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During her tenure as director general of the WHO, a past official famously remarked that all of the “simple” antimicrobials had long since been discovered. The argument was that in tackling the pressing threat of antibiotic-resistant infections, we would face difficulties to find new medicines – or conserve the existing ones – without developing new ways of operating. This assessment was correct.

A Sluggish and Unprofitable Development Path

Since the late 2010s, only sixteen antimicrobial agents have received broad regulatory approval – primarily close relatives of medicines already in use and thus unlikely to overcome resistance for long. The development of new ones is a slow and financially unattractive endeavor, given that curative treatments are less lucrative 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 FDA-approved antibiotics against gonorrhoea is good news and, importantly, confirms a new way of incentivising research. One of the recently approved medications, Zoliflodacin, is the product of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and managed testing phases to defray costs and clear regulatory hurdles. This sort of assistance in advance helps direct the sector towards fields of greatest global need.

This model and another praised revenue guarantee scheme – initiated to ensure income to firms investing in certain antibiotics – represent the best hope of sustaining a trickle of novel treatments from the existing framework.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of drugs in the pipeline is not sufficient. Zoliflodacin is sometimes categorized as a new class of antimicrobial, indicating it targets a component of the pathogen that no other drug does, theoretically compelling the pathogen to begin anew in evolving a countermeasure to it. Scientists and doctors are relieved to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but caution that future resistance to it is certain.

As has grown customary with recent antimicrobials, there is consequently an argument about whether it should be stockpiled, restricted to highly resistant infections only – limiting its application to settings where high‑end lab testing is available. This kind of rational approach should be the worldwide norm, but often can't be implemented readily in many regions.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the stream of additional new antibiotics we need could possibly come from. The former official's statement acknowledged the fact that searching the living world for biological compounds – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been proposed to accelerate the discovery process, although a highly-touted initial discovery identified in 2020 has not yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are continually in development, but often confront the iron laws of molecular science – the fact that we envision 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 truly just to remain in the same place. Careful, internationally coordinated use is the only way to maintain our therapeutic edge. Regrettably, the scale of forthcoming breakthroughs is going to seem miserly in contrast to the curative bonanza of the 20th century.