Antimicrobial resistance
Antimicrobial resistance occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria, viruses, parasites, and fungi. Together, these adaptations fall under the AMR umbrella, posing significant challenges to healthcare worldwide. Misuse and improper management of antimicrobials are primary drivers of this resistance, though it can also occur naturally through genetic mutations and the spread of resistant genes. Antimicrobials are medicines that fight infections. These medicines are used to prevent and treat infections in humans, animals, and plants.
Antibiotic resistance, a significant AMR subset, enables bacteria to survive antibiotic treatment, complicating infection management and treatment options. Resistance arises through spontaneous mutation, horizontal gene transfer, and increased selective pressure from antibiotic overuse, both in medicine and agriculture, which accelerates resistance development. Treaments become less effective or stop working altogether, making infections harder or even impossible to treat. This increases the risk of disease spread, severe illness, disability, and death.
The burden of AMR is immense, with nearly 5 million annual deaths associated with resistant infections. Infections from AMR microbes are more challenging to treat and often require costly alternative therapies that may have more severe side effects. Preventive measures, such as using narrow-spectrum antibiotics and improving hygiene practices, aim to reduce the spread of resistance. Microbes resistant to multiple drugs are termed multidrug-resistant and are sometimes called superbugs. Although AMR can occur naturally over time, human activities such as the misuse and overuse of antimicrobials greatly speed up the development and spread of resistance. AMR is a complex problem that cannot be solved by one sector alone. It affects human health, animals, food production, and the environment. The One Health approach brings these sectors together. It recognizes that the health of people, animals, and the environment is closely connected.
The World Health Organization claims that AMR is one of the top global public health and development threats, estimating that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. Moreover, the WHO and other international bodies warn that AMR could lead to up to 10 million deaths annually by 2050 unless actions are taken. Global initiatives, such as calls for international AMR treaties, emphasize coordinated efforts to limit misuse, fund research, and provide access to necessary antimicrobials in developing nations. However, the COVID-19 pandemic redirected resources and scientific attention away from AMR, intensifying the challenge.
Definition
Antimicrobial resistance means that a microorganism is resistant 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. 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.
Overview
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."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. Deaths attributable to AMR vary by area:
| Place | Deaths per 100,000 attributable to AMR |
| North Africa and Middle East | 11.2 |
| Southeast and East Asia, and Oceania | 11.7 |
| Latin America and Caribbean | 14.4 |
| Central and Eastern Europe and Central Asia | 17.6 |
| South Asia | 21.5 |
| Sub-Saharan Africa | 23.7 |
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. In 2019 there were 133,000 deaths caused by AMR.
Causes
AMR is driven largely by the misuse and overuse of antimicrobials. They reproduce and spread quickly, and they also can adapt to their environment and change how well they can survive. .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. Genetic changes can also occur, which would allow the microbe to survive. 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.Although many microbes develop resistance to antibiotics over time through natural mutation, overprescribing and inappropriate prescription of antibiotics have accelerated the problem. During mutation, when replication happens, these mutations help individual microbes survive exposure. It is possible that as many as 1 in 3 prescriptions written for antibiotics are unnecessary. 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. 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. Microbes may also get genes from each other, which makes them drug-resistant. Bacteria that have drug-resistant DNA often transfer a copy of these genes to the other bacteria. They can then multiply and thrive.
Bacteria become resistant to antibiotics by changing themselves or acquiring resistance genes from other bacteria. Over the past 20 years, antimicrobial resistance has grown, making common infections like respiratory infections, urinary tract infections, STDs, and tuberculosis harder to treat. New antibiotics are not being developed fast enough, and without action, we may enter a “post-antibiotic era” where some infections are untreatable.
AMR makes infections more difficult and costly to treat. Proper antibiotic use—correct drug, dose, and duration—and strict hospital hygiene are essential. Combating AMR requires cooperation among governments, healthcare workers, researchers, pharmaceutical companies, farmers, and the public through responsible antibiotic use, monitoring resistance, limiting antibiotics in animals, and improving access to medicines, vaccines, and tests.
Prevention is the most effective strategy. Along with careful antibiotic use, there is a need for new drugs, alternative treatments, better diagnostics, and vaccines. Without coordinated global action, vital medical procedures like surgery, organ transplants, neonatal care, and cancer treatment could be at risk.
Natural occurrence
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. 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. 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 are currently in clinical use.
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.
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.