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During her time as director general of the WHO, a former leader famously stated that all of the “easy” antibiotics had already been found. The argument was that in tackling the urgent danger of drug-resistant infections, we would face difficulties to find new medicines – or conserve the existing ones – without finding new ways of working. This view proved accurate.

A Sluggish and Unprofitable Development Path

Since 2017, only sixteen antimicrobial agents have received broad official clearance – mostly close relatives of medicines already in use and thus unlikely to overcome bacterial resistance for long. The development of new ones is a slow and financially unattractive business, given that one-off medicines are not as profitable as ones treating chronic ailments. The overall prospect remains bleak.

A Glimmer of Hope and a New Model

Nevertheless, the news this month of two new FDA-approved antibiotics against gonorrhea is good news and, crucially, confirms a new way of encouraging research. A particular of the recently approved medications, Zoliflodacin, is the result of a unique type of partnership between a global health organization and a pharmaceutical company. The public health partnership provided funding and managed clinical trials to defray costs and navigate regulatory hurdles. This type of assistance in advance helps direct the industry towards fields of most pressing global need.

This model and a separate lauded “subscription model” – initiated to ensure revenue to companies that invest in specific antibiotics – represent the strongest chance of maintaining a dripfeed of novel treatments from the current framework.

The Inevitable Challenge of Drug Resistance

But even hurrying the production of drugs currently in development is not enough. The new drug is at times described as a novel type of antimicrobial, indicating it targets a component of the infectious bacteria that no other drug does, theoretically compelling the bacterium to start from zero in evolving a defense to it. Researchers and physicians are grateful to have a new drug for gonorrhoea – which has strains resistant to every known antibiotic – but caution that future resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is therefore an debate about whether it should be held in reserve, rationed to highly resistant cases only – confining its use to settings where high‑end lab testing is available. This kind of prudent strategy should be the worldwide norm, but often can't be deployed easily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is hard to see where the flow of additional new antibiotics we need could possibly originate. The former official's comment acknowledged the fact that searching the natural world for natural sources – as with the first antibiotic – has had declining success. Use of AI has been proposed to accelerate the discovery process, although a highly-touted early candidate found in recent years has not yet progressed past preclinical studies. Fully lab-created compounds, that are mainly or fully lab-created, are constantly in research, but often confront the fundamental rules of chemistry – the fact that we envision a molecule does not guarantee we can create it easily.

Running Fast to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to stay in the same place. Prudent, globally managed use is the sole method to maintain our advantage. Sadly, the scale of future breakthroughs is going to seem meager compared with the therapeutic revolution of the 20th century.