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During her tenure as director general of the WHO, a past official famously remarked that all of the “simple” antibiotics had long since been discovered. The point was that in tackling the urgent threat of antibiotic-resistant infections, we would struggle to discover new treatments – or preserve the existing ones – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Development Path

Since the late 2010s, only 16 antimicrobial agents have gained widespread regulatory approval – mostly similar derivatives of medicines already in use and thus not expected to evade resistance for an extended period. The creation of new ones is a lengthy and financially unattractive business, given that one-off medicines are not as profitable as those treating longer-term conditions. The scientific outlook remains bleak.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved drugs against gonorrhea is a welcome development and, importantly, validates a innovative method of incentivising research. A particular of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit supplied financial support and managed testing phases to offset expenses and navigate regulatory hurdles. This sort of assistance in advance helps direct the industry towards areas of most pressing public health necessity.

This model and another praised “subscription model” – initiated to guarantee income to companies investing in certain antimicrobials – constitute the best hope of maintaining a dripfeed of novel treatments from the existing framework.

The Inevitable Problem of Resistance

But even hurrying the development of drugs in the pipeline isn't sufficient. The new drug is at times described as a new class of antibiotic, meaning it targets a component of the pathogen that existing treatments does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Scientists and doctors are grateful to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to it is certain.

As has grown customary with new antibiotics, there is consequently an argument about whether it should be stockpiled, rationed to highly resistant infections only – limiting its use to situations where high‑end lab testing is available. This kind of rational strategy should be the worldwide norm, but often cannot be deployed readily in many regions.

A Dwindling Stream of Discovery

On a wider scale, it is difficult to see where the flow of additional new antibiotics we need could realistically come from. The former official's statement acknowledged the fact that searching the living world for natural sources – as with the first antibiotic – has had declining success. Use of artificial intelligence has been proposed to accelerate the search, although a highly-touted initial discovery identified in recent years hasn't yet advanced past preclinical studies. Fully lab-created compounds, that are mainly or fully synthesized, are constantly in development, 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.

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, internationally coordinated use is the only way to maintain our therapeutic edge. Regrettably, the scale of forthcoming discoveries is likely to seem meager compared with the therapeutic revolution of the 20th century.