Fungal infections are becoming harder to treat as the fungi develop resistance to current drugs, according to new research published Wednesday in The Lancet Microbe.
The study focused on Aspergillus fumigatus, a fungus found worldwide in soil and decaying matter. People inhale its spores regularly without harm. However, for those with weak immune systems or lung problems, the fungus can cause serious illness.
Aspergillus is listed by the World Health Organization as a top fungal threat. Death rates from drug-resistant infections can range from 47% to 88%.
Researchers found drug resistance in this fungus is rising. Additionally, patients are often infected by multiple fungal strains, each with different resistance genes, which complicates treatment.
“This creates major challenges in treating patients,” said Jochem Buil, a microbiologist at Radboud University Medical Centre in the Netherlands and co-author of the study.
Buil’s team examined over 12,600 samples of Aspergillus fumigatus collected from Dutch patients’ lungs over 30 years. About 2,000 samples had mutations linked to resistance against azoles, a common class of antifungal drugs. Most samples carried two well-known mutations, but 17% showed variations.
Among nearly 60 patients with invasive infections—where the fungus spreads beyond the lungs—13 had azole-resistant strains. Of these, 86% were infected with multiple fungal strains, making treatment even harder.
“It is becoming more difficult for doctors to identify if the fungal infection is drug-resistant,” said Dr. Arturo Casadevall of Johns Hopkins Bloomberg School of Public Health, who was not involved in the study.
Doctors usually test for resistance genes before treatment to decide the best drug. When multiple strains infect a patient, different strains may respond to different drugs, complicating the choice.
“Azoles work well for strains that are susceptible, but resistant strains require other drugs that are less effective and have worse side effects,” Buil explained. Sometimes multiple antifungal drugs must be used together.
The research highlights a bigger problem: there are very few antifungal drugs available. Only three main classes of antifungals exist, compared to dozens of antibiotics for bacterial infections. Drug resistance is rising, but developing new antifungals is difficult.
Humans share about half their DNA with fungi, making it hard to target fungi without harming human cells. This limits the number of safe drug targets.
“Resistance often affects entire drug classes, not just one drug,” said Jarrod Fortwendel, a clinical pharmacy professor at the University of Tennessee Health Science Center, who was not involved with the study. “So when resistance appears, we lose many treatment options.”
Much of the azole resistance in Aspergillus fumigatus comes from agricultural use of fungicides. These chemicals, sprayed on crops like wheat and barley, target the same fungal proteins as medical antifungals. Although Aspergillus is not the target, exposure helps it develop resistance genes even before related drugs are used in medicine.
This agricultural link accounted for most of the resistance found in the study.
Fortwendel added that drug-resistant fungi are found worldwide. “Wherever we look, we find resistant fungi. Azole resistance is growing in the U.S. and likely will continue to rise.”
While individual risk remains low, mainly affecting immunocompromised patients, the trend of rising fungal drug resistance is concerning.
“The fungi that cause disease are becoming more drug-resistant,” Casadevall said. “It’s not a sudden pandemic like COVID, but this problem has worsened over the past two decades.”
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