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

A Sluggish and Unprofitable Pipeline

Since 2017, just 16 antibiotics have gained widespread regulatory approval – primarily close relatives of drugs already in use and thus not expected to evade bacterial resistance for long. The development of new ones is a slow and unprofitable business, given that curative treatments are not as profitable as ones managing chronic ailments. The overall prospect remains grim.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved drugs against gonorrhea is a welcome development and, crucially, confirms a new way of incentivising research. A particular of the new drugs, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a pharmaceutical company. The non-profit supplied funding and organised testing phases to offset expenses and clear regulatory hurdles. This type of support upfront helps steer the industry towards fields of greatest global need.

This approach and a separate praised “subscription model” – initiated to guarantee income to companies that invest in certain antibiotics – represent the strongest chance of sustaining a trickle of novel treatments from the existing framework.

The Inevitable Challenge of Drug Resistance

But even accelerating the development of drugs currently in development isn't sufficient. The new drug is sometimes described as a novel type of antibiotic, indicating it attacks a component of the pathogen that no other drug does, theoretically compelling the pathogen to begin anew in evolving a defense to it. Researchers and doctors are grateful to have a new option for gonorrhoea – which has strains resistant to all existing treatments – but caution that future resistance to it is certain.

As has become the norm with new antibiotics, exists consequently an debate about whether it should be stockpiled, rationed to highly resistant cases only – limiting its application to situations where sophisticated diagnostics is accessible. This sort of rational approach should be the worldwide norm, but often cannot be implemented readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the flow of other new antibiotics we need could realistically come from. The former official's statement acknowledged the fact that searching the natural world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been proposed to speed up the search, although a much-celebrated initial discovery found in recent years hasn't yet progressed past animal trials. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often run up against the fundamental rules of chemistry – just because we imagine a molecule doesn't mean we can synthesise it without great difficulty.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to stay in the current position. Careful, globally managed use is the only way to preserve our therapeutic edge. Regrettably, the magnitude of forthcoming breakthroughs is likely to seem miserly compared with the therapeutic revolution of the 20th century.