🔗 Share this article

During a time as head of the World Health Organization, a former leader famously stated that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the urgent threat of antibiotic-resistant infections, we would struggle to discover new medicines – or conserve the existing ones – without developing new ways of working. This assessment proved correct.

A Sluggish and Unprofitable Development Path

Since 2017, only 16 antimicrobial agents have gained broad official clearance – primarily similar derivatives of medicines already in use and thus unlikely to overcome bacterial resistance for long. The development of novel compounds is a slow and unprofitable endeavor, given that curative medicines are not as profitable as ones managing longer-term conditions. The overall prospect remains grim.

A Spark of Optimism and a New Model

However, the recent announcement of a pair of novel regulator-approved antibiotics for gonorrhea is good news and, importantly, validates a innovative method of encouraging development. A particular of the new drugs, Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a pharmaceutical company. The non-profit provided financial support and organised clinical trials to defray expenses and navigate regulatory hurdles. This sort of support upfront helps steer the industry towards fields of greatest public health necessity.

This model and another lauded revenue guarantee scheme – initiated to guarantee revenue to companies investing in specific antimicrobials – constitute the strongest chance of maintaining a trickle of new drugs from the existing framework.

The Inevitable Problem of Resistance

But even hurrying the development of compounds currently in development is not enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, meaning it attacks a component of the infectious bacteria that no other drug does, in principle forcing the bacterium 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 certain.

As has become the norm with new antibiotics, there is therefore an debate about whether it should be held in reserve, rationed to highly resistant cases only – confining its application to settings where high‑end lab testing is available. This sort of rational strategy should be the worldwide norm, but often cannot be implemented easily in many parts of the world.

A Diminishing Pipeline of Innovation

More broadly, it is hard to see where the stream of other new antibiotics we require could realistically originate. The former official's statement acknowledged the fact that searching the living world for natural sources – as with the first antibiotic – has had diminishing returns. The application of AI has been mooted to accelerate the discovery process, although a highly-touted early candidate found in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, that are largely or entirely synthesized, are continually in research, but often confront the fundamental rules of molecular science – just because we imagine a compound does not guarantee we can create it easily.

Moving Quickly to Stay in Place

The dominant scientific evaluation is that when it comes to antibiotics, we must run very fast indeed just to remain in the same place. Careful, internationally coordinated deployment is the only way to maintain our advantage. Regrettably, the magnitude of forthcoming discoveries is going to seem meager compared with the curative bonanza of the 20th century.