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During her 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 tackling the urgent threat of antibiotic-resistant bacterial infections, we would face difficulties to discover new medicines – or conserve the existing ones – without finding novel approaches of operating. This assessment proved accurate.

A Sluggish and Unprofitable Development Path

Since 2017, only sixteen antibiotics have gained widespread regulatory approval – mostly close relatives of drugs currently available and thus unlikely to overcome resistance for long. The development of novel compounds is a slow and financially unattractive business, given that curative medicines are less lucrative as ones managing longer-term ailments. The scientific outlook remains grim.

A Spark of Optimism and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs for gonorrhea is a welcome development and, crucially, validates a innovative method of encouraging development. A particular of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of partnership between a global health organization and a drug firm. The non-profit supplied financial support and organised clinical trials to defray costs and navigate approval processes. This type of assistance upfront helps steer the industry towards areas of most pressing global need.

This approach and another praised revenue guarantee scheme – initiated to ensure income to firms investing in specific antibiotics – constitute the strongest chance of sustaining a trickle of novel treatments from the existing system.

The Inevitable Challenge of Drug Resistance

But even hurrying the production of compounds currently in development isn't enough. The new drug is sometimes categorized as a new class of antimicrobial, indicating it attacks a component of the infectious bacteria that existing treatments does, in principle forcing the pathogen to start from zero in developing a countermeasure to it. Researchers and physicians are relieved to have a new option for gonorrhea – which has strains resistant to all existing treatments – but caution that future resistance to it is certain.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, rationed to highly resistant cases only – limiting its use to situations where sophisticated diagnostics is available. This sort of rational strategy should be the worldwide norm, but often can't be deployed easily in many parts of the world.

A Dwindling Pipeline of Discovery

More broadly, it is hard to see where the stream of additional novel antimicrobials we require could realistically originate. The aforementioned comment nodded to the fact that surveying the natural world for natural sources – as with the first antibiotic – has had diminishing returns. The application of AI has been proposed to accelerate the search, although a highly-touted early candidate found in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are continually in research, but often run up against the iron laws of chemistry – the fact that we envision a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to stay in the current position. Prudent, globally managed deployment is the sole method to maintain our therapeutic edge. Sadly, the magnitude of forthcoming breakthroughs is likely to seem meager in contrast to the therapeutic revolution of the 20th century.