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During a tenure as director general of the WHO, a past official famously remarked that all of the “simple” antibiotics had already been found. The point was that in tackling the urgent danger of drug-resistant infections, we would struggle to find new treatments – or preserve the existing ones – without developing new ways of operating. This view was accurate.

A Slow and Challenging Development Path

Since the late 2010s, just sixteen antimicrobial agents have received broad regulatory approval – primarily close relatives of medicines already in use and thus not expected to evade resistance for an extended period. The creation of new ones is a slow and financially unattractive business, given that curative treatments are not as profitable as those treating longer-term conditions. The overall prospect continues to be bleak.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved drugs against gonorrhoea is a welcome development and, importantly, validates a innovative method of incentivising research. One of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a drug firm. The non-profit supplied funding and managed testing phases to offset expenses and navigate regulatory hurdles. This sort of support upfront helps direct the industry towards areas of greatest global need.

This model and another lauded revenue guarantee scheme – initiated to ensure income to companies that invest in certain antibiotics – constitute the strongest chance of sustaining a dripfeed of new drugs from the existing framework.

The Inevitable Challenge of Drug Resistance

But even hurrying the production 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 infectious bacteria that no other drug does, in principle compelling the bacterium to begin anew in evolving a defense to it. Researchers and doctors are grateful to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but caution that eventual drug resistance to this compound is inevitable.

As has grown customary with new antibiotics, there is therefore an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its use to situations where sophisticated diagnostics is available. This sort of rational strategy should be the worldwide norm, but often can't be implemented readily in many parts of the world.

A Diminishing Pipeline of Innovation

On a wider scale, it is hard to see where the flow of other novel antimicrobials we require could possibly originate. The former official's statement nodded to the fact that searching the natural world for natural sources – as with the first antibiotic – has had diminishing returns. Use of AI has been proposed to speed up the search, although a highly-touted initial discovery found in 2020 hasn't yet progressed past animal trials. Synthetic drugs, which are mainly or fully lab-created, are continually in development, but often confront the fundamental rules of chemistry – the fact that we imagine a molecule doesn't mean we can create it without great difficulty.

Moving Quickly to Stay in Place

The dominant scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Prudent, internationally coordinated use is the sole method to preserve our therapeutic edge. Sadly, the magnitude of forthcoming discoveries is likely to seem meager compared with the therapeutic revolution of the previous century.