🔗 Share this article

During her time as head of the World Health Organization, a former leader famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in addressing the urgent danger of drug-resistant infections, we would struggle to find new medicines – or preserve the current arsenal – without finding new ways of operating. This view was accurate.

A Sluggish and Unprofitable Pipeline

Since 2017, only 16 antimicrobial agents have gained widespread official clearance – primarily close relatives of drugs currently available and thus unlikely to overcome resistance for an extended period. The creation of new ones is a lengthy and unprofitable business, given that curative treatments are not as profitable as ones treating chronic conditions. The scientific outlook continues to be grim.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of two new regulator-approved drugs against gonorrhoea is good news and, importantly, confirms a new way of encouraging research. One of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to defray expenses and clear approval processes. This sort of assistance in advance helps steer the sector towards fields of most pressing global need.

This model and a separate praised “subscription model” – initiated to ensure revenue to companies investing in certain antimicrobials – represent the best hope of sustaining a trickle of new drugs from the existing system.

The Unavoidable Problem of Resistance

But even accelerating the production of drugs in the pipeline is not enough. The new drug is sometimes categorized as a novel type of antibiotic, indicating it targets a component of the infectious bacteria that existing treatments does, theoretically forcing the pathogen to start from zero in developing a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that future resistance to it is inevitable.

As has become the norm with recent antimicrobials, there is consequently an argument about whether it should be stockpiled, rationed to extremely drug-resistant cases only – confining its use to situations where high‑end lab testing is accessible. This sort of prudent strategy should be the worldwide norm, but frequently cannot be implemented easily in many regions.

A Diminishing Stream of Discovery

On a wider scale, it is difficult to see where the flow of additional novel antimicrobials we require could realistically come from. The aforementioned comment acknowledged the fact that searching the natural world for natural sources – as with the first antibiotic – has had declining success. The application of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery identified in 2020 hasn't yet progressed past animal trials. Fully lab-created compounds, that are mainly or fully synthesized, are continually in research, but often confront the iron laws of molecular science – just because we imagine a compound doesn't mean we can synthesise it without great difficulty.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must run very fast indeed just to remain in the current position. Prudent, globally managed deployment is the only way to preserve our advantage. Sadly, the magnitude of future breakthroughs is likely to seem miserly compared with the therapeutic revolution of the previous century.