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During a tenure as director general of the World Health Organization, a past official famously stated that all of the “easy” antimicrobials 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 treatments – or preserve the current arsenal – without developing new ways of working. This assessment was correct.

A Slow and Challenging Development Path

Since the late 2010s, just sixteen antimicrobial agents have received broad regulatory approval – mostly close relatives of medicines already in use and thus not expected to overcome bacterial resistance for long. The creation of new ones is a slow and financially unattractive endeavor, given that one-off medicines are less lucrative as those treating longer-term conditions. The scientific outlook remains grim.

A Glimmer of Hope and a New Model

Nevertheless, the recent announcement of two new FDA-approved antibiotics against gonorrhoea is good news and, importantly, confirms a new way of incentivising development. One of the new drugs, Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to defray costs and navigate regulatory hurdles. This sort of assistance in advance helps direct the industry towards fields of most pressing public health necessity.

This model and a separate lauded revenue guarantee scheme – launched to ensure income to firms that invest in specific antibiotics – constitute the strongest chance of maintaining a trickle of new drugs from the current system.

The Unavoidable Challenge of Resistance

But even hurrying the development of compounds in the pipeline isn't enough. The new drug is sometimes categorized as a new class of antibiotic, meaning it targets a component of the pathogen that no other drug does, theoretically forcing the bacterium to begin anew in developing a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that future resistance to it is certain.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be stockpiled, rationed to extremely drug-resistant cases only – limiting its use to settings where sophisticated diagnostics is available. This sort of prudent strategy should be the global standard, but frequently cannot be implemented readily in many parts of the world.

A Dwindling Stream of Discovery

On a wider scale, it is difficult to see where the stream of additional novel antimicrobials we need could realistically originate. The former official's comment nodded to the fact that surveying the natural world for natural sources – as with penicillin – has had diminishing returns. The application of artificial intelligence has been proposed to speed up the search, although a much-celebrated early candidate identified in recent years has not yet advanced past animal trials. Synthetic drugs, which are largely or entirely lab-created, are constantly in development, but often confront the iron laws of chemistry – just because we imagine a molecule does not guarantee we can synthesise it easily.

Moving Quickly to Stay in Place

The dominant scientific evaluation is that when it comes to antibiotics, we must move with great speed indeed just to stay in the current position. Careful, globally managed deployment is the sole method to preserve our advantage. Sadly, the magnitude of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the 20th century.