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During her tenure as director general of the WHO, a former leader famously remarked that all of the “easy” antibiotics had long since been discovered. The argument was that in addressing the urgent danger of antibiotic-resistant bacterial infections, we would face difficulties to discover new treatments – or preserve the current arsenal – without developing novel approaches of working. This assessment proved correct.

A Slow and Challenging Pipeline

Since 2017, only 16 antimicrobial agents have received widespread official clearance – primarily close relatives of medicines already in use and thus unlikely to evade resistance for long. The development of new ones is a lengthy and financially unattractive endeavor, given that one-off treatments are less lucrative as ones treating longer-term ailments. The scientific outlook continues to be bleak.

A Glimmer of Optimism and a New Model

However, the recent announcement of two new FDA-approved antibiotics against gonorrhoea is good news and, crucially, confirms a innovative method of incentivising research. A particular of the new drugs, a compound called 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 managed clinical trials to offset costs and clear approval processes. This type of assistance upfront helps steer the industry towards areas of most pressing public health necessity.

This model and a separate lauded revenue guarantee scheme – initiated to ensure revenue to firms that invest in specific antimicrobials – represent the best hope of sustaining a trickle of novel treatments from the existing system.

The Inevitable Problem of Drug Resistance

But even hurrying the production of drugs currently in development is not sufficient. The new drug is at times described as a novel type of antimicrobial, indicating it targets a part of the pathogen that existing treatments does, theoretically compelling the pathogen to begin anew in evolving a countermeasure to it. Researchers and doctors are relieved to have a new option for gonorrhea – which has strains resistant to every known antibiotic – but caution that eventual drug resistance to this compound is certain.

As has grown customary with recent antimicrobials, exists consequently an debate about whether it should be held in reserve, rationed to highly resistant infections only – confining its application to situations where sophisticated diagnostics is accessible. This kind of prudent strategy should be the global standard, but often can't be implemented easily in many regions.

A Dwindling Stream of Discovery

More broadly, it is hard to see where the stream of additional new antibiotics we require could realistically come from. The former official's statement nodded to the fact that surveying the living world for biological compounds – as with the first antibiotic – has had declining success. Use of AI has been mooted to accelerate the discovery process, although a highly-touted initial discovery identified in 2020 hasn't yet advanced past animal trials. Synthetic drugs, that are mainly or fully lab-created, are constantly in research, but often run up against the fundamental rules of molecular science – just because we envision a molecule doesn't mean we can synthesise it easily.

Running Fast to Stay in Place

The prevailing expert assessment is that when it comes to antimicrobials, we must move with great speed truly just to remain in the current position. Careful, internationally coordinated use is the sole method to preserve our therapeutic edge. Regrettably, the magnitude of forthcoming breakthroughs is likely to seem meager in contrast to the curative bonanza of the 20th century.