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During her time as director general of the World Health Organization, a past official famously stated that all of the “easy” antibiotics had long since been discovered. The point was that in addressing the pressing threat of drug-resistant infections, we would face difficulties to discover new medicines – or preserve the current arsenal – without developing new ways of operating. This assessment was accurate.

A Slow and Unprofitable Pipeline

Since the late 2010s, just sixteen antimicrobial agents have received broad regulatory approval – mostly close relatives of drugs already in use and thus not expected to overcome bacterial resistance for long. The creation of new ones is a slow and financially unattractive business, given that curative treatments are not as profitable as those managing longer-term ailments. The overall prospect continues to be bleak.

A Glimmer of Optimism and a Novel Approach

Nevertheless, the recent announcement of two new regulator-approved antibiotics against gonorrhea is a welcome development and, crucially, confirms a new way of encouraging development. A particular of the recently approved medications, Zoliflodacin, is the result of a novel kind of collaboration between a global health organization and a pharmaceutical company. The public health partnership provided financial support and managed clinical trials to defray costs and clear approval processes. This type of assistance in advance helps steer the industry towards fields of most pressing public health necessity.

This model and another praised “subscription model” – launched to guarantee income to firms investing in specific antimicrobials – constitute the strongest chance of maintaining a dripfeed of new drugs from the current framework.

The Inevitable Problem of Drug Resistance

But even accelerating the development of compounds in the pipeline isn't sufficient. The new drug is sometimes categorized as a novel type of antimicrobial, meaning it targets a part of the infectious bacteria that existing treatments does, theoretically forcing the bacterium to begin anew in evolving a defense to it. Scientists and physicians are relieved to have a new drug for gonorrhoea – which has resistant strains to every known antibiotic – but warn that eventual drug resistance to it is inevitable.

As has become the norm with recent antimicrobials, exists consequently an debate about whether it should be held in reserve, rationed to extremely drug-resistant cases only – limiting its use to situations where high‑end lab testing is available. This kind of prudent approach should be the worldwide norm, but often cannot be deployed easily in many regions.

A Dwindling Pipeline of Discovery

More broadly, it is difficult to see where the stream of additional novel antimicrobials we require could realistically originate. The aforementioned comment acknowledged the fact that searching the natural world for biological compounds – as with penicillin – has had declining success. The application of AI has been mooted to speed up the search, although a highly-touted initial discovery identified in recent years has not yet progressed past preclinical studies. Synthetic drugs, which are mainly or fully synthesized, are constantly in development, but often confront the fundamental rules of chemistry – just because we imagine a molecule doesn't mean we can create it easily.

Moving Quickly to Stay in Place

The dominant expert assessment is that when it comes to antimicrobials, we must run very fast indeed just to stay in the same place. Prudent, globally managed use is the only way to maintain our advantage. Sadly, the magnitude of forthcoming discoveries is likely to seem meager in contrast to the curative bonanza of the 20th century.