Dduring his tenure as Director General of the World Health Organization, Dr. Margaret Chan I used to say that everything “easy“Antibiotics had already been found. Her point was that, in responding to the urgent threat of antibiotic-resistant infections, we will have to scramble to find new drugs – or maintain the ones we have – unless we find new ways of working. She was right.
Since 2017, only 16 antibiotics has received widespread regulatory approval – these are mostly close relatives of drugs that are already in use and are therefore unlikely to avoid resistance for long. Developing new drugs is a slow and money-losing business because curative drugs are less profitable than drugs that treat long-term diseases. The scientific outlook remains grim.
However, this month's announcement two new antibiotics approved by the US Food and Drug Administration against gonorrhea is good news and, crucially, confirms a new way to stimulate research. One of the new drugs, Zoliflodacin, is the product of a new type of partnership between the Swiss non-profit Global Antibiotic Research and Development Partnership (GARDP) and the pharmaceutical company Innoviva. GARDP provided funding and organized clinical trials to cover costs and remove regulatory barriers. This upfront assistance helps target the industry in areas of greatest global need.
This approach and the approval of the UK government “subscription model” – launched in 2022 to guarantee returns to companies that have invested in certain antibiotics – represents the best hope of maintaining a trickle of new drugs from the current system.
But even accelerating the production of drugs currently in development is not enough. Zoliflodacin is sometimes described as a new class of antibiotic, one that targets a subset of infectious bacteria in a way that no other drug does, theoretically forcing the pathogen to start from scratch when developing treatments to counter it. Scientists and doctors are excited about the arrival of a new gonorrhea drug whose strains are resistant to all known antibiotics, but warn that future resistance to zoliflodacin is inevitable.
How this became the norm with the advent of new antibiotics, so there is an argument about whether it should be kept in reserve, distributed only to highly resistant infections, limiting its use where high-quality laboratory testing is available. This rational approach should become the global norm, but it is often difficult to apply in the global south.
More broadly, it's hard to know where the flow of other new antibiotics we need might come from. Dr Chan's comment points to the fact that exploring the living world for natural sources – as with penicillin – has diminishing returns. The use of artificial intelligence to speed up the discovery process has been discussed, although a widely known early candidate called halicin, identified in 2020, has not yet been tested in animals. Synthetic drugs, which are mostly or entirely created in laboratories, are constantly in development, but often violate the iron laws of chemistry – just because we imagine a molecule does not mean we can easily synthesize it.
The prevailing scientific assessment is that when it comes to antibiotics, we really have to run really fast to stay in the same place. Careful, internationally coordinated use is the only way to maintain our advantage. Unfortunately, the scale of future breakthroughs will dwarf the healing achievements of the 20th century.
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