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During her tenure as head of the World Health Organization, a former leader famously stated that all of the “simple” antimicrobials had long since been discovered. The point was that in tackling the urgent danger of antibiotic-resistant bacterial infections, we would face difficulties to discover new treatments – or preserve the current arsenal – without developing new ways of operating. This view was correct.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only sixteen antibiotics have received broad regulatory approval – mostly close relatives of drugs currently available and thus not expected to evade bacterial resistance for an extended period. 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 grim.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel FDA-approved antibiotics against gonorrhoea is a welcome development and, crucially, confirms a innovative method of incentivising research. A particular of the recently approved medications, Zoliflodacin, is the product of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided financial support and managed testing phases to offset costs and navigate regulatory hurdles. This type of support in advance helps steer the sector towards fields of greatest global need.

This model and another praised revenue guarantee scheme – launched to guarantee revenue to companies that invest in specific antimicrobials – constitute the best hope of sustaining a trickle of novel treatments from the current framework.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of compounds currently in development is not enough. Zoliflodacin is sometimes described as a novel type of antimicrobial, indicating it targets a part of the infectious bacteria that no other drug does, in principle compelling the bacterium to start from zero in developing a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but caution that future resistance to this compound is inevitable.

As has grown customary with new antibiotics, there is therefore an argument about whether it should be stockpiled, restricted to extremely drug-resistant infections only – limiting its use to settings where sophisticated diagnostics is available. This sort of rational strategy should be the global standard, but often cannot be deployed easily in many parts of the world.

A Dwindling Stream of Innovation

More broadly, it is hard to see where the stream of additional novel antimicrobials we need could realistically originate. The former official's comment acknowledged the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. The application of AI has been proposed to accelerate the discovery process, although a much-celebrated initial discovery identified in 2020 hasn't yet progressed past preclinical studies. Fully lab-created compounds, that are mainly or fully synthesized, are constantly in development, but often run up against the fundamental rules of chemistry – just because we imagine a compound doesn't mean we can create it without great difficulty.

Moving Quickly to Stand Still

The prevailing scientific evaluation is that when it comes to antibiotics, we must move with great speed truly just to remain in the same place. Prudent, globally managed use is the only way to maintain our therapeutic edge. Sadly, the scale of forthcoming discoveries is going to seem miserly compared with the curative bonanza of the 20th century.