🔗 Share this article

During her time as director general of the World Health Organization, a past official famously remarked that all of the “simple” antibiotics had already been found. The argument was that in tackling the pressing threat of antibiotic-resistant infections, we would struggle to find new treatments – or preserve the existing ones – without developing new ways of operating. This view was correct.

A Slow and Unprofitable Pipeline

Since the late 2010s, only sixteen antibiotics have gained widespread regulatory approval – primarily similar derivatives of drugs currently available and thus unlikely to overcome bacterial resistance for long. The creation of novel compounds is a slow and financially unattractive endeavor, given that one-off medicines are less lucrative as ones managing chronic conditions. The scientific outlook continues to be bleak.

A Glimmer of Hope and a Novel Approach

Nevertheless, the recent announcement of two new FDA-approved antibiotics against gonorrhoea is good news and, crucially, validates a new way of incentivising development. A particular of the new drugs, Zoliflodacin, is the product of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit provided financial support and managed testing phases to defray costs and navigate regulatory hurdles. This type of assistance upfront helps direct the sector towards fields of greatest public health necessity.

This model and a separate praised “subscription model” – launched to ensure income to companies investing in certain antimicrobials – represent the strongest chance of sustaining a dripfeed of new drugs from the existing framework.

The Inevitable Problem of Resistance

But even hurrying the development of compounds currently in development is not sufficient. Zoliflodacin is at times categorized as a novel type of antimicrobial, meaning it attacks a component of the pathogen that no other drug does, in principle compelling the bacterium to begin anew in developing a defense to it. Researchers and physicians are grateful to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to this compound is inevitable.

As has become the norm with recent antimicrobials, exists consequently an argument about whether it should be stockpiled, rationed to highly resistant cases only – confining its use to settings where sophisticated diagnostics is accessible. This kind of prudent approach should be the global standard, but often cannot be deployed easily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the flow of other new antibiotics we require could possibly come from. The former official's statement acknowledged the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had declining success. Use of AI has been mooted to speed up the discovery process, although a highly-touted initial discovery identified in 2020 has not yet advanced past animal trials. Fully lab-created compounds, that are largely or entirely lab-created, are constantly in development, but often confront the fundamental rules of molecular science – just because we imagine a molecule does not guarantee we can synthesise it without great difficulty.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must run very fast indeed just to stay in the current position. Prudent, internationally coordinated use is the only way to maintain our therapeutic edge. Sadly, the magnitude of forthcoming breakthroughs is likely to seem meager in contrast to the curative bonanza of the 20th century.