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During a tenure as head of the WHO, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The argument was that in tackling the pressing danger of drug-resistant infections, we would face difficulties to discover new treatments – or preserve the current arsenal – without developing new ways of working. This view proved accurate.

A Slow and Challenging Pipeline

Since 2017, only 16 antimicrobial agents have received broad official clearance – primarily close relatives of drugs already in use and thus not expected to overcome resistance for long. The development of novel compounds is a lengthy and unprofitable business, given that curative treatments are less lucrative as those managing chronic ailments. The scientific outlook continues to be grim.

A Spark of Optimism and a New Model

However, the news this month of a pair of novel regulator-approved drugs for gonorrhoea is good news and, importantly, validates a new way of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the product of a unique type of partnership between a Swiss non‑profit and a drug firm. The public health partnership supplied funding and organised clinical trials to offset costs and clear approval processes. This type of assistance in advance helps steer the industry towards areas of most pressing global need.

This model and a separate praised “subscription model” – initiated to guarantee income to companies that invest in certain antimicrobials – represent the strongest chance of sustaining a trickle of new drugs from the existing system.

The Unavoidable Challenge of Drug Resistance

But even hurrying the development of compounds currently in development is not sufficient. The new drug is sometimes categorized as a novel type of antimicrobial, indicating it attacks a component of the infectious bacteria that existing treatments does, theoretically forcing the bacterium to begin anew in developing a defense to it. Researchers and doctors are relieved to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is consequently an argument about whether it should be held in reserve, restricted to extremely drug-resistant infections only – limiting its use to settings where high‑end lab testing is available. This kind of prudent approach should be the global standard, but frequently can't be implemented readily in many parts of the world.

A Dwindling Pipeline of Discovery

More broadly, it is hard to see where the flow of additional novel antimicrobials we need could possibly come from. The aforementioned comment nodded to the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. Use of artificial intelligence has been mooted to accelerate the discovery process, 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 continually in research, but often confront the fundamental rules of molecular science – the fact that we imagine a compound does not guarantee we can create it without great difficulty.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed truly just to remain in the same place. Careful, globally managed deployment is the only way to maintain our advantage. Sadly, the scale of forthcoming discoveries is going to seem meager in contrast to the therapeutic revolution of the 20th century.