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During her tenure as head of the World Health Organization, a former leader famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the pressing threat of antibiotic-resistant bacterial infections, we would struggle to find new medicines – or preserve the current arsenal – without finding new ways of working. This assessment was correct.

A Slow and Unprofitable Development Path

Since the late 2010s, only 16 antimicrobial agents have received widespread official clearance – primarily similar derivatives of medicines already in use and thus not expected to overcome bacterial resistance for long. The development of new ones is a lengthy and financially unattractive endeavor, given that curative treatments are not as profitable as ones treating longer-term ailments. The overall prospect remains bleak.

A Glimmer of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved antibiotics against gonorrhea is good news and, crucially, validates a innovative method of encouraging development. A particular of the new drugs, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a Swiss non‑profit and a drug firm. The public health partnership supplied financial support and managed testing phases to defray costs and clear approval processes. This sort of assistance in advance helps direct the sector towards areas of most pressing public health necessity.

This model and a separate lauded “subscription model” – initiated to guarantee income to firms that invest in certain antimicrobials – constitute the best hope of sustaining a dripfeed of novel treatments from the current framework.

The Unavoidable Challenge of Resistance

But even accelerating the production of drugs in the pipeline isn't sufficient. The new drug is at times described as a new class of antimicrobial, meaning it targets a component of the pathogen that no other drug does, theoretically forcing the pathogen to begin anew in developing a countermeasure to it. Researchers and physicians 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 new antibiotics, there is therefore an argument about whether it should be held in reserve, rationed to extremely drug-resistant infections only – confining its use to situations where sophisticated diagnostics is available. This kind of rational approach should be the global standard, but often can't be implemented readily in many parts of the world.

A Diminishing Stream of Innovation

More broadly, it is difficult to see where the stream of other new antibiotics we need could realistically come from. The former official's statement nodded to the fact that surveying the living world for natural sources – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been mooted to speed up the discovery process, although a much-celebrated initial discovery found in 2020 hasn't yet progressed past animal trials. Fully lab-created compounds, that are largely or entirely synthesized, are constantly in development, but often confront the iron laws of molecular science – the fact that we imagine a compound does not guarantee we can create it without great difficulty.

Running Fast to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must move with great speed truly just to remain in the same place. Prudent, globally managed use is the sole method to preserve our therapeutic edge. Sadly, the magnitude of future breakthroughs is going to seem miserly in contrast to the curative bonanza of the 20th century.