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During her time as director general of the WHO, a past official famously stated that all of the “easy” antibiotics had already been found. The point was that in tackling the pressing threat of drug-resistant bacterial infections, we would struggle to discover new treatments – or preserve the existing ones – without developing novel approaches of working. This assessment proved correct.

A Slow and Unprofitable Development Path

Since the late 2010s, just sixteen antimicrobial agents have gained broad official clearance – mostly close relatives of drugs currently available and thus unlikely to evade bacterial resistance for an extended period. The development of new ones is a lengthy and unprofitable endeavor, given that curative medicines are not as profitable as those managing longer-term conditions. The overall prospect remains bleak.

A Glimmer of Hope and a Novel Approach

However, the news this month of a pair of novel FDA-approved antibiotics against gonorrhea is good news and, importantly, confirms a innovative method of incentivising development. One of the recently approved medications, Zoliflodacin, is the result of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided financial support and organised clinical trials to offset expenses and navigate approval processes. This type of support in advance helps direct the sector towards fields of most pressing public health necessity.

This approach and a separate praised revenue guarantee scheme – initiated to ensure income to firms investing in specific antimicrobials – constitute the best hope of sustaining a dripfeed of novel treatments from the existing framework.

The Unavoidable Problem of Drug Resistance

But even hurrying the development of compounds in the pipeline isn't sufficient. Zoliflodacin is at times described as a novel type of antibiotic, meaning it attacks a part of the infectious bacteria that existing treatments does, theoretically forcing the pathogen to begin anew in developing a countermeasure to it. Scientists and physicians are relieved to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to this compound is certain.

As has become the norm with recent antimicrobials, exists therefore an debate about whether it should be stockpiled, rationed to highly resistant infections only – limiting its application to settings where high‑end lab testing is accessible. This kind of rational approach should be the global standard, but often cannot be deployed easily in many regions.

A Dwindling Stream of Discovery

On a wider scale, it is difficult to see where the flow of additional novel antimicrobials we require could realistically come from. The former official's statement nodded to the fact that surveying the living world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of AI has been mooted to accelerate the discovery process, although a highly-touted early candidate found in recent years hasn't yet advanced past animal trials. Synthetic drugs, that are mainly or fully lab-created, are continually in research, but often confront the fundamental rules of molecular science – just because we envision a molecule doesn't mean we can synthesise it without great difficulty.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to stay in the current position. Prudent, internationally coordinated deployment is the only way to preserve our therapeutic edge. Regrettably, the scale of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.