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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 already been found. The argument was that in tackling the urgent threat of antibiotic-resistant infections, we would struggle to find new treatments – or conserve the current arsenal – without finding novel approaches of working. This view was accurate.

A Sluggish and Unprofitable Development Path

Since 2017, just 16 antimicrobial agents have gained broad official clearance – mostly similar derivatives of medicines currently available and thus not expected to evade bacterial resistance for an extended period. The development of new ones is a slow and financially unattractive business, given that one-off treatments are not as profitable as those treating chronic conditions. The scientific outlook remains grim.

A Glimmer of Hope and a New Model

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs against gonorrhea is good news and, crucially, validates a new way of incentivising development. One of the new drugs, a compound called Zoliflodacin, is the result of a unique type 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 support in advance helps steer the sector towards fields of greatest public health necessity.

This approach and a separate praised revenue guarantee scheme – initiated to guarantee income to companies that invest in certain antibiotics – constitute the best hope of sustaining a dripfeed of new drugs from the existing system.

The Inevitable Challenge of Resistance

But even hurrying the production of compounds in the pipeline isn't enough. Zoliflodacin is sometimes described as a novel type of antibiotic, indicating it attacks a component of the pathogen that no other drug does, in principle forcing the pathogen to begin anew in developing a countermeasure to it. Researchers and physicians are grateful to have a new option for gonorrhoea – which has strains resistant to every known antibiotic – but warn that future resistance to this compound is inevitable.

As has grown customary with new antibiotics, there is therefore an argument about whether it should be held in reserve, restricted to highly resistant cases only – confining its use to settings where sophisticated diagnostics is available. This sort of prudent strategy should be the global standard, but frequently cannot be implemented easily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the stream of additional novel antimicrobials we need could realistically originate. The aforementioned comment nodded to the fact that surveying the natural world for natural sources – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been proposed to speed up the discovery process, although a much-celebrated early candidate found in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, that are largely or entirely synthesized, are constantly in development, but often run up against the iron laws of molecular science – the fact that we envision a compound doesn't mean we can synthesise it easily.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the same place. Careful, globally managed use is the sole method to maintain our therapeutic edge. Regrettably, the scale of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.