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Real-Time Outbreak Sequencing

Sarah C.P. Williams

Researchers at the NIH Clinical Center used genetic sequencing to track an infectious and deadly outbreak in their hospital.

Last year, researchers at the National Institutes of Health (NIH) were planning a study where they would use next-generation sequencing to track hospital-acquired infections. The group was deciding which organism to follow when they got word of multiple reported cases of a rare and dangerous bacterium at the NIH Clinical Center. For the next six months, the team used DNA sequencing to trace the outbreak, which left 11 out of 17 infected patients dead—six from the infection and five from their underlying disease.

A timeline of patients’ diagnoses (A) and physical locations in the hospital (B), accompanied by genetic data helped researchers figure out the possible transmission links (C) between patients. Source: Science Translational Medicine

The target was a bacterium called carbapanem-resistant Klebsiella pneumonia, specifically a strain dubbed KPC. In the summer of 2011, researchers at the hospital treated a clinical trial patient infected with the deadly microbe using standard containment efforts. But those efforts failed; a second patient in the hospital got infected by the microbe.

“KPC Klebsiella is extremely resistant to drugs,” said Tara Palmore, deputy hospital epidemiologist at the NIH Clinical Center and an author of the new study. “It’s very difficult to treat, and it can become impossible to treat.”

Standard microbial cultures can tell epidemiologists which microbe a patient is infected with and what drugs it is resistant to. But to determine how that microbe spread between multiple patients and how the microbe evolved, gene sequencing is required.

“The sequencing could tell us who got it from whom. That helped us because we could then infer where it was being transmitted, and where our infection control measures had failed,” said Palmore.

For example, if researchers determined that one patient had become infected from the bacteria colonizing a second person, and the only place both patients overlapped was in the X-ray department, they could target efforts there. But in the case of the NIH Klebsiella outbreak, patients overlapped in the intensive care unit as well as in patient hospital wards. Because of the broad range of transmission locations and times, the hospital implemented strict outbreak containment efforts, testing every patient and isolating those infected in a separate ward.

“What we found was that the standard shoe-leather epidemiology techniques really didn’t give us the whole picture,” said Palmore. “The sequence in which the patients were identified was nothing like the sequence in which transmission occurred.”

Since last summer, the hospital has continued culturing patients, testing each patient at least once per month. This summer, their sequencing methods were put to the test a second time: a new transfer patient tested positive for KPC Klebsiella. Was this was a new strain or a re-emegence of the strain from the previous outbreak? Within two days, the sequence data showed that it was a new strain; they isolated the patient to prevent another outbreak.

“I think that this is the future in hospital epidemiology,” said Palmore. “At facilities that have resources, equipment, and interest, it can be done.”


  1. Snitkin, E.S., A.M. Zelanzy, P.J. Thomas, F. Stock, NISC Comparative Sequencing Program, TD.K. Henderson, T.N. Palmore, J.A. Segre. Tracking a Hospital Outbreak of Carbapanem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing (2012). Science Translational Medicine 148ra116.

Keywords:  sequencing