New drugs for old bugs: The need for new drugs and approaches to preventing antimicrobial resistance

Antimicrobial resistance (AMR) is one of the biggest healthcare time bombs we currently face. Without effective antibiotics, routine operations could prove fatal. England’s Chief Medical Officer, Dame Sally Davies, has warned of the threat posed by AMR, saying “The world is facing an antibiotic apocalypse.”

What is antimicrobial resistance?

It occurs when microbes (bacteria, viruses, fungi and parasites) stop responding to the drugs designed to kill them and therefore become resistant.

This is not a new problem: since the discovery of penicillin by Alexander Fleming in 1928, microbes have been constantly evolving to fight antibiotics and drug development has always been running to keep up. By the 1950s, scientists were encountering resistant strains. As new antibiotics were also being discovered, however, it wasn’t seen as something to worry about - developers could simply switch weapons in the war against microbes, staying one step ahead. Or so they thought.

How did this happen?

Pharmaceutical companies started making drugs which killed a much broader range of bacteria and doctors were encouraged to prescribe the drugs more often when they weren’t needed, to treat colds and other viruses in case they gave way to bacterial infections. This was compounded when farmers began routinely feeding livestock antibiotics, so they would grow bigger.

Rampant overuse over the last ~50 years has seen an increasing number of microbes evolve to become resistant. In fact, AMR could be responsible for 10 million deaths by 2050 if nothing is done. So, R&D organisations should be investing more into drug discovery and development, right? Unfortunately not. Large pharma companies are withdrawing from antibiotic research at an alarming rate, and currently only four (Merck, Roche, GlaxoSmithKline and Pfizer) have active programmes. The bottom line is that this kind of antibiotic development is just not profitable compared to, say, treatments for cancer or chronic illnesses. Consequently, only 12 antibiotics have been approved since 2000 and the pipeline has virtually ground to a halt.

On top of this, the general public’s understanding of antimicrobial resistance is often misinformed; almost 2/3 of respondents to a global 2015 WHO survey believed antibiotics could be used to treat colds and flu and nearly 1/3 believed they should stop taking antibiotics when they felt better, not when the course was finished. There was also a widely-held misconception among three-quarters of respondents that individual humans or animals become resistant to antibiotics, when in fact it is the bacteria that become resistant.

How do you solve a problem like AMR?

It’s not all doom and gloom, however, with both public and private sectors’ ongoing initiatives aimed at increasing awareness, generating revenue and encouraging drug development.

Antibiotic Guardian by Public Health England (PHE), for instance, is an online resource offering information and guidance regarding AMR and how to combat it. Everyone from scientists to farmers to educators to the public can make a “pledge” to do their bit, whether it be disposing of antibiotics correctly or collaborating on AMR research. Alongside this, PHE will run its “Keep Antibiotics Working” awareness campaign again this year.

In September, Pew launched the Shared Platform for Antibiotic Research and Knowledge (SPARK), a virtual lab enabling scientists to share data, learn from past research and collaborate to develop new insights. In tandem, LifeArc and the Defence Science and Technology Laboratory in the UK are collaborating with Canada’s Centre for Drug Research and Development to conduct studies into the properties of drug compounds that can break into multi drug-resistant bacteria. The results will then be fed into the SPARK database to help scientists develop their own research.

CARB-X, a non-profit initiative funded by Wellcome and BARDA, currently has over $500 million to invest in global research and development of antibiotics, vaccines, rapid diagnostics and other products to prevent and treat life-threatening bacterial infections.

The UK government is also stepping into the fray, with Innovate UK’s recent £10 million AMR competition which will fund new therapies or approaches to infection prevention and control. Even Contract Research Organisations are getting involved in developing new antibiotics: Evotec has a dedicated discovery and development arm for anti-infectives.

It’s just a phage

Scientists are looking to the future by delving into the past, reviving bacteriophage or “phage” therapy, a 100-year-old, previously discontinued viral treatment that injects its DNA into bacteria cells before replicating quickly and causing the cells to burst. This largely abandoned method was rediscovered by Steffanie Strathdee at UC San Diego, when her husband contracted a deadly bacterial infection in 2015 and conventional antibiotics had failed. The phage therapy worked and since then doctors at UC San Diego Health have successfully treated 5 patients with phages. Demand for the treatment has been so high that in June this year, UC San Diego opened the Center for Innovative Phage Applications and Therapeutics, the first facility in North America to conduct phage therapy clinical trials for people living with severe drug-resistant infections.

Phage therapy research is gaining pace. AmpliPhi Biosciences is targeting multi-drug resistant strains of S. aureus and P. aeruginosa, two of the microbes on the WHO’s 2017 Priority Pathogens List. C3J Therapeutics is engineering synthetic phages to improve their ability to kill pathogens, with several products in the pipeline, including a treatment for cystic fibrosis patients. Locus Biosciences is using CRISPR technology to engineer phage therapies with treatments for E. coli and C. difficile being developed.

Are there still jobs?

As large Pharma companies have continued to pull out of this space over the last 5 years, the recruitment market has consequently declined. However, the recent government funding schemes have ensured that new antibiotic development and the job market are becoming more buoyant. The roles currently in demand include microbiologists, process development technologists, bioinformaticians and manufacturing scientists.

As market exclusivity initiatives, like GAIN (Generating Antibiotic Incentives Now), gather momentum the job market will continue to grow and, hopefully, we can stave off the “antibiotic apocalypse”.

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