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Gene Detectives Find New Tool to Contain Deadly Bacteria

Scientists using rapid genetic testing to track the path of a deadly bacterium in a Maryland medical center discovered unsuspected ways pathogens can spread and learned a new tool to combat hospital-acquired infections.
The DNA screening allowed staff at the National Institutes of Health’s research hospital in Bethesda, Maryland, to link infections with a multidrug resistant strain of Klebsiella pneumoniae weeks after the first case was found, even though there were no obvious ties among the patients. Uncovering the way the bacteria moved silently though the hospital for weeks confirmed an outbreak was under way and prompted aggressive measures to control the pathogen that infected 18 people.
“This has changed the practice of medicine in our hospital and we hope it will change the way other hospitals would control a similar outbreak,” said Julie Segre, a senior investigator at the National Human Genome Research Institute.
Advances in genetic sequencing allowed researchers to map minute differences in the DNA of the bacterium in less than a week, proving all 18 cases began with a single patient in June 2011.
The first patient, a 43-year-old New York woman, was isolated as soon as she arrived at NIH’s 243-bed hospital in Bethesda. Infection-control procedures, such as gloves and gowns for all staff and visitors, were used to contain the dangerous bacteria.

More Infections
The effort was unsuccessful. Seventeen other patients subsequently fell ill, at an alarming rate of one a week. Eleven people died, six from K. pneumoniae and five from underlying diseases that were exacerbated by the bacteria, which evaded all commonly used antibiotics, including carbapenem, one of the most potent germ-killers.
“It’s an emerging pathogen, but we’ve never had a patient with it in our hospital or in this area that we were aware of,” Segre said.
Hospital-acquired infections aren’t new, occurring in more than 1 million patients each year in the U.S. The mystery of the K. pneumoniae case, detailed yesterday in the journal Science Translational Medicine, arose because the second case of infection didn’t emerge until three weeks after the first patient was treated and discharged. The bacteria turned up in a trachea of an immune-compromised patient, who had never been in the same hospital ward as the woman from New York.
After the first patient was released, “we did routine surveillance to see if anyone in the hospital was exposed and the tests came back negative for weeks,” Segre said. “On August 5, we got our second patient with a Klebsiella infection. We were stunned.”

Finding Links
The staff needed to know if the bacteria had spread from the isolated New York woman to the second patient. The time gap between the two cases would have required an infection with no symptoms in the second patient, an unlikely event in someone with a weakened immune system, Segre said. Alternatively, it could have been a new case, suggesting the infection control methods used for the New York patient would work again. At the same time, other patients also were getting sick.
The National Human Genome Research Institute was already developing tools to track and diagnose ailments based on their molecular makeup. Segre led a team that ran whole-genome testing on samples of bacteria taken from all the infected patients, proving that the entire outbreak stemmed from the New Yorker.

Mystery Solved
The genetic testing showed she had infected the third person identified with the bacteria, who was in the intensive care unit with her at one point. That patient passed the pathogen to the person who was diagnosed second, showing that they both had infections with no symptoms at one point.
“We didn’t expect that a patient who was immune-compromised could harbor a Klebsiella infection without showing signs of being sick or infected for three or four weeks,” Segre said. “That seemed inconsistent with what we knew from talking with other experts in the field.”
The pathogen causes about 15 percent of gram-negative infections that occur each year in U.S. intensive care units, mainly infecting patients with weakened immune systems. The development of drug-resistant strains of the bacteria has contributed to its lethality, with death rates of 50 percent or more, the researchers said.
The germ can survive in the hospital environment and live for hours on people’s hands and skin, making it easier to spread. It can creep into the gastrointestinal tract of patients and healthy individuals without causing symptoms or revealing its presence, allowing the bacteria to multiply and act as a reservoir for subsequent infections for long periods of time.

Prevention Practices
The hospital ultimately contained the infection by segregating patients with the bacteria, literally opening a new wing of the hospital and cloistering patients from outsiders. They were treated with the same staff and equipment, which wasn’t allowed to be used on other patients even after it was disinfected. Doctors weren’t allowed to carry pagers, and a person was assigned to monitor everyone in the wing to make sure hand-washing and other safety measures were observed.
Rectal swabs identified the last two patients with the bacteria in December, before either started showing symptoms. There have been no new cases discovered since then.
“By marshaling the ability to sequence bacterial genomes in real time to accurately trace the bacteria as it spread among our Clinical Center patients, our researchers successfully elucidated what happened, which in turn has taught us some important lessons,” said Eric Green, director of the National Human Genome Research Institute. “This study gives us a glimpse of how genomic technologies will alter our approach to microbial epidemics in the future.”
Source: Bloomberg Businessweek (

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