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During her tenure as director general of the WHO, a former leader famously stated that all of the “easy” antibiotics had long since been discovered. The point was that in tackling the urgent threat of antibiotic-resistant infections, we would face difficulties to find new medicines – or conserve the existing ones – without developing new ways of operating. This view proved correct.

A Slow and Unprofitable Development Path

Since the late 2010s, just sixteen antibiotics have received broad official clearance – primarily close relatives of medicines currently available and thus unlikely to overcome resistance for an extended period. The development of new ones is a lengthy and financially unattractive business, given that one-off treatments are not as profitable as ones treating longer-term conditions. The overall prospect remains grim.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of a pair of novel regulator-approved antibiotics against gonorrhea is a welcome development and, importantly, validates a innovative method of encouraging development. A particular of the new drugs, Zoliflodacin, is the result of a novel kind of partnership between a global health organization and a drug firm. The public health partnership supplied financial support and organised testing phases to offset expenses and clear approval processes. This type of assistance in advance helps steer 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 certain antibiotics – constitute the strongest chance of maintaining a dripfeed of novel treatments from the existing framework.

The Inevitable Problem of Resistance

But even accelerating the production of compounds currently in development isn't enough. Zoliflodacin is sometimes described as a new class of antimicrobial, meaning it attacks a part of the infectious bacteria that no other drug does, in principle compelling the pathogen to start from zero in evolving a countermeasure to it. Researchers and doctors 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 new antibiotics, there is consequently an argument about whether it should be stockpiled, restricted to extremely drug-resistant cases only – confining its use to situations where sophisticated diagnostics is accessible. This kind of prudent approach should be the worldwide norm, but frequently can't be implemented easily in many regions.

A Dwindling Stream of Discovery

On a wider scale, it is hard to see where the stream of other new antibiotics we need could realistically come from. The former official's statement acknowledged the fact that searching the living world for natural sources – as with penicillin – has had diminishing returns. Use of artificial intelligence has been mooted to accelerate the search, although a much-celebrated early candidate found in 2020 has not yet progressed past preclinical studies. Fully lab-created compounds, that are mainly or fully synthesized, are continually in development, but often confront the iron laws of molecular science – the fact that we envision a molecule doesn't mean we can synthesise it without great difficulty.

Running Fast to Stay in Place

The dominant scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the current position. Careful, globally managed deployment is the only way to maintain our advantage. Regrettably, the scale of future discoveries is going to seem meager in contrast to the therapeutic revolution of the 20th century.