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During a time as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had already been found. The argument was that in addressing the urgent threat of drug-resistant infections, we would struggle to discover new treatments – or conserve the existing ones – without finding new ways of working. This view was correct.

A Slow and Challenging Development Path

Since the late 2010s, only sixteen antibiotics have received broad regulatory approval – primarily close relatives of medicines already in use and thus not expected to overcome resistance for an extended period. The creation of new ones is a lengthy and unprofitable business, given that one-off medicines are not as profitable as ones managing longer-term conditions. The scientific outlook remains grim.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel regulator-approved drugs against gonorrhea is a welcome development and, importantly, validates a innovative method of encouraging research. One of the recently approved medications, Zoliflodacin, is the result of a unique type of partnership between a Swiss non‑profit and a drug firm. The public health partnership provided financial support and managed clinical trials to offset costs and clear approval processes. This sort of assistance upfront helps steer the sector towards areas of greatest global need.

This model and a separate praised “subscription model” – launched to ensure income to firms investing in certain antibiotics – represent the best hope of maintaining a dripfeed of novel treatments from the current system.

The Inevitable Problem of Resistance

But even hurrying the production of compounds currently in development isn't sufficient. The new drug is at times described as a novel type of antimicrobial, indicating it targets a component of the pathogen that no other drug does, theoretically compelling the bacterium to start from zero in developing a defense to it. Scientists and physicians are grateful to have a new option for gonorrhoea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to this compound is certain.

As has become the norm with new antibiotics, there is therefore an argument about whether it should be held in reserve, restricted to highly resistant infections only – confining its application to situations where sophisticated diagnostics is accessible. This sort of rational approach should be the worldwide norm, but often can't be implemented readily in many parts of the world.

A Dwindling Pipeline of Innovation

On a wider scale, it is difficult to see where the flow of additional novel antimicrobials we need could possibly come from. The former official's statement acknowledged the fact that surveying the living world for biological compounds – as with penicillin – has had diminishing returns. The application of AI has been proposed to accelerate the discovery process, although a highly-touted early candidate found in 2020 has not yet progressed past preclinical studies. Fully lab-created compounds, that are largely or entirely synthesized, are constantly in development, but often confront the iron laws of chemistry – just because we imagine a molecule doesn't mean we can synthesise it easily.

Moving Quickly to Stand Still

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 deployment is the sole method to preserve our advantage. Regrettably, the magnitude of future discoveries is likely to seem meager in contrast to the therapeutic revolution of the 20th century.