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During her tenure as head of the WHO, a past official famously stated that all of the “simple” antibiotics had already been found. The point was that in addressing the urgent threat of drug-resistant infections, we would face difficulties to discover new treatments – or conserve the current arsenal – without developing new ways of working. This view proved accurate.

A Sluggish and Challenging Development Path

Since 2017, only sixteen antibiotics have gained broad official clearance – mostly similar derivatives of medicines already in use and thus not expected to overcome resistance for long. The development of novel compounds is a slow and financially unattractive endeavor, given that curative treatments are not as profitable as ones managing longer-term ailments. The scientific outlook remains bleak.

A Glimmer of Optimism and a New Model

However, the recent announcement of two new regulator-approved drugs against gonorrhea is a welcome development and, crucially, confirms a new way of incentivising development. One of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a drug firm. The public health partnership provided funding and managed testing phases to offset expenses and navigate approval processes. This sort of assistance upfront helps steer the industry towards fields of most pressing global need.

This model and another praised revenue guarantee scheme – initiated to ensure revenue to firms investing in certain antimicrobials – constitute the best hope of maintaining a dripfeed of novel treatments from the current framework.

The Unavoidable Challenge of Drug Resistance

But even accelerating the production of drugs in the pipeline isn't sufficient. Zoliflodacin is sometimes described as a new class of antibiotic, indicating it attacks a component of the pathogen that existing treatments does, in principle forcing the pathogen to begin anew in evolving a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhoea – which has strains resistant to every known antibiotic – but warn that future resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be held in reserve, rationed to highly resistant infections only – limiting its use to settings where sophisticated diagnostics is available. This kind of rational strategy should be the global standard, but often can't be implemented readily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the flow of additional novel antimicrobials we require could possibly originate. The former official's statement acknowledged the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had declining success. The application of artificial intelligence has been proposed to accelerate the discovery process, although a highly-touted early candidate found in 2020 has not yet advanced past animal trials. Synthetic drugs, which are mainly or fully lab-created, are continually in development, but often run up against the fundamental rules of molecular science – just because we imagine a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Prudent, internationally coordinated use is the only way to maintain our advantage. Sadly, the scale of future discoveries is likely to seem miserly compared with the curative bonanza of the previous century.