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During her tenure as head of the World Health Organization, a former leader famously remarked that all of the “simple” antibiotics had long since been discovered. The point was that in addressing the urgent threat of drug-resistant 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 Slow and Unprofitable Development Path

Since 2017, just 16 antimicrobial agents have received broad regulatory approval – primarily close relatives of drugs currently available and thus not expected to overcome bacterial resistance for an extended period. The development of novel compounds is a lengthy and unprofitable endeavor, given that one-off treatments are less lucrative as those managing chronic ailments. The overall prospect continues to be grim.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved drugs for gonorrhoea is a welcome development and, crucially, confirms a new way of encouraging research. A particular of the new drugs, a compound called Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to defray expenses and clear regulatory hurdles. This type of support upfront helps direct the sector towards areas of greatest public health necessity.

This approach and another lauded revenue guarantee scheme – launched to guarantee income to firms investing in specific antibiotics – constitute the best hope of sustaining a trickle of new drugs from the existing framework.

The Unavoidable Challenge of Drug Resistance

But even hurrying the development of compounds in the pipeline is not sufficient. Zoliflodacin is sometimes described as a new class of antibiotic, indicating it targets a component of the infectious bacteria that no other drug does, theoretically forcing the bacterium to start from zero in developing a countermeasure to it. Researchers and doctors are relieved to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but warn that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, exists consequently an argument about whether it should be stockpiled, rationed to highly resistant cases only – limiting its application to settings where high‑end lab testing is accessible. This sort of rational strategy should be the worldwide norm, but often cannot be implemented easily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is hard to see where the flow of other novel antimicrobials we require could possibly originate. The aforementioned statement acknowledged the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had declining success. Use of artificial intelligence has been proposed to accelerate the discovery process, although a much-celebrated early candidate identified in 2020 hasn't yet advanced past preclinical studies. Synthetic drugs, which are mainly or fully lab-created, are continually in development, but often run up against the fundamental rules of chemistry – just because we imagine a compound doesn't mean we can synthesise it easily.

Running Fast to Stay in Place

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 use is the sole method to preserve our therapeutic edge. Regrettably, the scale of future breakthroughs is likely to seem miserly compared with the curative bonanza of the previous century.