Just one week after the season finale of the HBO show “The Last of Us,” about a zombie apocalypse caused by a fungal infection, the Centers for Disease Control and Prevention issued a warning about Candida auris spreading in U.S. health care facilities. Twenty-seven states and Washington, D.C. have reported cases of the deadly fungal infection that often doesn’t respond to common antifungal drugs, with southern Nevada emerging as a hotspot of infections. Clinical cases have risen each year since it was first publicly reported in 2016, with 2,377 reported in 2022, and the CDC notes that based on limited information, 30–60% of those infected with C. auris have died. C. auris infects people whose immune systems are already weakened due to other health issues. This makes it difficult to determine the precise number of deaths specifically attributable to C. auris itself.
The C. auris outbreak is alarming. But even scarier is the issue it highlights: We’re not taking appropriate steps to monitor, track, and stop fungal pathogens that can infect people and resist current treatments.
For millennia, fungi evolved to survive in the natural environment and only rarely caused serious infections in people. However, since the 1980s, we’ve seen a marked increase in fungal infections, including the emergence of newly recognized species and strains that are resistant to our best antifungal drugs. According to Tom Chiller, deputy chief of the Mycotic Diseases Branch at the CDC, there are about 300 fungal pathogens that can currently infect humans, a small sliver of the 5 million or so fungal species present in our environment. But more may be coming: As our environment changes, that massive reservoir of fungi can adapt, spread and potentially infect humans.
Unlike in “The Last of Us,” there won’t be any zombies. But a strained health care system and increased mortality for patients are both extremely possible, even likely. And a worst-case scenario is that a new fungal pathogen emerges, infects healthy people on a broad scale, and resists our limited treatment options.
The good news is that there’s still time for policymakers and government agencies to mitigate the risk of antifungal-resistant pathogens.
The first gap to fill is surveillance of fungal pathogens that currently infect people and those that may in the future. For example, estimates show that invasive infections due to Aspergillus, a fungal pathogen that infects people when they breathe in its spores from the environment, cause 15,000 hospitalizations and 800 deaths per year in the United States. Chiller notes that the true numbers are likely much higher, but we just don’t have systems in place to accurately measure the impact of Aspergillus.
The second problem to tackle is the overuse of current antifungals. There are only three main classes of antifungals used to treat invasive fungal infections in humans, compared with at least 12 classes of medically important antibiotics used to treat bacterial infections. The more you use antifungals, the more you drive the evolution of fungal pathogens that resist these drugs. Most people are familiar with athlete’s foot or yeast infections that require treatment with antifungals. Misusing antifungals in human medicine, including not finishing the entire course of treatment or taking too low of a dose, can drive resistance.
What most people don’t realize is that antifungals are increasingly overused in plant agriculture — tulip production in the Netherlands provides a cautionary tale. Not long ago, Dutch health professionals started seeing patients with Aspergillus fumigatus infections that didn’t respond to the antifungal drug typically used to treat them. Researchers eventually linked resistant strains of Aspergillus to tulip farms, where farmers were widely using antifungals as pesticides, otherwise known as fungicides. That overuse bred deadly drug-resistant strains of Aspergillus that can drift on the wind from tulip farms to people. The terrifying thing about these fungi is that they kill four out of five people that they infect.
The Environmental Protection Agency has allowed fungicide use on crops like fruit orchards, wheat and soy for decades to prevent or mitigate fruit and crop spoilage. On one hand, we haven’t seen the same kind of distressing uptick in antifungal-resistant infections that occurred in the Netherlands from overuse of fungicides on tulip farms. On the other hand, we’re not looking that hard to find any potential uptick even though fungicide use in agriculture has exploded in recent years. According to data from California, the only state that has such information, triazoles, a critical class of antifungals in human medicine, are used at a rate that’s 20 times higher in food production compared with nonfood use.
There are also serious communication failures among the agencies charged with regulating and assessing antifungal use in human medicine and agriculture. While the CDC expresses concern about overusing antifungals, the EPA continues to approve expanded fungicide use in agriculture. For example, the EPA recently approved the fungicide ipflufenoquin for use on pome fruits even though it has the same mode of action as olorofim, a new antifungal being developed for use in humans. This is a recipe for disaster, where the effectiveness of a critical human drug is undermined by agricultural use before it’s even used to treat people.
As a first step, the EPA should withdraw its approval of ipflufenoquin for use in agriculture. And policymakers should restrict the use of any new antifungals to human medicine. That will help ensure that when new fungal pathogens emerge, we’ll have the tools we need to keep people safe. We’re far from the dystopian scenes of “The Last of Us,” but without swift action to keep antifungals effective, we face a darkened future.
Matthew Wellington is the public health campaigns director with PIRG. Lance Price is director of the Antibiotic Resistance Action Center at the George Washington University Milken Institute School of Public Health.