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During her time as director general of the WHO, a former leader famously remarked that all of the “easy” antibiotics had already been found. The point was that in tackling the pressing danger of drug-resistant bacterial infections, we would struggle to discover new treatments – or conserve the existing ones – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Development Path

Since 2017, only sixteen antimicrobial agents have received widespread official clearance – primarily close relatives of medicines already in use and thus unlikely to overcome bacterial resistance for long. The creation of novel compounds is a lengthy and financially unattractive endeavor, given that one-off medicines are less lucrative as those managing longer-term ailments. The overall prospect remains grim.

A Spark of Hope and a New Model

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs against gonorrhoea is good news and, crucially, confirms a innovative method of encouraging development. One of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of collaboration between a global health organization and a drug firm. The non-profit provided funding and organised testing phases to offset expenses and clear approval processes. This sort of support upfront helps steer the sector towards fields of greatest public health necessity.

This model and a separate praised “subscription model” – launched to guarantee income to companies that invest in specific antibiotics – represent the best hope of sustaining a trickle of new drugs from the existing system.

The Unavoidable Challenge of Resistance

But even accelerating the development of drugs in the pipeline isn't sufficient. Zoliflodacin is at times categorized as a novel type of antimicrobial, meaning it attacks a component of the infectious bacteria that existing treatments does, theoretically compelling the bacterium to start from zero in developing a countermeasure to it. Researchers and doctors are grateful to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but warn that eventual drug resistance to this compound is inevitable.

As has become the norm with recent antimicrobials, there is therefore an debate about whether it should be stockpiled, restricted to highly resistant infections only – confining its application to situations where high‑end lab testing is available. This sort of prudent approach should be the worldwide norm, but frequently cannot be deployed easily in many regions.

A Dwindling Stream of Innovation

More broadly, it is hard to see where the stream of other novel antimicrobials we need could realistically originate. The aforementioned comment nodded to the fact that surveying the living world for natural sources – as with penicillin – has had declining success. The application of artificial intelligence has been mooted to accelerate the search, although a highly-touted early candidate identified in 2020 hasn't yet progressed past animal trials. Synthetic drugs, that are mainly or fully lab-created, are constantly in research, but often run up against the iron laws of chemistry – the fact that we envision a molecule doesn't mean we can create it without great difficulty.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the current position. Careful, internationally coordinated deployment is the sole method to maintain our advantage. Sadly, the scale of future breakthroughs is going to seem meager in contrast to the curative bonanza of the previous century.