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During her tenure as director general of the World Health Organization, a former leader famously stated that all of the “simple” antibiotics had long since been discovered. The argument was that in addressing the pressing threat of antibiotic-resistant infections, we would face difficulties to discover new treatments – or conserve the existing ones – without finding novel approaches of working. This view was accurate.

A Sluggish and Unprofitable Development Path

Since 2017, just 16 antimicrobial agents have received widespread official clearance – primarily close relatives of drugs currently available and thus unlikely to overcome resistance for long. The development of new ones is a lengthy and unprofitable endeavor, given that one-off treatments are not as profitable as those treating longer-term conditions. The overall prospect continues to be bleak.

A Spark of Optimism and a New Model

However, the news this month of a pair of novel regulator-approved antibiotics against gonorrhea is good news and, crucially, confirms a new way of incentivising development. One of the new drugs, a compound called Zoliflodacin, is the product of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit supplied funding and organised clinical trials to defray expenses and navigate regulatory hurdles. This type of support upfront helps direct the sector towards areas of most pressing global need.

This approach and a separate praised revenue guarantee scheme – launched to ensure revenue to firms that invest in certain antimicrobials – represent the strongest chance of sustaining a dripfeed of new drugs from the current system.

The Inevitable Challenge of Drug Resistance

But even accelerating the development of compounds currently in development isn't enough. The new drug is at times categorized as a new class of antibiotic, meaning it targets a part of the infectious bacteria that existing treatments does, theoretically forcing the bacterium to begin anew in developing a countermeasure to it. Researchers and physicians are relieved to have a new option 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, exists consequently an debate about whether it should be stockpiled, restricted to highly resistant infections only – limiting its application to settings where high‑end lab testing is accessible. This sort of rational strategy should be the worldwide norm, but often cannot be implemented easily in many parts of the world.

A Dwindling Pipeline of Discovery

On a wider scale, it is hard to see where the flow of additional new antibiotics we need could realistically come from. The aforementioned statement nodded to the fact that surveying the natural world for biological compounds – as with penicillin – has had declining success. The application of artificial intelligence has been mooted to accelerate the search, although a highly-touted initial discovery identified in 2020 hasn't yet progressed past animal trials. Fully lab-created compounds, that are mainly or fully lab-created, are continually in research, but often confront the iron laws of molecular science – just because we envision a compound doesn't mean we can create it easily.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to stay in the current position. Prudent, globally managed use is the only way to preserve our advantage. Regrettably, the scale of future discoveries is going to seem meager in contrast to the curative bonanza of the 20th century.