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Whole-genome Sequencing Tracks Hospital Outbreak in Real Time

NEW YORK (GenomeWeb News) – A study published today in Science Translational Medicine shows how whole-genome sequencing in real time during an outbreak can help change hospital management to control the outbreak.

Researchers from the National Institutes of Health, sequenced isolates of drug resistant Klebsiella pneumoniae during an outbreak in the NIH Clinical Center, demonstrating that sequencing is effective for tracking outbreaks and can do so at a greater resolution than traditional typing techniques such as pulsed-field gel electrophoresis or PCR.

"For decades, we used pulsed-field gel electrophoresis to differentiate bacterial strains," said Tara Palmore, the NIH Clinical Center's deputy hospital epidemiologist who led the outbreak investigation. However, because 70 percent of K. pneumoniae infections belong to one strain and are indistinguishable with pulsed-field gel electrophoresis, "this test is not very helpful for that organism," she said in a statement.

The outbreak began in June 2011, when a New York City hospital transferred a 43-year-old woman to the NIH that was infected with multiple-drug resistant K. pneuomoniae. The patient was immediately put into isolation, recovered, and discharged in July.

During her stay, no other infected patients had been discovered. Then in August, additional patients became infected. Between August and December, 17 patients became infected. Of those, 11 passed away, six due to K. pneumoniae.

At the beginning of the outbreak, the hospital's staff teamed up with NIH researchers, led by Julie Segre, a senior investigator in the NIH's genetics and molecular biology branch. Segre's team performed whole-genome sequencing from isolates taken from four different body sites from the index patient, and also from each additional patient that became infected.

They used the 454 GS FLX for the sequencing, and discovered just 41 single nucleotide variants between the strains.

Analysing the genomes allowed them to cluster the isolates based on similarities between the genome and helped them to determine that the outbreak was a single-source transmission.

The team pieced together a most likely transmission route, discovering that the index patient 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.

Palmore told GenomeWeb Daily News that the results were not necessarily intuitive and could not have been have been predicted without the sequence data. For instance, the order in which patients were discovered to be infected did not always correspond with the order of transmission. In one cluster, for example, patient 1 most likely infected patient 3, who then infected patient 5, who infected patient 2 — despite the fact that patient 2 presented with infection 10 days earlier than patient 3.

"That was a big surprise for us," said Palmore.

Additionally, after recognizing that the pathogen had been transmitted from the first patient, despite the level of precaution that was taken, the hospital realized that even further steps needed to be implemented.

The analysis of the sequence data made it "very clear that it was patient-to-patient transmission," Segre said. "The contact isolation that had been used for patient one was insufficient, so we needed to step up hospital control."

So, while the sequencing didn't change the care of the infected patients, it did change how the hospital managed the outbreak. "By showing that patients 2, 3, and 4 are linked to patient 1, that supported the hospital's decision to open up a cohorted area," Segre said.

Instead of just putting the infected patients in contact isolation, they were now in their own section of the hospital. Any staff that was caring for those patients would care only for those patients and equipment would not be transferred between the cohort area and the rest of the hospital.

The research team also tested various pieces of equipment for the pathogen, and in one case detected the pathogen on a ventilator that already been extensively cleaned, including with bleach. The ventilator had only been used on one infected patient, so was not responsible for any transmission events, but finding it "demonstrated that the organism could be tenacious in the environment, and could evade standard cleaning techniques," Palmore said.

The pathogen was also found in sink drains and on other equipment, but transmission from the environment to a patient was never demonstrated, Palmore said.

This article is a condensed version of a story appearing in GWDN sister publication Clinical Sequencing News.