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Sequencing a Superbug

Over at Wired, Carl Zimmer takes an in-depth look at how the US National Institutes of Health used next-gen sequencing to track a lethal outbreak of Klebsiella pneumoniae at the NIH Clinical Center.

Zimmer provides a detailed account of how the hospital first tried to handle the outbreak of the so-called superbug through traditional epidemiological methods before accepting an offer from NHGRI researchers Evan Snitkin and Julie Segre to sequence the bacteria in real time in hopes of stopping it from spreading.

Tara Palmore, the NIH center's deputy epidemiologist, and her team were particularly stumped by the fact that the first patient who was colonized with the bacteria was discharged in mid-July, but the second patient didn't test positive until Aug. 5 — "an uncommon onset for this particular bacterium," Zimmer notes.

As reported by our sister publication Clinical Sequencing News, between August and December, an additional 16 patients at the clinic became infected with carbapenem-resistant K. pneumoniae. A total of 11 infected patients died during that time, with six of the deaths attributable to the pathogen.

Once the sequencing data was analyzed, "I was speechless," Palmore tells Wired. Snitkin and Segre had assembled a phylogenetic tree that showed a likely transmission route in which patient 1 transmitted the bacteria to other patients on two different occasions from infections from different strains on different parts of her body. This ruled out the possibility that another infected patient or some other outside source was responsible for the spread of the different strains of the bacteria.

By early October, the researchers determined that patient 1 actually harbored three separate strains of the bacteria. Furthermore, the analysis showed that a ventilator in the hospital's intensive care unit harbored the bug, even after it had supposedly been sterilized.

By November, the hospital staff had developed a protocol for testing patients directly for the specific strains responsible for the outbreak. "When Palmore came across a newly infected patient, Snitkin would put the bacteria through his pipeline and send her the results," Zimmer writes.

Snitkin, Segre and colleagues published their results in Science Translational Medicine in August. Snitkin (chosen as one of our sister publication Genome Technology magazine's young investigators to watch in 2012) told GT that the work is "a nice proof of principle [about] where hospital infection control is going."

He added that it was "really exciting to our clinical collaborators who were new to this technology and now see possibilities where it could totally change the way they protect patients from infections."

Zimmer cautions that, in the short term, it's unlikely that most hospitals will be able to take the same approach to fighting a superbug outbreak. "The NIH Clinical Center had access to a scientific brain trust and a massive genome sequencing center to go with it. For now, smaller hospitals don’t have a labful of sequencing equipment, let alone the necessary expertise," he says.

Nevertheless, the rapidly falling costs of sequencing point toward this becoming a reality at some point down the road. Zimmer reports that Segre and Snitkin are currently developing a pipeline based on Illumina's MiSeq that would reduce the cost of sequencing a bacterial genome to $500, while cutting turnaround time to a few days. "Newer sequencers, made by companies such as Oxford Nanopore Technologies and Ion Torrent, might reduce the expense even more," Zimmer adds.