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During a tenure as head of the WHO, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in addressing the urgent threat of drug-resistant infections, we would struggle to discover new medicines – or preserve the current arsenal – without finding new ways of operating. This view proved correct.

A Slow and Challenging Development Path

Since 2017, just 16 antibiotics have gained widespread regulatory approval – mostly similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for an extended period. The development of new ones is a slow and financially unattractive endeavor, given that one-off treatments are less lucrative as ones treating longer-term conditions. The scientific outlook remains bleak.

A Glimmer of Hope and a Novel Approach

However, the news this month of a pair of novel regulator-approved antibiotics for gonorrhea is good news and, importantly, confirms a innovative method of incentivising development. One of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided funding and organised testing phases to defray costs and clear approval processes. This sort of support in advance helps steer the industry towards areas of greatest global need.

This model and a separate lauded “subscription model” – initiated to ensure revenue to firms that invest in specific antimicrobials – constitute the strongest chance of maintaining a dripfeed of new drugs from the existing system.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of compounds currently in development is not enough. The new drug is at times categorized as a novel type of antibiotic, indicating it targets a part of the pathogen that existing treatments does, theoretically compelling the bacterium to begin anew in evolving a defense to it. Researchers and physicians are grateful to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, there is therefore an debate about whether it should be held in reserve, rationed to highly resistant infections only – confining its use to situations where sophisticated diagnostics is available. This kind of rational strategy should be the worldwide norm, but frequently can't be deployed readily in many parts of the world.

A Diminishing Pipeline of Discovery

On a wider scale, it is difficult to see where the stream of other novel antimicrobials we require could realistically originate. The former official's statement nodded to the fact that surveying the natural world for natural sources – as with penicillin – has had declining success. Use of AI has been proposed to speed up the discovery process, although a much-celebrated early candidate found in recent years hasn't yet advanced past preclinical studies. Fully lab-created compounds, that are mainly or fully synthesized, are constantly in research, but often confront the iron laws of molecular science – the fact that we envision a molecule does not guarantee we can create it easily.

Moving Quickly to Stand Still

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the current position. Prudent, internationally coordinated deployment is the sole method to maintain our advantage. Sadly, the scale of forthcoming discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.