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During a time as head of the WHO, a past official famously stated that all of the “simple” antibiotics had long since been discovered. The argument was that in tackling the pressing threat of drug-resistant bacterial infections, we would struggle to discover new medicines – or preserve the existing ones – without finding novel approaches of working. This assessment proved accurate.

A Slow and Unprofitable Pipeline

Since 2017, just 16 antimicrobial agents have received widespread official clearance – mostly close relatives of drugs currently available and thus unlikely to evade bacterial resistance for an extended period. The creation of novel compounds is a lengthy and financially unattractive endeavor, given that one-off medicines are less lucrative as those managing longer-term conditions. The scientific outlook remains grim.

A Glimmer of Hope and a Novel Approach

However, the recent announcement of a pair of novel regulator-approved antibiotics for gonorrhoea is a welcome development and, importantly, confirms a innovative method of encouraging research. A particular of the new drugs, Zoliflodacin, is the result of a unique type of collaboration between a global health organization and a drug firm. The non-profit supplied funding and organised testing phases to defray expenses and navigate regulatory hurdles. This type of assistance upfront helps steer the industry towards fields of greatest public health necessity.

This approach and another lauded “subscription model” – initiated to guarantee income to companies that invest in certain antimicrobials – constitute the best hope of maintaining a trickle of new drugs from the existing framework.

The Unavoidable Challenge of Drug Resistance

But even hurrying the development of compounds in the pipeline is not sufficient. Zoliflodacin is sometimes described as a new class of antimicrobial, indicating it targets a part of the infectious bacteria that no other drug does, in principle compelling the pathogen to begin anew in developing a defense to it. Scientists and doctors are grateful to have a new drug for gonorrhoea – which has strains resistant to all existing treatments – but caution that eventual drug resistance to it is certain.

As has grown customary with recent antimicrobials, exists consequently an debate about whether it should be stockpiled, restricted to highly resistant cases only – limiting its use to situations where high‑end lab testing is accessible. This kind of prudent strategy should be the global standard, but often can't be implemented easily in many regions.

A Diminishing Pipeline of Discovery

On a wider scale, it is hard to see where the stream of other novel antimicrobials we need could realistically originate. The aforementioned statement acknowledged the fact that searching the natural world for biological compounds – as with the first antibiotic – has had diminishing returns. The application of artificial intelligence has been proposed to accelerate the discovery process, although a much-celebrated early candidate identified in 2020 hasn't yet advanced past preclinical studies. Synthetic drugs, which are largely or entirely lab-created, are continually in research, but often run up against the iron laws of molecular science – just because we imagine a molecule doesn't mean we can synthesise it easily.

Running Fast to Stay in Place

The dominant expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to remain in the same place. Prudent, globally managed use is the only way to preserve our advantage. Regrettably, the scale of future discoveries is going to seem miserly compared with the curative bonanza of the 20th century.