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During a time as director general of the World Health Organization, a former leader famously stated that all of the “simple” antimicrobials had already been found. The argument was that in addressing the pressing danger of antibiotic-resistant bacterial infections, we would struggle to find new treatments – or preserve the existing ones – without finding new ways of working. This view was accurate.

A Slow and Challenging Pipeline

Since 2017, only sixteen antimicrobial agents have received widespread regulatory approval – mostly similar derivatives of medicines currently available and thus unlikely to overcome resistance for long. The development of novel compounds is a lengthy and unprofitable endeavor, given that curative medicines are not as profitable as ones treating chronic ailments. The scientific outlook continues to be bleak.

A Spark of Optimism and a Novel Approach

Nevertheless, the recent announcement of two new FDA-approved drugs for gonorrhoea is a welcome development and, importantly, confirms a innovative method of encouraging development. One of the recently approved medications, Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided funding and organised testing phases to offset costs and navigate regulatory hurdles. This type of support upfront helps steer the sector towards fields of greatest global need.

This model and a separate lauded “subscription model” – initiated to guarantee revenue to companies that invest in specific antibiotics – constitute the strongest chance of sustaining a trickle of new drugs from the current system.

The Inevitable Challenge of Resistance

But even hurrying the production of compounds in the pipeline is not enough. Zoliflodacin is at times categorized as a new class of antimicrobial, indicating it targets a component of the pathogen that existing treatments does, theoretically compelling the bacterium to start from zero in developing a defense to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but caution that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, exists consequently an argument about whether it should be held in reserve, rationed to extremely drug-resistant infections only – limiting its use to settings where high‑end lab testing is available. This kind of prudent strategy should be the worldwide norm, but often cannot be implemented easily in many parts of the world.

A Diminishing Stream of Discovery

On a wider scale, it is hard to see where the stream of additional new antibiotics we require could possibly originate. The aforementioned statement nodded to the fact that searching the natural world for natural sources – as with the first antibiotic – has had diminishing returns. Use of AI has been mooted to accelerate the search, although a much-celebrated initial discovery found in recent years has not yet progressed past animal trials. Synthetic drugs, that are largely or entirely synthesized, are continually in research, but often run up against the fundamental rules of molecular science – just because we imagine a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the current position. Prudent, globally managed deployment is the sole method to maintain our advantage. Regrettably, the scale of future discoveries is likely to seem miserly in contrast to the curative bonanza of the previous century.