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During her time as director general of the World Health Organization, a former leader famously stated that all of the “simple” antibiotics had long since been discovered. The argument was that in tackling the pressing threat of antibiotic-resistant infections, we would struggle to find new treatments – or preserve the existing ones – without finding novel approaches of operating. This view was correct.

A Sluggish and Challenging Pipeline

Since the late 2010s, just sixteen antibiotics have gained broad official clearance – primarily similar derivatives of drugs currently available and thus not expected to evade resistance for an extended period. The development of new ones is a lengthy and financially unattractive endeavor, given that one-off treatments are less lucrative as ones managing chronic conditions. The scientific outlook continues to be bleak.

A Glimmer of Hope and a New Model

However, the recent announcement of two new FDA-approved antibiotics for gonorrhea is a welcome development and, crucially, validates a innovative method of incentivising research. One of the new drugs, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a drug firm. The public health partnership provided financial support and managed testing phases to offset expenses and navigate approval processes. This sort of assistance in advance helps direct the sector towards areas of greatest public health necessity.

This model and a separate praised revenue guarantee scheme – launched to guarantee income to companies that invest in specific antimicrobials – represent the strongest chance of sustaining a dripfeed of new drugs from the existing system.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of drugs in the pipeline isn't sufficient. Zoliflodacin is sometimes categorized as a new class of antimicrobial, meaning it attacks a component of the pathogen that existing treatments does, in principle forcing the bacterium to begin anew in developing a countermeasure to it. Scientists and doctors are grateful to have a new option for gonorrhoea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to this compound is inevitable.

As has become the norm with new antibiotics, there is therefore an argument about whether it should be held in reserve, rationed to extremely drug-resistant cases only – confining its use to settings where high‑end lab testing is accessible. This kind of prudent strategy should be the global standard, but often cannot be implemented easily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the flow of additional novel antimicrobials we require could possibly originate. The former official's statement acknowledged the fact that searching the natural world for biological compounds – as with the first antibiotic – has had declining success. Use of AI has been proposed to speed up the search, although a much-celebrated initial discovery identified in recent years hasn't yet progressed past animal trials. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often run up against the fundamental rules of chemistry – just because we envision a molecule does not guarantee we can create it easily.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to remain in the same place. Careful, globally managed use is the only way to maintain our advantage. Regrettably, the scale of forthcoming breakthroughs is going to seem miserly in contrast to the therapeutic revolution of the 20th century.