Mining MRSA genetic code halts superbug outbreak

For the first time, an MRSA outbreak has been stopped in its tracks using whole genome sequencing.

Methicillin-resistant staphylococcus aureus (MRSA) resides harmlessly in the nostrils and on the skin of around one per cent of the population. But when the bacteria get into a person's blood and internal organs, they can cause problematic infections that are difficult to treat, earning the bacteria its "superbug" title.

How can a hospital tell if it has an MRSA outbreak or a string of unrelated infections? Currently, techniques involve sequencing seven of the bacterium's genes to work out what type of MRSA has colonised or infected a person. But because most people have the same type of MRSA, the test results are rarely able to confirm whether or not individuals transmitted the bug to each other.

Red flag

Sequencing the bacterium's entire genome can provide a much more detailed picture of where the bug came from, says Sharon Peacock at the Wellcome Trust Sanger Institute in Cambridge, UK. When her team noticed several cases of MRSA in the special care baby unit of the Rosie Hospital in Cambridge, they decided to use whole genome sequencing to investigate whether the infections were related.

The first red flag was raised when doctors noticed three cases of MRSA infection in the ward, which called for a deep clean of the premises. The hospital's infection control team compared isolates of bacteria taken from each baby to a hospital catalogue of those taken from 13 babies who had screened positive for MRSA in the previous six months.

All the new cases appeared to have been caused by a strain of MRSA similar to the one that had colonised 8 of these 13 earlier cases. Four days after the deep clean, doctors diagnosed another infant with MRSA that was genetically identical to the bacteria that had caused two of the three newest cases.

Mutation rate

To find out whether the new cases were independent, linked to each other, or linked to the older infections, Peacock's team turned to whole genome sequencing. The group's investigation revealed that, of the 17 cases, 14 appeared to result from a new strain of MRSA.

MRSA bacteria are known to mutate fairly regularly. When the team considered this mutation rate, along with the timing of each MRSA infection, they were able to conclude that the 14 cases were related.

"The original investigation was inconclusive, we couldn't say whether it was an outbreak or not," says study co-author Julian Parkhill. Using whole genome sequencing "we were immediately able to say that they were an outbreak? and it was almost certain that transmission had occurred on the ward."

Single carrier found

When the team extended their investigation beyond the hospital's baby unit, they identified 10 other cases that appeared to have been caused by the same strain. "They were part of the same outbreak," says Parkhill.

Peacock and her colleagues then attempted to work out what the common factor between all these people might have been. Which wards had they, their doctors or family members visited? A screen of 154 staff revealed one person carrying the same MRSA strain. "We could say fairly conclusively that the staff member had been involved in the outbreak," says Parkhill. "This is really exciting for us ? it gave the hospital the opportunity to intervene." The person was treated with an antiseptic to remove the bacteria before returning to work.

Since then, there have been no more MRSA infections on the ward, the group say. "This is the first case where whole genome sequencing technologies have led to a clinical intervention and brought an outbreak to a close," says Parkhill.

Routine tool

The group hope that this approach will offer a cost-effective tool to help hospitals control the spread of infections. "I think that in the future this will? be used alongside current approaches to improve patient care and to stop outbreaks," says Peacock. "It's not just a theoretical or research tool ? it can change patient care."

The team estimate that the whole genome sequencing of each MRSA isolate cost them ?50 to ?100, although an official cost-benefit analysis will have to be done before wider use of the technique.

"It's one of the first clear demonstrations that we can use this as a routine tool," says Scott Weese at the University of Guelph in Ontario, Canada. "It really is the wave of the future."

Journal reference: The Lancet doi.org/jq9

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