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During her time as director general of the World Health Organization, a former leader famously remarked that all of the “easy” antimicrobials had already been found. The point was that in tackling the urgent threat of antibiotic-resistant infections, we would face difficulties to find new treatments – or conserve the existing ones – without finding new ways of operating. This view proved correct.

A Sluggish and Challenging Pipeline

Since 2017, only sixteen antibiotics have received widespread official clearance – mostly similar derivatives of drugs currently available and thus not expected to overcome resistance for long. The creation of novel compounds is a slow and unprofitable endeavor, given that curative medicines are not as profitable as those managing chronic conditions. The scientific outlook remains grim.

A Glimmer of Hope and a New Model

Nevertheless, the recent announcement of two new FDA-approved antibiotics for gonorrhoea is good news and, crucially, validates a innovative method of incentivising development. One of the recently approved medications, a compound called Zoliflodacin, is the product of a novel kind of partnership between a global health organization and a pharmaceutical company. The non-profit provided financial support and managed clinical trials to offset costs and clear regulatory hurdles. This type of assistance upfront helps steer the industry towards areas of most pressing public health necessity.

This model and a separate lauded “subscription model” – initiated to ensure income to firms that invest in specific antibiotics – represent the best hope of sustaining a trickle of novel treatments from the current framework.

The Inevitable Problem of Drug Resistance

But even accelerating the production of drugs currently in development isn't enough. Zoliflodacin is sometimes described as a novel type of antimicrobial, meaning it targets a part of the infectious bacteria that existing treatments does, theoretically forcing the pathogen to start from zero in developing a defense to it. Scientists and physicians are grateful to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but caution that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, restricted to highly resistant infections only – limiting its application to settings where sophisticated diagnostics is accessible. This kind of rational approach should be the global standard, but frequently cannot be deployed easily in many regions.

A Dwindling Pipeline of Innovation

On a wider scale, it is hard to see where the stream of other new antibiotics we require could realistically come from. The aforementioned comment nodded to the fact that surveying the natural world for natural sources – as with the first antibiotic – has had diminishing returns. The application of AI has been proposed to speed up the discovery process, although a much-celebrated early candidate identified in 2020 hasn't yet progressed past animal trials. Synthetic drugs, that are largely or entirely lab-created, are continually in development, but often confront the fundamental rules of molecular science – just because we imagine a molecule does not guarantee we can create it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Prudent, globally managed deployment is the sole method to maintain our advantage. Regrettably, the magnitude of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the 20th century.