries with weaker healthcare systems are more affected, with mortality being the highest in sub-Saharan Africa.[10][12] During the COVID-19 pandemic, priorities changed with action against antimicrobial resistance slowing due to scientists and governments focusing more on SARS-CoV-2 research.[29][30] At the same time the threat of AMR has increased during the pandemic.[31]
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History[edit]
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.[201] 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[202] shown over time and the continued misuse and overuse of antibiotics in treatment.[203]
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."[204][205] 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.[206] 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.[203]
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Society and culture[edit]
Innovation policy[edit]
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".[207] 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".[207] 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.[208]
Legal frameworks[edit]
Some global health scholars have argued that a global, legal framework is needed to prevent and control antimicrobial resistance.[209][210][28][211] For instance, binding global policies could be used to create antimicrobial use standards, regulate antibiotic marketing, and strengthen global surveillance systems.[28][209] Ensuring compliance of involved parties is a challenge.[28] 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.[212]
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United Kingdom[edit]
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.[197]
United States[edit]
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%.[198]
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.[199] 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.[200]
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