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During a tenure as director general of the World Health Organization, a former leader famously remarked that all of the “easy” antibiotics had already been found. The point was that in addressing the urgent threat of antibiotic-resistant infections, we would face difficulties to find new medicines – or preserve the existing ones – without finding new ways of operating. This assessment was correct.

A Slow and Challenging Pipeline

Since the late 2010s, just sixteen antimicrobial agents have gained widespread regulatory approval – mostly similar derivatives of drugs currently available and thus not expected to overcome resistance for long. The creation of novel compounds is a slow and unprofitable business, given that one-off treatments are not as profitable as those managing longer-term ailments. The overall prospect remains grim.

A Spark of Hope and a New Model

However, the recent announcement of a pair of novel regulator-approved drugs for gonorrhea is good news and, importantly, validates a innovative method of incentivising development. One of the new drugs, Zoliflodacin, is the product of a unique type of collaboration between a Swiss non‑profit and a pharmaceutical company. The non-profit provided financial support and organised testing phases to defray costs and clear approval processes. This sort of assistance in advance helps direct the industry towards fields of most pressing global need.

This model and a separate lauded “subscription model” – launched to ensure revenue to firms that invest in specific antimicrobials – represent the best hope of maintaining a dripfeed of new drugs from the current system.

The Unavoidable Problem of Drug Resistance

But even hurrying the development of compounds in the pipeline isn't enough. Zoliflodacin is at times categorized as a novel type of antimicrobial, indicating it attacks 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. Scientists and doctors are grateful to have a new option for gonorrhoea – which has strains resistant to all existing treatments – but warn that eventual drug resistance to this compound is inevitable.

As has become the norm with new antibiotics, there is consequently an debate about whether it should be stockpiled, restricted to extremely drug-resistant cases only – confining its application to situations where sophisticated diagnostics is available. This sort of rational strategy should be the global standard, but often can't be deployed easily in many regions.

A Diminishing Stream of Innovation

On a wider scale, it is difficult to see where the stream of other new antibiotics we need could possibly come from. The former official's statement acknowledged the fact that searching the natural world for biological compounds – as with penicillin – has had diminishing returns. The application of artificial intelligence has been proposed to speed up the discovery process, although a highly-touted early candidate found in recent years hasn't yet advanced past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are constantly in research, but often run up against the fundamental rules of molecular science – the fact that we imagine a compound doesn't mean we can create it without great difficulty.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antibiotics, we must run very fast truly just to stay in the current position. Careful, globally managed use is the sole method to preserve our therapeutic edge. Sadly, the magnitude of future discoveries is going to seem miserly in contrast to the curative bonanza of the 20th century.