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During a tenure as director general of the World Health Organization, a former leader famously remarked that all of the “simple” antibiotics had long since been discovered. The argument was that in tackling the pressing danger of antibiotic-resistant infections, we would struggle to discover new treatments – or preserve the existing ones – without developing new ways of operating. This assessment proved accurate.

A Slow and Challenging Pipeline

Since 2017, just sixteen antibiotics have gained widespread official clearance – mostly similar derivatives of drugs already in use and thus not expected to overcome bacterial resistance for an extended period. The development of new ones is a slow and unprofitable endeavor, given that one-off treatments are less lucrative as those treating longer-term conditions. The overall prospect continues to be bleak.

A Glimmer of Hope and a New Model

However, the recent announcement of two new FDA-approved drugs against gonorrhoea is good news and, crucially, validates a new way of incentivising development. A particular of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided financial support and organised testing phases to offset costs and navigate approval processes. This type of support in advance helps steer the sector towards areas of most pressing global need.

This approach and a separate praised “subscription model” – initiated to guarantee income to firms investing in certain antimicrobials – constitute the best hope of sustaining a dripfeed of novel treatments from the current system.

The Inevitable Challenge of Drug Resistance

But even accelerating the development of drugs currently in development isn't sufficient. The new drug is at times categorized as a new class of antimicrobial, indicating it attacks a part of the pathogen that existing treatments does, in principle forcing the bacterium to begin anew in evolving a countermeasure to it. Researchers and doctors are grateful to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to it is certain.

As has grown customary with recent antimicrobials, there is therefore an debate about whether it should be stockpiled, rationed to extremely drug-resistant infections only – limiting its application to settings where sophisticated diagnostics is accessible. This sort of prudent approach should be the global standard, but frequently can't be deployed readily in many regions.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the flow of additional novel antimicrobials we need could possibly come from. The former official's comment acknowledged the fact that searching the living world for biological compounds – as with penicillin – has had diminishing returns. The application of AI has been mooted to accelerate the search, although a highly-touted initial discovery identified in recent years has not yet advanced past animal trials. Synthetic drugs, which are largely or entirely synthesized, are constantly in development, but often confront the fundamental rules of chemistry – the fact that we envision a molecule does not guarantee we can synthesise it easily.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to stay in the same place. Careful, internationally coordinated use is the only way to maintain our advantage. Sadly, the magnitude of forthcoming breakthroughs is likely to seem meager in contrast to the curative bonanza of the previous century.