A Global Threat to Humanity: Anti-Microbial Resistance

Antimicrobial resistance (AMR) is spreading at an alarming rate, yet the antibiotic industry is only shrinking—could a pre-antibiotic era return as our future?

Antimicrobials revolutionised medicine. Before antibiotics, the average life expectancy was 47 years. Infections such as pneumonia could easily be fatal, and to put it bluntly, a scratch could kill. There is no better example than the First World War, where at least one-third of soldiers were killed by infections and diseases.

But now, the rise of antimicrobial resistance (AMR) makes it possible for the horrors of the pre- antibiotic era to return. AMR includes anti‐biotic resistance, which is when bacteria survive exposure to antibiotics that usually kill or slow their growth. Resistance is present naturally in some bacteria and can arise due to random mutation, while microbes can also acquire resistance from others through gene transfer.

Antimicrobials are targeted at infections caused by bacteria, viruses, and fungi, enabling us to treat life- threatening illnesses from tuberculosis to HIV, and malaria. Resistance not only paves the path for a future without such treatments, but it also means that common surgical procedures such as organ transplants and C-sections will be‐come infeasible due to the high risk of infection. This risk is even larger for those with compromised immune systems, such as cancer patients undergoing chemotherapy.

Yet resistance is not new. Sir Alexander Fleming—the discoverer of the first antibiotic penicillin, warned us of this danger more than 50 years ago in his Nobel lecture. Fleming noted that if bacteria were exposed to non-lethal concentrations of the antibiotic, resistance can arise. Moreover, resistant bacteria have existed long before humans used antibiotics, even being found in Egyptian mummies from 9000 years ago.

But now, resistance has become a threat comparable to climate change due to the overuse of antimicrobials. It is reported that 700,000 people die every year due to resistant microbes. At this rate, resistance could kill up to 10 million people each year by 2050, which translates to a devastating one person every three seconds. The more we use antimicrobials, the more resistance: by exposing pathogens to antibiotics, selective pressure is applied so that only resistant strains will survive and multiply, leading to greater numbers of resistant bacteria.

A prominent example of overuse is overprescription. In 2016, the Centres of Disease Control and Prevention (CDC) reported that at least 30% of antibiotics prescribed to outpatients in the US were unnecessary, with more than 60% of respiratory disease patients given antibiotics when not required. Antibiotics only work against bacterial infections, so taking them for a viral infection such as the common cold will not do anything but drive resistance in the individual’s microbiome.

General practitioners still rely on the patient’s symptoms and slow diagnostic tools such as a blood or culture tests to distinguish between viral and bacterial infections. Better diagnostics such as the point-of-care C-reactive protein (CRP) testing have been trialled in the UK. The test only requires a finger prick, a few extra minutes, and a cost of approximately £4, but it has not proven effective in reducing unneeded prescriptions.

However, such tests are yet to be‐come routine as it is still far cheaper and faster to prescribe antibiotics ‘just in case’. Therefore, not only do rapid diagnostics need to be made available and affordable to doctors, policies must be put in place to make such testing compulsory.

But reducing antibiotic use in humans is simply not enough to tackle resistance. The FDA reports that 70% of the antibiotics (by-weight), critical in treating human infections, are used in agriculture and aquaculture. Al‐though they are needed to treat animal or plant infections, most of these including last-line antibiotics, are instead used to promote organism growth or prevent potential infections.

As AMR becomes increasingly deadly, it is critical that we reduce our unnecessary demand for antimicrobials. But even if antimicrobials were used completely appropriately, resistance as a natural process can only be slowed down, not eradicated. There‐fore, not only do we need to make existing drugs stay effective longer by reducing use, the development of new drugs is essential.

The Antibiotic market: a commercial failure

That being said, no new classes of antibiotics have been introduced since the 1980s. R&D in antimicrobials is shrinking faster than ever, while the global threat of resistance is only looming closer. At this rate, there would be no pharmaceutical companies developing antibiotics by 2025. As JimO’Neill the former chief economist of Goldman Sachs puts it, we are ‘facing a growing enemy with a largely depleted armoury’.

This paradoxical situation results from decades of under-investment by companies and the government in antimicrobial R&D.

Drug development is time consuming and costly, a single drug takes at least 10 years and 1 billion pounds to reach the patient. If it finally makes it to the market, new antibiotics are of‐ten reserved as a last-line defence. With cheap, existing generic drugs still effective enough, competitive pressure means that newly patented drugs are not sold much. In other words, resistance is a problem, but with our present market system, its occurrence is not high enough to yield a sufficient market to sustain the development of new drugs.

So it is unsurprising that no one wants to develop antibiotics despite the urgent and increasing need for them. Between 2003 and 2013, less than 5% of venture capital investments in pharmaceuticals were for antimicrobial development. With too little money and market interest, too little time and natural resources, and the in‐creasing threat of AMR and unpredictable occurrence, we need to focus on antimicrobial drug discovery with renewed vigour and sense of emergency.

Economic solutions to an economic problem

The current system of antibiotic development and distribution needs changing, to align commercial incentives with public needs. According to the Review of Antimicrobial Resistance led by O’Neill, the heart of the problem is that the current system predicates drug profitability on their price and quantity sold. Therefore, it is critical to shift to a system that rewards innovation instead, based on its value to society. The review goes on to state that this could be achieved with a global ‘market entry reward’ system for antibiotics and alternative therapies. Companies that are successful in developing a much-needed drug will be rewarded with a lump sum of 1.3 billion USD, effectively reimbursing them for the high costs of drug development.

Of course, the funding must come from somewhere. The Review argues that since effective antibiotics are widely required in the field, the whole industry should be involved in developing new antibiotics. This has led to the suggestion of an ‘Antibiotic investment charge’, where pharma companies not doing AMR-based research would be levied depending on their sales, while those investing an equivalent amount or more would be spared – a ‘pay-or-play’ system. Those that are not doing AMR-related re‐search would be levied depending on their sales, while companies that are investing an equivalent or greater amount will be spared. This would provide funding, and also but encourage AMR-related research to benefit the industry as a whole.

We must slow down resistance, reduce un‐necessary antibiotic demand, and boost new drug development. We can outrace resistance if we act now—and it starts with recognising resistance as a global threat to humanity

This article was first published in our Michaelmus Term 2019 Issue: Perspective

Artwork by Maria Kostylew