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During a time as director general of the WHO, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the urgent danger of drug-resistant infections, we would face difficulties to discover new treatments – or conserve the existing ones – without finding novel approaches of operating. This view was accurate.

A Slow and Unprofitable Development Path

Since 2017, just sixteen antimicrobial agents have received widespread regulatory approval – mostly similar derivatives of drugs 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 less lucrative as those treating longer-term ailments. The overall prospect remains bleak.

A Spark of Optimism and a New Model

However, the recent announcement of a pair of novel FDA-approved antibiotics against gonorrhoea is good news and, importantly, validates a new way of incentivising research. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied financial support and organised testing phases to defray expenses and navigate regulatory hurdles. This sort of support in advance helps direct the sector towards fields of most pressing public health necessity.

This approach and another lauded “subscription model” – launched to ensure revenue to firms that invest in specific antibiotics – constitute the best hope of maintaining a trickle of new drugs from the existing framework.

The Inevitable Challenge of Drug Resistance

But even accelerating the development of compounds currently in development isn't sufficient. Zoliflodacin is at times described as a new class of antibiotic, meaning it targets a part of the infectious bacteria that no other drug does, theoretically compelling the pathogen to start from zero in evolving a countermeasure to it. Scientists and physicians are relieved to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but caution that future resistance to it is inevitable.

As has become the norm with recent antimicrobials, there is consequently an argument about whether it should be stockpiled, rationed to extremely drug-resistant infections only – confining its use to settings where sophisticated diagnostics is accessible. This sort of rational strategy should be the worldwide norm, but frequently can't be implemented readily in many regions.

A Diminishing Stream of Innovation

On a wider scale, it is hard to see where the flow of additional new antibiotics we require could possibly originate. The aforementioned comment acknowledged the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of AI has been mooted to speed up the search, although a highly-touted initial discovery found in 2020 has not yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully lab-created, are continually in research, but often confront the iron laws of chemistry – just because we envision a molecule does not guarantee we can create it without great difficulty.

Running Fast to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Prudent, internationally coordinated deployment is the only way to maintain our therapeutic edge. Sadly, the scale of future discoveries is likely to seem meager compared with the therapeutic revolution of the 20th century.