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During her tenure as director general of the WHO, a former leader 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 infections, we would struggle to discover new medicines – or conserve the current arsenal – without developing new ways of working. This view proved accurate.

A Slow and Challenging Pipeline

Since the late 2010s, just 16 antibiotics have gained widespread regulatory approval – primarily close relatives of drugs already in use and thus not expected to overcome resistance for an extended period. The development of new ones is a slow and financially unattractive business, given that curative treatments are not as profitable as ones treating longer-term conditions. The scientific outlook remains bleak.

A Spark of Optimism and a New Model

Nevertheless, the recent announcement of two new FDA-approved antibiotics against gonorrhea is a welcome development and, importantly, validates a innovative method of encouraging development. One of the new drugs, Zoliflodacin, is the product of a novel kind of partnership between a global health organization and a drug firm. The public health partnership provided funding and managed testing phases to offset expenses and navigate regulatory hurdles. This sort of support in advance helps steer the industry towards areas of most pressing public health necessity.

This approach and another lauded revenue guarantee scheme – launched to ensure revenue to companies investing in specific antibiotics – constitute the best hope of sustaining a dripfeed of novel treatments from the current system.

The Unavoidable Challenge of Resistance

But even hurrying the development of compounds in the pipeline is not sufficient. Zoliflodacin is sometimes categorized as a novel type of antibiotic, indicating it attacks a part of the pathogen that existing treatments does, in principle compelling the pathogen to start from zero in evolving a countermeasure to it. Scientists and doctors are grateful to have a new option for gonorrhoea – which has resistant strains to all existing treatments – but caution that eventual drug resistance to this compound is certain.

As has grown customary with new antibiotics, exists therefore an debate about whether it should be stockpiled, rationed to extremely drug-resistant cases only – limiting its application to settings where sophisticated diagnostics is available. This sort of rational approach should be the global standard, but often can't be deployed readily in many parts of the world.

A Diminishing Stream of Discovery

More broadly, it is difficult to see where the flow of additional new antibiotics we require could realistically originate. The aforementioned comment acknowledged the fact that searching the living world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been proposed to speed up the discovery process, although a highly-touted early candidate identified in 2020 hasn't yet advanced past animal trials. Synthetic drugs, which are mainly or fully synthesized, are continually in research, but often confront the fundamental rules of molecular science – just because we imagine a molecule doesn't mean we can create it without great difficulty.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antimicrobials, we must run very fast indeed just to remain in the current position. Careful, internationally coordinated use is the only way to preserve our therapeutic edge. Regrettably, the scale of forthcoming breakthroughs is likely to seem meager compared with the therapeutic revolution of the previous century.