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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 already been found. The point was that in tackling the pressing threat of antibiotic-resistant infections, we would face difficulties to find new treatments – or conserve the existing ones – without finding new ways of working. This view proved correct.

A Slow and Challenging Pipeline

Since the late 2010s, just 16 antibiotics have received broad regulatory approval – primarily close relatives of drugs already in use and thus unlikely to overcome bacterial resistance for an extended period. The creation of novel compounds is a slow and unprofitable endeavor, given that one-off treatments are not as profitable as ones treating longer-term conditions. The scientific outlook remains bleak.

A Spark of Optimism and a Novel Approach

However, the recent announcement of a pair of novel regulator-approved antibiotics against gonorrhea is good news and, importantly, confirms a new way of incentivising development. One of the new drugs, Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided financial support and managed testing phases to defray costs and clear approval processes. This sort of support upfront helps steer the sector towards fields of greatest global need.

This model and a separate lauded “subscription model” – initiated to guarantee revenue to firms investing in specific antibiotics – represent the best hope of sustaining a dripfeed of novel treatments from the existing system.

The Inevitable Challenge of Drug Resistance

But even accelerating the production of compounds currently in development isn't enough. The new drug is at times described as a novel type of antimicrobial, indicating it attacks a component of the pathogen that existing treatments does, theoretically compelling the pathogen to begin anew in developing a countermeasure to it. Scientists and doctors are relieved to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to it is inevitable.

As has become the norm with new antibiotics, there is therefore an debate about whether it should be stockpiled, rationed to highly resistant infections only – limiting its application to situations where high‑end lab testing is accessible. This sort of rational strategy should be the worldwide norm, but frequently cannot be deployed easily in many regions.

A Dwindling Pipeline of Discovery

More broadly, it is difficult to see where the flow of other new antibiotics we require could possibly originate. The former official's statement nodded to the fact that searching the natural world for natural sources – as with penicillin – has had diminishing returns. Use of AI has been proposed to speed up the search, although a highly-touted initial discovery found in recent years has not yet progressed past animal trials. Synthetic drugs, that are mainly or fully synthesized, are continually in research, but often run up against the iron laws of chemistry – just because we imagine a molecule doesn't mean we can create it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to stay in the same place. Careful, internationally coordinated deployment is the sole method to maintain our therapeutic edge. Regrettably, the magnitude of forthcoming discoveries is likely to seem meager compared with the therapeutic revolution of the 20th century.