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During a time 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 point was that in addressing the pressing danger of drug-resistant infections, we would struggle to discover new medicines – or conserve the existing ones – without finding new ways of working. This view proved accurate.

A Slow and Challenging Development Path

Since 2017, just sixteen antimicrobial agents have gained widespread official clearance – primarily similar derivatives of medicines already in use and thus not expected to evade bacterial resistance for an extended period. The creation of novel compounds is a lengthy and financially unattractive business, given that curative medicines are less lucrative as ones treating longer-term ailments. The overall prospect continues to be grim.

A Spark of Optimism and a Novel Approach

However, the recent announcement of two new regulator-approved antibiotics for gonorrhoea is a welcome development and, crucially, validates a innovative method of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the product of a unique type of partnership between a global health organization and a pharmaceutical company. The public health partnership supplied financial support and organised clinical trials to defray costs and clear approval processes. This sort of assistance in advance helps direct the industry towards fields of greatest public health necessity.

This model and a separate lauded revenue guarantee scheme – launched to guarantee revenue to companies investing in certain antimicrobials – constitute the best hope of sustaining a trickle of novel treatments from the current system.

The Inevitable Challenge of Resistance

But even hurrying the development of drugs in the pipeline is not enough. Zoliflodacin is sometimes categorized as a new class of antibiotic, meaning it attacks a component of the pathogen that no other drug does, in principle compelling the pathogen to begin anew in evolving a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but warn that future resistance to it is inevitable.

As has grown customary with new antibiotics, there is therefore an argument about whether it should be held in reserve, rationed to highly resistant infections only – limiting its use to situations where sophisticated diagnostics is available. This sort of rational approach should be the worldwide norm, but frequently cannot be deployed readily in many regions.

A Diminishing Pipeline of Innovation

On a wider scale, it is hard to see where the flow of other novel antimicrobials we need could realistically come from. The aforementioned statement acknowledged the fact that searching the natural world for biological compounds – as with the first antibiotic – has had declining success. The application of AI has been proposed to accelerate the discovery process, although a highly-touted initial discovery found in 2020 has not yet advanced past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are continually in research, but often confront the fundamental rules of molecular science – the fact that we imagine a molecule doesn't mean we can create it without great difficulty.

Moving Quickly to Stand Still

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast truly just to remain in the same place. Careful, internationally coordinated deployment is the only way to preserve our therapeutic edge. Sadly, the scale of forthcoming discoveries is likely to seem meager compared with the therapeutic revolution of the 20th century.