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During a time as head of the WHO, a past official famously remarked that all of the “easy” antimicrobials had long since been discovered. The point was that in tackling the urgent threat of antibiotic-resistant infections, we would face difficulties to find new medicines – or conserve the current arsenal – without developing novel approaches of operating. This view was accurate.

A Slow and Challenging Development Path

Since 2017, only 16 antibiotics have received broad official clearance – mostly close relatives of medicines currently available and thus not expected to overcome resistance for an extended period. The creation of new ones is a slow and unprofitable business, given that one-off medicines are not as profitable as ones treating chronic conditions. The overall prospect continues to be grim.

A Spark of Optimism and a New Model

However, the recent announcement of a pair of novel FDA-approved drugs for gonorrhea is good news and, importantly, confirms a innovative method of incentivising research. One of the recently approved medications, a compound called Zoliflodacin, is the product of a unique type of partnership between a global health organization and a drug firm. The non-profit supplied funding and managed clinical trials to defray expenses and navigate approval processes. This type of assistance in advance helps direct the industry towards areas of most pressing global need.

This approach and another lauded revenue guarantee scheme – launched to guarantee income to companies that invest in specific antimicrobials – constitute the strongest chance of maintaining a dripfeed of new drugs from the current system.

The Inevitable Problem of Resistance

But even hurrying the production of drugs currently in development is not enough. Zoliflodacin is at times categorized as a new class of antibiotic, meaning it attacks a component of the pathogen that existing treatments does, in principle compelling the pathogen to start from zero in evolving a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhoea – which has strains resistant to every known antibiotic – but caution that future resistance to this compound is certain.

As has grown customary with recent antimicrobials, there is consequently an debate about whether it should be stockpiled, rationed to extremely drug-resistant infections only – confining its use to situations where sophisticated diagnostics is available. This sort of rational strategy should be the worldwide norm, but frequently cannot be implemented readily in many parts of the world.

A Dwindling Stream of Innovation

More broadly, it is hard to see where the flow of additional novel antimicrobials we need could realistically come from. The aforementioned statement acknowledged the fact that searching the natural world for natural sources – as with penicillin – has had declining success. The application of AI has been proposed to speed up the search, although a much-celebrated initial discovery identified in recent years hasn't yet progressed past preclinical studies. Fully lab-created compounds, that are mainly or fully synthesized, are continually in research, but often run up against the fundamental rules of chemistry – just because we imagine a compound does not guarantee we can create it easily.

Running Fast to Stay in Place

The prevailing expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the current position. Prudent, globally managed use is the sole method to preserve our therapeutic edge. Sadly, the magnitude of future breakthroughs is likely to seem miserly in contrast to the curative bonanza of the 20th century.