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During a tenure as head of the WHO, a former leader famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in addressing the urgent danger of antibiotic-resistant bacterial infections, we would struggle to discover new medicines – or preserve the current arsenal – without developing new ways of working. This view was correct.

A Sluggish and Challenging Development Path

Since the late 2010s, only 16 antibiotics have gained widespread regulatory approval – primarily close relatives of medicines already in use and thus unlikely to evade bacterial resistance for long. The development of novel compounds is a lengthy and financially unattractive endeavor, given that one-off medicines are not as profitable as those managing chronic ailments. The overall prospect continues to be grim.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel FDA-approved drugs for gonorrhoea is a welcome development and, crucially, validates a innovative method of incentivising development. A particular of the recently approved medications, Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided funding and organised testing phases to offset costs and clear approval processes. This type of assistance upfront helps steer the industry towards fields of greatest public health necessity.

This model and another praised “subscription model” – launched to ensure income to companies investing in specific antibiotics – constitute the strongest chance of sustaining a dripfeed of novel treatments from the existing framework.

The Unavoidable Challenge of Resistance

But even hurrying the development of compounds currently in development isn't enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, indicating it targets a part of the pathogen that no other drug does, in principle compelling the bacterium to start from zero in evolving a defense to it. Researchers and physicians are relieved to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but warn that future resistance to it is certain.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, rationed to highly resistant infections only – confining its application to settings where high‑end lab testing is accessible. This sort of rational approach should be the global standard, but frequently cannot be implemented readily in many parts of the world.

A Dwindling Pipeline of Innovation

More broadly, it is difficult to see where the flow of additional novel antimicrobials we require could realistically originate. The former official's statement acknowledged the fact that searching the living world for natural sources – 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 recent years has not yet advanced past preclinical studies. Synthetic drugs, that are largely or entirely synthesized, are continually in development, but often confront the fundamental rules of molecular science – the fact that we envision a compound doesn't mean we can create it without great difficulty.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must run very fast indeed just to remain in the same place. Prudent, globally managed deployment is the sole method to maintain our therapeutic edge. Regrettably, the scale of forthcoming breakthroughs is going to seem miserly compared with the curative bonanza of the previous century.