During her leadership at the World Health Organization, Dr. Margaret Chan often remarked that all the “easy” antibiotics had been discovered. Her intention was to highlight the challenges we face in combating antibiotic-resistant infections. Without innovative approaches, developing new medicines or preserving existing ones would remain difficult. Her prediction was accurate.

Since 2017, a mere 16 antibiotics have achieved broad regulatory approval, mostly variants of existing drugs, which likely won’t resist bacterial resistance for long. The development of new antibiotics is a slow and financially unrewarding process, as curative treatments are less profitable than those for chronic conditions. The scientific outlook remains grim.

However, the recent approval of two new antibiotics by the US Food and Drug Administration to treat gonorrhea is promising news. This development also highlights a new method of incentivizing research. One of these antibiotics, Zoliflodacin, emerged from an innovative partnership between the Swiss non-profit Global Antibiotic Research and Development Partnership (GARDP) and the pharmaceutical company Innoviva. GARDP provided funding and orchestrated clinical trials to reduce costs and navigate regulatory challenges, directing industry efforts toward areas of significant global need.

This strategy, along with the UK government’s well-regarded “subscription model” launched in 2022, which guarantees revenue for companies investing in specific antibiotics, offers the best prospects for a steady flow of new drugs from the current system.

Yet, accelerating the development of drugs currently in the pipeline is not enough. Zoliflodacin is sometimes described as a new class of antibiotics, targeting a unique part of infectious bacteria, theoretically making it harder for pathogens to develop resistance. While scientists and doctors welcome this new treatment for gonorrhea, which has resistant strains to every known antibiotic, they warn that resistance to Zoliflodacin is inevitable.

As with many new antibiotics, there’s debate about whether Zoliflodacin should be reserved for severely resistant infections, limiting its use to facilities with advanced lab testing. While this rational approach should be globally standard, it’s often challenging to implement in the global south.

More broadly, it is hard to see where the stream of other new antibiotics we need could possibly come from. Dr Chan’s comment nodded to the fact that surveying the living world for natural sources – as with penicillin – has had diminishing returns. Use of artificial intelligence has been mooted to speed up the discovery process, although a much-celebrated early candidate called halicin, identified in 2020, hasn’t yet progressed past animal trials. Synthetic drugs, which are mainly or fully lab-created, are constantly in development, but often run up against the iron laws of chemistry – just because we imagine a molecule doesn’t mean we can synthesise it easily.

The prevailing scientific evaluation is that when it comes to antibiotics, we must run very fast indeed just to stay in the same place. Careful internationally coordinated use is the only way to preserve our advantage. Sadly, the scale of future breakthroughs is going to seem miserly compared with the curative bonanza of the 20th century.

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