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During a tenure as head of the World Health Organization, a past official famously stated that all of the “simple” antibiotics had already been found. The point was that in addressing the pressing threat of drug-resistant bacterial infections, we would struggle to discover new medicines – or conserve the existing ones – without developing new ways of working. This view proved accurate.

A Sluggish and Unprofitable Pipeline

Since 2017, only 16 antibiotics have received widespread official clearance – mostly close relatives of drugs already in use and thus not expected to evade resistance for an extended period. The development of novel compounds is a slow and financially unattractive business, given that curative treatments are less lucrative as ones managing chronic ailments. The overall prospect continues to be bleak.

A Glimmer of Hope and a New Model

Nevertheless, the recent announcement of two new regulator-approved drugs for gonorrhea is a welcome development and, importantly, validates a new way of incentivising development. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and organised testing phases to defray costs and navigate regulatory hurdles. This sort of support upfront helps direct the industry towards fields of most pressing public health necessity.

This model and a separate praised “subscription model” – initiated to guarantee income to firms that invest in certain antimicrobials – represent the strongest chance of maintaining a dripfeed of novel treatments from the current system.

The Unavoidable Problem of Resistance

But even hurrying the production of drugs currently in development is not enough. Zoliflodacin is at times categorized as a novel type of antibiotic, meaning it targets a part of the infectious bacteria that no other drug does, theoretically compelling the bacterium to begin anew in evolving a countermeasure to it. Scientists and physicians are grateful to have a new option for gonorrhea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to it is inevitable.

As has grown customary with recent antimicrobials, exists therefore an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its application to situations where sophisticated diagnostics is accessible. This kind of rational strategy should be the global standard, but often can't be deployed readily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the flow of other novel antimicrobials we require could possibly originate. The former official's statement 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 proposed to speed up the discovery process, 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 lab-created, 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 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 truly just to remain in the current position. Careful, globally managed use is the sole method to maintain our therapeutic edge. Regrettably, the magnitude of future discoveries is going to seem meager compared with the curative bonanza of the previous century.