They quickly teased apart a bacterium's DNA to stop a deadly superbug.
The ambulance sped up to the red brick federal research hospital on June 13, 2011, and paramedics rushed a gravely ill 43-year-old woman straight to intensive care. She had a rare lung disease and was gasping for breath. And, just hours before, the hospital learned she had been infected with a deadly strain of bacteria resistant to nearly all antibiotics.
The hospital employed the most stringent and severe form of isolation, but soon the bacterium, Klebsiella pneumoniae, was spreading through the hospital. Seventeen patients got it, and six of them died. Had they been infected by the woman? And, if so, how did the bacteria escape strict controls in one of the nation's most sophisticated hospitals, the Clinical Center of the National Institutes of Health in Bethesda, Md.?
What followed was a medical detective story that involved the rare use of rapid genetic sequencing to map the entire genome of a bacterium as it spread and to use that information to detect its origins and trace its route. "We had never done this type of research in real time," said Julie Segre, the researcher who led the effort.
The results, published online Wednesday in the journal Science Translational Medicine, revealed an unexpected chain of transmission and an organism that can lurk undetected for much longer than anyone had known. The method used may eventually revolutionize how hospitals deal with hospital-acquired infections, which contribute to more than 99,000 deaths a year.
Tracking a killer
At first, the hospital was confident that it could contain bacteria that could easily kill other patients whose immune systems were weakened, said Dr. Tara Palmore, deputy epidemiologist at the Clinical Center. The doctors knew the bacteria would be almost impossible to stop once they got into patients' bloodstreams.
So the hospital kept the patient in a single room. Everyone who entered wore masks and gloves. Every piece of equipment that touched the patient had to be disinfected. And items like blood pressure cuffs and stethoscopes that could not be disinfected were thrown away.
A month later, she was discharged. It seemed no one had picked up the bacteria. But on Aug. 5, lab technicians found the bacterium in the trachea of a man who had never been in the same area as the woman.
On Aug. 15, another patient tested positive, and another on Aug. 23. About a patient a week was turning up positive.
Segre proposed sequencing the entire genome of the first patient's bacterium and comparing it with the genome sequences of bacteria from other infected patients. When the first bacterial genome was sequenced, in 1995, it took three years. This time, researchers did it in just a couple of days.
Sequencing revealed that all the K. pneumoniae originated from the first patient, who transmitted the bacteria on three occasions. But patients were not infected in the order that they appeared to acquire the bacterium. It had smoldered in many of them, below the level of detection.
How did the bacteria travel from the first patient to the others? The hospital staff had been scrupulous. But they discovered the bacteria in a respirator that had been used by a patient who had the bacteria but had not gotten ill. The respirator had been cleaned, but the disinfecting procedure had failed. The bacteria were also in the sink drains after the rooms had been cleaned. The hospital ended up removing plumbing to get rid of it. Segre said, "We didn't understand the environmental stability of this organism."