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During her tenure as head of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had already been found. The argument was that in addressing the urgent threat of drug-resistant infections, we would struggle to discover new treatments – or conserve the existing ones – without finding new ways of working. This assessment proved accurate.

A Sluggish and Challenging Development Path

Since the late 2010s, only 16 antibiotics have gained widespread official clearance – mostly similar derivatives of medicines currently available and thus not expected to evade bacterial resistance for long. The creation of new ones is a slow and unprofitable endeavor, given that one-off treatments are less lucrative as ones treating chronic conditions. The scientific outlook continues to be bleak.

A Spark of Optimism and a Novel Approach

Nevertheless, the news this month of two new FDA-approved drugs against gonorrhoea is a welcome development and, crucially, validates a new way of encouraging research. One of the new drugs, a compound called Zoliflodacin, is the result of a novel kind of partnership between a Swiss non‑profit and a drug firm. The non-profit supplied financial support and managed clinical trials to offset costs and navigate approval processes. This sort of support upfront helps direct the sector towards fields of most pressing public health necessity.

This model and another praised “subscription model” – launched to ensure income to firms investing in specific antimicrobials – constitute the strongest chance of maintaining a trickle of new drugs from the existing system.

The Inevitable Challenge of Drug Resistance

But even hurrying the development of drugs 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, theoretically forcing the bacterium to start from zero in evolving a defense to it. Researchers and physicians are grateful to have a new option for gonorrhea – which has resistant strains to all existing treatments – but warn that eventual drug resistance to it is inevitable.

As has grown customary with recent antimicrobials, there is therefore an argument about whether it should be stockpiled, rationed to extremely drug-resistant infections only – confining its application to settings where high‑end lab testing is available. This kind of rational strategy should be the global standard, but frequently cannot be implemented readily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the flow of other novel antimicrobials we need could possibly come from. The former official's comment nodded to the fact that surveying the living world for natural sources – as with penicillin – has had declining success. Use of artificial intelligence has been mooted to accelerate the search, although a much-celebrated early candidate identified in 2020 hasn't yet progressed past animal trials. Fully lab-created compounds, which are largely or entirely lab-created, are constantly in research, but often confront the iron laws of molecular science – just because we imagine a compound doesn't mean we can create it without great difficulty.

Running Fast to Stay in Place

The prevailing scientific evaluation is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Careful, globally managed use is the only way to preserve our therapeutic edge. Regrettably, the scale of future discoveries is likely to seem meager compared with the curative bonanza of the previous century.