topics|Mould breakers

Antifungal Resistance

Fungi are evolving resistance to the drugs used to treat them, mirroring the better-known problem of antibiotic resistance in bacteria. Dangerous fungal infections are rising worldwide, especially among the growing number of people with weakened immune systems. Systemic fungal infections are responsible for an estimated 7m life-threatening infections and more than 2.5m deaths a year.

The existing arsenal

There are currently only three main classes of antifungal drugs, compared with more than a dozen types of antibiotics:

Polyenes — target the fungal cell membrane
Azoles — target an enzyme involved in building and maintaining the fungal cell membrane
Echinocandins — attack the fungal cell wall; introduced in the early 2000s, they are the newest approved class

Part of the reason so few antifungal classes exist is that fungi are much more closely related to animals than bacteria are, meaning that compounds lethal to fungi may also harm human cells.

Agricultural cross-resistance

Resistance mutations often arise when human-infecting fungi are exposed to agricultural fungicides in compost heaps or soil. When a fungicide works by a similar mechanism to an antifungal medicine — for example, by targeting the same enzyme — fungi can develop resistance to the medical drug even though they have been exposed only to the agricultural one.

New drugs in development

Ibrexafungerp — developed by Scynexis and commercialised by GSK; attacks the cell wall by a novel mechanism. Phase-two trial data suggest effectiveness in around 80% of patients.
Fosmanogepix — made by Amplyx Pharmaceuticals (since acquired by Pfizer); also targets the cell wall via a new approach. Phase-two data likewise suggest around 80% effectiveness.
Olorofim — developed by F2G, a company based in Manchester; interferes with a fungus's ability to make DNA rather than attacking the cell wall. In a phase-two trial against invasive moulds, it showed a 29% success rate in patients whose infections could not be treated by other drugs.

In March 2025 Chinese scientists reported in Nature the discovery of a new polyene compound that targets a different part of the fungal cell membrane than older polyenes, showing effectiveness against multi-drug-resistant fungi with lower toxicity.

Regulatory concerns

American, Canadian, Japanese and South Korean regulators have already approved a fungicide called ipflufenoquin that works by the same mechanism as olorofim. A 2023 study showed that strains of one fungus that evolved resistance to ipflufenoquin also showed resistance to olorofim in the laboratory. Similarly, aminopyrifen, a new fungicide, targets the same enzyme as fosmanogepix.

America's Environmental Protection Agency decided in October 2024 to assess resistance risks when approving new fungicides. The European Union investigated the use of azole antifungals and fungicides for the first time in January 2025 and recommended that approval of new fungicides should bear antifungal resistance in mind.

The food-security dilemma

Fungal infections are the leading cause of crop failures, destroying up to 40% of the world's annual harvest — the equivalent of food for 4bn people. Regulators therefore cannot simply ban agricultural fungicides without risking food security.