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During a tenure as director general of the WHO, a former leader famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the urgent threat of drug-resistant infections, we would struggle to discover new treatments – or preserve the existing ones – without developing new ways of working. This assessment proved accurate.

A Sluggish and Challenging Pipeline

Since 2017, only sixteen antimicrobial agents have received broad regulatory approval – primarily similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for long. The development of new ones is a lengthy and financially unattractive business, given that curative treatments are not as profitable as those managing chronic ailments. The overall prospect continues to be bleak.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of a pair of novel regulator-approved antibiotics against gonorrhea is a welcome development and, crucially, confirms a new way of incentivising development. A particular of the recently approved medications, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided financial support and managed clinical trials to offset expenses and navigate approval processes. This sort of support upfront helps steer the industry towards fields of most pressing public health necessity.

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 existing system.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of drugs currently in development isn't sufficient. The new drug is sometimes categorized as a novel type of antibiotic, indicating it targets a component of the infectious bacteria that existing treatments does, in principle compelling the bacterium to begin anew in evolving a countermeasure to it. Researchers and physicians are relieved to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but warn that future resistance to this compound is inevitable.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its application to situations where high‑end lab testing is accessible. This sort of prudent approach should be the worldwide norm, but frequently can't be deployed easily in many regions.

A Diminishing Stream of Innovation

On a wider scale, it is difficult to see where the stream of additional new antibiotics we require could realistically originate. 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. The application of AI has been proposed to speed up the search, although a much-celebrated early candidate identified in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are continually in research, but often confront the iron laws of molecular science – just because we envision a molecule does not guarantee we can synthesise it easily.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to stay in the current position. Prudent, globally managed deployment is the sole method to maintain our therapeutic edge. Regrettably, the scale of forthcoming discoveries is going to seem meager in contrast to the curative bonanza of the previous century.