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During her time as head of the World Health Organization, a former leader famously remarked that all of the “simple” antimicrobials had long since been discovered. The point was that in tackling the pressing threat of antibiotic-resistant infections, we would struggle to discover new treatments – or preserve the existing ones – without developing novel approaches of operating. This view proved accurate.

A Slow and Challenging Pipeline

Since 2017, only 16 antibiotics have received widespread regulatory approval – mostly close relatives of medicines currently available and thus unlikely to overcome resistance for long. The creation of new ones is a lengthy and unprofitable endeavor, given that curative medicines are not as profitable as those treating chronic conditions. The overall prospect remains grim.

A Spark of Optimism and a Novel Approach

However, the recent announcement of a pair of novel FDA-approved drugs against gonorrhea is good news and, importantly, confirms a new way of encouraging research. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and managed clinical trials to offset expenses and clear regulatory hurdles. This sort of support in advance helps steer the sector towards areas of most pressing global need.

This model and a separate praised “subscription model” – initiated to guarantee revenue to companies investing in specific antibiotics – constitute the strongest chance of sustaining a dripfeed of novel treatments from the current framework.

The Inevitable Challenge of Drug Resistance

But even hurrying the development of compounds in the pipeline isn't enough. Zoliflodacin is sometimes categorized as a new class of antibiotic, indicating it targets a component of the pathogen that no other drug does, in principle compelling the bacterium to begin anew in evolving a defense to it. Researchers and doctors are relieved to have a new option for gonorrhea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to it is certain.

As has become the norm with recent antimicrobials, there is therefore an argument about whether it should be held in reserve, restricted to highly resistant infections only – confining its application to settings where sophisticated diagnostics is accessible. This kind of prudent strategy should be the global standard, but often cannot be implemented readily in many regions.

A Dwindling Pipeline of Discovery

More broadly, it is difficult to see where the stream of other new antibiotics we require could possibly come from. The aforementioned statement acknowledged the fact that surveying the natural world for biological compounds – as with penicillin – has had declining success. The application of artificial intelligence has been mooted to speed up the search, although a much-celebrated initial discovery identified in 2020 hasn't yet advanced past animal trials. Synthetic drugs, that are largely or entirely synthesized, are continually in development, but often confront the fundamental rules of chemistry – just because we imagine a molecule does not guarantee we can synthesise it easily.

Running Fast to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to stay in the current position. Careful, internationally coordinated use is the only way to maintain our advantage. Regrettably, the scale of future discoveries is going to seem miserly compared with the curative bonanza of the 20th century.