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During a tenure as director general of the World Health Organization, a past official famously remarked that all of the “easy” antibiotics had already been found. The argument was that in tackling the urgent threat of antibiotic-resistant infections, we would face difficulties to discover new treatments – or preserve the current arsenal – without developing new ways of working. This assessment was correct.

A Slow and Challenging Pipeline

Since 2017, just sixteen antibiotics have gained widespread official clearance – primarily similar derivatives of drugs currently available and thus not expected to evade bacterial resistance for long. The development of new ones is a lengthy and unprofitable business, given that one-off treatments are less lucrative as those managing longer-term ailments. The overall prospect remains bleak.

A Glimmer of Hope and a Novel Approach

However, the news this month of two new FDA-approved antibiotics for gonorrhoea is a welcome development and, importantly, validates a new way of incentivising development. One of the new drugs, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a Swiss non‑profit and a drug firm. The non-profit provided financial support and managed clinical trials to offset expenses and clear approval processes. This type of support in advance helps steer the sector towards areas of greatest public health necessity.

This model and another praised revenue guarantee scheme – initiated to guarantee revenue to companies investing in certain antimicrobials – constitute the best hope of sustaining a trickle of new drugs from the current framework.

The Inevitable Problem of Resistance

But even hurrying the production of compounds in the pipeline isn't sufficient. Zoliflodacin is at times described as a new class of antibiotic, meaning it targets a part of the pathogen that existing treatments does, theoretically compelling the bacterium to start from zero in developing a defense to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to this compound is certain.

As has grown customary with new antibiotics, there is consequently an argument about whether it should be held in reserve, rationed to highly resistant infections only – confining its use to situations where sophisticated diagnostics is accessible. This kind of prudent strategy should be the global standard, but frequently can't be deployed readily in many parts of the world.

A Dwindling Pipeline of Discovery

More broadly, it is hard to see where the flow of other novel antimicrobials we need could possibly originate. The aforementioned statement nodded to the fact that surveying the natural world for natural sources – as with penicillin – has had declining success. Use of AI has been proposed to speed up the discovery process, although a highly-touted initial discovery found in 2020 hasn't yet advanced past preclinical studies. Synthetic drugs, which are mainly or fully lab-created, are continually in development, but often confront the fundamental rules of chemistry – the fact that we envision a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must run very fast truly just to remain in the same place. Careful, globally managed deployment is the only way to maintain our therapeutic edge. Regrettably, the scale of future breakthroughs is going to seem miserly compared with the curative bonanza of the 20th century.