Drug-resistant superbug may be more widespread than previously known
By Susan Scutti, CNN
Updated 9:15 AM ET, Tue January 17, 2017
CDC sees 'steady
increase' in drug-resistant bacteria02:07
(CNN)One family
of superbugs, known as carbapenem-resistant
Enterobacteriaceae or CRE, may be spreading more widely
than previously thought, according to
a study published Monday (PDF) in the
journal Proceedings of the National Academy of Sciences.
In fact, transmission of these bacteria person-to-person
may be occurring without symptoms, say the researchers,
from the Harvard T.H. Chan School of Public Health and
the Broad Institute.
"We often talk about the rising tide of antibiotic
resistance in apocalyptic terms," said William Hanage,
senior author of the study and an associate professor of
epidemiology at the Harvard Chan School. "But we should
always remember that the people who are most at risk of
these things would be at risk for any infection, because
they are often among the frailer people in the health
care system."
When an illness-causing bug won't disappear with the
usual drugs, patients are given last-resort
antibiotics such as carbapenem. Still, some
"nightmare bacteria" continue to thrive even when
given the strongest medicines reserved for the
toughest cases. CRE, which tend to spread in
hospitals and long-term care facilities, cause an
estimated
9,300 infections and 600 deaths each year in the
United States, according to the Centers for
Disease Control and Prevention.
And they are on the rise.
The genetics of infection
Over a 16-month period, the Harvard-MIT research
team examined genetic sequences from about 250
samples of patients who had CRE in four
hospitals in Boston and Irvine, California.
"A lot of people have done a lot of really good
work by focusing on things like outbreaks,"
Hanage said. He and his colleagues were aiming
instead to get a "population snapshot" of CRE,
to define how frequently these infections
occurred and to understand which bacterial
strains were causing infections within
hospitals.
"We tried to get an idea of what the population
was, and that enabled us to capture the
diversity of these things, which were causing
disease in the hospitals we studied," Hanage
said.
First, the researchers found very little
evidence of direct transmission between patients
who became sick. "There's one, maybe two, in all
the samples we looked at," Hanage said. Based on
this, he and his colleagues believe transmission
may be occurring without causing symptoms.
In other words, people colonized with these
germs may spread them, a la Typhoid Mary,
without ever becoming sick themselves.
According to Dr. Alex Kallen, a medical
officer in the CDC's Division of Healthcare
Quality Promotion, who was not involved in
the study, "the most common source of
transmission with CRE is asymptomatic." Most
patients will not have any symptoms of CRE,
which lives in the gastrointestinal tract,
according to Kallen.
The study also documented "the identical
gene in different species. ... The extent to
which this has happened is really quite
surprising," Hanage said. Also, "we found
two cases of high-level resistance we could
not explain."
This he compared to "dark matter: We know
it's there because we can see its effects,
but what's actually making it happen at the
moment is unknown."
"If I were to criticize my own work, I would
say it is a shame that we weren't able to
get more hospitals and more samples from
elsewhere within the health care systems,"
Hanage said.
Limited by funding, the researchers could
not track whether transmission had occurred
in a long-term care facility or in the
community, outside the hospitals they
studied.
The patient, a Washoe County woman in her
70s, had been living for an extended period
in India. She returned to the US in early
August.
On returning, the woman suffered
systemic inflammatory response syndrome
-- a whole-body immune system reaction
to an infection -- and was admitted to a
Reno hospital. Notably, she had been
hospitalized in India just two months
before, one of several hospitalizations
due to complications from a thighbone
fracture.
She was in the Reno hospital almost six
days before the CDC confirmed her
infection as a strain of CRE called NDM.
"There are two primary types of CRE. One
of them is called New Delhi
metallo-beta-lactamase, or NDM, and
another one is called Klebsiella
pneumoniae carbapenemase, or KPC," said
Lei Chen, senior epidemiologist for the
Washoe County Health District.
Both strains both have specific enzymes
that can break down carbapenem
antibiotics, rendering these powerful
drugs ineffective, explained Chen.
Generally,
KPC is more prevalent in the US than
NDM: The CDC recorded 175 NDM cases as
of January 6.
In the case of the woman in Washoe
County, her infection was resistant to
all 26 antibiotics available in the US,
which is very rare.
"The treating physicians were trying
their best," Chen said. Once they
received the advanced lab results, the
doctors switched antibiotics
accordingly, but their patient still
developed septic shock and died in early
September.
"Unfortunately, the patient progressed
very fast," Chen said, explaining that
things are sometimes just beyond the
doctor's control: "They just run out of
options."
However, there was still work to be done
in order to protect the community. To
find out whether others had been
infected, Chen and her colleagues
performed a survey among patients
admitted to that same unit.
"We did a rectal swab for those
patients, and the laboratory didn't
identify any additional CRE," she said.
The ongoing surveillance program for
monitoring CRE, which had been in effect
since 2010, also has not identified any
additional cases up to and including
today.
"I think the hospital did an
excellent job in identification of
the case and putting contact
precautions immediately after," Chen
said. "This hospital is doing an
excellent job in terms of
hand-washing compliance, according
to the infection-control people, so
I think that contributed to that, as
well."
Another lucky break: The woman was
in a single-patient room from the
start of her hospitalization and so
did not spread her infection to a
roommate.
Hanage sees this case as "an
illustration of the sort of thing
that we are up against. These
bacteria are deadly. ... So we would
be well-advised to do everything we
can to keep them rare."
"If we want to keep them rare, we
have to understand first how much of
them are out there, how many there
are out there, where they are and
how they're transmitting from person
to person," he said.
"The best way to stop a person from
dying from this is to stop them from
getting sick with this, and the best
way to stop them from getting sick
with it is to make sure they never
pick it up in the first place," he
said, adding that "it's incumbent
upon us to understand transmission."
The Dutch have one of the lowest
rates of antibiotic resistance
globally, he noted, because they
identify people who are at risk
before they come into the hospital.
The importance of handwashing
Though it is easy to feel helpless,
each of us can play a role in
preventing the spread of these
terrifying bacteria.
Hand hygiene and environmental
sanitation are essential to
preventing the spread of all
bacteria, according to Kallen.
"Make sure people are washing
their hands when caring for you.
Make sure they are cleaning
equipment," he said. Though we
may feel at our weakest while
staying in a hospital, it is
important to speak up if health
care providers do not stop and
clean their hands.
Chen and her colleagues suggest
an approach quite like that of
the Dutch, where health care
facilities get a history of
health care exposures outside
their region upon admission, and
consider screening for CRE when
patients report having visited a
place with a higher incidence of
CRE.
"Of course, obtaining the
history is not difficult, right?
It can just be implemented into
the intake questions," Chen
said. After Ebola, measles and
Zika, many hospitals are already
noting travel history during
admission.
"For CRE testing/screening,
every hospital can do that. It's
just a routine bacteria culture
first, and then after
identifying the organism, they
perform the antibiotic
susceptibility testing," she
said.
Not every hospital has the
capacity to detect the exact
CRE mechanism. Still, she
said, the patient can be
immediately isolated while
the hospital waits for more
advanced results.
According to Hanage, the
trend is toward using
genomics to identify
patterns of transmission,
the amounts of gene
diversity and the presence
of resistant organisms.
In 10 years, he imagines a
system that is "rapidly
taking environmental
samples."
"New threats would be
identified and flagged
quickly so we can direct our
resources most effectively,"
Hanage said. "In order to be
able to do that, you have to
know what you are looking
for, and so work like this
is helpful to tell us what
we should be looking for and
where we should be worried."