Antibiotics: victims of their own success

This article was written by Liam Tom Martin and Arundhati Maitra from the ISMB-Mycobacteria Research laboratory, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck. Birkbeck Science Week runs from 3-6 April 2017.

antibioticsSince the development of penicillin as a treatment for bacterial infections in the 1940s, antibiotics have played an integral role in modern medicine. Beyond their obvious utility in treating serious diseases like tuberculosis and pneumonia, antibiotics have facilitated a vast array of modern surgical treatments. Without them, major procedures from organ transplants to hip replacements and cancer chemotherapy would carry too great a risk of infection to be feasible. Antibiotics have become so deeply woven into the fabric of modern life that a future without them borders on the unimaginable.

Over the past few decades, strains of bacteria have emerged which are resistant to most, if not all, of the antibiotics in our current arsenal. Coupled with a near total halt in the development of new antimicrobial therapeutics, the rising tide of antibiotic resistance threatens to compromise the very bedrock of modern medicine. If those foundations were to crumble, it would usher in an era in which minor infections can develop into chronic and potentially fatal illnesses; an era in which surgical interventions and immunosuppressive chemotherapies are simply not possible.

The most recent World Health Organisation (WHO) report states that 480,000 people each year develop multi-drug resistant tuberculosis (MDR-TB), while strains of gonorrhoea which are resistant to all available antibiotics have been observed in 10 countries, including the UK. Methicillin-resistant Staphylococcus aureus (MRSA) also continues to cause potentially deadly infections in hospitals, putting significant strain on healthcare resources. The UK government report into antimicrobial resistance, chaired by Lord Jim O’Neill predicted that if antimicrobial resistance were to continue to rise around the world, we could see as many as 10 million more deaths annually, with a total economic cost of $100 trillion. The majority of this burden would likely fall on low- to middle-income countries. This threat has grown to such a proportion that recently, the United Nations General Assembly (UNGA) met to discuss the steps which could be taken by global organisations including the WHO, the World Bank, the Food and Agriculture Organisation of the United Nations (FAO) and the World Organisation for Animal Health (OIE) to help to slow the spread of antibiotic resistance and to incentivise the development of novel antimicrobial drugs.

Antibiotics, it seems, have been victims of their own success. Their effectiveness and convenience have led to a ubiquity which provides a wealth of opportunities for development of antibiotic resistance; an issue exacerbated by misuse and overuse in mankind, animal farming and agriculture. The conditions which accelerate the development of resistance, however, are just one side of the coin. The emergence of new antibiotics onto the market has slowed to a glacial place over the last 20 to 30 years, as pharmaceutical companies have diverted their focus onto other areas. This move has been driven primarily by the limited profitability and steep challenges in developing new antibiotics with novel mechanisms of action. There is a sense that all of the low hanging fruit were picked during the golden age of antibiotic discovery in the 1940s and 50s, and that new classes of antibiotic are becoming harder and harder to come by.

As we have come to expect antibiotics to be inexpensive, pharmaceutical companies must sell them at low cost or lose out to the generics market. The short treatment times required to cure most infections also present little opportunity for pharmaceutical companies to recoup their billion dollar investments in research and development, while the rapid emergence of resistance following deployment of a drug can quickly stifle demand. The result is that pharmaceutical and biotechnology companies preferentially invest in treatments for chronic conditions which require long-term treatments and thus generate a more reliable revenue stream. Essential research into novel antimicrobials is thus left by the wayside. This market failure is exacerbated by conservation programs which discourage the use of newly discovered antibiotics until resistance has developed to the standard treatments, as well as by variable regulations which create uncertainty in the market.

On positive notes, there are a number of initiatives providing funding for further research in academia, promoting collaboration between academia and industry and incentivising industry investment into antibiotic research. These include the Fleming Fund, £195 million collaboration between the UK government, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Institut Pasteur International Network, among others. The UK government is also involved in a variety of other funds aimed at tackled antibiotic resistance, such as the Ross Fund and the Global AMR Innovation Fund, which are collaborations with the Bill and Melinda Gates Foundation and the Chinese government, respectively.

The past 5 years have seen the emergence of the first new antibiotics for decades. Bedaquillin was approved as part of a second-line combination therapy for use against multiple drug resistant tuberculosis (MDR-TB) in 2012, following an accelerated approval process lasting just six months. There are currently numerous other novel antibiotics at some stage in the development pipeline, including Teixobactin, a promising candidate which has been found to have broad antibacterial activity while acting through a novel mechanism which may slow or prevent the development of resistance. A collaborative effort between Sequella Inc. and members of the National Institute of Infectious Diseases in the USA, and Janssen Infectious Diseases in Belgium, has led to the development of the antibiotic SQ109. This is testament to the ability of private-public partnerships in spreading the risk of drug development and incentivising biotechnology companies to proceed with research into novel antibiotics.

A number of academic institutions, bolstered by increased funding from government bodies, are beginning to undertake significant research into means by which to tackle antimicrobial resistance. At the University of Birmingham Institute of Microbiology and Infection, critical research is being conducted into understanding the transmission and mechanisms of antibiotic resistance, under the direction of Professor Ian Henderson and Professor Laura Piddock. In the Bloomsbury area, the London School of Hygiene and Tropical Medicine have recently opened their Centre for Antimicrobial Resistance, which will include sociological research alongside traditional lab-based research in order to understand the spread of antimicrobial resistance on a large scale. Just a stones-throw from the London School, the Mycobacteria Research Lab lead by Dr Sanjib Bhakta at the Institute of Structural and Molecular Biology, Birkbeck College, University of London, are investigating new means to tackle antibiotic resistance tuberculosis, including a “drug repositioning” approach, by which drugs which are currently on the market for the treatment of a separate ailment may be repurposed to act as antibiotics in the fight against MDR-TB.

Science Week 2017: Microbes in the Real World

Date: Monday 3 April

Talk by Sophie Downes – ‘The Interactions Between Fungi and Heritage Buildings’
Clore Management Centre B01, 5:30-6:30pm

Screening of the film Resistance followed by panel discussion: ‘Tackling antibiotic resistance and the rise of superbugs
Speakers: Dr Sanjib Bhakta, Dr Jane Nicklin, Professor Nick Keep and Arundhati Maitra
43 Gordon Square Cinema, 7:00-9:00pm

“Antibiotics were first mass-produced in the 1940s and their ability to fight and kill bacteria revolutionized medicine and profoundly impacted everything from agriculture to war. After less than 80 years, however, these miracle drugs are failing. Resistant infections kill hundreds of thousands of people around the world each year and there are now dozens of so-called Superbugs each with its own challenges and costs. How did this happen? Using microscopic footage, harrowing personal stories, and expert insights RESISTANCE clarifies the problem of antibiotic resistance, how we got to this point, and what we can do to turn the tide.”

Leave a Reply

Your email address will not be published. Required fields are marked *