The fight against antimicrobial resistance

The threat posed by antimicrobial resistance (AMR) is enormous and could throw modern medical practice back into the “dark ages” – as then-Prime Minister David Cameron stressed 10 years ago. AMR is not a brand new challenge for politicians, decision-makers and health workers. Rather, many scientists would describe it as an insidious threat that is growing against a backdrop of chaotic global affairs.

What is antimicrobial resistance?

You may already be familiar with Charles Darwin’s theory of evolution. AMR arises through evolutionary adaptation. The use of antimicrobials triggers an arms race with the pathogen (bacteria, viruses, fungi or parasites) being attacked. As a result, a few pathogens within the infection mutate, allowing them to evade the effects of the antimicrobial drug used. This leads to the spread of a resistant subpopulation and triggers an AMR infection. As a result, we are now facing the emergence of “superbugs” that are resistant to existing antimicrobials.

Although AMR can refer to drug-resistant bacteria, viruses, fungi, or parasites, antibiotic-resistant bacteria appear to pose the greatest threat to humanity. It is estimated that bacterial AMR contributed to 4.95 million deaths in 2019. Therefore, the consequences of antibiotic resistance are not just a perceived future, but a grim reality. Bacterial AMR affects both those who contract bacterial infections and patients being treated for other conditions. This is because modern medicine relies on the use of preventative or “prophylactic” antibiotics. Any patient requiring surgery or chemotherapy requires antibiotics to reduce the risk of infection. In addition to the threat of antibiotic-resistant bacteria, patients with nonbacterial infections such as malaria are also at increasing risk of developing untreatable infections. In the 1980s, a wave of resistance to chloroquine (then the drug of choice for malaria) swept the African continent, killing millions and making this treatment obsolete. Worryingly, this may happen again: in recent years, resistance to artemisinin, which is now the basis for malaria treatment, has been detected in several places across Africa.

“AMR can refer to drug-resistant bacteria, viruses, fungi or parasites, but antibiotic-resistant bacteria appear to pose the greatest threat to humanity.”

AMR is considered inevitable, but is there anything that can be done to slow the emergence of drug-resistant microbes? Antimicrobial stewardship is the optimization of antibiotic use through careful drug selection, dosage, route of administration, and duration of administration. Healthcare providers can apply antimicrobial stewardship in their daily practice to slow the emergence of AMR. For example, physicians should reduce unnecessary antibiotic prescribing by avoiding prescribing antibacterial drugs for a viral chest infection, for example.

AMR can also be promoted by factors outside the hospital. The use of antibiotics in livestock farming is known to further promote AMR. In addition, environments without adequate sanitation, hygiene and access to clean water, coupled with inadequate infection prevention measures, favor the development of AMR. This is illustrated by a report by Swedish researchers at Lund University who “observed widespread antibiotic resistance in Gram-negative bacteria isolated from injured, hospital-treated war victims with nosocomial infections in Ukraine.” The report highlighted that inadequate infection prevention and control contribute to the development of AMR in Ukrainian hospitals, as the war in Ukraine is enormous due to the enormous pressure on limited resources.

“Developing countries may lack the critical investments needed to implement effective AMR action plans”

What is being done to combat AMR?

Recent developments in national and international policy to combat rising levels of antimicrobial resistance provide hope that a united front can be formed against the threat of ‘superbugs’. A key shortcoming in global action on antimicrobial resistance, highlighted by the World Health Organization (WHO), is the lack of ‘sustainable funding to implement activities across all sectors’. Many countries do not allocate sufficient financial resources to effectively implement the ‘national action plans’ outlined by the WHO. In the UK, a 5-year plan to combat antimicrobial resistance was published this year. The plan sets out the need for increased surveillance and monitoring of antimicrobial resistance. The implementation of antimicrobial-related policy in the UK is already promising, with sales of antibiotics for use in livestock falling by almost 10% last year and more than halving since 2014. However, the comprehensive action plan introduced in the UK is unlikely to be implemented uniformly around the world. Developing countries may lack the critical investment needed to implement effective action plans on AMR. In 2022, the UK invested £210 million to work with countries in Asia and Africa to tackle AMR. However, it remains to be seen whether such development assistance deals will correct developing countries’ fragile action plans on AMR or whether they will simply serve to paper over the cracks.

“Large pharmaceutical companies often view the development of antimicrobial drugs as less profitable”

Development of new antimicrobials and novel therapeutics

Running out of suitable antimicrobials to treat drug-resistant infections is becoming increasingly common. Pharmaceutical companies can therefore play a key role in developing new antimicrobials to treat drug-resistant infections. However, many criticise big pharma for abandoning antimicrobial drug development. Big pharma often view antimicrobial drug development as less profitable compared to other therapeutic options, such as cancer treatment. This is due to a combination of the low selling price and low sales volumes of most antimicrobials, and concerns that doctors may avoid prescribing antibiotics for fear of AMR. In addition, the short treatment cycle of antibiotics contrasts with therapies for chronic diseases, which can be taken over many months, providing pharmaceutical companies with a safer and longer-term source of revenue. Governments can solve this pipeline problem by adopting creative policies to support antibiotic development. For example, the UK has committed (in its Five Year Plan) to a world-first ‘subscription model’ for antimicrobials. The pharmaceutical industry is encouraged to support the development of antimicrobial drugs, with companies receiving a “fixed annual fee” based primarily on their value to the National Health Service (NHS) rather than on the amount used.

In addition, advances in biomedicine have spurred research into potential non-traditional antimicrobial agents based on biologics such as bacteriophages, antibodies, antivirulence agents, and immunomodulatory agents. New 21st century technologies paving the way for a “fourth industrial revolution” are also providing new opportunities for innovation in antimicrobial drug development. For example, artificial intelligence is increasingly being used in biomedical research. Recently, researchers collaborating between McMaster and Stanford universities have developed a generative AI model called SyntheMol that can design easily synthesized antibiotic compounds using already established reactant molecules and synthesis reaction pathways.

The challenges posed by antibiotic resistance require mitigation of both biological and organizational challenges through international cooperation. Combating antibiotic resistance ultimately depends on the introduction of policies that are effectively implemented. While the incoming Labour government has committed to getting public services in order, it cannot afford to neglect the existential threats, such as antibiotic resistance, that humanity faces in the 21st century.