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During her tenure as director general of the World Health Organization, a former leader famously remarked that all of the “simple” antibiotics had already been found. The point was that in tackling the pressing threat of drug-resistant infections, we would face difficulties to find new medicines – or conserve the existing ones – without finding new ways of operating. This assessment proved accurate.

A Slow and Challenging Development Path

Since 2017, just sixteen antibiotics have received widespread regulatory approval – mostly close relatives of medicines already in use and thus unlikely to overcome resistance for long. The creation of novel compounds is a lengthy and unprofitable endeavor, given that curative medicines are less lucrative as ones managing chronic conditions. The scientific outlook remains grim.

A Glimmer of Optimism and a Novel Approach

However, the recent announcement of a pair of novel FDA-approved antibiotics for gonorrhoea is good news and, importantly, validates a innovative method of incentivising research. One of the recently approved medications, Zoliflodacin, is the result of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied financial support and organised clinical trials to offset expenses and navigate approval processes. This sort of support in advance helps direct the industry towards areas of most pressing public health necessity.

This model and a separate praised “subscription model” – initiated to ensure revenue to companies that invest in certain antibiotics – constitute the strongest chance of sustaining a dripfeed of new drugs from the existing system.

The Inevitable Problem of Drug Resistance

But even accelerating the development of drugs currently in development is not sufficient. Zoliflodacin is at times described as a new class of antimicrobial, meaning it targets a component of the infectious bacteria that no other drug does, in principle compelling the pathogen to start from zero in evolving a countermeasure to it. Researchers and doctors are grateful to have a new drug for gonorrhea – which has strains resistant to all existing treatments – but warn that future resistance to it is inevitable.

As has become the norm with recent antimicrobials, there is consequently an debate about whether it should be held in reserve, restricted to extremely drug-resistant infections only – limiting its use to settings where sophisticated diagnostics is available. This sort of prudent strategy should be the global standard, but often cannot be deployed readily in many regions.

A Dwindling Stream of Innovation

On a wider scale, it is hard to see where the flow of other novel antimicrobials we require could possibly originate. The aforementioned statement acknowledged the fact that surveying the natural world for biological compounds – as with penicillin – has had declining success. The application of AI has been proposed to speed up the search, although a much-celebrated early candidate identified in recent years hasn't yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely synthesized, are continually in development, but often run up against the iron laws 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 expert assessment is that when it comes to antibiotics, we must move with great speed indeed just to remain in the same place. Careful, internationally coordinated deployment is the only way to preserve our advantage. Sadly, the scale of future breakthroughs is going to seem meager compared with the curative bonanza of the previous century.