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During a tenure as head of the WHO, a former leader famously stated that all of the “simple” antibiotics had already been found. The argument was that in addressing the urgent danger of drug-resistant bacterial infections, we would struggle to find new medicines – or conserve the existing ones – without finding new ways of operating. This view was correct.

A Sluggish and Unprofitable Development Path

Since 2017, just 16 antibiotics have gained broad official clearance – mostly similar derivatives of medicines currently available and thus not expected to evade resistance for long. The development of novel compounds is a slow and financially unattractive endeavor, given that curative medicines are less lucrative as ones managing chronic conditions. The overall prospect continues to be bleak.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, importantly, validates a innovative method of incentivising research. One of the new drugs, Zoliflodacin, is the result of a novel kind of partnership between a global health organization and a drug firm. The non-profit supplied financial support and organised clinical trials to defray costs and navigate approval processes. This type of assistance upfront helps direct the industry towards fields of most pressing global need.

This model and another praised revenue guarantee scheme – launched to ensure income to firms that invest in certain antimicrobials – constitute the best hope of sustaining a trickle of novel treatments from the existing framework.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of drugs currently in development isn't sufficient. The new drug is sometimes categorized as a novel type of antimicrobial, meaning it attacks a component of the infectious bacteria that no other drug does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Scientists and doctors are relieved to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but warn that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is therefore an debate about whether it should be held in reserve, rationed to highly resistant infections only – confining its application to settings where sophisticated diagnostics is accessible. This sort of prudent strategy should be the worldwide norm, but frequently cannot be deployed readily in many regions.

A Dwindling Stream of Innovation

More broadly, it is difficult to see where the flow of other new antibiotics we need could possibly come from. The former official's comment acknowledged the fact that surveying the natural world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been mooted to accelerate the discovery process, although a much-celebrated early candidate identified in 2020 hasn't yet advanced past preclinical studies. Fully lab-created compounds, which are largely or entirely synthesized, are continually in research, but often run up against the iron laws of chemistry – just because we envision a molecule doesn't mean we can synthesise it without great difficulty.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed truly just to stay in the same place. Prudent, globally managed deployment is the sole method to maintain our advantage. Regrettably, the magnitude of forthcoming breakthroughs is likely to seem meager compared with the therapeutic revolution of the 20th century.