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During a tenure as head of the World Health Organization, a past official famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the urgent threat of drug-resistant infections, we would face difficulties to find new treatments – or conserve the existing ones – without developing novel approaches of operating. This view proved accurate.

A Slow and Challenging Development Path

Since the late 2010s, only 16 antimicrobial agents have gained widespread official clearance – mostly similar derivatives of medicines already in use and thus not expected to evade resistance for an extended period. The creation of novel compounds is a slow and unprofitable endeavor, given that curative medicines are not as profitable as ones treating longer-term conditions. The scientific outlook remains bleak.

A Glimmer of Optimism and a New Model

Nevertheless, the news this month of a pair of novel FDA-approved drugs against gonorrhoea is good news and, crucially, confirms 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 drug firm. The non-profit supplied financial support and managed clinical trials to defray expenses and navigate approval processes. This sort of support upfront helps steer the sector towards fields of greatest public health necessity.

This approach and another lauded revenue guarantee scheme – initiated to ensure revenue to firms investing in certain antimicrobials – constitute the best hope of maintaining a trickle of new drugs from the existing framework.

The Inevitable Problem of Resistance

But even accelerating the development of drugs in the pipeline is not enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, meaning it attacks a part of the pathogen that no other drug does, theoretically forcing the bacterium to begin anew in developing a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that future resistance to it is inevitable.

As has become the norm with new antibiotics, there is consequently an argument about whether it should be held in reserve, rationed to highly resistant cases only – limiting its use to situations where high‑end lab testing is available. This kind of rational strategy should be the global standard, but frequently can't be implemented easily in many parts of the world.

A Diminishing Pipeline of Discovery

On a wider scale, it is hard to see where the stream of additional novel antimicrobials we require could possibly originate. The aforementioned comment nodded to the fact that surveying the natural world for natural sources – as with penicillin – has had diminishing returns. The application of artificial intelligence has been proposed to speed up the search, although a highly-touted initial discovery identified in recent years has not yet progressed past preclinical studies. Synthetic drugs, that are largely or entirely lab-created, are constantly in research, but often run up against the fundamental rules of molecular science – the fact that we imagine a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Careful, globally managed use is the only way to preserve our advantage. Regrettably, the magnitude of future discoveries is likely to seem miserly in contrast to the curative bonanza of the previous century.