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During a tenure as director general of the World Health Organization, a former leader famously stated that all of the “simple” antimicrobials had already been found. The argument was that in addressing the urgent threat of drug-resistant bacterial infections, we would struggle to discover new medicines – or preserve the current arsenal – without finding new ways of operating. This assessment proved accurate.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only 16 antibiotics have gained broad official clearance – primarily similar derivatives of drugs currently available and thus unlikely to overcome bacterial resistance for an extended period. The development of new ones is a slow and unprofitable endeavor, given that curative treatments are less lucrative as those treating chronic conditions. The scientific outlook continues to be grim.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, crucially, validates a new way of encouraging development. One of the new drugs, a compound called Zoliflodacin, is the product of a unique type of partnership between a global health organization and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to offset costs and navigate regulatory hurdles. This sort of support upfront helps steer the industry towards fields of greatest global need.

This model and a separate praised revenue guarantee scheme – launched to guarantee income to firms that invest in specific antimicrobials – represent the strongest chance of sustaining a trickle of new drugs from the current framework.

The Unavoidable Problem of Resistance

But even hurrying the production of compounds in the pipeline is not sufficient. Zoliflodacin is at times categorized as a novel type of antibiotic, indicating it attacks 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 relieved to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but warn that future resistance to it is certain.

As has grown customary with new antibiotics, there is therefore an debate about whether it should be held in reserve, restricted to highly resistant cases only – limiting its application to settings where high‑end lab testing is accessible. This sort of rational approach should be the worldwide norm, but often can't be implemented readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the stream of additional novel antimicrobials we require could possibly originate. The former official's statement nodded to the fact that surveying the natural world for natural sources – as with penicillin – has had diminishing returns. The application of artificial intelligence has been mooted to speed up the discovery process, although a highly-touted early candidate found in 2020 has not yet advanced past preclinical studies. Synthetic drugs, that are largely or entirely lab-created, are continually in development, but often confront the fundamental rules of molecular science – the fact that we imagine a molecule does not guarantee we can synthesise it without great difficulty.

Moving Quickly to Stand Still

The prevailing expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to remain in the same place. Careful, internationally coordinated use is the only way to maintain our therapeutic edge. Regrettably, the magnitude of forthcoming discoveries is going to seem miserly compared with the curative bonanza of the previous century.