Infection experts warn of more U.S. superbug
cases in coming months
by Ransdell Pierson
NEW YORK (Reuters) - After two confirmed U.S. cases of a superbug that
thwarts a last-resort antibiotic, infectious disease experts say they
expect more cases in coming months because the bacterial gene behind it
is likely far more widespread than previously believed.
Army scientists in May reported finding E. coli bacteria that harbor a
gene which renders the antibiotic colistin useless. The gene, called
mcr-1, was found in a urine sample of a Pennsylvania woman being treated
for a urinary tract infection.
On Monday, researchers confirmed preliminary findings that E. coli
carrying the same mcr-1 gene were found in a stored bacterial sample of
a New York patient who had been treated for an infection last year, as
well as in patient samples from nine other countries.
The report came from a global effort called the SENTRY Antimicrobial
Surveillance Program, led by Mariana Castanheira of JMI Laboratories
based in North Liberty, Iowa.
The mcr-1 superbug has been identified over the past six months in farm
animals and people in about 20 countries, including China, Germany and
The bacteria can be transmitted by fecal contact and poor hygiene, which
suggests a far wider likely presence than the documented cases so far,
according to leading infectious disease experts.
Health officials fear the mcr-1 gene, carried by a highly mobile piece
of DNA called a plasmid, will soon be found in bacteria already
resistant to all or virtually all other types of antibiotics,
potentially making infections untreatable.
"You can be sure (mcr-1) is already in the guts of people throughout the
United States and will continue to spread," said Dr. Brad Spellberg,
professor of medicine at the University of Southern California.
Dr. David Van Duin, an infectious disease expert at the University of
North Carolina in Chapel Hill, said he expects more documented U.S.
cases of mcr-1 in coming months because it is already here and will
spread from abroad. "We will see a lot more of this gene."
Colistin causes kidney damage, but doctors have opted for it as other
antibiotics increasingly fail. Its overuse, especially in overseas farm
animals, has allowed bacteria to develop resistance to it.
PAST AND PRESENT INFECTIONS
To track the mcr-1 gene, U.S. hospitals are working together with state
and federal agencies to test bacteria samples of patients that have
recently been treated for infections. Many of the largest research
hospitals are examining samples of antibiotic-resistant bacteria that
have long been stored in their freezers.
Gautam Dantas, associate professor of pathology at Washington University
Medical Center in St. Louis, has tested hundreds of U.S. samples of
archived bacteria in recent months and has not yet detected mcr-1. But
he expects dozens of confirmed cases of the gene will be documented by
next year in the country, mostly among current patients.
The concern of many disease experts is that mcr-1 could soon show up in
bacteria also resistant to carbapenems, one of the few remaining
dependable classes of antibiotics. In that event, with colistin no
longer a last-ditch option, some patients would have to rely on their
immune systems to fight off infection.
"Within the next two to three years, it's going to be fairly routine for
infections to occur in the United States for which we have no
(effective) drugs available," Dantas said.
Castanheira also believes mcr-1 will find its way into carbapenem-resistant
bacteria, formally known as carbapenem-resistant enterobacteriaceae (CRE).
In an interview, she said the resulting virtually impervious bacterium
would likely spread slowly inside the United States because CRE
themselves are not yet widespread in the country, giving drugmakers some
time to create new antibiotics.
Beginning in August, the U.S. Centers for Disease Control and Prevention
will use $21 million to expand surveillance at laboratories operated by
all 50 state health departments and seven larger regional labs. The
federal funding will help pay for more-sensitive equipment to test for
antibiotic resistance in bacteria samples provided by hospitals.
A 'slow catastrophe' unfolds as the golden age of antibiotics comes
to an end
by Melissa Healy
In early April, experts at a military lab outside Washington intensified
their search for evidence that a dangerous new biological threat had
penetrated the nation’s borders.
They didn’t have to hunt long before they found it.
On May 18, a team working at the Walter Reed Army Institute of Research
here had its first look at a sample of the bacterium Escherichia coli,
taken from a 49-year-old woman in Pennsylvania. She had a urinary tract
infection with a disconcerting knack for surviving the assaults of
antibiotic medications. Her sample was one of six from across the
country delivered to the lab of microbiologist Patrick McGann.
Within hours, a preliminary analysis deepened concern at the lab. Over
the next several days, more sophisticated genetic sleuthing confirmed
McGann’s worst fears.
There, in the bacterium’s DNA, was a gene dubbed mcr-1. Its presence
made the pathogen impervious to the venerable antibiotic colistin.
We’re seeing more drug-resistant infections. And people will die. —
William P. Hanage, Harvard University infectious disease epidemiologist
More ominously, the gene’s presence on a plasmid — a tiny mobile loop of
DNA that can be readily snapped off and attached to other bacteria —
suggested that it could readily jump to other E. coli bacteria, or to
entirely different forms of disease-causing organisms. That would make
them impervious to colistin as well.
It was a milestone public health officials have been anticipating for
years. In a steady march, disease-causing microbes have evolved ways to
evade the bulwark of medications used to treat bacterial infections. For
a variety of those illnesses, only colistin continued to work every
time. Now this last line of defense had been breached as well.
A second U.S. case of E. coli with the mcr-1 resistance gene was
reported this week in the journal Antimicrobial Agents and Chemotherapy.
Researchers are still working to determine whether it, or any of 18
other samples from around the world, contained the gene on an
Note: See the source for a graphic on the failing of antibiotics.
In 1928, British bacteriologist Alexander Fleming discovered that an
errant penicillin mold growing in one of his petri dishes had the power
to kill staphylococcus, a type of bacteria that causes pneumonia, skin
infections and food poisoning. It took scientists, industrialists and
the pressures of a world war to convert the mold into a mass-produced
medicine, which was ready in time for troops to pack on D-Day.
More than 100 antibiotic compounds have been introduced since. But
almost as soon as they were given to patients, scientists began finding
evidence that disease-causing bacteria were developing resistance to
these new wonder drugs.
Bacteria meet, mate, compete and evolve inside living bodies. When an
antibiotic is added to the mix, only the strongest survive.
Humans have accelerated this natural process by indiscriminately
prescribing antibiotics and by routinely feeding the drugs to livestock,
scientists say. Multiply the number of humans and animals taking these
drugs, and you multiply the opportunities for antibiotic-resistant
strains to emerge.
Until very recently, few made the connection between antibiotic use in
individual cases and the emergence of antibiotic resistance, said Dr.
Susan Bleasdale, an infection-control expert at the University of
Illinois in Chicago. Patients with earaches, sinus pressure and sore
throats demanded antibiotics, and physicians tended to oblige.
The results have been deadly. Each year, more than 2 million people in
the U.S. are infected with a bacterium that has become resistant to one
or more antibiotic medication designed to kill it, according to the
federal Centers for Disease Control and Prevention. At least 23,000
people die as a direct result of antibiotic-resistant infections, and
many more die from other conditions that were complicated by an
antibiotic-resistant infection, the agency says.
As medicines such as tetracycline, erythromycin and vancomycin lost much
of their effectiveness, colistin continued to overwhelm trouble-making
bacteria such as Salmonella, Klebsiella and E. coli.
Colistin is toxic to the human kidney, and doctors largely stopped using
it in the 1970s when safer medications became available. But now that so
many antibiotics have lost their ability to vanquish E. coli and other
bacterial invaders, colistin has become the only hope for some desperate
It’s not apocalyptic until it is. Shame on us if we wait till bodies are
in the street. — Peter Pitts, president of the Center for Medicine in
the Public Interest
The slow, steady march of antibiotic resistance doesn’t cause people to
bleed to death in the streets, the way the Ebola virus does. It doesn’t
cause heart-rending birth defects, as the Zika virus does.
And it rarely makes headlines. A survey released in June by the
Infectious Diseases Society of America found that only 30% of Americans
believe that antibiotic resistance is a significant problem for public
Yet officials at the World Health Organization warn that gonorrhea “may
soon become untreatable” because of growing resistance to the antibiotic
ceftriaxone, a member of the cephalosporin class. The WHO also notes
that extensively-drug-resistant tuberculosis is now circulating in 100
countries, and that worldwide resistance to carbapenem antibiotics has
weakened physicians’ last line of attack against life-threatening
intestinal enterbacteriacaea infections.
“It’s a slow catastrophe,” said Army Col. Emil Lesho, director of the
Defense Department’s Multidrug-resistant Organism Repository and
The problem goes beyond treating infections. As bacterial resistance
grows, Lesho said, “we’re all at risk of losing our access” to medical
miracles we’ve come to take for granted: elective surgeries, joint
replacements, organ transplants, cancer chemotherapies. These treatments
give bacteria an opportunity to hitch a ride on a catheter or an
unwashed hand and invade an already vulnerable patient.
The struggle to sustain the effectiveness of antibiotics is a
never-ending arms race. If humankind were regularly finding new
anti-microbial agents and turning them into medicines, there might be
less cause for worry.
Researchers haven’t identified a new class of antibiotic medication
since 1987. As a result, while bacteria have continuously evolved new
ways to thwart antibiotics, the medicines have not gained new mechanisms
to fight back.
The economics of drug development are partly to blame.
To offset the millions of dollars they pour into research, clinical
trials and the FDA approval process, pharmaceutical companies aim to
develop blockbuster drugs, said Dr. Anthony Fauci, director of the
National Institute for Allergies and Infectious Diseases. An ideal
candidate would be used by millions of people every day for the rest of
their lives, like pills to keep cholesterol or blood pressure in check.
Antibiotics won’t pay the freight. They should be prescribed sparingly
and only used for about a week. They could be rendered obsolete at any
time by resistance genes. Worst of all, they compete in a field of
Without government policies that encourage investment in the
antibiotics, “there’s very little incentive” for companies to do it
themselves, Fauci said.
Other approaches can help. Under Fauci, the NIAID is funding the
development of tests that would speed the diagnosis of infections and
prompt more careful use of antibiotics by physicians and hospitals.
New vaccines to prevent bacterial infections are under study, and
existing vaccines could be more widely used. The use of bacteria-killing
viruses — an approach called phage therapy that revives an idea largely
abandoned in the 1930s — is getting a second look.
The Pennsylvania patient whose infection was impervious to colistin was
able to beat back the bacteria in her urinary tract with the help of
other antibiotics. She survived.
Others have not been so lucky. Hospital patients infected by
antibiotic-resistant bacteria are twice as likely to die as those
infected by the non-resistant strains of the same bacteria, studies
Experts say it’s just a matter of time before other disease-causing
bacteria pick up the fateful mcr-1 gene. Since its discovery was first
reported in China in November 2015, it has spread to human, animal, food
and environmental bacteria on every continent.
“It’s not apocalyptic until it is,” said Peter Pitts, president of the
Center for Medicine in the Public Interest and former associate
commissioner of the FDA. “Shame on us if we wait till bodies are in the
Follow me on Twitter @LATMelissaHealy and "like" Los Angeles Times
Science & Health on Facebook.
Superbug E. Coli Found for Just Second Time in US
by Gillian Mohney
For just the second time in the U.S., researchers have found evidence of
E. coli bacteria that are genetically resistant to a last-resort
antibiotic, according to a report published today in the medical journal
Antimicrobial Agents and Chemotherapy.
The superbug has a gene that makes it resistant to treatment with
colistin, an antibiotic often used by doctors as a last resort for
antibiotic-resistant infections, the report states.
In this case, the bacteria were genetically resistant to colistin but
not to other forms of antibiotics that could be used to kill the E.
coli. However, researchers are concerned that these bacteria could
transfer genes to other E. coli and different bacteria that are already
resistant to all forms of antibiotics except colistin, leading to the
chance of a fully antibiotic-resistant strain of bacterium. Researchers
are especially concerned about the possibility that the gene could be
transferred within the Enterobacteriaceae family of bacteria, which
includes E. coli. Some strains in that family are already largely
resistant to many kind of antibiotics in the U.S.
Researchers found the strain by testing 13,562 E. coli strains collected
at hospitals across the globe. They found 19 strains had the gene mcr-1,
which makes E.coli resistant to colistin. In one case, that strain was
found in the U.S.
Researchers said the global findings are alarming because it means there
may be an increasing likelihood of having outbreaks of E. coli bacteria
that are totally resistant to antibiotics.
"The fact that the gene has been detected in food livestock and raw meat
is also concerning," said report co-author Mariana Castanheira, the
director of micro- and molecular biology at JMI Laboratories.
Dr. Frank Esper, a pediatric infectious disease specialist at University
Hospitals Case Medical Center, said the report was alarming but not
surprising for infectious disease experts.
"It's basically a wake-up call," he told ABC News. "It's only going to
be a matter of time where the perfect storm happens ... Next thing you
know, you throw your hands up and say we're out of ammunition" to fight
Dr. William Schaffner, an infectious disease expert at Vanderbilt
University Medical Center, said health experts have been worried for
years that there will be a rise in completely drug-resistant bacteria,
especially since there have been few antibiotic breakthroughs in recent
He said there are several things that need to happen to minimize the
chance of creating antibiotic-resistant bacteria.
"[No. 1], we prescribe antibiotics much more prudentially ... No. 2, we
have to stop using antibiotics as freely as we do in our food industry,"
said Schaffner. "No. 3, we need to energize and create environments so
pharmaceutical companies will once again start" developing antibiotics.
He said many pharmaceutical companies have little incentive to find and
test new antibiotics, since they are usually used sparingly for a
limited time and because the bacteria immediately start to become
resistant to them, making them more likely to be rendered useless.
But Schaffner emphasized that more needs to be done to develop new
antibiotics because there could be a spike of antibiotic-resistant
bacteria outbreaks in the coming years.
"Developing new antibiotics is a long-term commitment, and we think in
terms of five to 10 years," he said. "As that Chinese proverb states,
the longest journey begins with first steps. We ought to make those
steps now, because we're going to need those new antibiotics years from