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During her time as director general of the WHO, a past official famously stated that all of the “easy” antimicrobials had already been found. The argument was that in addressing the urgent threat of drug-resistant infections, we would struggle to discover new medicines – or preserve the current arsenal – without developing novel approaches of operating. This assessment was correct.

A Slow and Unprofitable Pipeline

Since 2017, only sixteen antimicrobial agents have gained widespread regulatory approval – mostly close relatives of drugs already in use and thus not expected to overcome bacterial resistance for long. The creation of novel compounds is a slow and financially unattractive business, given that curative medicines are less lucrative as those managing longer-term ailments. The scientific outlook remains bleak.

A Spark of Hope and a Novel Approach

Nevertheless, the news this month of two new FDA-approved drugs for gonorrhea is a welcome development and, importantly, confirms a new way of incentivising development. One of the new drugs, Zoliflodacin, is the result of a novel kind 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 sort of support in advance helps steer the industry towards fields of greatest global need.

This approach and another praised revenue guarantee scheme – initiated to ensure revenue to companies that invest in specific antibiotics – constitute the strongest chance of sustaining a dripfeed of novel treatments from the existing system.

The Unavoidable Challenge of Resistance

But even accelerating the production of compounds currently in development is not sufficient. The new drug is sometimes categorized as a new class of antimicrobial, meaning it attacks a part of the infectious bacteria that existing treatments does, in principle compelling the bacterium to begin anew in developing a countermeasure to it. Researchers and doctors are relieved to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but caution that eventual drug resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, exists therefore an argument about whether it should be stockpiled, restricted to highly resistant infections only – limiting its use to settings where sophisticated diagnostics is available. This kind of rational approach should be the worldwide norm, but frequently can't be deployed readily in many parts of the world.

A Diminishing Stream of Innovation

More broadly, it is difficult to see where the flow of additional novel antimicrobials we need could realistically originate. The aforementioned statement nodded to the fact that searching the living world for biological compounds – as with penicillin – has had diminishing returns. Use of artificial intelligence has been mooted to accelerate the search, although a much-celebrated early candidate identified in recent years has not yet progressed past animal trials. Synthetic drugs, that are largely or entirely synthesized, are continually in research, but often confront the iron laws of molecular science – the fact that we envision a compound doesn't mean we can synthesise it easily.

Running Fast to Stand Still

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed truly just to remain in the current position. Prudent, globally managed deployment is the only way to preserve our advantage. Sadly, the scale of forthcoming breakthroughs is going to seem miserly compared with the therapeutic revolution of the previous century.