🔗 Share this article

During her time as director general 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 pressing threat of antibiotic-resistant infections, we would struggle to find new treatments – or conserve the current arsenal – without developing new ways of operating. This assessment proved accurate.

A Slow and Unprofitable Development Path

Since 2017, just sixteen antibiotics have gained widespread official clearance – primarily similar derivatives of drugs currently available and thus not expected to evade bacterial resistance for long. The development of novel compounds is a lengthy and unprofitable business, given that curative medicines are less lucrative as those treating longer-term ailments. The overall prospect remains grim.

A Spark of Hope and a Novel Approach

Nevertheless, the news this month of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, crucially, validates a innovative method of incentivising research. A particular of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided financial support and managed testing phases to offset expenses and clear regulatory hurdles. This sort of assistance in advance helps direct the industry towards fields of greatest global need.

This approach and another lauded “subscription model” – launched to ensure revenue to firms that invest 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 hurrying the development of drugs currently in development is not enough. The new drug is sometimes categorized as a novel type of antimicrobial, meaning it targets a part of the pathogen that existing treatments does, theoretically forcing the bacterium to begin anew in evolving a defense to it. Researchers and doctors are relieved to have a new option for gonorrhea – which has resistant strains to every known antibiotic – but warn that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is therefore an argument about whether it should be stockpiled, rationed to highly resistant infections only – confining its use to settings where high‑end lab testing is accessible. This kind of prudent strategy should be the worldwide norm, but frequently can't be deployed easily in many parts of the world.

A Dwindling Stream of Discovery

More broadly, it is hard to see where the flow of other novel antimicrobials we need could realistically originate. The former official's comment nodded to the fact that searching the natural world for natural sources – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been proposed to accelerate the search, although a much-celebrated early candidate found in 2020 has not yet advanced past preclinical studies. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often confront the iron laws of molecular science – just because we envision a molecule doesn't mean we can create it easily.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must move with great speed truly just to stay in the current position. Careful, globally managed use is the only way to preserve our advantage. Regrettably, the magnitude of future breakthroughs is going to seem miserly compared with the therapeutic revolution of the previous century.