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During a tenure as director general of the WHO, a former leader famously remarked that all of the “easy” antibiotics had long since been discovered. The point was that in addressing the urgent danger of antibiotic-resistant infections, we would face difficulties to find new medicines – or preserve the current arsenal – without developing novel approaches of operating. This assessment was accurate.

A Slow and Unprofitable Pipeline

Since the late 2010s, only 16 antibiotics have received broad regulatory approval – primarily close relatives of drugs already in use and thus unlikely to overcome resistance for long. The creation of new ones is a lengthy and financially unattractive business, given that curative treatments are not as profitable as ones treating longer-term conditions. The scientific outlook remains bleak.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel FDA-approved drugs for gonorrhea is a welcome development and, crucially, validates a new way of encouraging research. A particular of the recently approved medications, 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 expenses and navigate regulatory hurdles. This sort of assistance upfront helps direct the sector towards fields of greatest public health necessity.

This approach and another praised revenue guarantee scheme – initiated to guarantee income to firms that invest in specific antimicrobials – constitute the best hope of sustaining a dripfeed of new drugs from the current system.

The Unavoidable Challenge of Resistance

But even accelerating the development of drugs in the pipeline is not enough. Zoliflodacin is sometimes described as a novel type of antibiotic, indicating it attacks a component of the infectious bacteria that existing treatments does, in principle forcing the bacterium to start from zero in evolving a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that future resistance to it is inevitable.

As has become the norm with new antibiotics, there is therefore an argument about whether it should be stockpiled, restricted to extremely drug-resistant infections only – confining its use to situations where sophisticated diagnostics is available. This kind of rational approach should be the global standard, but often can't be implemented readily in many regions.

A Dwindling Pipeline of Discovery

On a wider scale, it is hard to see where the flow of other new antibiotics we need could realistically come from. The former official's statement acknowledged the fact that searching the living world for biological compounds – as with the first antibiotic – has had declining success. Use of AI has been proposed to speed up the search, although a much-celebrated initial discovery identified in recent years hasn't yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully lab-created, are continually in development, but often run up against the fundamental rules of chemistry – the fact that we envision a compound doesn't mean we can synthesise it without great difficulty.

Moving Quickly to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to remain in the current position. Prudent, internationally coordinated use is the only way to preserve our therapeutic edge. Sadly, the magnitude of future discoveries is likely to seem miserly in contrast to the therapeutic revolution of the 20th century.