The growing threat of drug-resistant, invasive fungi

Large numbers of COVID-19 hospitalizations and more immunocompromised people in general are fueling a global spread of a different threatening microbe: invasive fungi.

Why it matters: These infections cause more than 1.6 million deaths worldwide every year, and the microorganisms responsible for them are starting to evade the small supply of antifungal drugs.

"Out of all the [hospitalized] people who have gotten bacterial infections, 5% will die from those infections. And that's a lot. ... When it comes to life-threatening fungal infections, 50% of those patients will die from that infection. And that message really isn't being told."

Background: Out of the 6 million species of fungi, some hold a positive benefit for humans, ranging from beer-making yeast to biotech ingredients to our gut microbiome.

• Some only pose mild harm to humans, such as ringworm, and most cannot thrive in human body temperature.
• But the newest emerging microbe threat is the growing number of invasive fungi that normally attack a large number of immunosuppressed people, like COVID-19 patients in India, but can sometimes infect healthy people as well.
• Exact numbers of fungal infections are unknown, as they are "often underdiagnosed or misdiagnosed," says Tom Chiller, chief of the CDC's Mycotic Diseases Branch.

There are only three main classes of drugs to fight invasive fungal infections.

• It can be difficult to find great treatments, partly because fungi are eukaryotes and similar to humans in how their cells are structured and get food, and "a lot of times something that's toxic to a fungus will also be toxic to humans" and cause liver or kidney damage, Kennedy says.
• Azoles are the only antifungal that can be administered in pill form, but there's growing resistance to it, partly from "extremely broad" use in agriculture, Kennedy adds.
• Drug resistance "is a real problem," says Chiller, who's also a physician and an epidemiologist. Over the past 5–10 years, the CDC has seen some worrisome trends in invasive fungi, including Candida auris, Aspergillus, Coccidioides immitis and Coccidioides posadasii (or Valley Fever), and Sporothrix brasiliensis.

What's happening: Invasive fungi — ones that become systemic or breach normal immune barriers — are a growing concern, Chiller says.

• Some studies have "found that Aspergillosis, which is a rare mold disease, is actually one of the more common things found in autopsy, and yet the death certificates or the reasons for dying do not include it," Chiller says.
• Drug-resistant C. auris can kill people, and some strains are becoming resistant to all three classes of antifungals. Plus, it often doesn't respond to traditional ammonia cleaners, and contaminated surfaces have caused some nursing homes, long-term care facilities and hospitals to rip out entire units.
• "And it's really transmissible — more like a bacteria than a fungus. We don't think of candida or candidemia as a contagious disease in a hospital, but now we need to because of this new species Candida auris," Chiller says.

• John Rex, chief medical officer of a rare fungal disease drug company called F2G, says "the really scary one" is Valley Fever, which is endemic to the Southwest U.S. but is spreading due to climate change. While most people who breathe in the spores are fine, "about 5% have an awful, awful outcome ... and we do not think we have anything that cures it, ever."
• Sporothrix brasiliensis, a fungus that has taken off in South America, is a concern because it's a zoonotic disease that can spread from cats or rats to humans, Chiller says.
• Even more worrisome: Both Valley Fever and sporotrichosis can infect healthy humans.

What's next: The FDA recently approved a new class of antifungal drugs for vaginal yeast infections — the first new class of antifungal drugs in 20 years — although it's not for invasive disease, Chiller says. But, he adds he's "excited" there may be new drugs soon that target invasive fungal disease using new mechanisms.

• Amplyx, which was recently sold to Pfizer, has the drug fosmanogepix in Phase II of clinical trials and targets a protein unique to fungi with the hope it will offer a new, safe and effective antifungal class, Kennedy says.
• Rex says he's also hopeful the bipartisan bill, the PASTEUR Act, will help bolster the drug pipeline for "new anti-infectives that have a value to society that is so wildly disproportionate to the value the innovator can receive based on sales, because we work so hard to not have the infection."