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During a tenure as director general of the World Health Organization, a former leader famously stated that all of the “simple” antibiotics had long since been discovered. The argument was that in addressing the pressing danger of drug-resistant bacterial infections, we would face difficulties to find new medicines – or conserve the current arsenal – without finding new ways of working. This view proved accurate.

A Slow and Unprofitable Development Path

Since 2017, only 16 antimicrobial agents have gained broad official clearance – mostly similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for long. The creation of novel compounds is a lengthy and unprofitable business, given that one-off medicines are not as profitable as ones managing chronic ailments. The scientific outlook continues to be grim.

A Spark of Hope and a New Model

However, the recent announcement of a pair of novel regulator-approved antibiotics against gonorrhea is a welcome development and, crucially, confirms a new way of incentivising development. A particular of the recently approved medications, a compound called Zoliflodacin, is the product of a novel kind of partnership between a global health organization and a pharmaceutical company. The non-profit provided funding and managed testing phases to offset costs and clear approval processes. This sort of support in advance helps steer the industry towards fields of greatest public health necessity.

This model and a separate lauded revenue guarantee scheme – initiated to ensure revenue to firms investing in certain antimicrobials – constitute the best hope of sustaining a dripfeed of new drugs from the current system.

The Unavoidable Problem of Resistance

But even accelerating the development of drugs currently in development isn't sufficient. The new drug is sometimes categorized as a novel type of antibiotic, indicating it targets a part of the pathogen that existing treatments does, in principle compelling the pathogen to start from zero in evolving a defense to it. Researchers and doctors are relieved to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but caution that future resistance to this compound is inevitable.

As has become the norm with new antibiotics, there is therefore an debate about whether it should be held in reserve, restricted to highly resistant infections only – limiting its application to situations where sophisticated diagnostics is available. This sort of prudent approach should be the worldwide norm, but often cannot be implemented readily in many regions.

A Diminishing Pipeline of Innovation

More broadly, it is difficult to see where the stream of other new antibiotics we require could possibly originate. The former official's statement nodded to the fact that surveying the living world for biological compounds – as with penicillin – has had diminishing returns. Use of artificial intelligence has been mooted to accelerate the search, although a highly-touted early candidate found in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, which are largely or entirely lab-created, are continually in development, but often confront the iron laws of chemistry – just because we imagine a compound doesn't mean we can synthesise it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the same place. Careful, globally managed use is the sole method to maintain our advantage. Sadly, the scale of future breakthroughs is likely to seem meager in contrast to the curative bonanza of the 20th century.