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During her 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 argument was that in addressing the urgent threat of antibiotic-resistant bacterial infections, we would face difficulties to find new medicines – or preserve the current arsenal – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Pipeline

Since the late 2010s, just 16 antimicrobial agents have received widespread regulatory approval – primarily close relatives of drugs already in use and thus not expected to evade resistance for long. The creation of new ones is a lengthy and unprofitable business, given that one-off treatments are not as profitable as ones managing longer-term conditions. The overall prospect remains bleak.

A Spark of Optimism and a Novel Approach

Nevertheless, the recent announcement of two new regulator-approved antibiotics for gonorrhea is good news and, crucially, validates a innovative method of encouraging development. A particular of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a drug firm. The non-profit provided funding and managed clinical trials to offset costs and clear regulatory hurdles. This sort of assistance upfront helps direct the industry towards areas of greatest public health necessity.

This model and a separate praised revenue guarantee scheme – initiated to guarantee income to firms investing in specific antibiotics – constitute the best hope of sustaining a dripfeed of new drugs from the current system.

The Inevitable Problem of Resistance

But even accelerating the production of compounds in the pipeline is not enough. Zoliflodacin is at times described as a novel type of antibiotic, indicating it targets a part of the pathogen that existing treatments does, in principle forcing the bacterium to start from zero in evolving a defense to it. Researchers and physicians are relieved to have a new option for gonorrhea – which has resistant strains to all existing treatments – but warn that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is therefore an argument about whether it should be stockpiled, rationed to extremely drug-resistant infections only – confining its application to settings where sophisticated diagnostics is available. This kind of rational strategy should be the worldwide norm, but often can't 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 additional new antibiotics we need could realistically originate. The aforementioned statement nodded to the fact that surveying the living world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery identified in recent years has not yet advanced past preclinical studies. Synthetic drugs, that are largely or entirely lab-created, are constantly in research, but often confront the fundamental rules of chemistry – just because we envision a molecule doesn't mean 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 same place. Prudent, globally managed use is the only way to maintain our advantage. Sadly, the scale of future breakthroughs is likely to seem miserly compared with the therapeutic revolution of the previous century.