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During a time as head of the World Health Organization, a past official famously remarked that all of the “simple” antimicrobials had long since been discovered. The argument was that in addressing the pressing threat of drug-resistant bacterial infections, we would struggle to find new medicines – or preserve the current arsenal – without developing novel approaches of working. This assessment proved correct.

A Slow and Unprofitable Development Path

Since the late 2010s, only 16 antibiotics have gained broad regulatory approval – mostly similar derivatives of drugs already in use and thus not expected to overcome bacterial resistance for an extended period. The development of novel compounds is a slow and financially unattractive endeavor, given that one-off medicines are not as profitable as ones treating chronic ailments. The scientific outlook continues to be grim.

A Glimmer of Hope and a Novel Approach

Nevertheless, the news this month of two new regulator-approved drugs against gonorrhoea is a welcome development and, crucially, validates a innovative method of incentivising research. A particular of the new drugs, a compound called Zoliflodacin, is the product of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided funding and managed clinical trials to defray expenses and navigate approval processes. This type of support upfront helps steer the sector towards areas of most pressing public health necessity.

This approach and a separate praised “subscription model” – initiated to guarantee income to companies investing in specific antimicrobials – represent the strongest chance of maintaining a trickle of novel treatments from the existing framework.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of compounds in the pipeline isn't sufficient. The new drug is sometimes categorized as a new class of antimicrobial, meaning it attacks a component of the infectious bacteria that existing treatments does, theoretically compelling the pathogen to begin anew in evolving a countermeasure to it. Researchers and physicians are relieved to have a new drug for gonorrhea – which has resistant strains to all existing treatments – but warn that eventual drug resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is therefore an argument about whether it should be stockpiled, restricted to highly resistant cases only – limiting its application to situations where high‑end lab testing is accessible. This kind of rational approach should be the worldwide norm, but often can't be deployed readily in many parts of the world.

A Diminishing Pipeline of Innovation

On a wider scale, it is hard to see where the stream of other novel antimicrobials we need could realistically come from. The former official's comment nodded to the fact that surveying the living world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been mooted to speed up the search, although a much-celebrated early candidate found in recent years has not yet advanced past preclinical studies. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often run up against the fundamental rules of molecular science – just because we imagine a molecule doesn't mean we can create it without great difficulty.

Running Fast to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the same place. Careful, globally managed deployment is the only way to preserve our therapeutic edge. Regrettably, the magnitude of forthcoming discoveries is going to seem meager compared with the curative bonanza of the 20th century.