During a tenure as head of the World Health Organization, a past official famously stated that all of the “easy” antimicrobials had already been found. The point was that in tackling the pressing danger of drug-resistant infections, we would struggle to find new medicines – or conserve the current arsenal – without developing novel approaches of working. This assessment proved accurate.
A Slow and Unprofitable Pipeline
Since the late 2010s, only 16 antibiotics have gained broad regulatory approval – primarily similar derivatives of drugs already in use and thus unlikely to overcome bacterial resistance for an extended period. The development of novel compounds is a lengthy and unprofitable endeavor, given that curative treatments are less lucrative as those treating longer-term conditions. The overall prospect continues to be grim.
A Spark of Hope and a New Model
However, the news this month of two new regulator-approved drugs for gonorrhea is a welcome development and, crucially, validates a new way of incentivising research. One of the new drugs, Zoliflodacin, is the result of a novel kind of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit supplied funding and organised clinical trials to defray expenses and clear regulatory hurdles. This type of assistance in advance helps direct the sector towards areas of greatest global need.
This approach and a separate praised revenue guarantee scheme – initiated to ensure income to companies that invest in specific antibiotics – represent the best hope of sustaining a trickle of new drugs from the current framework.
The Unavoidable Challenge of Resistance
But even hurrying the development of compounds currently in development is not sufficient. The new drug is at times categorized as a new class of antimicrobial, meaning it targets a component of the infectious bacteria that existing treatments does, in principle forcing the pathogen to begin anew in evolving a countermeasure to it. Researchers and doctors are grateful 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 become the norm with recent antimicrobials, exists therefore an argument about whether it should be stockpiled, restricted to highly resistant cases only – confining its application to settings where sophisticated diagnostics is accessible. This kind of rational approach should be the worldwide norm, but frequently can't be implemented readily in many regions.
A Dwindling Stream of Innovation
On a wider scale, it is hard to see where the stream of additional novel antimicrobials we need could realistically come from. The aforementioned statement nodded to the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. The application of AI has been proposed to accelerate the search, although a highly-touted early candidate identified in recent years has not yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are continually in research, but often confront the iron laws of molecular science – just because we imagine a compound does not guarantee we can create it easily.
Moving Quickly to Stand Still
The prevailing expert assessment is that when it comes to antibiotics, we must run very fast truly just to stay in the same place. Careful, internationally coordinated use is the only way to preserve our therapeutic edge. Regrettably, the scale of forthcoming breakthroughs is going to seem miserly compared with the curative bonanza of the previous century.
