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During her tenure as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had long since been discovered. The argument was that in tackling the urgent danger of antibiotic-resistant bacterial infections, we would struggle to find new medicines – or preserve the current arsenal – without developing novel approaches of operating. This view was accurate.

A Sluggish and Unprofitable Pipeline

Since 2017, just sixteen antibiotics have gained widespread regulatory approval – mostly close relatives of drugs already in use and thus unlikely to evade resistance for long. The creation of novel compounds is a slow and financially unattractive business, given that one-off medicines are not as profitable as those managing longer-term conditions. The scientific outlook continues to be grim.

A Spark of Hope and a Novel Approach

However, the recent announcement of two new FDA-approved antibiotics for gonorrhea is good news and, crucially, confirms a new way of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit provided funding and organised testing phases to offset costs and navigate regulatory hurdles. This sort of support in advance helps direct the industry towards areas of greatest global need.

This model and another lauded “subscription model” – launched to guarantee income to companies that invest in specific antimicrobials – constitute the strongest chance of maintaining a dripfeed of novel treatments from the existing system.

The Unavoidable Problem of Drug Resistance

But even hurrying the production of compounds currently in development isn't sufficient. Zoliflodacin is sometimes categorized as a new class of antimicrobial, meaning it attacks a part of the pathogen that no other drug does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Scientists and physicians are grateful to have a new option for gonorrhoea – which has resistant strains to every known antibiotic – but caution that eventual drug resistance to it is inevitable.

As has grown customary with recent antimicrobials, there is consequently an argument about whether it should be stockpiled, rationed to highly resistant cases only – confining its application to situations where high‑end lab testing is accessible. This sort of rational strategy should be the worldwide norm, but often can't be implemented easily in many regions.

A Dwindling Pipeline of Discovery

On a wider scale, it is difficult to see where the stream of other novel antimicrobials we require could realistically originate. The former official's comment nodded to the fact that surveying the living world for natural sources – as with penicillin – has had declining success. The application of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery found in recent years hasn't yet progressed past animal trials. Synthetic drugs, which are largely or entirely synthesized, are constantly in development, but often run up against the fundamental rules of molecular science – just because we envision a molecule doesn't mean we can create it easily.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to remain in the current position. Careful, internationally coordinated use is the only way to maintain our therapeutic edge. Sadly, the scale of forthcoming breakthroughs is likely to seem miserly compared with the therapeutic revolution of the 20th century.