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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 bacterial infections, we would face difficulties to find new treatments – or conserve the existing ones – without finding new ways of operating. This view was correct.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only sixteen antimicrobial agents have received widespread official clearance – primarily similar derivatives of medicines already in use and thus not expected to overcome resistance for an extended period. The development of novel compounds is a slow and unprofitable endeavor, given that one-off medicines are not as profitable as ones treating longer-term conditions. The overall prospect remains grim.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new regulator-approved antibiotics against gonorrhoea is good news and, crucially, confirms a new way of encouraging development. One of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a drug firm. The public health partnership supplied funding and organised clinical trials to offset costs and navigate regulatory hurdles. This type of support upfront helps direct the industry towards areas of greatest public health necessity.

This model and a separate praised revenue guarantee scheme – launched to guarantee income to firms investing in specific antimicrobials – represent the strongest chance of maintaining a trickle of novel treatments from the current framework.

The Unavoidable Problem of Resistance

But even accelerating the development of compounds in the pipeline isn't enough. Zoliflodacin is at times categorized as a new class of antimicrobial, indicating it targets a part of the infectious bacteria that existing treatments does, theoretically compelling the bacterium to begin anew in evolving a countermeasure to it. Researchers and doctors are relieved to have a new option for gonorrhea – which has resistant strains to all existing treatments – but caution that future resistance to it is certain.

As has grown customary with new antibiotics, there is consequently an argument about whether it should be stockpiled, rationed to extremely drug-resistant cases only – limiting its application to settings where high‑end lab testing is available. This kind of prudent strategy should be the global standard, but frequently can't be deployed easily in many parts of the world.

A Diminishing Stream of Innovation

More broadly, it is difficult to see where the flow of other new antibiotics we need could realistically originate. The aforementioned statement acknowledged the fact that surveying the living world for natural sources – as with penicillin – has had declining success. The application of AI has been proposed to accelerate the search, although a highly-touted early candidate identified in recent years has not yet progressed past animal trials. Fully lab-created compounds, that are largely or entirely synthesized, are continually in research, but often confront the iron laws of molecular science – the fact that we envision a compound doesn't mean we can create it easily.

Running Fast to Stay in Place

The prevailing scientific evaluation is that when it comes to antibiotics, we must move with great speed truly just to stay in the same place. Careful, globally managed use is the only way to preserve our therapeutic edge. Regrettably, the scale of future discoveries is likely to seem miserly compared with the curative bonanza of the 20th century.