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During a tenure as director general of the World Health Organization, a past official famously remarked that all of the “simple” antimicrobials had already been found. The argument was that in tackling the urgent threat of drug-resistant bacterial infections, we would face difficulties to discover new medicines – or preserve the current arsenal – without finding novel approaches of working. This view proved accurate.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, just sixteen antibiotics have received widespread regulatory approval – mostly similar derivatives of drugs already in use and thus not expected to overcome resistance for an extended period. The creation of new ones is a lengthy and financially unattractive business, given that one-off medicines are not as profitable as those managing longer-term ailments. The overall prospect continues to be grim.

A Spark of Hope and a Novel Approach

However, the news this month of two new regulator-approved drugs for gonorrhoea is a welcome development and, crucially, validates a innovative method of encouraging development. One of the recently approved medications, Zoliflodacin, is the product of a novel kind of partnership between a global health organization and a pharmaceutical company. The public health partnership provided funding and managed testing phases to defray costs and navigate regulatory hurdles. This type of support upfront helps steer the industry towards areas of greatest global need.

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

The Inevitable Problem of Resistance

But even accelerating the development of compounds in the pipeline is not sufficient. Zoliflodacin is sometimes described as a novel type of antibiotic, indicating it attacks a component of the pathogen that existing treatments does, theoretically forcing the bacterium to begin anew in developing a defense to it. Researchers and doctors are grateful to have a new option for gonorrhea – which has resistant strains to all existing treatments – but warn that future resistance to it is certain.

As has grown customary with new antibiotics, there is consequently an argument about whether it should be stockpiled, rationed to extremely drug-resistant cases only – confining its use to situations where high‑end lab testing is accessible. This kind of rational approach should be the global standard, but frequently can't be deployed easily in many parts of the world.

A Diminishing Pipeline of Innovation

On a wider scale, it is difficult to see where the flow of additional new antibiotics we require could possibly come from. The aforementioned statement nodded to the fact that surveying the natural world for biological compounds – as with penicillin – has had declining success. Use of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery found in recent years hasn't yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely synthesized, are continually in research, but often run up against the iron laws of chemistry – the fact that we imagine a compound doesn't mean we can synthesise it easily.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to stay in the same place. Careful, internationally coordinated use is the sole method to maintain our advantage. Regrettably, the magnitude of future discoveries is likely to seem meager in contrast to the therapeutic revolution of the 20th century.