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During a time as head of the WHO, a past official famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the pressing danger of antibiotic-resistant infections, we would struggle to find new medicines – or preserve the current arsenal – without finding new ways of working. This assessment proved correct.

A Sluggish and Challenging Development Path

Since the late 2010s, only sixteen antibiotics have gained broad official clearance – primarily similar derivatives of drugs already in use and thus not expected to evade 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 overall prospect remains grim.

A Glimmer of Optimism and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs for gonorrhea is a welcome development and, importantly, confirms a new way of incentivising development. One of the new drugs, Zoliflodacin, is the result of a novel kind of partnership between a global health organization and a drug firm. The non-profit provided financial support and managed testing phases to offset expenses and clear regulatory hurdles. This type of assistance in advance helps direct the industry towards fields of most pressing public health necessity.

This approach and another praised “subscription model” – initiated to ensure income to firms that invest in specific antimicrobials – represent the strongest chance of sustaining a dripfeed of novel treatments from the current framework.

The Unavoidable Problem of Resistance

But even hurrying the development of drugs in the pipeline is not sufficient. The new drug is at times described as a novel type of antimicrobial, indicating it targets a part of the infectious bacteria that no other drug does, in principle compelling the bacterium to begin anew in evolving a defense to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to this compound is certain.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be stockpiled, restricted to highly resistant cases only – limiting its application to settings where sophisticated diagnostics is accessible. This kind of prudent approach should be the global standard, but often cannot be deployed easily in many parts of the world.

A Diminishing Stream of Innovation

More broadly, it is difficult to see where the stream of additional new antibiotics we require could possibly come from. The former official's statement acknowledged the fact that surveying the living world for natural sources – as with penicillin – has had diminishing returns. The application of artificial intelligence has been proposed to accelerate the discovery process, although a much-celebrated initial discovery identified in 2020 hasn't yet progressed past animal trials. Fully lab-created compounds, that are mainly or fully synthesized, are continually in research, but often confront the iron laws of molecular science – the fact that we imagine a molecule does not guarantee we can synthesise it easily.

Moving Quickly to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to stay in the same place. Careful, globally managed use is the sole method to preserve our therapeutic edge. Regrettably, the scale of forthcoming discoveries is going to seem meager in contrast to the curative bonanza of the 20th century.