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During her tenure as director general of the WHO, a former leader famously stated that all of the “easy” antimicrobials had already been found. The argument was that in tackling the urgent threat of drug-resistant bacterial infections, we would struggle to discover new treatments – or preserve the current arsenal – without developing novel approaches of working. This assessment proved correct.

A Slow and Unprofitable Development Path

Since the late 2010s, just 16 antimicrobial agents have received widespread regulatory approval – mostly close relatives of medicines currently available and thus unlikely to evade bacterial resistance for long. The development of new ones is a lengthy and unprofitable business, given that one-off treatments are less lucrative as those treating chronic ailments. The scientific outlook continues to be bleak.

A Glimmer of Hope and a New Model

Nevertheless, the recent announcement of two new regulator-approved antibiotics for gonorrhea is good news and, importantly, confirms a innovative method of encouraging research. One of the new drugs, Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a drug firm. The public health partnership supplied financial support and managed testing phases to defray costs and navigate approval processes. This type of support in advance helps steer the sector towards fields of most pressing global need.

This approach and another praised revenue guarantee scheme – launched to guarantee revenue to companies that invest in specific antibiotics – represent the best hope of maintaining a trickle of novel treatments from the existing system.

The Unavoidable Problem of Resistance

But even hurrying the production of compounds in the pipeline is not sufficient. Zoliflodacin is at times described as a new class of antibiotic, meaning it attacks a part of the pathogen that no other drug does, in principle compelling the pathogen to start from zero in developing a defense to it. Researchers and physicians are grateful to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that future resistance to this compound is inevitable.

As has become the norm with new antibiotics, exists therefore an argument about whether it should be held in reserve, rationed to extremely drug-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 Innovation

On a wider scale, it is hard to see where the stream of additional new antibiotics we need could possibly come from. The aforementioned comment nodded to the fact that searching the living world for biological compounds – as with penicillin – has had declining success. The application of artificial intelligence has been proposed to accelerate the search, although a much-celebrated early candidate identified in recent years hasn't yet progressed past animal trials. Synthetic drugs, which are largely or entirely synthesized, are constantly in research, but often confront the fundamental rules of molecular science – just because we envision a compound does not guarantee we can synthesise it easily.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the same place. Prudent, globally managed deployment is the only way to maintain our therapeutic edge. Sadly, the scale of future breakthroughs is going to seem meager in contrast to the therapeutic revolution of the previous century.