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During her tenure as director general of the World Health Organization, a former leader famously stated that all of the “easy” antimicrobials had long since been discovered. The argument was that in tackling the urgent threat of antibiotic-resistant bacterial infections, we would face difficulties to discover new medicines – or preserve the current arsenal – without finding novel approaches of operating. This view proved accurate.

A Sluggish and Challenging Pipeline

Since 2017, just sixteen antibiotics have gained widespread official clearance – mostly similar derivatives of medicines already in use and thus unlikely to evade bacterial resistance for long. The development of new ones is a slow and financially unattractive business, given that curative treatments are less lucrative as ones treating chronic conditions. The overall prospect continues to be bleak.

A Spark of Hope and a Novel Approach

However, the news this month of two new regulator-approved antibiotics for gonorrhoea is good news and, importantly, validates a new way of incentivising development. One of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The non-profit provided financial support and managed clinical trials to defray costs and clear approval processes. This type of assistance upfront helps direct the sector towards areas of most pressing public health necessity.

This approach and another lauded revenue guarantee scheme – initiated to guarantee income to companies investing in certain antimicrobials – constitute the strongest chance of sustaining a trickle of novel treatments from the current system.

The Inevitable Problem of Resistance

But even accelerating the production of drugs in the pipeline isn't sufficient. Zoliflodacin 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 compelling the pathogen to start from zero in developing a countermeasure to it. Researchers and doctors are grateful to have a new option for gonorrhea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to this compound is inevitable.

As has become the norm with recent antimicrobials, there is consequently an debate about whether it should be held in reserve, rationed to extremely drug-resistant infections only – limiting its use to situations where high‑end lab testing is available. This kind of prudent approach should be the worldwide norm, but frequently can't be implemented easily in many parts of the world.

A Dwindling Pipeline of Innovation

On a wider scale, it is hard to see where the flow of other new antibiotics we require could possibly come from. The former official's statement nodded to the fact that surveying the natural world for biological compounds – as with penicillin – has had declining success. The application of AI has been proposed to accelerate the discovery process, although a highly-touted early candidate identified in recent years has not yet progressed past preclinical studies. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often confront the iron laws of chemistry – the fact that we envision a compound doesn't mean we can synthesise it easily.

Moving Quickly to Stand Still

The dominant scientific evaluation is that when it comes to antibiotics, we must move with great speed indeed just to remain in the current position. Prudent, internationally coordinated deployment is the only way to maintain our advantage. Regrettably, the scale of forthcoming discoveries is likely to seem miserly compared with the therapeutic revolution of the previous century.