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During her tenure as head of the WHO, a past official famously stated that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the urgent danger of drug-resistant bacterial infections, we would face difficulties to find new medicines – or conserve the existing ones – without developing novel approaches of operating. This assessment proved accurate.

A Slow and Challenging Pipeline

Since 2017, only 16 antimicrobial agents have received broad official clearance – primarily close relatives of drugs currently available and thus not expected to evade resistance for long. The creation of new ones is a lengthy and financially unattractive business, given that curative treatments are not as profitable as those treating chronic ailments. The scientific outlook remains grim.

A Spark of Optimism and a Novel Approach

Nevertheless, the recent announcement of two new regulator-approved drugs against gonorrhoea is a welcome development and, crucially, confirms a new way of incentivising research. One of the recently approved medications, Zoliflodacin, is the result of a novel kind of partnership between a global health organization and a drug firm. The public health partnership provided financial support and organised clinical trials to defray costs and navigate approval processes. This type of support upfront helps direct the sector towards areas of greatest global need.

This approach and a separate lauded “subscription model” – initiated to ensure revenue to firms investing in specific antimicrobials – constitute the best hope of maintaining a trickle of new drugs from the existing system.

The Inevitable Challenge of Resistance

But even hurrying the production of compounds currently in development is not sufficient. Zoliflodacin is sometimes described as a new class of antimicrobial, indicating it attacks a component of the pathogen that no other drug does, theoretically forcing the bacterium to begin anew in evolving a defense to it. Researchers and physicians are relieved to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that future resistance to it is inevitable.

As has grown customary with recent antimicrobials, there is therefore an argument about whether it should be stockpiled, restricted to extremely drug-resistant infections only – limiting its application to settings where high‑end lab testing is available. This sort of rational strategy should be the worldwide norm, but often cannot be deployed easily in many regions.

A Dwindling Pipeline of Discovery

More broadly, it is hard to see where the flow of other new antibiotics we need could possibly originate. The former official's comment nodded to the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. Use of artificial intelligence has been mooted to speed up the discovery process, although a highly-touted early candidate identified in 2020 has not yet progressed past preclinical studies. Fully lab-created compounds, that are largely or entirely lab-created, are continually in development, but often run up against the fundamental rules of chemistry – the fact that we imagine a compound does not guarantee we can create it easily.

Running Fast to Stand Still

The prevailing expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to stay in the current position. Prudent, globally managed use is the sole method to maintain our therapeutic edge. Sadly, the magnitude of future breakthroughs is likely to seem meager compared with the therapeutic revolution of the previous century.