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Sunday, April 05, 2020

The rise of drug-resistant infections: Fungus immune to drugs secretly sweeps the globe

Candida auris is so tenacious, in part, because it is impervious to major antifungal medications, making it a new example of one of the world’s most intractable health threats: the rise of drug-resistant infections.

By: New York Times | Updated: April 7, 2019 12:13:35 pm
Candida auris, mysterious global infections, fungal infections Dr Shawn Lockhart, a fungal disease specialist, holds a microscope slide with inactive Candida auris, in Atlanta. (Melissa Golden/The New York Times)

In May, an elderly man was admitted to the Brooklyn branch of Mount Sinai Hospital for abdominal surgery. A blood test revealed that he was infected with a newly discovered germ as deadly as it was mysterious.

The germ, a fungus called Candida auris, preys on people with weakened immune systems, and it is quietly spreading across the globe. Recently C. auris reached New York, New Jersey and Illinois, leading the federal Centers for Disease Control and Prevention to add it to a list of germs deemed “urgent threats.”

The man at Mount Sinai died after 90 days in the hospital, but C. auris did not. Tests showed it was everywhere in his room, so invasive that the hospital needed special cleaning equipment and had to rip out some of the ceiling and floor tiles to eradicate it.

C. auris is so tenacious, in part, because it is impervious to major antifungal medications, making it a new example of one of the world’s most intractable health threats: the rise of drug-resistant infections.

For decades, public health experts have warned that the overuse of antibiotics was reducing the effectiveness of drugs that have lengthened life spans by curing bacterial infections once commonly fatal. But lately, there has been an explosion of resistant fungi as well.

“It’s an enormous problem,” said Matthew Fisher, a professor of fungal epidemiology at Imperial College London. “We depend on being able to treat those patients with antifungals.”

Simply put, fungi, just like bacteria, are evolving defenses to survive modern medicines. A study the British government funded projects that if policies are not put in place to slow the rise of drug resistance, 10 million people could die worldwide of all such infections in 2050, eclipsing the 8 million expected to die that year from cancer.

Antibiotics and antifungals are essential to combat infections in people, but antibiotics are also used widely to prevent disease in farm animals, and antifungals are also applied to prevent agricultural plants from rotting. Some scientists cite evidence that rampant use of fungicides on crops is contributing to the surge in drug-resistant fungi infecting humans.

Yet as the problem grows, it is little understood by the public — in part because the very existence of resistant infections is often cloaked in secrecy. With bacteria and fungi alike, hospitals and local governments are reluctant to disclose outbreaks for fear of being seen as infection hubs.

C. auris, which infected the man at Mount Sinai, is one of dozens of dangerous bacteria and fungi that have developed resistance. Yet, like most of them, it is a threat that is virtually unknown to the public.

Candida auris, mysterious global infections, fungal infections Dr Tom Chiller heads the fungal division at the Centers for Disease Control and Prevention, leading the team researching the emerging Candida Auris crisis, in Atlanta, August 23, 2018. (Melissa Golden/The New York Times)

Other prominent strains of the fungus Candida — one of the most common causes of bloodstream infections in hospitals — have not developed significant resistance to drugs, but more than 90 percent of C. auris infections are resistant to at least one drug, and 30 percent are resistant to two or more drugs, the CDC said.

Nearly half of patients who contract C. auris die within 90 days, according to the CDC. Yet the world’s experts have not nailed down where it came from in the first place.

“It is a creature from the black lagoon,” said Dr Tom Chiller, who heads the fungal branch at the CDC. “It bubbled up and now it is everywhere.”

‘No Need’ to Tell the Public

In late 2015, Dr Johanna Rhodes, an infectious disease expert at Imperial College London, got a panicked call from the Royal Brompton Hospital outside London. C. auris had taken root there months earlier, and the hospital couldn’t clear it.

“‘We have no idea where it’s coming from. We’ve never heard of it. It’s just spread like wildfire,’” Rhodes said she was told. She agreed to help the hospital identify the fungus’ genetic profile and clean it from rooms.

It was spreading, but word of it was not. The hospital, a specialty lung and heart center that draws wealthy patients from the Middle East and around Europe, alerted the British government and told infected patients, but made no public announcement.

This hushed panic is playing out in hospitals around the world. Individual institutions and national, state and local governments have been reluctant to publicize outbreaks of resistant infections, arguing there is no point in scaring patients — or prospective ones.

Candida auris, mysterious global infections, fungal infections Dr Johanna Rhodes, an infectious disease expert, in her lab at the Department of Infectious Disease Epidemiology, Imperial College School of Public Health, St. Mary’s Campus London, August 13, 2018. (Tom Jamieson/The New York Times)

Dr Silke Schelenz, Royal Brompton’s infectious disease specialist, found the lack of urgency from the government and hospital in the early stages of the outbreak “very, very frustrating.”

“They obviously didn’t want to lose reputation,” Schelenz said. “It hadn’t impacted our surgical outcomes.”

By the end of June 2016, a scientific paper reported “an ongoing outbreak of 50 C. auris cases” at Royal Brompton, and the hospital took an extraordinary step: It shut down its ICU for 11 days, again with no announcement.

Days later the hospital finally acknowledged to a newspaper that it had a problem. A headline in The Daily Telegraph warned, “Intensive Care Unit Closed After Deadly New Superbug Emerges in the U.K.”

Yet the issue remained little known internationally, while an even bigger outbreak had begun in Valencia, Spain, at the Hospital Universitari i Politècnic La Fe. As with Royal Brompton, the hospital in Spain did not make any public announcement. It still has not.

The secrecy infuriates patient advocates, who say people have a right to know if there is an outbreak. “Why the heck are we reading about an outbreak almost a year and a half later — and not have it front-page news the day after it happens?” said Dr Kevin Kavanagh, chairman of Health Watch USA, a nonprofit patient advocacy group.

Health officials say that disclosing outbreaks frightens patients about a situation they can do nothing about, particularly when the risks are unclear. “It’s hard enough with these organisms for health care providers to wrap their heads around it,” said Dr Anna Yaffee, a former CDC outbreak investigator. “It’s really impossible to message to the public.”

Officials in London did alert the CDC to the Royal Brompton outbreak while it was occurring. And the CDC realized it needed to get the word to U.S. hospitals. On June 24, 2016, the CDC blasted a nationwide warning and set up an email address,, to field queries. Dr Snigdha Vallabhaneni, a key member of the fungal team, expected to get a trickle — “maybe a message every month.”

Candida auris, mysterious global infections, fungal infections Dr Snighdha Vallabhaneni is a fungal expert and epidemiologist at the Centers for Disease Control and Prevention and has been closely involved with the emerging Candida Auris crisis. (Melissa Golden/The New York Times)

Instead, within weeks, her inbox exploded. In the United States, 587 cases of people having contracted C. auris have been reported, according to the CDC. The symptoms — fever, aches and fatigue — are seemingly ordinary, but when a person gets infected, particularly someone already unhealthy, such commonplace symptoms can be fatal.

The Role of Pesticides?

As the CDC works to limit the spread of drug-resistant C. auris, its investigators have been trying to answer the vexing question: Where in the world did it come from?

The first time doctors encountered C. auris was in the ear of a woman in Japan in 2009 (auris is Latin for ear). It seemed innocuous at the time, a cousin of common, easily treated fungal infections. Three years later, it appeared in an unusual test result in the lab of Dr Jacques Meis, a microbiologist in Nijmegen, Netherlands, who was analyzing a bloodstream infection in 18 patients from four hospitals in India. Soon, new clusters of C. auris seemed to emerge with each passing month in different parts of the world.

When the CDC investigators compared the entire genome of auris samples from India and Pakistan, Venezuela, South Africa and Japan, they found that its origin was not a single place, and there was not a single auris strain. The genome sequencing showed that there were four distinctive versions of the fungus, with differences so profound that they suggested that these strains had diverged thousands of years ago and emerged as resistant pathogens from harmless environmental strains in four different places at the same time.

“Somehow, it made a jump almost seemingly simultaneously, and seemed to spread and it is drug-resistant, which is really mind-boggling,” Vallabhaneni said.

There are different theories as to what happened with C. auris. Meis, the Dutch researcher, said he believed that drug-resistant fungi were developing thanks to heavy use of fungicides on crops.

Meis became intrigued by resistant fungi when he heard about the case of a 63-year-old patient in the Netherlands who died in 2005 from a fungus called Aspergillus. It proved resistant to a front-line antifungal treatment called itraconazole. That drug is a virtual copy of the azole pesticides that are used to dust crops the world over.

Chiller of the CDC theorizes that C. auris may have benefited from the heavy use of fungicides. His idea is that C. auris actually has existed for thousands of years, a not particularly aggressive bug. But as azoles began destroying more prevalent fungi, an opportunity arrived for C. auris to enter the breach.

The mystery of C. auris’ emergence remains unsolved, and its origin seems, for the moment, to be less important than stopping its spread.

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