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During her tenure as director general of the WHO, a former leader famously stated that all of the “easy” antimicrobials had already been found. The argument was that in tackling the pressing threat of drug-resistant bacterial infections, we would face difficulties to find new medicines – or conserve the current arsenal – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Pipeline

Since 2017, only 16 antimicrobial agents have gained broad official clearance – primarily similar derivatives of medicines already in use and thus unlikely to evade resistance for an extended period. The development of novel compounds is a slow and financially unattractive endeavor, given that one-off treatments are less lucrative as ones managing longer-term conditions. The overall prospect continues to be grim.

A Glimmer of Optimism and a New Model

However, the recent announcement of a pair of novel FDA-approved drugs against gonorrhea is good news and, importantly, confirms a innovative method of encouraging development. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and managed clinical trials to defray expenses and clear approval processes. This type of assistance in advance helps direct the sector towards areas of greatest public health necessity.

This model and another praised “subscription model” – initiated to ensure revenue to companies that invest in certain antimicrobials – represent the best hope of maintaining a dripfeed of novel treatments from the existing system.

The Inevitable Challenge of Drug Resistance

But even hurrying the development of compounds currently in development isn't sufficient. Zoliflodacin is sometimes described as a novel type of antibiotic, indicating it attacks a component of the pathogen that existing treatments does, in principle compelling the pathogen to start from zero in developing a defense to it. Researchers and physicians are relieved to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but warn that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is consequently an argument about whether it should be stockpiled, restricted to highly resistant cases only – limiting its use to situations 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 Innovation

On a wider scale, it is hard to see where the flow of other novel antimicrobials we need could realistically come from. The aforementioned comment nodded to the fact that searching the natural world for natural sources – as with the first antibiotic – has had declining success. Use of AI has been proposed to speed up the discovery process, although a highly-touted initial discovery identified in recent years has not yet progressed past preclinical studies. Fully lab-created compounds, which are largely or entirely lab-created, are continually in research, but often run up against the fundamental rules of chemistry – just because we imagine a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Careful, internationally coordinated use is the sole method to maintain our therapeutic edge. Sadly, the scale of forthcoming breakthroughs is likely to seem meager in contrast to the curative bonanza of the 20th century.