NIH uses genome sequencing to help quell bacterial outbreak in Clinical Center

Aug. 30, 2012

For six months last year, a deadly outbreak of antibiotic-resistant bacteria kept infection-control specialists at the National Institutes of Health’s Clinical Center in a state of high alert. A New York City patient carrying a multi-drug resistant strain of Klebsiella pneumoniae, a microbe frequently associated with hospital-borne infections, introduced the dangerous bacteria into the 243-bed research hospital while participating in a clinical study in the summer of 2011. Despite enhanced infection-control practices, including patient isolation, the K. pneumoniae began to spread to other Clinical Center patients at the alarming rate of one a week, ultimately colonizing 17 patients, of whom 11 died.

To get the outbreak under control, Clinical Center staff collaborated with investigators at the National Human Genome Research Institute (NHGRI), also part of NIH, to use genome sequencing in the middle of this active hospital epidemic to learn how the microbe spread.

As the outbreak began, the Clinical Center staff teamed up with NHGRI researchers led by Julie Segre, PhD, an NHGRI senior investigator. Dr. Segre had been working with the Clinical Center's Clinical Microbiology Department to study the evolution of bacterial antibiotic resistance when she heard about the outbreak.

The hospital team sent samples of bacteria isolated from infected patients to the NIH Intramural Sequencing Center (NISC), a component of the NHGRI. NISC sequenced the DNA samples, and Dr. Segre’s team analyzed the results. Where the pulse-field gel electrophoresis technique shows relatively crude patterns, genome sequence data shows precise differences, down to single genetic letters in the bacterial genome. This sequencing proved that the strain of K. pneumoniae sickening all the patients in the Clinical Center originated with one patient; the outbreak had a single source.

When combined with the traditional epidemiology tracking data, the genome sequence results showed that Patient 1 transmitted the bacteria to other patients on two separate occasions from infections on different parts of her body, creating two major clusters of infected patients. Even as the epidemiologic and genomic investigation proceeded, the infection-control team in the NIH Clinical Center employed increasingly intensive strategies to stop the infection from spreading. Read the abstract of the article from Science Translational Medicine.