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During a tenure as director general of the World Health Organization, a former leader famously stated that all of the “simple” antimicrobials had long since been discovered. The point was that in addressing the pressing danger of antibiotic-resistant bacterial infections, we would struggle to discover new medicines – or preserve the existing ones – without finding novel approaches of operating. This assessment proved accurate.

A Slow and Unprofitable Development Path

Since the late 2010s, just sixteen antimicrobial agents have received widespread official clearance – primarily similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for an extended period. The creation of new ones is a lengthy and unprofitable business, given that one-off treatments are less lucrative as those treating chronic conditions. The scientific outlook remains grim.

A Spark of Optimism and a New Model

However, the news this month of a pair of novel FDA-approved antibiotics against gonorrhea is good news and, crucially, confirms a new way of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the product of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided financial support and organised clinical trials to offset expenses and navigate approval processes. This type of assistance in advance helps direct the industry towards fields of greatest public health necessity.

This approach and a separate praised “subscription model” – launched to guarantee revenue to companies investing in certain antibiotics – represent the best hope of maintaining a trickle of novel treatments from the current system.

The Inevitable Problem of Resistance

But even hurrying the production of compounds in the pipeline isn't sufficient. The new drug is sometimes described as a novel type of antimicrobial, meaning it targets a component of the infectious bacteria that no other drug does, in principle compelling the bacterium to start from zero in evolving a countermeasure to it. Scientists and doctors 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, there is consequently an argument about whether it should be held in reserve, rationed to highly resistant cases only – confining its use to situations where sophisticated diagnostics is accessible. This kind of prudent approach should be the worldwide norm, but frequently can't be implemented readily in many parts of the world.

A Dwindling Stream of Innovation

On a wider scale, it is hard to see where the flow of additional novel antimicrobials we need could possibly come from. The former official's comment acknowledged the fact that searching the living world for biological compounds – as with penicillin – has had declining success. Use of AI has been proposed to speed up the discovery process, although a highly-touted initial discovery identified in 2020 hasn't yet advanced past animal trials. Synthetic drugs, which are mainly or fully lab-created, are constantly in research, but often run up against the iron laws of molecular science – just because we envision a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antimicrobials, we must move with great speed indeed just to stay in the current position. Careful, internationally coordinated use is the only way to preserve our therapeutic edge. Regrettably, the scale of future breakthroughs is likely to seem miserly in contrast to the curative bonanza of the previous century.