CDC/James Archer
Bacteria that cause many
hospital-associated infections are ready to quickly share genes that
allow them to resist powerful antibiotics. The illustration, based on
electron micrographs and created by the Centers for Disease Control and
Prevention, shows one of these antibiotic-resistant bacteria.
Antibiotic resistance is poised to spread globally among bacteria
frequently implicated in respiratory and urinary infections in hospital
settings, according to new research at Washington University School of Medicine in St. Louis.
The study shows that two genes that confer resistance against a
particularly strong class of antibiotics can be shared easily among a
family of bacteria responsible for a significant portion of
hospital-associated infections.
Drug-resistant germs in the same family of bacteria recently infected
several patients at two Los Angeles hospitals. The infections have been
linked to medical scopes believed to have been contaminated with
bacteria that can resist carbapenems, potent antibiotics that are
supposed to be used only in gravely ill patients or those infected by
resistant bacteria.
“Carbapenems
are one of our last resorts for treating bacterial infections, what we
use when nothing else works,” said senior author Gautam Dantas, PhD,
associate professor of pathology and immunology. “Given what we know
now, I don’t think it’s overstating the case to say that for certain
types of infections, we may be looking at the start of the
post-antibiotic era, a time when most of the antibiotics we rely on to
treat bacterial infections are no longer effective.”
Follow the School of Medicine
Dantas and other experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.
The study, conducted by researchers at Washington University,
Barnes-Jewish Hospital and the National University of Sciences and
Technology in Pakistan, is available online in Emerging Infectious
Diseases.
The researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiella pneumoniae and Enterobacter.
Some strains of these bacteria do not cause illness and can help keep
the body healthy. But in people with weakened immune systems, infections
with carbapenem-resistant versions of these bacteria can be deadly.
The Centers for Disease Control and Prevention named
carbapenem-resistant Enterobacteriaceae as one of the three most urgent
threats among emerging forms of antibiotic-resistant disease. Studies
have shown the fatality rate for these infections is above 50 percent in
patients with weakened immune systems.
Two genes are primarily responsible for carbapenem-resistant versions of these disease-causing bacteria. One gene, KPC,
was detected in New York in 2001 and quickly spread around most of the
world, with the exception of India, Pakistan and other South Asian
countries. This gene was present in the bacteria that recently
contaminated medical equipment in a Los Angeles hospital where two
patients died.
A second carbapenem resistance gene, NDM-1, was identified
in 2006 in New Delhi, India. It was soon detected throughout South Asia,
and most patients infected by bacteria with NDM-1 have had an epidemiological link to South Asian countries.
Dantas and his collaborators were curious about why the two
resistance genes seemed to be geographically exclusive. For the study,
they compared the genomes of carbapenem-resistant bacteria isolated in
the United States with those of carbapenem-resistant bacteria isolated
in Pakistan.
Based on the apparent geographic exclusivity of the two resistance
genes, the scientists expected to find that bacteria from the two
regions were genetically different. Such differences could explain why
the two resistance genes weren’t intermingling. But the researchers’
results showed otherwise. The bacteria’s high genetic similarity
suggests that the antibiotic resistance genes could be shared easily
between bacteria from the two geographic regions.
The researchers also sequenced a special portion of bacterial genetic
material called plasmids. Most of a bacteria’s DNA is found in its
chromosome, but bacteria also have many extra, smaller and circular bits
of DNA known as plasmids that easily can pass from one bacterial strain
to another. A plasmid is like a bacterial gene delivery truck; it is
the primary way antibiotic resistance genes spread between bacteria.
The researchers identified a few key instances in which the plasmids carrying NDM-1 or KPC
were nearly identical, meaning they easily could facilitate the spread
of antibiotic resistance between disease-causing bacteria found in the
United States and South Asia. Recent evidence suggests that this
intermingling already may be happening in parts of China.
“Our findings also suggest it’s going to get easier for strains of
these bacteria that are not yet resistant to pick up a gene that lets
them survive carbapenem treatment,” Dantas said. “Typically, that’s not
going to be a problem for most of us, but as drug-resistant forms of
Enterobacteriaceae become more widespread, the odds will increase that
we’ll pass one of these superbugs on to a friend with a weakened immune
system who can really be hurt by them.”
This research was supported by the National Institutes of Health
(NIH) Director’s New Innovator Award, the National Institute of Diabetes
and Digestive and Kidney Diseases, and the National Institute of
General Medical Sciences, grant numbers DP2DK098089 and R01GM099538.
Pesesky MW, Hussain T, Wallace M, Wang B, Andleeb S, Burnham C-AD, Dantas G. KPC and NDM-1
are harbored by related Enterobacteriaceae strains and plasmid
backbones form distinct geographies. Emerging Infectious Diseases, June
2015; http://dx.doi.org/10.3201/eid2106.141504.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of
Barnes-Jewish and
St. Louis Children’s
hospitals. The School of Medicine is one of the leading medical
research, teaching and patient-care institutions in the nation,
currently ranked sixth in the nation by U.S. News & World Report.
Through its affiliations with Barnes-Jewish and St. Louis Children’s
hospitals, the School of Medicine is linked to
BJC HealthCare.