Trickling antibiotic pipeline leads to superbug warning

Scores of new antibiotics currently under development will likely not be enough to prevent a worldwide increase in antimicrobial resistance, according to the co-author of a new report reviewing the state of novel antibiotic research.
 
Professor Mark Blaskovich, Director of Translation at the University of Queensland’s Institute for Molecular Bioscience, told newsGP deaths linked to antimicrobial resistance will outstrip cancer fatalities by 2050 unless new ways of sourcing research investment are found.
 
‘[The crisis] is already here,’ he said.
 
‘A recent report in The Lancet calculated almost 1.3 million deaths globally in 2019 were directly attributed to resistant bacterial infections, with a total of nearly five million associated with resistant infections.
 
‘There is promising work in the early stages of development, but not so many in later stage clinical development.’
 
The report, which monitored the clinical pipeline for more than a decade, found 62 new antibiotics are currently in development, including 34 based on structures not previously used as an antibiotic.
 
However, the majority of these are still in early-stage clinical trials, with only two new small molecule antibacterial drugs first approved between 2020 and 2022.
 
One of the most advanced examples cited in the paper is Afabicin, a first-in-class antibiotic that targets fatty acid synthesis in Staphylococcus bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA or ‘golden staph’).
 
Another approach attracting increased attention, Professor Blaskovich said, is the use of antivirulence factors – new drugs used in combination with traditional antibiotics that help reduce the ability of bacteria to grow and thrive, allowing them to be more easily killed by the antibiotic.
 
But while he said it is encouraging to have so many novel antibiotic candidates, which are less likely to have existing resistance in the bacteria, it is still a ‘glass half-empty situation’ compared to other classes of drugs.
 
‘Sixty-two new antibiotics in development is still very low compared to almost 2000 in the cancer drug pipeline,’ Professor Blaskovich said.
 
‘We’re still not where we need to be given the urgency of the situation.’
 
The report says the lack of progress can be put down to a failure of the healthcare system marketplace to ‘adequately recognise and compensate for these products’, despite funding initiatives such as Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) appearing to have some impact in the early stages of the antibiotic pipeline.
 
‘New incentives are needed to help make it financially viable for pharmaceutical companies to advance new antibiotics through the later stages of clinical testing,’ Professor Blaskovich said.
 
‘These include the Netflix-style subscription payment model recently being tested in the UK, where the government pays for access to an antibiotic regardless of the quantity.
 
‘It means the pharmaceutical company is less interested in sales volume and more likely to invest in developing novel treatments.
 
‘It also discourages doctors from overprescribing antibiotics which leads to resistance.’
 
Increased investment may also lead to the development of a ‘Holy Grail’ antibiotic, which utilises completely new chemical structures that kill bacteria via a mechanism that existing antibiotics currently do not.
 
Professor Blaskovich said such a drug would help overcome the resistance mechanism that bacteria have developed to all existing antibiotics, while there is also hope that non-antibiotic approaches such as vaccines developed with mRNA technologies can also reduce the impact of superbugs.
 
‘[These] have been incredibly effective,’ he said. ‘And unlike antibiotics, can be lucrative products for pharmaceutical companies.’
 
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antibiotics antimicrobial resistance