Last
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.
Doctors swiftly isolated him in the intensive care unit.
The germ, a fungus called Candida auris, preys on people with
weakened immune systems, and it is quietly spreading across the globe.
Over the last five years, it has hit a neonatal unit in Venezuela, swept through a hospital
in Spain, forced a prestigious British medical center to shut down its
intensive care unit, and taken root in India, Pakistan and South Africa.
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.
“Everything
was positive — the walls, the bed, the doors, the curtains, the phones,
the sink, the whiteboard, the poles, the pump,” said Dr. Scott Lorin,
the hospital’s president. “The mattress, the bed rails, the canister
holes, the window shades, the ceiling, everything in the room was
positive.”
C. auris is so tenacious, in part, because it is impervious to major antifungal medications, makingued.
Resistant
germs are often called “superbugs,” but this is simplistic because they
don’t typically kill everyone. Instead, they are most lethal to people
with immature or compromised immune systems, including newborns and the
elderly, smokers, diabetics and people with autoimmune disorders who
take steroids that suppress the body’s defenses.
Scientists say
that unless more effective new medicines are develop 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, adding a new and frightening dimension to a
phenomenon that is undermining a pillar of modern medicine.
“It’s
an enormous problem,” said Matthew Fisher, a professor of fungal
epidemiology at Imperial College London, who was a co-author of a recent scientific review on the rise of resistant fungi. “We depend on being able to treat those patients with antifungals.”
Simply put, fungi, just like bacteria, are evolving defenses to survive modern medicines.
Yet
even as world health leaders have pleaded for more restraint in
prescribing antimicrobial drugs to combat bacteria and fungi — convening
the United Nations General Assembly in 2016 to manage an emerging
crisis — gluttonous overuse of them in hospitals, clinics and farming
has contined and unnecessary use of antimicrobial drugs is sharply
curbed, risk will spread to healthier populations. 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 eight million expected to die that year from
cancer.
In the United States, two million people contract
resistant infections annually, and 23,000 die from them, according to
the official C.D.C. estimate. That number was based on 2010 figures;
more recent estimates from researchers at Washington University School of Medicine put the death toll at 162,000. Worldwide fatalities from resistant infections are estimated at 700,000.
Antibiotics
and antifungals are both 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. Even the C.D.C., under its agreement with
states, is not allowed to make public the location or name of hospitals
involved in outbreaks. State governments have in many cases declined to
publicly share information beyond acknowledging that they have had
cases.
All the while, the germs are easily spread — carried on
hands and equipment inside hospitals; ferried on meat and
manure-fertilized vegetables from farms; transported across borders by
travelers and on exports and imports; and transferred by patients from
nursing home to hospital and back.
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.
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 C.D.C. said.
Dr. Lynn
Sosa, Connecticut’s deputy state epidemiologist, said she now saw C.
auris as “the top” threat among resistant infections. “It’s pretty much
unbeatable and difficult to identity,” she said.
Nearly half of
patients who contract C. auris die within 90 days, according to the
C.D.C. 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 C.D.C., which is
spearheading a global detective effort to find treatments and stop the
spread. “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, a
British medical center 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,’” Dr. Rhodes said she was told. She agreed to help the
hospital identify the fungus’s genetic profile and clean it from rooms.
Under
her direction, hospital workers used a special device to spray
aerosolized hydrogen peroxide around a room used for a patient with C.
auris, the theory being that the vapor would scour each nook and cranny.
They left the device going for a week. Then they put a “settle plate”
in the middle of the room with a gel at the bottom that would serve as a
place for any surviving microbes to grow, Dr. Rhodes said.
Only one organism grew back. C. auris.
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.
“There was no need to put out a news release during the outbreak,” said Oliver Wilkinson, a spokesman for the hospital.
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.
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,” Dr. 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 I.C.U. for 11 days, moving intensive care patients to another
floor, 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.” (Later research said there were
eventually 72 total cases, though some patients were only carriers and
were not infected by the fungus.)
Yet the issue remained little
known internationally, while an even bigger outbreak had begun in
Valencia, Spain, at the 992-bed Hospital Universitari i Politècnic La
Fe. There, unbeknown to the public or unaffected patients, 372 people
were colonized — meaning they had the germ on their body but were not
sick with it — and 85 developed bloodstream infections. A paper in the journal Mycoses reported that 41 percent of the infected patients died within 30 days.
A
statement from the hospital said it was not necessarily C. auris that
killed them. “It is very difficult to discern whether patients die from
the pathogen or with it, since they are patients with many underlying
diseases and in very serious general condition,” the statement said.
As with Royal Brompton, the hospital in Spain did not make any public announcement. It still has not.
One
author of the article in Mycoses, a doctor at the hospital, said in an
email that the hospital did not want him to speak to journalists because
it “is concerned about the public image of the hospital.”
The
secrecy infuriates patient advocates, who say people have a right to
know if there is an outbreak so they can decide whether to go to a
hospital, particularly when dealing with a nonurgent matter, like
elective surgery.
“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, a physician in Kentucky and
board chairman of Health Watch USA, a nonprofit patient advocacy group. “You wouldn’t tolerate this at a restaurant with a food poisoning outbreak.”
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
C.D.C. outbreak investigator who dealt with resistant infection
outbreaks in Kentucky in which the hospitals were not publicly
disclosed. “It’s really impossible to message to the public.”
Officials
in London did alert the C.D.C. to the Royal Brompton outbreak while it
was occurring. And the C.D.C. realized it needed to get the word to
American hospitals. On June 24, 2016, the C.D.C. blasted a nationwide
warning to hospitals and medical groups and set up an email address, candidaauris@cdc.gov,
to field queries. Dr. Snigdha Vallabhaneni, a key member of the fungal
team, expected to get a trickle — “maybe a message every month.”
Instead, within weeks, her inbox exploded.
Coming to America
In
the United States, 587 cases of people having contracted C. auris have
been reported, concentrated with 309 in New York, 104 in New Jersey and
144 in Illinois, according to the C.D.C.
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 earliest known case in the United
States involved a woman who arrived at a New York hospital on May 6,
2013, seeking care for respiratory failure. She was 61 and from the
United Arab Emirates, and she died a week later, after testing positive
for the fungus. At the time, the hospital hadn’t thought much of it, but
three years later, it sent the case to the C.D.C. after reading the
agency’s June 2016 advisory.
This woman probably was not America’s
first C. auris patient. She carried a strain different from the South
Asian one most common here. It killed a 56-year-old American woman who
had traveled to India in March 2017 for elective abdominal surgery,
contracted C. auris and was airlifted back to a hospital in Connecticut
that officials will not identify. She was later transferred to a Texas
hospital, where she died.
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The
germ has spread into long-term care facilities. In Chicago, 50 percent
of the residents at some nursing homes have tested positive for it, the
C.D.C. has reported. The fungus can grow on intravenous lines and
ventilators.
Workers who care for patients infected with C. auris
worry for their own safety. Dr. Matthew McCarthy, who has treated
several C. auris patients at Weill Cornell Medical Center in New York,
described experiencing an unusual fear when treating a 30-year-old man.
“I
found myself not wanting to touch the guy,” he said. “I didn’t want to
take it from the guy and bring it to someone else.” He did his job and
thoroughly examined the patient, but said, “There was an overwhelming
feeling of being terrified of accidentally picking it up on a sock or
tie or gown.”
The role of pesticides?
As
the C.D.C. 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, the 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.
The C.D.C. investigators theorized
that C. auris started in Asia and spread across the globe. But when the
agency compared the entire genome of auris samples from India and
Pakistan, Venezuela, South Africa and Japan, it 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,” Dr. Vallabhaneni said.
There are different
theories as to what happened with C. auris. Dr. Meis, the Dutch
researcher, said he believed that drug-resistant fungi were developing
thanks to heavy use of fungicides on crops.
Dr. 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 and account for
more than one-third of all fungicide sales.
A 2013 paper
in Plos Pathogens said that it appeared to be no coincidence that
drug-resistant Aspergillus was showing up in the environment where the
azole fungicides were used. The fungus appeared in 12 percent of Dutch
soil samples, for example, but also in “flower beds, compost, leaves,
plant seeds, soil samples of tea gardens, paddy fields, hospital
surroundings, and aerial samples of hospitals.”
Dr. Meis visited
the C.D.C. last summer to share research and theorize that the same
thing is happening with C. auris, which is also found in the soil:
Azoles have created an environment so hostile that the fungi are
evolving, with resistant strains surviving.
This is similar to
concerns that resistant bacteria are growing because of excessive use of
antibiotics in livestock for health and growth promotion. As with
antibiotics in farm animals, azoles are used widely on crops.
“On
everything — potatoes, beans, wheat, anything you can think of,
tomatoes, onions,” said Dr. Rhodes, the infectious disease specialist
who worked on the London outbreak. “We are driving this with the use of
antifungicides on crops.”
Dr. Chiller 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, hidden in the world’s
crevices, a not particularly aggressive bug. But as azoles began
destroying more prevalent fungi, an opportunity arrived for C. auris to
enter the breach, a germ that had the ability to readily resist
fungicides now suitable for a world in which fungi less able to resist
are under attack.
The mystery of C. auris’s emergence remains
unsolved, and its origin seems, for the moment, to be less important
than stopping its spread.
Resistance and denial
For now, the uncertainty around C. auris has led to a climate of fear, and sometimes denial.
Last
spring, Jasmine Cutler, 29, went to visit her 72-year-old father at a
hospital in New York City, where he had been admitted because of
complications from a surgery the previous month.
When she arrived
at his room, she discovered that he had been sitting for at least an
hour in a recliner, in his own feces, because no one had come when he
had called for help to use the bathroom. Ms. Cutler said it became clear
to her that the staff was afraid to touch him because a test had shown
that he was carrying C. auris.
“I saw doctors and nurses looking
in the window of his room,” she said. “My father’s not a guinea pig.
You’re not going to treat him like a freak at a show.”
He was
eventually discharged and told he no longer carried the fungus. But he
declined to be named, saying he feared being associated with the
frightening infection.
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