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During a time as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had already been found. The point was that in tackling the urgent danger of antibiotic-resistant bacterial infections, we would face difficulties to discover new medicines – or conserve the existing ones – without developing new ways of operating. This assessment proved correct.

A Slow and Unprofitable Development Path

Since the late 2010s, only sixteen antimicrobial agents have received broad official clearance – mostly close relatives of medicines already in use and thus unlikely to evade resistance for an extended period. The creation of novel compounds is a slow and unprofitable business, given that one-off medicines are less lucrative as ones managing longer-term ailments. The overall prospect continues to be bleak.

A Spark of Hope and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs for gonorrhoea is a welcome development and, crucially, confirms a new way of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the product of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and managed clinical trials to defray expenses and clear approval processes. This sort of support upfront helps steer the sector towards fields of most pressing public health necessity.

This approach and a separate lauded revenue guarantee scheme – initiated to guarantee revenue to firms that invest in certain antimicrobials – represent the best hope of maintaining a dripfeed of new drugs from the current framework.

The Inevitable Challenge of Drug Resistance

But even accelerating the production of drugs in the pipeline isn't enough. The new drug is sometimes categorized as a novel type of antimicrobial, indicating it attacks a part of the infectious bacteria that existing treatments does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Scientists and doctors are grateful to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but caution that future resistance to this compound is inevitable.

As has become the norm with recent antimicrobials, exists therefore an argument about whether it should be stockpiled, rationed to highly resistant cases only – limiting its use to settings where sophisticated diagnostics is available. This sort of rational approach should be the global standard, but often cannot be implemented easily in many parts of the world.

A Diminishing Pipeline of Discovery

On a wider scale, it is difficult to see where the stream of other new antibiotics we need could realistically originate. The aforementioned statement acknowledged the fact that searching the living world for biological compounds – as with the first antibiotic – has had diminishing returns. Use of AI has been mooted to accelerate the search, although a much-celebrated early candidate identified in 2020 hasn't yet advanced past preclinical studies. Fully lab-created compounds, that are mainly or fully lab-created, are continually in development, but often run up against the fundamental rules of chemistry – just because we envision a compound doesn't mean we can create it without great difficulty.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed truly just to stay in the current position. Careful, internationally coordinated use is the only way to preserve our advantage. Sadly, the magnitude of forthcoming breakthroughs is likely to seem miserly compared with the curative bonanza of the 20th century.