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During her tenure as director general of the WHO, a past official famously stated that all of the “easy” antibiotics had long since been discovered. The point was that in tackling the pressing danger of antibiotic-resistant infections, we would struggle to discover new medicines – or conserve the current arsenal – without developing new ways of working. This view proved correct.

A Slow and Challenging Development Path

Since the late 2010s, just 16 antimicrobial agents have received widespread regulatory approval – primarily close relatives of medicines already in use and thus unlikely to evade resistance for an extended period. The development of new ones is a lengthy and unprofitable endeavor, given that one-off medicines are less lucrative as ones treating longer-term conditions. The overall prospect remains grim.

A Spark of Hope and a Novel Approach

However, the recent announcement of a pair of novel FDA-approved antibiotics for gonorrhea is good news and, crucially, confirms a new way of incentivising development. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to offset costs and clear approval processes. This type of assistance upfront helps direct the sector towards areas of greatest global need.

This approach and a separate praised revenue guarantee scheme – initiated to ensure income to firms investing in certain antibiotics – represent the best hope of maintaining a dripfeed of novel treatments from the current framework.

The Inevitable Problem of Drug Resistance

But even hurrying the production of drugs in the pipeline is not enough. Zoliflodacin is sometimes described as a novel type of antimicrobial, meaning it targets a part of the pathogen that existing treatments does, theoretically forcing the pathogen to begin anew in developing a defense to it. Scientists and doctors are relieved to have a new option for gonorrhoea – which has strains resistant to all existing treatments – but warn that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, exists consequently an debate about whether it should be stockpiled, restricted to highly resistant cases only – confining its use to settings where sophisticated diagnostics is available. This sort of prudent strategy should be the worldwide norm, but often cannot be deployed readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the flow of other new antibiotics we need could possibly originate. The former official's comment acknowledged the fact that searching the living world for natural sources – as with penicillin – has had diminishing returns. Use of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery identified in recent years hasn't yet progressed past animal trials. Synthetic drugs, which are mainly or fully synthesized, are constantly in research, but often run up against the fundamental rules of chemistry – just because we imagine a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stay in Place

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to stay in the same place. Careful, internationally coordinated deployment is the sole method to preserve our therapeutic edge. Sadly, the scale of future discoveries is likely to seem meager compared with the curative bonanza of the 20th century.