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During her tenure as head of the WHO, a past official famously remarked that all of the “simple” antibiotics had long since been discovered. The argument was that in addressing the urgent danger of drug-resistant bacterial infections, we would struggle to find new medicines – or conserve the existing ones – without finding new ways of working. This assessment was correct.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, only 16 antibiotics have received broad regulatory approval – primarily similar derivatives of drugs already in use and thus unlikely to evade resistance for an extended period. The creation of novel compounds is a slow and unprofitable business, given that one-off treatments are not as profitable as those treating chronic ailments. The scientific outlook continues to be grim.

A Glimmer of Optimism and a Novel Approach

Nevertheless, the news this month of a pair of novel regulator-approved antibiotics against gonorrhoea is good news and, importantly, confirms a new way of encouraging development. One of the new drugs, a compound called Zoliflodacin, is the product of a novel kind of collaboration between a global health organization and a drug firm. The public health partnership provided financial support and organised testing phases to offset expenses and clear regulatory hurdles. This type of assistance upfront helps direct the sector towards areas of most pressing global need.

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

The Inevitable Problem of Resistance

But even accelerating the production of drugs in the pipeline is not enough. Zoliflodacin is at times categorized as a novel type of antibiotic, meaning it targets a part of the infectious bacteria that existing treatments does, in principle forcing the bacterium to begin anew in evolving a countermeasure to it. Scientists and physicians are relieved to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to it is certain.

As has grown customary with new antibiotics, there is therefore an argument about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its use to situations where high‑end lab testing is accessible. This sort of rational approach should be the global standard, but often can't be deployed readily in many regions.

A Diminishing Stream of Discovery

More broadly, it is hard to see where the stream of other new antibiotics we require could realistically come from. The aforementioned comment acknowledged the fact that searching the natural world for natural sources – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been mooted to accelerate the discovery process, although a much-celebrated early candidate found in recent years has not yet progressed past preclinical studies. Synthetic drugs, that are largely or entirely lab-created, are continually in development, but often confront the fundamental rules of molecular science – just because we imagine a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stand Still

The dominant expert assessment is that when it comes to antimicrobials, we must run very fast truly just to remain in the current position. Prudent, internationally coordinated use is the sole method to maintain our therapeutic edge. Sadly, the scale of future discoveries is likely to seem miserly in contrast to the therapeutic revolution of the 20th century.