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During a time as head of the WHO, a former leader famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in addressing the urgent threat of drug-resistant infections, we would struggle to discover new medicines – or conserve the current arsenal – without finding novel approaches of working. This assessment was correct.

A Sluggish and Challenging Development Path

Since 2017, only 16 antibiotics have gained broad official clearance – mostly close relatives of drugs currently available and thus unlikely to overcome resistance for long. The creation of novel compounds is a slow and unprofitable business, given that one-off treatments are not as profitable as ones treating longer-term conditions. The scientific outlook continues to be grim.

A Spark of Hope and a Novel Approach

However, the news this month of two new regulator-approved drugs for gonorrhoea is good news and, crucially, validates a innovative method of incentivising development. One of the new drugs, Zoliflodacin, is the result of a unique type of partnership between a Swiss non‑profit and a drug firm. The public health partnership supplied financial support and organised clinical trials to offset expenses and clear regulatory hurdles. This type of assistance in advance helps steer the industry towards areas of greatest public health necessity.

This model and a separate praised “subscription model” – launched to guarantee income to companies investing in specific antimicrobials – constitute the strongest chance of maintaining a trickle of new drugs from the current framework.

The Unavoidable Challenge of Resistance

But even accelerating the development of compounds currently in development isn't enough. The new drug is at times categorized as a new class of antimicrobial, meaning it attacks a part of the infectious bacteria that existing treatments does, in principle compelling the pathogen to begin anew in evolving a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to it is inevitable.

As has become the norm with new antibiotics, exists consequently an debate about whether it should be held in reserve, rationed to extremely drug-resistant infections only – confining its application to situations where sophisticated diagnostics is accessible. This kind of rational strategy should be the worldwide norm, but frequently cannot be deployed easily in many regions.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the flow of other novel antimicrobials we need could possibly originate. The former official's comment acknowledged the fact that surveying the living 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 advanced past animal trials. Fully lab-created compounds, that are mainly or fully lab-created, are continually in development, but often confront the fundamental rules of molecular science – the fact that we envision a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Prudent, globally managed use is the sole method to preserve our therapeutic edge. Sadly, the scale of future breakthroughs is going to seem miserly compared with the therapeutic revolution of the previous century.