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During a tenure as director general of the World Health Organization, a former leader famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in tackling the urgent threat of drug-resistant bacterial infections, we would struggle to discover new medicines – or conserve the existing ones – without finding novel approaches of operating. This assessment proved accurate.

A Sluggish and Unprofitable Pipeline

Since 2017, just 16 antimicrobial agents have gained broad regulatory approval – mostly close relatives of drugs already in use and thus unlikely to overcome bacterial resistance for long. The creation of novel compounds is a lengthy and financially unattractive endeavor, given that one-off treatments are not as profitable as ones managing chronic ailments. The overall prospect remains grim.

A Spark of Optimism and a Novel Approach

However, the news this month of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, importantly, validates a new way of encouraging development. 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 pharmaceutical company. The public health partnership supplied funding and organised testing phases to defray costs and clear regulatory hurdles. This sort of assistance in advance helps steer the sector towards areas of greatest global need.

This model and a separate praised revenue guarantee scheme – launched to guarantee income to firms investing in certain antimicrobials – constitute the best hope of sustaining a dripfeed of new drugs from the existing framework.

The Unavoidable Challenge of Resistance

But even hurrying the development of drugs currently in development is not sufficient. The new drug is sometimes categorized as a novel type of antimicrobial, meaning it targets a component of the pathogen that no other drug does, theoretically compelling the bacterium to begin anew in evolving a defense to it. Scientists and doctors are relieved to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but warn that future resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, exists consequently an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – confining its use to settings where high‑end lab testing is accessible. This sort of prudent strategy should be the global standard, but often cannot be implemented easily in many regions.

A Dwindling Stream of Innovation

More broadly, it is difficult to see where the stream of additional new antibiotics we require could realistically originate. The aforementioned statement acknowledged the fact that searching the natural world for natural sources – as with penicillin – has had declining success. The application of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery found in recent years has not yet advanced past animal trials. Fully lab-created compounds, which are mainly or fully synthesized, are constantly in research, but often run up against the iron laws of molecular science – the fact that we imagine a molecule doesn't mean we can create it without great difficulty.

Running Fast 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 deployment is the only way to preserve our advantage. Sadly, the magnitude of future discoveries is likely to seem miserly compared with the curative bonanza of the 20th century.