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During a time as head of the World Health Organization, a past official famously stated that all of the “simple” antimicrobials had long since been discovered. The point was that in tackling the pressing threat of drug-resistant infections, we would struggle to find new treatments – or preserve the current arsenal – without finding novel approaches of working. This view was correct.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only sixteen antimicrobial agents have received widespread official clearance – mostly close relatives of medicines currently available and thus not expected to evade resistance for an extended period. The creation of novel compounds is a lengthy and unprofitable business, given that curative treatments are less lucrative as ones treating longer-term ailments. The overall prospect remains bleak.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of a pair of novel FDA-approved antibiotics for gonorrhoea is a welcome development and, importantly, validates a innovative method of encouraging research. One of the new drugs, Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and managed testing phases to defray expenses and navigate approval processes. This type of support in advance helps steer the industry towards fields of most pressing public health necessity.

This model and another praised revenue guarantee scheme – launched to ensure income to companies that invest in specific antimicrobials – constitute the best hope of sustaining a trickle of new drugs from the current framework.

The Unavoidable Problem of Resistance

But even hurrying the production of compounds in the pipeline is not enough. Zoliflodacin is sometimes described as a novel type of antimicrobial, indicating it targets a component of the pathogen that no other drug does, theoretically forcing the bacterium to start from zero in developing a countermeasure to it. Scientists and physicians are relieved to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but caution that future resistance to it is certain.

As has grown customary with new antibiotics, there is therefore an argument about whether it should be held in reserve, restricted to extremely drug-resistant cases only – confining its use to settings where sophisticated diagnostics is accessible. This sort of rational approach should be the worldwide norm, but frequently cannot be implemented easily in many regions.

A Dwindling Pipeline of Discovery

On a wider scale, it is difficult to see where the flow of additional novel antimicrobials we need could realistically originate. The aforementioned comment nodded to the fact that surveying the natural world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of AI has been proposed to accelerate the discovery process, although a highly-touted initial discovery identified in recent years hasn't yet advanced past animal trials. 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 envision a molecule doesn't mean we can synthesise it easily.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must run very fast truly just to remain in the current position. Prudent, globally managed deployment is the sole method to maintain our advantage. Regrettably, the scale of forthcoming breakthroughs is going to seem miserly in contrast to the curative bonanza of the previous century.