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During a tenure as director general of the WHO, a past official famously remarked that all of the “simple” antimicrobials had already been found. The point was that in addressing the pressing threat of drug-resistant infections, we would face difficulties to discover new medicines – or conserve the current arsenal – without finding novel approaches of working. This view was accurate.

A Slow and Unprofitable Pipeline

Since the late 2010s, just sixteen antibiotics have received broad regulatory approval – mostly close relatives of medicines already in use and thus not expected to evade bacterial resistance for long. The creation of new ones is a slow and financially unattractive business, given that curative treatments are less lucrative as those treating chronic ailments. The scientific outlook remains bleak.

A Spark of Hope and a New Model

However, the news this month of a pair of novel FDA-approved drugs against gonorrhea is a welcome development and, crucially, validates a new way of encouraging research. One of the new drugs, a compound called Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a drug firm. The non-profit supplied funding and managed testing phases to offset costs and navigate approval processes. This sort of support upfront helps steer the industry towards areas of most pressing global need.

This model and another lauded “subscription model” – launched to guarantee income to companies that invest in certain antimicrobials – represent the best hope of sustaining a dripfeed of novel treatments from the current framework.

The Unavoidable Problem of Drug Resistance

But even hurrying the development of compounds in the pipeline is not sufficient. The new drug is at times categorized as a novel type of antimicrobial, meaning it targets a component of the pathogen that existing treatments does, in principle forcing the bacterium to begin anew in developing a countermeasure to it. Researchers and physicians are relieved to have a new option for gonorrhoea – which has resistant strains to every known antibiotic – but warn that future resistance to it is certain.

As has grown customary with new antibiotics, exists consequently an debate about whether it should be held in reserve, rationed to extremely drug-resistant infections only – limiting its use to situations where high‑end lab testing is available. This kind of rational approach should be the worldwide norm, but often can't be implemented readily in many regions.

A Diminishing Pipeline of Innovation

More broadly, it is hard to see where the stream of other novel antimicrobials we require could realistically come from. The aforementioned comment nodded to the fact that surveying the living world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of artificial intelligence has been mooted to speed up the search, although a highly-touted early candidate found in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, which are mainly or fully synthesized, are constantly in research, but often confront the fundamental rules of molecular science – the fact that we envision a compound does not guarantee we can create it easily.

Moving Quickly to Stay in Place

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Careful, globally managed use is the only way to preserve our therapeutic edge. Regrettably, the scale of forthcoming discoveries is likely to seem meager compared with the curative bonanza of the 20th century.