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During her time as head of the World Health Organization, a former leader famously stated that all of the “easy” antibiotics had already been found. The argument was that in tackling the urgent threat of drug-resistant bacterial infections, we would struggle to find new medicines – or conserve the current arsenal – without developing novel approaches of operating. This assessment proved correct.

A Sluggish and Unprofitable Pipeline

Since 2017, just sixteen antimicrobial agents have gained widespread regulatory approval – mostly similar derivatives of medicines currently available and thus unlikely to overcome bacterial resistance for an extended period. The creation of new ones is a slow and unprofitable endeavor, given that one-off medicines are less lucrative as ones treating longer-term conditions. The overall prospect continues to be bleak.

A Glimmer of Optimism and a Novel Approach

However, the news this month of a pair of novel regulator-approved antibiotics for gonorrhea is a welcome development and, crucially, confirms a innovative method of encouraging research. 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 supplied financial support and organised testing phases to defray costs and navigate regulatory hurdles. This type of support in advance helps direct the industry towards fields of most pressing global need.

This model and another lauded revenue guarantee scheme – launched to guarantee income to firms investing in certain antibiotics – represent the strongest chance of maintaining a trickle of new drugs from the current framework.

The Inevitable Challenge of Resistance

But even accelerating the production of drugs currently in development isn't enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, indicating it attacks a component of the infectious bacteria that no other drug does, in principle forcing the pathogen to begin anew in evolving a countermeasure to it. Scientists and physicians are grateful to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but caution that eventual drug resistance to it is inevitable.

As has become the norm with recent antimicrobials, exists consequently an debate about whether it should be held in reserve, restricted to extremely drug-resistant infections only – limiting its application to situations where high‑end lab testing is accessible. This kind of prudent strategy should be the worldwide norm, but often can't be implemented easily in many regions.

A Dwindling Stream of Discovery

More broadly, it is difficult to see where the stream of additional novel antimicrobials we require could possibly originate. The aforementioned statement acknowledged the fact that searching the living world for natural sources – as with the first antibiotic – has had diminishing returns. Use of AI has been proposed to speed up the discovery process, although a much-celebrated initial discovery identified in recent years hasn't yet advanced past preclinical studies. Synthetic drugs, that are mainly or fully synthesized, are constantly in research, but often run up against the fundamental rules of molecular science – the fact that we envision a molecule does not guarantee we can create it without great difficulty.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must move with great speed indeed just to remain in the same place. Prudent, globally managed deployment is the only way to preserve our therapeutic edge. Regrettably, the magnitude of future discoveries is going to seem meager compared with the curative bonanza of the previous century.