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Genome Sequencing Provides High-Tech Tracking of Intensive-Care Outbreaks

Whole-genome sequencing of drug-resistant bacteria during a hospital outbreak could help infection control efforts, reports a new study in the 22 August issue of the journal Science Translational Medicine.

The report details the steps taken after a 2011 outbreak of Klebsiella pneumoniae at a clinical center located at the National Institutes of Health. Six of the 18 patients infected during the outbreak died.

Because a careful analysis of bed locations in the intensive care unit revealed no clues as to how the bacteria (which can cause pneumonia, bloodstream infections, meningitis, and other problems) traveled from patient to patient, the research team turned to whole-genome sequencing to piece together what happened.

“By allowing infection control personnel to generate and test hypotheses as to how an outbreak has spread, whole genome sequencing can facilitate the implementation of targeted infection control procedures,” said Evan Snitkin, a postdoctoral fellow at the National Institutes of Health and lead author of the study.

While only a few of the 6 million nucleotides—DNA building blocks—in the K. pneumoniae genome change as the bacterium multiplies, the difference was enough for the team to trace bacterial spread. The researchers sequenced bacterial samples taken from each patient and found that the outbreak initially stemmed from a patient who had left the hospital three weeks before another infected patient was discovered.

The DNA changes in the evolving bacteria gave the researchers a sort of genetic time stamp, revealing that K. pneumoniae was initially transmitted from patient 1 to patient 3. Patient 3 then exposed patient 2, who had a weakened immune system and became ill faster than patient 3. Moreover, the data confirmed that patient 4 was not infected by patients 2 or 3, but directly by patient 1.

The research team traced one of these infections back to the contamination of a ventilator that had undergone rigorous cleaning. The results suggest that real-time whole-genome sequencing of bacteria that commonly infect patients in intensive care units boosts bacterial sleuthing capabilities, and could potentially improve hospital outbreak control.

Tara Palmore, a deputy hospital epidemiologist at the National Institutes of Health clinical center and senior author of the study, said: “Whole genome sequencing provides epidemiologic data that are leaps and bounds ahead of what we can learn from standard practice.”

Read the abstract, “Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing,” by E.S. Snitkin and colleagues.