Around 700,000 people worldwide die every year from bacteria that have developed resistance to antibiotics. In the UK alone, that figure is at least 12,000 – more deaths than from breast cancer. And those numbers look set to rise even higher.
‘It’s not just the fact that resistance is increasing – that’s inevitable,’ says Nick Brown, Director of advocacy group, Antibiotic Action. ‘The issue is more the rate of increase in resistance, which appears to be accelerating.’
The Infectious Diseases Society of America recently reported resistance to drugs within six months of antibiotics coming onto the market, and in some cases, even before the drug goes on the market. Many bacterial strains are increasingly displaying resistance to combinations of commonly used and last-resort antibiotics.
Of 33 antibiotics in development targeting priority pathogens, just nine belong to five new antibiotic classes. Image: Public Domain Pictures
‘The end of the antibiotic era isn’t on the horizon just yet,’ Brown says. ‘But we can see it wouldn’t take much to get that way.’
Failure to tackle antibiotic-resistant superbugs could result in 10m deaths a year by 2050, according to the UK government-commissioned Review on Antimicrobial Resistance. The UN and G20 have both made political commitments to combat the problem. Nevertheless, time is running out.
‘This is an urgent and rapidly rising global health problem,’ says Ghada Zoubiane, science lead for the Wellcome Trusts’ drug-resistant infections team. ‘We need greater investment in developing new ways to treat and protect people from these deadly infections and we need better understanding of how resistance spreads.’
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Despite calls for increased R&D, no new classes of antibiotics have been approved since the early 1980s, apart from the approval of linezolid in 2000, and the last new class to treat Gram-negative bacteria was discovered in 1962, Zoubiane says.
Big pharma withdrew en masse from the antibiotic space in the 1990s, due to the low returns on the high level of investment required in antibiotic R&D. Recognising the urgency of the problem, however, in January 2016 more than 90 pharma and biotech companies committed to enhancing antibiotic discovery.
The move has been accompanied by more research into understanding resistance mechanisms, as well as a shift to more outside-of-the-box thinking about alternative treatments.
In 2016, over $500m was invested into research into antibiotic resistance. Image: PxHere
In February 2017, the World Health Organization (WHO) published its list of 12 antibiotic-resistant ‘priority pathogens’ that pose the greatest threat to human health. Most notable are the Gram-negative bacteria, which possess an additional outer cell membrane and are harder to treat with antibiotics than Gram-positive bacteria.
‘These bacteria have been assessed as the most critical priority for antibiotic R&D, as strains are emerging worldwide that cannot be treated with any of the antibiotics currently on the market,’ WHO says.
Despite the increased commitment to R&D, however, a WHO report in September 2017 lamented the ‘serious lack of new antibiotics under development’. Among the 33 new chemical entity antibiotics in development targeting priority pathogens, just nine belong to five new antibiotic classes.
There are 16 products, both antibiotics and biologics, with activity against one or more Gram-positive priority pathogens – although mostly targeting methicillin-resistant Staphylococcus aureus (MRSA) – including two new antibiotic classes.
Meanwhile, ‘the situation is worse for Gram-negative bacterial infections’, says WHO. Of ten products in Phase 1 trials, ‘almost all the agents are modifications of existing antibiotic classes […] active only against specific pathogens or a limited subset of resistant strains’.
The 2016 Lister Memorial Lecture: Dame Sally Davies on Global antiiotic resistance. Video: SCI
WHO warns that ‘more investment is needed in basic science, drug discovery and clinical development, especially for the critical priority Gram-negative carbapenem-resistant pathogens P. aeruginosa, A. baumannii, and Enterobacteriaceae.’
‘We need to find a strategy not to overcome resistance, but to be able to live with and manage it,’ Brown reflects. ‘I’m more optimistic than some. It’s important to remember that before antibiotics were discovered, the human race didn’t die out.’
Antimicrobial drug discovery