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During a tenure as head of the WHO, a past official famously stated that all of the “simple” antimicrobials had long since been discovered. The point was that in tackling the pressing threat of antibiotic-resistant infections, we would struggle to find new medicines – or conserve the current arsenal – without developing novel approaches of working. This assessment proved accurate.

A Sluggish and Challenging Development Path

Since 2017, only 16 antibiotics have received widespread official clearance – primarily close relatives of drugs currently available and thus not expected to evade bacterial resistance for long. The creation of novel compounds is a lengthy and financially unattractive endeavor, given that one-off medicines are less lucrative as those managing longer-term ailments. The overall prospect remains bleak.

A Spark of Hope and a Novel Approach

Nevertheless, the news this month of two new FDA-approved drugs for gonorrhea is a welcome development and, crucially, validates a innovative method of encouraging development. A particular of the new drugs, a compound called Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit provided funding and organised clinical trials to offset expenses and clear regulatory hurdles. This sort of support upfront helps direct the industry towards fields of greatest public health necessity.

This model and a separate praised revenue guarantee scheme – launched to ensure revenue to companies that invest in certain antibiotics – represent the best hope of maintaining a trickle of novel treatments from the current framework.

The Unavoidable Problem of Drug Resistance

But even accelerating the production of compounds currently in development is not enough. Zoliflodacin is at times categorized as a novel type of antibiotic, indicating it targets a component of the infectious bacteria that existing treatments does, in principle forcing the bacterium to begin anew in evolving a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to this compound is certain.

As has become the norm with recent antimicrobials, there is consequently an debate about whether it should be held in reserve, rationed to extremely drug-resistant cases only – limiting its use to situations where high‑end lab testing is available. This sort of prudent approach should be the global standard, but frequently can't be deployed easily in many regions.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the stream of other novel antimicrobials we need could possibly come from. The aforementioned comment acknowledged the fact that searching the natural world for biological compounds – as with penicillin – has had diminishing returns. Use of artificial intelligence has been mooted to speed up the search, although a highly-touted initial discovery found in 2020 has not yet progressed past animal trials. Fully lab-created compounds, which are largely or entirely synthesized, are constantly in research, but often run up against the iron laws of chemistry – the fact that we imagine a compound does not guarantee we can create it without great difficulty.

Running Fast to Stand Still

The prevailing expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to stay in the current position. Prudent, internationally coordinated use is the sole method to preserve our advantage. Regrettably, the magnitude of future discoveries is likely to seem miserly compared with the therapeutic revolution of the 20th century.