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During a time as director general of the World Health Organization, a former leader famously remarked that all of the “simple” antibiotics had already been found. The point was that in tackling the pressing danger of antibiotic-resistant infections, we would face difficulties to find new treatments – or conserve the existing ones – without finding new ways of operating. This assessment proved correct.

A Sluggish and Challenging Pipeline

Since the late 2010s, only 16 antimicrobial agents have gained broad official clearance – mostly similar derivatives of drugs already in use and thus not expected to evade resistance for long. The development of novel compounds is a slow and unprofitable endeavor, given that curative treatments are not as profitable as ones treating longer-term conditions. The scientific outlook remains grim.

A Glimmer of Optimism and a New Model

However, the news this month of a pair of novel FDA-approved drugs against gonorrhea is good news and, importantly, confirms a new way of incentivising research. 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 pharmaceutical company. The public health partnership supplied funding and managed testing phases to defray costs and clear approval processes. This sort of assistance upfront helps direct the industry towards areas of greatest global need.

This approach and another praised revenue guarantee scheme – launched to guarantee income to firms investing in specific antibiotics – represent the strongest chance of maintaining a dripfeed of new drugs from the current system.

The Inevitable Problem of Resistance

But even hurrying the production of compounds in the pipeline isn't enough. The new drug is at times described as a novel type of antibiotic, indicating it targets a part of the infectious bacteria that existing treatments does, in principle compelling the pathogen to start from zero in developing a defense to it. Scientists and physicians are relieved to have a new option for gonorrhoea – which has resistant strains to every known antibiotic – but caution that eventual drug resistance to it is certain.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be held in reserve, restricted to highly resistant cases only – confining its application to settings where sophisticated diagnostics is accessible. This sort of prudent strategy should be the global standard, but often cannot be deployed readily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the flow of additional novel antimicrobials we need could realistically originate. The aforementioned comment nodded to the fact that searching the living world for biological compounds – as with penicillin – has had diminishing returns. Use of AI has been mooted to accelerate the discovery process, although a much-celebrated initial discovery identified in recent years hasn't yet advanced past animal trials. Synthetic drugs, that are largely or entirely synthesized, are constantly in development, but often run up against the iron laws of molecular science – the fact that we envision a molecule doesn't mean we can synthesise it easily.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antibiotics, we must move with great speed truly just to remain in the current position. Prudent, internationally coordinated use is the sole method to preserve our advantage. Regrettably, the magnitude of future discoveries is likely to seem meager in contrast to the therapeutic revolution of the 20th century.