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During her tenure as head of the WHO, a past official famously remarked that all of the “simple” antibiotics had already been found. The argument was that in addressing the pressing threat of drug-resistant bacterial infections, we would face difficulties to find new medicines – or preserve the current arsenal – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Development Path

Since the late 2010s, only sixteen antimicrobial agents have received widespread regulatory approval – mostly similar derivatives of medicines already in use and thus unlikely to evade bacterial resistance for long. The creation of novel compounds is a slow and unprofitable business, given that one-off treatments are less lucrative as ones treating chronic ailments. The overall prospect remains grim.

A Spark of Hope and a Novel Approach

Nevertheless, the news this month of a pair of novel regulator-approved drugs for gonorrhoea is a welcome development and, importantly, confirms a new way of incentivising research. A particular of the recently approved medications, Zoliflodacin, is the result of a novel kind of partnership between a Swiss non‑profit and a drug firm. The non-profit supplied financial support and organised testing phases to offset expenses and navigate regulatory hurdles. This type of assistance in advance helps steer the industry towards fields of greatest global need.

This approach and a separate praised “subscription model” – launched to guarantee revenue to firms investing in certain antibiotics – represent the strongest chance of sustaining a trickle of new drugs from the current system.

The Inevitable Problem of Drug Resistance

But even accelerating the development of compounds currently in development is not enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, indicating it targets a part of the infectious bacteria that existing treatments does, theoretically compelling the bacterium to begin anew in evolving a countermeasure to it. Scientists and doctors are relieved to have a new option for gonorrhea – which has strains resistant 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 argument about whether it should be stockpiled, restricted to highly resistant infections only – limiting its use to situations where sophisticated diagnostics is available. This sort of prudent strategy should be the worldwide norm, but often cannot be implemented easily in many parts of the world.

A Dwindling Pipeline of Innovation

More broadly, it is difficult to see where the stream of other novel antimicrobials we need could realistically originate. The former official's statement nodded to the fact that searching the natural world for natural sources – as with penicillin – has had declining success. Use of artificial intelligence has been mooted to accelerate the discovery process, although a highly-touted initial discovery found in 2020 has not yet progressed past preclinical studies. Synthetic drugs, that are mainly or fully lab-created, are constantly in development, but often confront the fundamental rules of molecular science – the fact that we envision a compound doesn't mean we can synthesise it easily.

Moving Quickly to Stand Still

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Prudent, globally managed deployment is the sole method to preserve our therapeutic edge. Sadly, the magnitude of forthcoming breakthroughs is going to seem miserly in contrast to the therapeutic revolution of the previous century.