🔗 Share this article

During her tenure as director general of the WHO, a past official famously stated that all of the “simple” antimicrobials had already been found. The argument was that in addressing the urgent threat of antibiotic-resistant infections, we would face difficulties to discover new treatments – or preserve the existing ones – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Pipeline

Since 2017, only 16 antibiotics have received broad official clearance – primarily close relatives of drugs already in use and thus unlikely to evade bacterial resistance for long. The development of novel compounds is a slow and unprofitable endeavor, given that curative medicines are less lucrative as those treating chronic ailments. The scientific outlook continues to be grim.

A Spark of Optimism and a Novel Approach

However, the news this month of two new regulator-approved drugs for gonorrhea is good news and, crucially, validates a innovative method of encouraging research. A particular of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of partnership between a Swiss non‑profit and a drug firm. The public health partnership supplied funding and managed testing phases to offset expenses and navigate approval processes. This sort of assistance upfront helps direct the sector towards fields of most pressing public health necessity.

This approach and a separate praised revenue guarantee scheme – launched to ensure revenue to firms investing in specific antimicrobials – represent the best hope of sustaining a dripfeed of new drugs from the existing framework.

The Inevitable Challenge of Resistance

But even accelerating the development of drugs currently in development isn't enough. The new drug is at times described as a novel type of antimicrobial, meaning it attacks a component of the infectious bacteria 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 resistant strains to every known antibiotic – but warn that future resistance to it is certain.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be held in reserve, restricted to extremely drug-resistant cases only – limiting its application to settings where sophisticated diagnostics is available. This sort of prudent approach should be the global standard, but frequently cannot be deployed readily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is hard to see where the stream of other novel antimicrobials we need could possibly come from. The former official's comment acknowledged the fact that surveying the living world for natural sources – as with penicillin – has had declining success. The application of AI has been mooted to speed up the discovery process, although a much-celebrated early candidate identified in 2020 hasn't yet progressed past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are constantly in research, but often run up against the fundamental rules of chemistry – just because we envision a compound does not guarantee we can create it without great difficulty.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antibiotics, we must run very fast indeed just to stay in the same place. Prudent, globally managed deployment is the only way to maintain our therapeutic edge. Sadly, the scale of future discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.