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During a time as head of the WHO, a former leader famously remarked that all of the “simple” antibiotics had long since been discovered. The point was that in addressing the urgent danger of drug-resistant infections, we would face difficulties to find new medicines – or conserve the current arsenal – without developing novel approaches of working. This assessment was correct.

A Sluggish and Challenging Development Path

Since 2017, only sixteen antimicrobial agents have gained broad regulatory approval – mostly close relatives of medicines currently available and thus unlikely to overcome bacterial resistance for an extended period. The creation of new ones is a slow and unprofitable business, given that one-off treatments are less lucrative as those treating longer-term conditions. The overall prospect continues to be grim.

A Glimmer 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, importantly, validates a new way of incentivising development. One of the new drugs, Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied funding and managed clinical trials to defray costs and clear approval processes. This type of support upfront helps steer the industry towards fields of most pressing global need.

This approach and a separate lauded “subscription model” – launched to guarantee income to companies that invest in certain antibiotics – represent the best hope of maintaining a trickle of new drugs from the existing system.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of compounds currently in development is not enough. The new drug is sometimes categorized as a new class of antimicrobial, indicating it targets a part of the pathogen that existing treatments does, in principle compelling the pathogen to begin anew in evolving a defense to it. Researchers and physicians are grateful to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but caution that eventual drug resistance to this compound is inevitable.

As has become the norm with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, rationed to highly resistant cases only – limiting its application to situations where high‑end lab testing is available. This kind of prudent approach should be the worldwide norm, but frequently can't be deployed easily in many regions.

A Dwindling Pipeline of Innovation

More broadly, it is hard to see where the flow of additional new antibiotics we need could realistically come from. The former official's comment nodded to the fact that searching the living world for natural sources – as with the first antibiotic – has had declining success. Use of AI has been mooted to speed up the discovery process, although a much-celebrated initial discovery found in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, that are mainly or fully lab-created, are continually in development, but often run up against the iron laws of chemistry – just because we envision a molecule doesn't mean we can create it without great difficulty.

Moving Quickly to Stay in Place

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 only way to preserve our therapeutic edge. Sadly, the scale of forthcoming breakthroughs is going to seem meager in contrast to the therapeutic revolution of the 20th century.