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During a time as director general of the World Health Organization, a past official famously remarked that all of the “easy” antimicrobials had already been found. The point was that in addressing the pressing threat of drug-resistant bacterial infections, we would face difficulties to find new treatments – or preserve the existing ones – without developing new ways of working. This view proved correct.

A Sluggish and Unprofitable Pipeline

Since the late 2010s, just 16 antimicrobial agents have received widespread regulatory approval – mostly similar derivatives of drugs currently available and thus unlikely to overcome bacterial resistance for long. The development of new ones is a slow and financially unattractive endeavor, given that one-off medicines are less lucrative as ones treating longer-term conditions. The overall prospect continues to be grim.

A Glimmer of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved antibiotics against gonorrhoea is a welcome development and, importantly, validates a new way of encouraging development. A particular of the new drugs, Zoliflodacin, is the product of a novel kind of partnership between a global health organization and a pharmaceutical company. The public health partnership supplied funding and organised testing phases to defray costs and navigate approval processes. This type of assistance in advance helps steer the sector towards fields of most pressing public health necessity.

This model and a separate lauded “subscription model” – launched to guarantee revenue to companies that invest in specific antimicrobials – represent the best hope of sustaining a dripfeed of novel treatments from the existing system.

The Unavoidable Challenge of Resistance

But even hurrying the development of drugs in the pipeline isn't enough. Zoliflodacin is sometimes categorized as a new class of antibiotic, indicating it attacks a component of the infectious bacteria that no other drug does, theoretically forcing the pathogen to start from zero in evolving a countermeasure to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but warn that eventual drug resistance to this compound is inevitable.

As has grown customary with recent antimicrobials, exists consequently an argument about whether it should be held in reserve, rationed to extremely drug-resistant cases only – confining its use to situations where sophisticated diagnostics is accessible. This kind of prudent strategy should be the worldwide norm, but frequently can't be deployed easily in many regions.

A Diminishing Stream of Discovery

On a wider scale, it is hard to see where the flow of additional novel antimicrobials we need could possibly come from. The aforementioned comment nodded to the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. Use of AI has been mooted to speed up the discovery process, although a highly-touted initial discovery found in recent years has not yet advanced past animal trials. Synthetic drugs, which are mainly or fully synthesized, are continually in development, but often confront the iron laws of molecular science – just because we imagine a compound 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 same place. Careful, internationally coordinated use is the sole method to maintain our advantage. Sadly, the scale of future breakthroughs is likely to seem miserly compared with the curative bonanza of the 20th century.