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During a time as head of the WHO, 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 antibiotic-resistant infections, we would face difficulties to find new medicines – or preserve the current arsenal – without developing new ways of operating. This assessment proved accurate.

A Slow and Unprofitable Development Path

Since 2017, only sixteen antibiotics have gained widespread regulatory approval – primarily similar derivatives of medicines already in use and thus not expected to overcome bacterial resistance for an extended period. The creation of novel compounds is a slow and financially unattractive business, given that curative medicines are less lucrative as those treating longer-term ailments. The overall prospect remains bleak.

A Spark of Optimism and a Novel Approach

However, the news this month of a pair of novel FDA-approved antibiotics against gonorrhoea is good news and, crucially, validates a new way of encouraging development. One of the recently approved medications, Zoliflodacin, is the result of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership provided funding and managed testing phases to defray expenses and navigate regulatory hurdles. This type of support in advance helps direct the industry towards areas of greatest global need.

This model and a separate praised revenue guarantee scheme – initiated to ensure income to firms investing in specific antibiotics – constitute the best hope of maintaining a dripfeed of novel treatments from the existing system.

The Inevitable Challenge of Resistance

But even accelerating the development of compounds currently in development isn't enough. Zoliflodacin is at times described as a novel type of antimicrobial, meaning it targets a part of the pathogen that no other drug does, theoretically compelling the pathogen to start from zero in evolving a countermeasure to it. Scientists and doctors are relieved to have a new drug for gonorrhea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to it is inevitable.

As has become the norm with recent antimicrobials, exists consequently an argument about whether it should be stockpiled, restricted to highly resistant infections only – confining its use to settings where sophisticated diagnostics is accessible. This sort of rational strategy should be the worldwide norm, but frequently cannot be implemented easily in many regions.

A Dwindling Stream of Discovery

More broadly, it is difficult to see where the flow of other novel antimicrobials we need could realistically come from. The aforementioned statement nodded to the fact that searching the natural world for natural sources – as with penicillin – has had diminishing returns. The application of AI has been proposed to accelerate the discovery process, although a much-celebrated early candidate found in recent years hasn't yet advanced past preclinical studies. Fully lab-created compounds, which are largely or entirely lab-created, are constantly in development, but often run up against the fundamental rules of molecular science – just because we imagine a molecule doesn't mean we can create it without great difficulty.

Moving Quickly to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must move with great speed truly just to remain in the current position. Prudent, internationally coordinated use is the only way to preserve our advantage. Sadly, the scale of future discoveries is going to seem meager in contrast to the curative bonanza of the previous century.