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During a tenure as head of the World Health Organization, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The argument was that in tackling the urgent threat of drug-resistant infections, we would face difficulties to discover new treatments – or conserve the existing ones – without finding novel approaches of operating. This view proved correct.

A Sluggish and Challenging Development Path

Since the late 2010s, only sixteen antibiotics have received broad regulatory approval – primarily similar derivatives of drugs currently available and thus not expected to evade resistance for long. The creation of new ones is a slow and unprofitable endeavor, given that curative treatments are less lucrative as ones managing longer-term conditions. The overall prospect continues to be grim.

A Glimmer of Optimism and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs for gonorrhoea is a welcome development and, crucially, validates a innovative method of encouraging research. One of the new drugs, Zoliflodacin, is the product of a unique type of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied funding and organised testing phases to defray costs and navigate approval processes. This type of assistance upfront helps steer the industry towards fields of most pressing public health necessity.

This model and another praised “subscription model” – initiated to ensure revenue to firms that invest in specific antimicrobials – constitute the strongest chance of maintaining a dripfeed of new drugs from the current framework.

The Inevitable Challenge of Resistance

But even hurrying the development of compounds currently in development is not enough. The new drug is sometimes described as a new class of antimicrobial, meaning it attacks a component of the pathogen that no other drug does, in principle forcing the bacterium to start from zero in developing a defense to it. Scientists and doctors are relieved to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but caution that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be held in reserve, restricted to highly resistant cases only – confining its application to situations where sophisticated diagnostics is accessible. This kind of rational strategy should be the global standard, but often cannot be implemented readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the flow of other new antibiotics we need could realistically originate. The former official's statement acknowledged the fact that surveying the natural world for natural sources – as with penicillin – has had diminishing returns. Use of AI has been proposed to accelerate the search, although a highly-touted early candidate found in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, that are mainly or fully lab-created, are constantly in research, but often run up against the iron laws of chemistry – just because we imagine a compound doesn't mean we can create it easily.

Moving Quickly to Stand Still

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