Antimicrobial resistance (AMR) is a quiet but dangerous threat to global healthcare, currently reshaping the landscape of modern medicine. Defined by the loss of effectiveness of antimicrobial medications, both naturally and through human fault, it challenges our ability to combat previously easily treatable infections. This article explores the complex issue of AMR, its origins and implications, and the urgent need for action on a worldwide scale.

Introduction 

Definition

Antimicrobial resistance (AMR) is the process of microbes (bacteria, viruses, fungi and parasites) going through genetic changes which allow them to become immune to the medication that would usually kill them. This makes it much harder to get rid of infection and leaves us with incredibly limited treatment options. 

This process can occur naturally, as all organisms will attempt to evolve in response to selection pressures, which in this case are the antimicrobials that would normally kill them. However, AMR is being rapidly accelerated by human activity, and now poses a major threat to the future of medical treatment, as microbes are developing resistance faster than new antimicrobials are being created. 

When AMR is discussed, the main focus tends to be on antibiotics, which are used to treat bacterial infections, as these are most affected by the issue of resistance. There are also issues affecting antifungals and antivirals as well. The terms antimicrobial and antibiotic are often used interchangeably. 

Global impact 

Due to the nature of infectious diseases, AMR is a global issue. The COVID-19 pandemic highlighted just how easy it is for infections to spread around the world, especially as travel becomes more accessible. If a resistant strain of a microbe arises in one country, it will not take long for that strain to be passed on to other countries, and then continents, which leads to difficulties in treating it even in the most medically advanced countries. This is why this issue must be addressed worldwide. 

Understanding antimicrobial resistance 

Causes

Overuse and misuse 

In some areas, antimicrobials are available without any medical supervision, meaning no formal diagnosis is needed to access them. This leads to an increase in resistance as patients are often misdiagnosing themselves, and using antimicrobials where they are not required.¹ 

The use of broad-spectrum antibiotics is also an issue. These are medications that are effective against a wider range of microbes. They are often used without proper identification of the specific germ causing the infection and therefore could be exposing it to ineffective antimicrobials, allowing it to develop resistance.

Incomplete treatment courses

One of the main ways bacteria can develop resistance in humans is by human error when prescribed antibiotics. It is incredibly important that if you are given antibiotics by your doctor, you take them exactly as instructed. Pay close attention to

• The amount you need to take in one dose
• Whether they should be taken with food or on an empty stomach
• How long the course of treatment is

It is important that you take the full course of the prescribed medication, even if you feel better before it’s finished. Just because you no longer feel ill, doesn’t mean the infection is fully clear, and there may still be germs in your system.

By finishing the treatment early, the remaining microbes that are still alive in your body have been exposed to the antimicrobials, and now know how to get around the mechanisms by which the medication works. They can then divide and grow in number, and suddenly you are full of microbes which will no longer respond to the treatment you’ve previously used.

Mismanagement in healthcare settings

In some countries, there is an epidemic of overprescription of antimicrobials. For example, in the US, there are 150 million outpatient antibiotic prescriptions every year. Many of these prescriptions are not necessary when the infections are minor and would clear up alone, or prescriptions for the wrong type of infection, e.g. antibiotics for viral infections like the common cold. This has no effect on the health outcome of the patient, but exposes the microbe to the antimicrobial, which then uses that exposure to its advantage. 

As well as this, poor infection control in hospitals contributes to the spread of pathogens, such as inadequate hygiene, lack of sanitation and improper waste disposal.

Global travel and trade

The accessibility of worldwide travel and trading of goods makes the spread of resistant strains much easier. With the movement of people, animals, and goods comes movement of microbes across borders, creating global interconnectedness.

Antibiotics in food production

In the past, antibiotics have commonly been overused in agriculture and food production. As well as treating sickness, they have been used in healthy animals to prevent disease and promote growth. This has been banned in the EU for many years, but is still prevalent in other parts of the world.

This is a great example of how microbes are able to develop resistance, as they are exposed to the antimicrobial when it is not necessary, allowing them to build mechanisms to evade them in the future. The now resistant strains can be passed on to humans through direct contact with the animal or consumption of animal products.

Lack of new antimicrobial development 

It is often difficult to get new antimicrobials developed, partly due to the fact there are few targets they can work against on the microbes, but mainly because of economic factors. Antibiotics are not a profitable form of medication for pharmaceutical companies as the course of treatment is relatively short, especially compared to drugs that are needed for lifelong conditions. This means that these companies are less likely to invest in their development, as they are unlikely to yield much profit. 

There are also strict requirements to get new antimicrobials approved for use. For example, they must be proven to be more effective than the current standard. This makes it difficult to have varied treatments for the same microbe, and even if one medication has many resistant strains, if it was once better at resolving the infection, the new treatment will not be approved. This forces reliance on old medications.

Inadequate surveillance and monitoring 

The lack of systems and infrastructure to monitor the use of antibiotics and patterns of resistance impairs our ability to respond to the threat of AMR. Many regions lack adequate data collection systems, and global reporting of this is already inconsistent, leading to delayed or incomplete reporting.

Mechanisms of resistance

There are a number of methods that microbes can use to defend themselves against antimicrobial treatments:

Changing the target of the antimicrobial 

Many antimicrobials specifically target one feature of a microbe, which allows them to be more accurate in their treatment. However, some microbes change the structure or function of the target, so the medication is no longer functional.

For example, E. coli bacteria can change the structure of its surface so the specific drug Colistin can no longer attack itself. This stops it from being able to enter the cell and therefore will have no effect.³

Getting rid of the antimicrobial 

Once the antimicrobial has entered the cell, the microbe is able to sense it and understand the danger it’s in. It then develops a pump system, which can remove the antimicrobial back into the environment, allowing the microbe to survive.

Restricting cellular access

The membrane that surrounds cells is considered ‘selectively permeable’, meaning they are able to select the things they allow to move both in and out. Some resistant microbes are able to change the entryways into the cell, blocking the antimicrobial from entering.³

Destroying the antimicrobial

Some microbes will use enzymes to break down the medication before it has the chance to have any effect.

Bypassing the effects

Many antimicrobials target specific cell processes, such as the process of cell division or the building of new proteins. Some microbes develop new methods of carrying out these processes so that they are no longer a target for the antimicrobials.

Implications of antimicrobial resistance

Healthcare

The threat that AMR poses to our ability to treat infections has proven to have a much wider impact than first thought. Routine medical procedures such as surgery and chemotherapy will become less safe and accessible, as they cause the immune system to be compromised. Without effective antimicrobials, there is a much greater risk of a patient picking up a procedure during treatment which is unable to be cleared.

It is becoming much more common for doctors to prescribe antimicrobials that were once considered ‘last-resorts’, as they usually would not be used unless everything else had failed, but now are becoming necessary. These last-resort antimicrobials are associated with higher costs and more severe side effects, and are also less accessible, particularly in lower income countries. 

Some microbes, such as those responsible for tuberculosis and gonorrhoea infections, have begun to show resistance to even the last-resort medications, leaving no alternative treatment options.¹

Economic

As well as having a major impact on the way we look at healthcare, AMR is also posing a major economic threat. In the EU alone, the extra healthcare costs associated with AMR has come to at least 1.5 billion euros. Multi-drug-resistant tuberculosis could cost as much as 15 trillion euros by 2050.

On top of healthcare costs, there is also the issue of lost labour caused by decreased productivity and early death. If there is no change in current rates, it is expected that the world’s working-age population will decrease by two years every decade. 

Regional disparities and challenges 

While these economic challenges will be seen worldwide, it will be much more prevalent in lower-income countries, leading to an increase in the already problematic wealth divide. Global GDP could decrease by 1% by 2050, but this number leaps to 5-7% in developing countries.

These places already have a bigger issue with AMR, as there is much more limited access to testing and treatments, leading to more chances for microbes to grow resistant. They also tend to have less access to technology to track antimicrobial use and the progression of AMR, meaning they are less able to deal with resistance when it does occur.

Addressing AMR

Global initiatives and policies 

WHO’s action plan 

In 2015, the World Health Organisation put together an extensive action plan on how to tackle this issue. They have set out five clear, main objectives:

• Improve public awareness of AMR through better education 
• Work on research to better understand AMR
• Reduce infection rates through preventative measures
• Optimise the use of antimicrobials
• Increase investment in new interventions such as medication, diagnostic tools, and vaccines in all countries1

Collaborative efforts 

As previously mentioned, due to the ability of resistant strains to travel across the world, the fight against AMR is a global effort. The World Economic Forum has stated that this is an issue no country will be able to handle alone. 

A current example of collaborative effort spanning continents comes from a partnership between the British/Indian research project DOSA2, who are trialling a new test which easily checks for UTIs in urine samples. UTIs are the second most common reason for antibiotic consumption worldwide, particularly in India.

Here they are often taken without approval from a medical professional, increasing the risk of resistance. This project aims to prevent this by making it clear when antibiotics are required, as well as making testing more accessible for lower-class, rural communities, who may have previously been unable to get a firm diagnosis. 

Strategies 

Stewardship programmes

These programs act as a guide for healthcare professionals, making sure they use antibiotics in the most effective way. It guides when to start, how much to give, length of treatment and which antimicrobials to use. This approach helps patients get better treatment while helping prevent the development of resistance by preventing overuse and misuse of antimicrobials. By using these medications only when truly necessary and in the right way, stewardship programmes ensure antimicrobials stay effective for as long as possible.

Research and development of new antimicrobials 

To help keep the threat of AMR at bay, it is important that we have constant production of new antimicrobials ready to use when current treatments become unusable. This involves researching new targets for treatments, as well as new methods of attacking current known targets.

Public awareness and education 

The more that general society is aware of the harmful effects of AMR, the more likely that they will be more vigilant when it comes to using antimicrobials correctly.

Education on proper sanitation and hygiene practices is also important in the fight against AMR, as every infection that is prevented is one that does not need to be treated, which will mean less chance for resistance to develop. 

Summary 

Antimicrobial resistance is a major global threat which is forcing us to change the ways we treat infections and therefore has an impact on the whole field of medicine. It is becoming increasingly dangerous, causing illnesses and infections which should be easily treatable to go unmanaged.

As individuals, it can seem overwhelming to think about. It is important we do what we can to stop the spread of resistance, including only taking antibiotics at the advice of our doctor’s and following their instructions down to the letter. It is vital that companies and governing bodies collaborate to face this issue head-on, as efforts will only be effective if society works together.