🔗 Share this article

During a tenure as director general of the World Health Organization, a former leader famously stated that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the urgent danger of drug-resistant bacterial infections, we would struggle to discover new medicines – or preserve the existing ones – without finding new ways of operating. This assessment proved accurate.

A Sluggish and Challenging Development Path

Since 2017, just 16 antibiotics have gained broad official clearance – primarily similar derivatives of medicines already in use and thus unlikely to evade bacterial resistance for long. The development of new ones is a slow and financially unattractive business, given that curative treatments are not as profitable as those managing chronic ailments. The scientific outlook remains grim.

A Spark of Hope and a Novel Approach

Nevertheless, the recent announcement of a pair of novel FDA-approved drugs against gonorrhea is a welcome development and, crucially, confirms a innovative method of incentivising research. One 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 supplied financial support and managed clinical trials to defray costs and clear regulatory hurdles. This type of assistance upfront helps steer the sector towards areas of most pressing public health necessity.

This model and a separate praised “subscription model” – launched to guarantee revenue to firms that invest in certain antibiotics – represent the strongest chance of maintaining a dripfeed of novel treatments from the current system.

The Unavoidable Challenge of Resistance

But even accelerating the production of compounds currently in development is not enough. The new drug is at times categorized as a new class of antibiotic, meaning it targets a part of the pathogen that existing treatments does, theoretically forcing the bacterium to begin anew in evolving a countermeasure to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has strains resistant to every known antibiotic – but caution that eventual drug resistance to it is certain.

As has become the norm with new antibiotics, there is therefore an argument about whether it should be held in reserve, rationed to highly resistant cases only – confining its use to settings where sophisticated diagnostics is accessible. This kind of prudent approach should be the worldwide norm, but frequently cannot be deployed readily in many regions.

A Dwindling Stream of Discovery

More broadly, it is hard to see where the flow of additional new antibiotics we require could possibly come from. The former official's comment acknowledged the fact that searching the natural world for natural sources – as with the first antibiotic – has had declining success. The application of artificial intelligence has been proposed to speed up the search, although a much-celebrated early candidate identified in 2020 hasn't yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely synthesized, are continually in development, but often confront the iron laws of molecular science – just because we envision a compound does not guarantee we can synthesise it without great difficulty.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must run very fast indeed just to remain in the same place. Careful, globally managed use is the sole method to maintain our therapeutic edge. Sadly, the scale of forthcoming breakthroughs is going to seem meager compared with the therapeutic revolution of the 20th century.