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During her time as head of the World Health Organization, a past official famously stated that all of the “simple” antibiotics had already been found. The point was that in tackling the urgent danger of drug-resistant bacterial infections, we would struggle to find new treatments – or conserve the existing ones – without developing new ways of working. This assessment proved correct.

A Slow and Challenging Development Path

Since 2017, only sixteen antibiotics have received broad regulatory approval – mostly similar derivatives of medicines already in use and thus not expected to overcome bacterial resistance for an extended period. The development of new ones is a lengthy and financially unattractive endeavor, given that one-off medicines are not as profitable as ones managing chronic conditions. The overall prospect remains grim.

A Glimmer of Hope and a Novel Approach

However, the news this month of two new FDA-approved antibiotics for gonorrhea is good news and, importantly, validates a new way of incentivising development. A particular of the recently approved medications, 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 supplied financial support and organised clinical trials to defray costs and clear approval processes. This type of assistance in advance helps direct the sector towards fields of greatest global need.

This approach and a separate praised “subscription model” – initiated to guarantee income to firms investing in specific antimicrobials – represent the best hope of maintaining a dripfeed of novel treatments from the existing system.

The Inevitable Problem of Drug Resistance

But even hurrying the production of drugs in the pipeline is not enough. Zoliflodacin is at times categorized as a new class of antimicrobial, indicating it targets a component of the infectious bacteria that existing treatments does, theoretically compelling the bacterium to begin anew in evolving a countermeasure to it. Researchers and physicians are relieved to have a new option for gonorrhea – which has resistant strains to every known antibiotic – but warn that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is therefore an debate about whether it should be held in reserve, rationed to highly resistant infections only – limiting its application to situations where sophisticated diagnostics is accessible. This sort of rational strategy should be the worldwide norm, but frequently can't be implemented readily in many parts of the world.

A Dwindling Pipeline of Innovation

More broadly, it is hard to see where the stream of additional novel antimicrobials we need could possibly come from. The former official's statement acknowledged the fact that surveying the natural world for natural sources – as with the first antibiotic – has had diminishing returns. The application of artificial intelligence has been mooted to speed up the search, although a much-celebrated early candidate identified in 2020 has not yet progressed past animal trials. Fully lab-created compounds, that are mainly or fully synthesized, are constantly in research, but often confront the iron laws of molecular science – just because we imagine a molecule does not guarantee we can create it easily.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to stay in the same place. Prudent, globally managed use is the sole method to preserve our advantage. Sadly, the scale of forthcoming discoveries is likely to seem miserly in contrast to the therapeutic revolution of the 20th century.