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During her time as head of the WHO, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the urgent threat of drug-resistant bacterial infections, we would face difficulties to discover new medicines – or conserve the existing ones – without developing novel approaches of working. This view proved accurate.

A Sluggish and Unprofitable Development Path

Since 2017, just 16 antimicrobial agents have gained broad regulatory approval – primarily close relatives of drugs already in use and thus unlikely to overcome bacterial resistance for long. The development of new ones is a slow and unprofitable endeavor, given that curative medicines are not as profitable as those managing chronic ailments. The overall prospect continues to be grim.

A Glimmer of Hope and a Novel Approach

However, the news this month of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, importantly, confirms a innovative method of incentivising development. A particular of the new drugs, 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 provided financial support and organised testing phases to defray expenses and clear regulatory hurdles. This sort of assistance upfront helps direct the sector towards fields of most pressing global need.

This approach and another praised revenue guarantee scheme – initiated to ensure income to companies that invest in specific antimicrobials – represent the best hope of maintaining a trickle of novel treatments from the existing framework.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of drugs currently in development is not sufficient. Zoliflodacin is sometimes categorized as a new class of antimicrobial, indicating it attacks a component of the pathogen that existing treatments does, in principle compelling the pathogen to begin anew in evolving a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, there is therefore an debate about whether it should be stockpiled, restricted to highly resistant cases only – confining its use to situations where sophisticated diagnostics is available. This sort of prudent strategy should be the worldwide norm, but often cannot be deployed readily in many parts of the world.

A Dwindling Stream of Innovation

On a wider scale, it is hard to see where the flow of additional new antibiotics we require could realistically come from. The aforementioned statement acknowledged the fact that searching the living world for biological compounds – as with penicillin – has had declining success. The application of artificial intelligence has been proposed to accelerate the search, although a much-celebrated initial discovery found in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, which are largely or entirely synthesized, are constantly in development, but often confront the fundamental rules of chemistry – the fact that we imagine a molecule does not guarantee we can create it without great difficulty.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Careful, globally managed deployment is the only way to maintain our advantage. Sadly, the magnitude of forthcoming discoveries is likely to seem meager in contrast to the curative bonanza of the 20th century.