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During a tenure as director general of the WHO, a former leader famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the pressing threat of antibiotic-resistant bacterial infections, we would struggle to discover new treatments – or preserve the current arsenal – without developing new ways of working. This assessment proved accurate.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only sixteen antibiotics have gained broad official clearance – mostly similar derivatives of medicines currently available and thus not expected to overcome resistance for an extended period. The creation of new ones is a lengthy and unprofitable endeavor, given that curative medicines are not as profitable as ones treating chronic ailments. The overall prospect continues to be bleak.

A Glimmer of Hope and a Novel Approach

Nevertheless, the recent announcement of two new FDA-approved drugs against gonorrhea is a welcome development and, importantly, validates a new way of encouraging development. A particular of the new drugs, Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a drug firm. The public health partnership supplied financial support and organised testing phases to defray costs and clear approval processes. This type of support upfront helps steer the sector towards fields of greatest public health necessity.

This model and a separate lauded revenue guarantee scheme – initiated to guarantee revenue to companies investing in certain antibiotics – constitute the strongest chance of maintaining a dripfeed of new drugs from the current system.

The Inevitable Challenge of Resistance

But even accelerating the development of drugs currently in development is not sufficient. Zoliflodacin is at times described as a new class of antimicrobial, meaning it targets a component of the pathogen that existing treatments does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Researchers and physicians are grateful to have a new drug for gonorrhea – which has resistant strains to all existing treatments – but caution that future resistance to this compound is inevitable.

As has grown customary with new antibiotics, exists consequently an debate about whether it should be stockpiled, restricted to highly resistant infections only – confining its use to settings where sophisticated diagnostics is accessible. This sort of rational approach should be the global standard, but frequently cannot be implemented readily in many regions.

A Dwindling Pipeline of Discovery

More broadly, it is hard to see where the stream of other novel antimicrobials we need could realistically come from. The aforementioned statement nodded to the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had declining success. Use of AI has been proposed to accelerate the discovery process, although a much-celebrated early candidate identified in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, which are mainly or fully synthesized, are continually in research, but often run up against the iron laws of chemistry – just because we imagine a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antibiotics, we must move with great speed indeed just to stay in the same place. Careful, internationally coordinated deployment is the only way to preserve our therapeutic edge. Regrettably, the magnitude of future discoveries is going to seem meager in contrast to the therapeutic revolution of the previous century.