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During her tenure as head of the WHO, a former leader famously remarked that all of the “easy” antibiotics had already been found. The point was that in addressing the pressing danger of drug-resistant infections, we would struggle to find new medicines – or conserve the current arsenal – without finding new ways of operating. This assessment was accurate.

A Sluggish and Challenging Pipeline

Since 2017, only 16 antibiotics have gained widespread regulatory approval – primarily close relatives of drugs already in use and thus unlikely to evade resistance for an extended period. The development of new ones is a lengthy and unprofitable endeavor, given that curative treatments are less lucrative as ones treating chronic ailments. The scientific outlook continues to be grim.

A Spark of Optimism and a New Model

However, the news this month of two new FDA-approved drugs for gonorrhoea is good news and, crucially, confirms a new way of incentivising research. One of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied financial support and managed clinical trials to offset expenses and clear regulatory hurdles. This type of support in advance helps steer the industry towards fields of greatest global need.

This approach and a separate lauded “subscription model” – launched to guarantee revenue to firms that invest in certain antibiotics – constitute the best hope of sustaining a dripfeed of new drugs from the existing system.

The Inevitable Challenge of Drug Resistance

But even accelerating the production of drugs in the pipeline is not sufficient. The new drug is at times categorized as a novel type of antibiotic, meaning it attacks a part of the infectious bacteria that existing treatments does, in principle forcing the pathogen to begin anew in developing a countermeasure to it. Scientists and physicians are grateful to have a new option for gonorrhoea – which has resistant strains to every known antibiotic – but caution that future resistance to this compound is inevitable.

As has become the norm with new antibiotics, there is consequently an argument about whether it should be held in reserve, restricted to highly resistant infections only – confining its use to settings where high‑end lab testing is accessible. This sort of rational approach should be the global standard, but often cannot be deployed readily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the flow of additional new antibiotics we require could realistically originate. The former official's statement nodded to the fact that searching the natural world for natural sources – as with the first antibiotic – has had declining success. The application of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery identified in 2020 has not yet progressed past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are continually in research, but often confront the iron laws of chemistry – just because we imagine a molecule doesn't mean we can create it easily.

Running Fast to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed truly just to remain in the same place. Prudent, internationally coordinated deployment is the only way to maintain our advantage. Regrettably, the scale of future breakthroughs is likely to seem miserly compared with the curative bonanza of the previous century.