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During her tenure as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had long since been discovered. The argument was that in tackling the pressing danger of antibiotic-resistant infections, we would struggle to find new treatments – or conserve the existing ones – without finding new ways of operating. This view was accurate.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, just 16 antibiotics have gained widespread regulatory approval – mostly similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for an extended period. The creation of novel compounds is a lengthy and unprofitable business, given that curative medicines are less lucrative as those treating longer-term conditions. The scientific outlook remains bleak.

A Spark of Hope and a New Model

However, the recent announcement of two new regulator-approved antibiotics against gonorrhea is good news and, crucially, validates a new way of encouraging development. A particular of the new drugs, a compound called Zoliflodacin, is the product of a unique type of partnership between a global health organization and a drug firm. The non-profit provided funding and organised testing phases to offset costs and navigate regulatory hurdles. This type of support in advance helps direct the industry towards areas of greatest global need.

This approach and a separate praised “subscription model” – launched to guarantee revenue to firms investing in specific antibiotics – constitute the strongest chance of maintaining a dripfeed of novel treatments from the current framework.

The Inevitable Problem of Drug Resistance

But even accelerating the development of compounds currently in development is not sufficient. Zoliflodacin is sometimes described as a new class of antimicrobial, indicating it targets a part of the infectious bacteria that existing treatments does, theoretically compelling the bacterium to start from zero in evolving a countermeasure to it. Scientists and physicians are grateful to have a new option for gonorrhea – which has strains resistant to all existing treatments – but warn that future resistance to this compound is inevitable.

As has grown customary with new antibiotics, there is therefore an debate about whether it should be held in reserve, restricted to highly resistant infections only – confining its application to situations where sophisticated diagnostics is available. This kind of prudent strategy should be the worldwide norm, but frequently can't be deployed readily in many parts of the world.

A Dwindling Stream of Discovery

On a wider scale, it is hard to see where the stream of additional new antibiotics we need could possibly originate. The aforementioned comment acknowledged the fact that searching the natural world for natural sources – as with penicillin – has had declining success. Use of AI has been proposed to accelerate the discovery process, although a highly-touted initial discovery identified in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are continually in research, but often confront the iron laws of molecular science – the fact that we envision a compound does not guarantee we can synthesise it without great difficulty.

Running Fast to Stay in Place

The dominant scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to stay in the same place. Prudent, internationally coordinated deployment is the only way to preserve our therapeutic edge. Regrettably, the scale of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the 20th century.