Since the dawn of existence, humanity has coexisted with a microscopic world unseen by the naked eye. These microorganisms trace their lineage back 3.5 billion years and have thrived in the modern world due to their ability to rapidly adapt. While many of these microbes are essential to life, some pose significant risks to human health and well-being.
Since the late 1930s, we have managed and reduced these risks through the discovery and widespread use of antimicrobial medications, mainly antibiotics, which we now heavily rely on to treat and prevent disease, as well as preventing infections during important surgical procedures. However, microbes have “fought back”, responding to our actions, and we are now facing a global antimicrobial resistance (AMR) crisis.
True to Darwin’s theory of evolution, antimicrobial resistance (AMR) is when microorganisms, such as bacteria, fungi, viruses and parasites, evolve to become resistant to antibiotics and other antimicrobials. This could be for example, by adapting their cell membranes or walls to prevent the antimicrobial entering, using efflux pumps to remove it from the cell, breaking it down with enzymes or by changing the target of the drug in some way. Hence when we use these medications to treat or prevent disease, they may not work as well or may not even work at all. The principal threat concerned is from antibiotic-resistant bacteria, but the effect also occurs in other types of microorganism.
The development of antibiotic resistance is a natural phenomenon and may occur by genetic mutation, resulting in genes conferring antibiotic resistance. Selective pressure is also important, when the majority of bacteria are killed by treatment but resistant survivors are then able to multiply, becoming the dominant form. Worse still, bacteria are able to pass on antibiotic resistance genes to each other through the exchange of mobile genetic elements such as plasmids – a process known as horizontal gene transfer (HGT). This exchange of mobile genetic elements is a significant way in which an increasing number of bacteria have become progressively resistant to new classes of antibiotic as we have introduced them.
There are now species and strains of bacteria that are becoming resistant to even our “last line of defence” antibiotics, meaning that some infections will soon be effectively untreatable. It is not surprising that these bacteria, sometimes referred to as “superbugs”, which include well-known species such as E. coli, Salmonella and methicillin-resistant Staphylococcus aureus (MRSA) are now a critical concern for many countries. There is also an alarming lack of new technology – there are limited options for new classes of antibiotic and increased research is needed.
The World Health Organization (WHO) has identified AMR as a top global public health and development threat. In 2019, AMR was responsible for 1.27 million deaths, and if current trends continue, it could kill more people annually than cancer by 2050. If AMR continues to increase, it means the cornerstone of modern medicine will no longer become effective in treatment – leading to more deaths, illnesses, and disability.
Although the development of resistance occurs naturally, the growing crisis around AMR has been accelerated through human activity. When antimicrobial medications were first introduced, they were seen as universal cures for many of humanity's issues - a quick and easy solution that effectively treated diseases without consequences. As a result, our reliance on antimicrobials grew and this notion of a "one cure for all" solution has led to microorganisms evolving rapidly to survive our treatments.
Such overuse and misuse of antimicrobials is the principal catalyst to AMR – the more microbes are exposed to antibiotics, the more opportunity there is for resistance to develop. Factors include excessive prescription and inappropriate use, for example in the absence of symptoms or use for viral infections, not completing the full course of medication and also self-medication, as antimicrobials are still readily available without prescription in many developing countries. Intensive and prolonged hospital use also plays an important role.
Antimicrobial use for food-producing animals and in agriculture has also been a significant cause of the current crisis, where these agents have been used extensively as growth promotors and for prevention of disease as well as for the treatment of actual conditions. Although use of antibiotics as growth promotors has been banned in Europe since 2006, these practices still take place in many countries throughout the world.
Further variables that have promoted the rapid increase in AMR include:
Other Affects
If AMR continues to rise, it will profoundly impact modern medicine, yet there are other areas of society that it will also affect:
Addressing AMR requires global action. The UK government has implemented a five-year action plan to combat AMR by reducing unnecessary antimicrobial use, optimising their usage, investing in innovation, and fostering global partnerships.
The WHO has also gathered data from global surveys on AMR, showing increased monitoring, awareness, and education efforts worldwide. Unified international efforts are essential to tackling this pressing issue and ensuring the efficacy of modern medicine for future generations.
Yet more research and action is needed to address the growing crisis around AMR. There is an urgent need for new antibiotic compounds and yet such agents can take many years and cost hundreds of millions of pounds to develop. An alternative approach is the preservation of existing antibiotics, perhaps by finding new ways to overcome microbial resistance strategies. Finally, use of antibiotic alternatives such as probiotics, bacteriophages (viruses which infect and kill bacteria), antimicrobial peptides and immunotherapies, must continue to be investigated.
Urgent action is required so that the AMR crisis does not allow our descendants to die from bacterial and other infections.