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During her tenure as head of the WHO, a former leader famously stated that all of the “simple” antimicrobials had already been found. The argument was that in tackling the pressing threat of drug-resistant bacterial infections, we would struggle to discover new medicines – or preserve the current arsenal – without finding novel approaches of operating. This assessment was accurate.

A Slow and Challenging Development Path

Since 2017, only 16 antimicrobial agents have gained widespread regulatory approval – primarily close relatives of medicines currently available and thus unlikely to evade resistance for an extended period. The development of new ones is a lengthy and unprofitable endeavor, given that curative treatments are less lucrative as those treating longer-term conditions. The scientific outlook remains bleak.

A Glimmer of Hope and a New Model

However, the recent announcement of two new FDA-approved drugs against gonorrhoea is a welcome development and, importantly, validates a innovative method of encouraging research. A particular of the new drugs, Zoliflodacin, is the product of a unique type of collaboration between a Swiss non‑profit and a drug firm. The non-profit supplied funding and organised clinical trials to defray expenses and clear approval processes. This type of assistance in advance helps direct the industry towards fields of greatest global need.

This model and a separate praised revenue guarantee scheme – initiated to guarantee revenue to firms that invest in specific antibiotics – constitute the best hope of maintaining a dripfeed of new drugs from the current system.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of compounds in the pipeline isn't enough. The new drug is at times described as a new class of antibiotic, meaning it targets 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 relieved to have a new option for gonorrhoea – which has strains resistant to every known antibiotic – but warn that eventual drug resistance to it is inevitable.

As has grown customary with recent antimicrobials, there is consequently an argument about whether it should be held in reserve, rationed to highly resistant infections only – confining its use to situations where high‑end lab testing is accessible. This sort of rational strategy should be the global standard, but often can't be implemented readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the flow of additional novel antimicrobials we require could realistically come from. The aforementioned comment nodded to the fact that searching the living world for biological compounds – as with penicillin – has had diminishing returns. The application of artificial intelligence has been proposed to accelerate the discovery process, although a highly-touted initial discovery identified in recent years has not yet advanced past animal trials. Fully lab-created compounds, that are mainly or fully lab-created, are continually in research, but often confront the iron laws of molecular science – just because we envision a molecule does not guarantee we can synthesise it easily.

Running Fast to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to stay in the same place. Careful, globally managed deployment is the sole method to maintain our therapeutic edge. Sadly, the magnitude of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.