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During her time as director general of the World Health Organization, a past official famously stated that all of the “simple” antimicrobials had long since been discovered. The argument was that in addressing the pressing danger of antibiotic-resistant infections, we would struggle to discover new treatments – or preserve the existing ones – without developing novel approaches of working. This assessment was accurate.

A Slow and Unprofitable Pipeline

Since the late 2010s, only sixteen antibiotics have received widespread regulatory approval – primarily similar derivatives of medicines already in use and thus unlikely to overcome bacterial resistance for long. The development of new ones is a lengthy and financially unattractive endeavor, given that curative treatments are less lucrative as those managing longer-term conditions. The overall prospect remains grim.

A Spark of Hope and a Novel Approach

However, the news this month of a pair of novel FDA-approved antibiotics against gonorrhea is good news and, crucially, validates a new way of incentivising development. A particular of the recently approved medications, Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a drug firm. The public health partnership supplied funding and organised testing phases to offset expenses and navigate approval processes. This sort of support upfront helps direct the industry towards fields of most pressing global need.

This approach and a separate lauded “subscription model” – launched to ensure revenue to firms investing in specific antimicrobials – constitute the strongest chance of sustaining a dripfeed of novel treatments from the existing framework.

The Unavoidable Challenge of Resistance

But even hurrying the development of drugs currently in development is not enough. Zoliflodacin is sometimes categorized as a new class of antibiotic, meaning it attacks a part of the infectious bacteria that no other drug does, theoretically compelling the bacterium to start from zero in developing a countermeasure 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 it is certain.

As has grown customary with recent antimicrobials, exists therefore an argument about whether it should be held in reserve, rationed to highly resistant infections only – confining its application to settings where sophisticated diagnostics is available. This kind of prudent approach should be the worldwide norm, but frequently cannot be implemented easily in many regions.

A Dwindling Stream of Innovation

On a wider scale, it is hard to see where the stream of additional new antibiotics we require could possibly come from. The former official's comment nodded to the fact that searching the living world for natural sources – as with penicillin – has had declining success. The application of artificial intelligence has been mooted to accelerate the search, although a much-celebrated early candidate identified in 2020 has not yet advanced past preclinical studies. Synthetic drugs, that are largely or entirely synthesized, are continually in development, but often run up against the iron laws of chemistry – just because we envision a compound does not guarantee we can synthesise it without great difficulty.

Running Fast to Stand Still

The dominant expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the current position. Prudent, globally managed use is the only way to maintain our therapeutic edge. Sadly, the magnitude of forthcoming discoveries is likely to seem meager compared with the curative bonanza of the 20th century.