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During a time as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had long since been discovered. The argument was that in addressing the urgent threat of drug-resistant infections, we would struggle to find new treatments – or conserve the existing ones – without developing new ways of operating. This view was accurate.

A Sluggish and Challenging Pipeline

Since 2017, just sixteen antimicrobial agents have received widespread regulatory approval – mostly close relatives of medicines currently available and thus unlikely to evade resistance for long. The development of new ones is a lengthy and unprofitable business, given that curative treatments are less lucrative as ones managing longer-term conditions. The overall prospect remains bleak.

A Spark of Optimism and a New Model

Nevertheless, the news this month of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, crucially, 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 partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided funding and managed clinical trials to offset costs and clear approval processes. This sort of assistance in advance helps direct the industry towards areas of greatest public health necessity.

This approach and a separate lauded revenue guarantee scheme – initiated to ensure revenue to firms that invest in specific antibiotics – represent the best hope of sustaining a dripfeed of new drugs from the current system.

The Unavoidable Problem of Resistance

But even hurrying the development of drugs currently in development is not sufficient. Zoliflodacin is sometimes categorized as a new class of antibiotic, indicating it attacks a component of the infectious bacteria that existing treatments does, theoretically forcing the bacterium to start from zero in evolving a defense to it. Researchers and doctors are relieved to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, restricted to highly resistant infections only – confining its application to situations where sophisticated diagnostics is available. This sort of rational approach should be the worldwide norm, but often cannot be deployed easily in many regions.

A Dwindling Pipeline of Discovery

On a wider scale, it is difficult to see where the flow of other new antibiotics we need could realistically come from. The aforementioned statement acknowledged the fact that surveying the living world for natural sources – as with penicillin – has had diminishing returns. The application of artificial intelligence has been mooted to accelerate the discovery process, although a much-celebrated initial discovery identified in recent years hasn't yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are continually in development, but often confront the fundamental rules of chemistry – just because we imagine a molecule does not guarantee we can create it without great difficulty.

Running Fast to Stand Still

The prevailing expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the same place. Prudent, internationally coordinated use is the sole method to maintain our advantage. Regrettably, the magnitude of future discoveries is going to seem miserly compared with the curative bonanza of the 20th century.