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During her time as director general of the World Health Organization, a past official famously remarked that all of the “simple” antimicrobials had already been found. The argument was that in addressing the urgent danger of antibiotic-resistant bacterial infections, we would struggle to discover new treatments – or conserve the existing ones – without developing new ways of operating. This assessment proved correct.

A Sluggish and Challenging Development Path

Since 2017, only 16 antimicrobial agents have received widespread regulatory approval – primarily similar derivatives of drugs already in use and thus unlikely to evade bacterial resistance for an extended period. The development of novel compounds is a lengthy and financially unattractive endeavor, given that one-off treatments are less lucrative as those managing chronic conditions. The overall prospect remains bleak.

A Glimmer of Optimism and a New Model

However, the recent announcement of two new FDA-approved antibiotics for gonorrhoea is a welcome development and, crucially, validates a new way of incentivising research. A particular of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and organised testing phases to defray expenses and navigate approval processes. This sort of support upfront helps steer the industry towards areas of most pressing public health necessity.

This approach and a separate praised “subscription model” – launched to ensure revenue to firms investing in certain antimicrobials – constitute the strongest chance of sustaining a trickle of novel treatments from the existing system.

The Inevitable Challenge of Resistance

But even accelerating the development of drugs in the pipeline is not sufficient. The new drug is at times described as a novel type of antimicrobial, meaning it attacks a component of the infectious bacteria that no other drug does, theoretically compelling the bacterium to start from zero in evolving a defense to it. Scientists and physicians are grateful to have a new option for gonorrhoea – which has strains resistant to every known antibiotic – but warn that eventual drug resistance to it is certain.

As has grown customary with recent antimicrobials, exists consequently an argument about whether it should be stockpiled, rationed to extremely drug-resistant infections only – limiting its application to settings where high‑end lab testing is available. This kind of prudent approach should be the worldwide norm, but often cannot be implemented easily in many regions.

A Diminishing Pipeline of Innovation

More broadly, it is hard to see where the flow of other novel antimicrobials we need could possibly originate. The former official's statement acknowledged the fact that surveying the living world for natural sources – as with penicillin – has had declining success. The application of artificial intelligence has been proposed to speed up the search, although a much-celebrated initial discovery found in recent years hasn't yet progressed past animal trials. Synthetic drugs, which are largely or entirely synthesized, are constantly in research, but often confront the iron laws of molecular science – the fact that we imagine a molecule does not guarantee we can create it without great difficulty.

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 stay in the current position. Careful, internationally coordinated deployment is the sole method to preserve our advantage. Regrettably, the scale of future breakthroughs is going to seem meager compared with the curative bonanza of the 20th century.