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During a tenure as director general of the World Health Organization, a former leader famously stated 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 struggle to discover new medicines – or conserve the current arsenal – without developing novel approaches of operating. This assessment proved accurate.

A Slow and Challenging Development Path

Since 2017, only 16 antimicrobial agents have gained broad regulatory approval – primarily similar derivatives of medicines already in use and thus not expected to overcome resistance for an extended period. The development of new ones is a lengthy and financially unattractive endeavor, given that one-off treatments are less lucrative as those treating chronic conditions. The overall prospect continues to be grim.

A Spark of Optimism and a New Model

Nevertheless, the news this month of a pair of novel regulator-approved antibiotics against gonorrhea is good news and, importantly, validates a new way of encouraging development. One of the recently approved medications, Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided financial support and organised clinical trials to offset expenses and navigate regulatory hurdles. This sort of assistance in advance helps steer the industry towards fields of most pressing global need.

This approach and a separate lauded revenue guarantee scheme – launched to guarantee income to companies investing in certain antimicrobials – represent the strongest chance of sustaining a trickle of new drugs from the current system.

The Inevitable Problem of Drug Resistance

But even hurrying the development of drugs in the pipeline is not enough. Zoliflodacin is at times described as a new class of antimicrobial, meaning it attacks a part of the infectious bacteria that existing treatments does, in principle compelling the pathogen to start from zero in evolving a countermeasure to it. Scientists and physicians are grateful to have a new drug for gonorrhea – which has strains resistant to every known antibiotic – but caution that eventual drug resistance to it is certain.

As has become the norm with new antibiotics, there is consequently an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its application to settings where sophisticated diagnostics is available. This kind of prudent approach should be the worldwide norm, but often can't be implemented readily in many regions.

A Diminishing Stream of Discovery

On a wider scale, it is difficult to see where the flow of other novel antimicrobials we require could realistically come from. The former official's statement nodded to the fact that searching the living world for natural sources – as with the first antibiotic – has had diminishing returns. The application of AI has been mooted to accelerate the search, although a much-celebrated initial discovery found in recent years has not yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are constantly in development, but often confront the fundamental rules of molecular science – just because we imagine a molecule does not guarantee we can create it without great difficulty.

Moving Quickly to Stand Still

The dominant scientific evaluation is that when it comes to antibiotics, we must run very fast indeed just to stay in the same place. Careful, internationally coordinated deployment is the sole method to maintain our therapeutic edge. Sadly, the magnitude of future discoveries is going to seem miserly in contrast to the curative bonanza of the 20th century.