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During her tenure as director general of the WHO, a past official famously remarked that all of the “easy” antimicrobials had already been found. The argument was that in addressing the pressing danger of antibiotic-resistant infections, we would struggle to discover new treatments – or preserve the current arsenal – without developing new ways of operating. This view was correct.

A Slow and Unprofitable Development Path

Since the late 2010s, only 16 antibiotics have received broad official clearance – mostly close relatives of drugs currently available and thus not expected to evade bacterial resistance for long. The creation of novel compounds is a lengthy and financially unattractive business, given that curative medicines are not as profitable as those managing chronic conditions. The overall prospect continues to be grim.

A Spark of Hope and a New Model

Nevertheless, the news this month of two new regulator-approved antibiotics for gonorrhoea is a welcome development and, importantly, confirms a new way of encouraging research. One of the recently approved medications, a compound called Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a drug firm. The non-profit provided financial support and managed clinical trials to defray costs and clear regulatory hurdles. This sort of assistance upfront helps direct the industry towards fields of greatest public health necessity.

This model and another lauded revenue guarantee scheme – launched to ensure revenue to firms that invest in specific antibiotics – constitute the best hope of maintaining a trickle of novel treatments from the existing framework.

The Inevitable Problem of Drug Resistance

But even accelerating the development of compounds currently in development isn't enough. The new drug is at times described as a novel type of antimicrobial, meaning it attacks a component of the pathogen that existing treatments does, in principle forcing the pathogen to start from zero in developing a countermeasure to it. Scientists and doctors are grateful to have a new option for gonorrhoea – which has strains resistant to every known antibiotic – but warn that future resistance to this compound is inevitable.

As has become the norm with new antibiotics, exists therefore an argument about whether it should be held in reserve, restricted to highly resistant infections only – limiting its application to settings where high‑end lab testing is accessible. This kind of rational approach should be the global standard, but frequently can't be deployed readily in many parts of the world.

A Diminishing Pipeline of Discovery

More broadly, it is difficult to see where the flow of additional novel antimicrobials we require could possibly come from. The aforementioned statement acknowledged the fact that surveying the natural world for natural sources – as with penicillin – has had declining success. Use of AI has been proposed to accelerate the search, although a highly-touted initial discovery found in 2020 hasn't yet advanced past preclinical studies. Synthetic drugs, that are largely or entirely synthesized, are continually in research, but often confront the iron laws of molecular science – just because we imagine a compound doesn't mean we can create it easily.

Running Fast to Stand Still

The prevailing scientific evaluation is that when it comes to antibiotics, we must run very fast indeed just to remain in the same place. Prudent, internationally coordinated deployment is the only way to maintain our advantage. Regrettably, the magnitude of forthcoming discoveries is going to seem miserly in contrast to the therapeutic revolution of the previous century.