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During a tenure as head of the WHO, a former leader famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the urgent danger of antibiotic-resistant infections, we would face difficulties to discover new medicines – or conserve the current arsenal – without finding novel approaches of working. This view was accurate.

A Sluggish and Unprofitable Development Path

Since the late 2010s, just 16 antibiotics have received broad official clearance – mostly close relatives of medicines already in use and thus unlikely to overcome resistance for long. The creation of novel compounds is a slow and financially unattractive business, given that curative treatments are not as profitable as those managing longer-term conditions. The overall prospect remains bleak.

A Spark of Optimism and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved antibiotics for gonorrhoea is good news and, importantly, confirms a new way of encouraging research. One of the recently approved medications, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided financial support and organised testing phases to offset costs and clear approval processes. This type of assistance in advance helps direct the sector towards fields of most pressing global need.

This approach and another lauded revenue guarantee scheme – launched to guarantee revenue to companies that invest in specific antimicrobials – represent the strongest chance of maintaining a trickle of new drugs from the current system.

The Inevitable Challenge of Resistance

But even accelerating the development of compounds in the pipeline isn't enough. The new drug is at times categorized as a novel type of antibiotic, meaning it targets a component of the pathogen that existing treatments does, in principle compelling the pathogen to begin anew in developing a defense to it. Scientists and doctors are relieved 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, exists therefore an argument about whether it should be stockpiled, rationed to extremely drug-resistant cases only – confining its application to settings where high‑end lab testing is accessible. This sort of prudent strategy should be the worldwide norm, but often cannot be deployed easily in many regions.

A Diminishing Pipeline of Innovation

More broadly, it is difficult to see where the flow of other new antibiotics we need could realistically come from. The former official's statement nodded to the fact that searching the natural world for biological compounds – as with penicillin – has had diminishing returns. Use of artificial intelligence has been proposed to accelerate the search, although a highly-touted initial discovery identified in recent years has not yet advanced past animal trials. Synthetic drugs, which are largely or entirely synthesized, are constantly in research, but often confront the iron laws of chemistry – just because we envision a molecule doesn't mean we can create it without great difficulty.

Running Fast to Stand Still

The prevailing expert assessment is that when it comes to antibiotics, we must run very fast indeed just to remain in the current position. Prudent, internationally coordinated deployment is the sole method to preserve our advantage. Sadly, the magnitude of future discoveries is likely to seem meager in contrast to the therapeutic revolution of the previous century.