During her time as director general of the WHO, a former leader famously stated that all of the “simple” antimicrobials had already been found. The point was that in addressing the urgent threat of antibiotic-resistant infections, we would face difficulties to find new treatments – or conserve the existing ones – without finding new ways of operating. This assessment proved accurate.
A Sluggish and Challenging Development Path
Since the late 2010s, just 16 antibiotics have gained widespread regulatory approval – mostly close relatives of drugs currently available and thus unlikely to overcome bacterial resistance for long. The development of new ones is a slow and unprofitable endeavor, given that one-off medicines are not as profitable as those managing longer-term conditions. The overall prospect remains bleak.
A Spark of Optimism and a New Model
However, the news this month of a pair of novel FDA-approved antibiotics for gonorrhoea is a welcome development and, importantly, confirms a new way of encouraging development. One of the recently approved medications, a compound called Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a drug firm. The non-profit provided financial support and managed clinical trials to offset costs and clear regulatory hurdles. This type of support in advance helps direct the sector towards fields of greatest global need.
This approach and another praised revenue guarantee scheme – launched to ensure revenue to companies investing in specific antimicrobials – constitute the best hope of maintaining a dripfeed of new drugs from the current system.
The Unavoidable Challenge of Resistance
But even hurrying the production of drugs in the pipeline isn't sufficient. The new drug is sometimes described as a new class of antibiotic, meaning it attacks a part of the pathogen that existing treatments does, theoretically compelling the bacterium to start from zero in evolving a defense to it. Researchers and doctors are relieved to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but warn that eventual drug resistance to it is certain.
As has grown customary with recent antimicrobials, exists consequently an argument about whether it should be stockpiled, rationed to highly resistant infections only – limiting its use to settings where sophisticated diagnostics is accessible. This sort of rational approach should be the global standard, but often can't be deployed easily in many regions.
A Dwindling Stream of Discovery
More broadly, it is hard to see where the flow of other new antibiotics we require could realistically originate. The former official's comment acknowledged the fact that surveying the living world for natural sources – as with the first antibiotic – has had diminishing returns. Use of artificial intelligence has been proposed to speed up the discovery process, although a highly-touted early candidate identified in 2020 has not yet progressed past preclinical studies. Fully lab-created compounds, that are largely or entirely synthesized, are constantly in development, but often confront the fundamental rules of molecular science – the fact that 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 truly just to stay in the same place. Prudent, internationally coordinated deployment is the only way to preserve our advantage. Sadly, the magnitude of forthcoming discoveries is going to seem meager in contrast to the therapeutic revolution of the 20th century.
