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During her tenure as head of the WHO, a former leader famously stated that all of the “simple” antimicrobials had long since been discovered. The point was that in addressing the pressing danger of drug-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 accurate.

A Slow and Unprofitable Pipeline

Since 2017, only 16 antibiotics have gained widespread regulatory approval – primarily similar derivatives of medicines currently available 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 not as profitable as those treating longer-term conditions. The scientific outlook remains bleak.

A Spark of Hope and a Novel Approach

Nevertheless, the news this month of two new regulator-approved drugs for gonorrhea is a welcome development and, importantly, confirms a new way of incentivising development. One of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership supplied financial support and managed testing phases to defray costs and clear regulatory hurdles. This type of support upfront helps direct the industry towards areas of greatest public health necessity.

This approach and another praised revenue guarantee scheme – initiated to guarantee income to firms investing in certain antibiotics – constitute the best hope of maintaining a dripfeed of new drugs from the existing system.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of drugs currently in development is not enough. The new drug is sometimes described as a novel type of antimicrobial, meaning it targets a component of the pathogen that existing treatments does, in principle forcing the pathogen to begin anew in developing a defense to it. Scientists and physicians are grateful to have a new option for gonorrhea – which has strains resistant to every known antibiotic – but warn that eventual drug resistance to it is inevitable.

As has become the norm with new antibiotics, there is therefore an debate about whether it should be held in reserve, rationed to extremely drug-resistant cases only – limiting its use to settings where sophisticated diagnostics is available. This kind of rational strategy should be the global standard, but often cannot be deployed easily in many parts of the world.

A Dwindling Pipeline of Innovation

On a wider scale, it is hard to see where the flow of additional new antibiotics we need could realistically originate. The former official's statement acknowledged the fact that searching the living world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been mooted to speed up the search, although a much-celebrated early candidate identified in recent years has not yet progressed past preclinical studies. Synthetic drugs, that are largely or entirely synthesized, are constantly in research, but often run up against the iron laws of molecular science – the fact that we envision a compound does not guarantee we can create it without great difficulty.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must run very fast indeed just to stay in the same place. Careful, globally managed deployment is the only way to preserve our therapeutic edge. Regrettably, the scale of forthcoming discoveries is going to seem miserly compared with the curative bonanza of the 20th century.