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During her tenure as director general of the WHO, a past official famously remarked that all of the “simple” antimicrobials had long since been discovered. The point was that in addressing the pressing danger of drug-resistant infections, we would struggle to discover new medicines – or conserve the existing ones – without finding novel approaches of operating. This assessment was accurate.

A Sluggish and Unprofitable Development Path

Since the late 2010s, just 16 antimicrobial agents have received broad regulatory approval – primarily close relatives of medicines currently available and thus not expected to evade bacterial resistance for an extended period. The development of new ones is a lengthy and financially unattractive endeavor, given that one-off medicines are not as profitable as ones treating longer-term conditions. The overall prospect remains bleak.

A Glimmer of Hope and a New Model

Nevertheless, the news this month of two new regulator-approved antibiotics for gonorrhea is a welcome development and, crucially, confirms a innovative method of encouraging development. A particular of the new drugs, Zoliflodacin, is the product of a novel kind of partnership between a Swiss non‑profit and a pharmaceutical company. The public health partnership supplied funding and organised clinical trials to defray expenses and navigate approval processes. This sort of assistance upfront helps direct the sector towards areas of most pressing global need.

This model and another praised revenue guarantee scheme – initiated to guarantee revenue to companies investing in certain antimicrobials – represent the strongest chance of maintaining a dripfeed of new drugs from the existing system.

The Inevitable Challenge of Resistance

But even hurrying the production of drugs currently in development is not sufficient. Zoliflodacin is at times categorized as a new class of antimicrobial, indicating it targets a part of the infectious bacteria that no other drug does, theoretically compelling the pathogen to start from zero in developing a countermeasure to it. Scientists and physicians are grateful to have a new drug for gonorrhoea – which has resistant strains to all existing treatments – but caution that future resistance to it is certain.

As has grown customary with recent antimicrobials, exists therefore an argument about whether it should be stockpiled, restricted to extremely drug-resistant cases only – limiting its use to situations where sophisticated diagnostics is accessible. This kind of prudent approach should be the global standard, but often cannot be deployed easily in many parts of the world.

A Dwindling Pipeline of Innovation

On a wider scale, it is difficult to see where the stream of additional new antibiotics we need could realistically come from. The former official's comment acknowledged the fact that searching the living world for biological compounds – as with penicillin – has had declining success. The application of AI has been mooted to speed up the discovery process, although a highly-touted initial discovery found in 2020 hasn't yet advanced past preclinical studies. Fully lab-created compounds, which are largely or entirely synthesized, are continually in development, but often run up against the fundamental rules of molecular science – just because we envision a compound does not guarantee we can synthesise it easily.

Moving Quickly to Stay in Place

The prevailing expert assessment is that when it comes to antibiotics, we must run very fast indeed just to remain in the current position. Prudent, globally managed use is the only way to maintain our advantage. Sadly, the magnitude of forthcoming discoveries is going to seem meager in contrast to the curative bonanza of the 20th century.