Researchers use genome sequencing to dissect and control an MRSA outbreak

For the first time, researchers have used DNA sequencing to help bring an infectious disease outbreak in a hospital to a close. The approach is much more accurate than current methods used to detect hospital outbreaks and has important implications for the future of infection control.

Researchers from the Wellcome Trust Sanger Institute, the University of Cambridge and Cambridge University Hospitals used advanced DNA sequencing technologies to confirm the presence of an ongoing outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a Special Care Baby Unit in real time. This helped the outbreak to be stopped earlier, preventing possible harm to patients.

Using this technology, the team revealed that the outbreak had extended into the wider community, a conclusion that could not be reached with available methods. They also used sequencing to link the outbreak to an unsuspecting carrier, who was treated to eradicate MRSA.

“We are always seeking ways to improve our patient care and wanted to explore the role that the latest sequencing technologies could play in the control of infections in hospitals,” says Dr Nick Brown, author, consultant microbiologist at the Health Protection Agency and infection control doctor at Addenbrooke’s Hospital, Cambridge. "Our aim is to prevent outbreaks, and in the event that they occur to identify these rapidly and accurately and bring them under control.

“What we have glimpsed through this pioneering study is a future in which new sequencing methods will help us to identify, manage and stop hospital outbreaks and deliver even better patient care.”

Over a six-month period, the hospital infection control team used standard protocols to identify 12 patients who were carrying MRSA. However, this standard approach alone could not give enough information to confirm whether an ongoing outbreak was actually taking place.

In this study, the researchers analysed MRSA isolates from these 12 patients with DNA sequencing technology and demonstrated clearly that all the MRSA bacteria were closely related and that this was an outbreak.

They also revealed that the outbreak was more extensive than previously realised, finding that more than twice as many people were carrying or were infected with the same outbreak strain. Many of these additional cases were people who had recent links to the hospital but were otherwise healthy and living in the community when they developed a MRSA infection.

While this sequencing study was underway, the infection control team identified a new case of MRSA carriage in the Special Care Baby Unit, which occurred 64 days after the last MRSA-positive patient had left the same unit. The team used advanced DNA sequencing to show in real time that this strain was also part of the outbreak, despite the lack of apparent links between this case and previous patients. This raised the possibility that an individual was unknowingly carrying and transmitting the outbreak MRSA strain.

The infection control team screened 154 healthcare workers for MRSA and found that one staff member was carrying MRSA. Using DNA sequencing, they confirmed that this MRSA strain was linked to the outbreak. This healthcare worker was quickly treated to eradicate their MRSA carriage and remove the risk of further spread.

“Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures,” says Dr Julian Parkhill, lead author from the Wellcome Trust Sanger Institute.

“There is a real health and cost burden from hospital outbreaks and significant benefits to be gained from their prevention and swift containment. This technology holds great promise for the quick and accurate identification of bacterial transmissions in our hospitals and could lead to a paradigm shift in how we manage infection control and practice.”

In this instance, DNA sequencing was a key step in bringing the outbreak to a close, saving possible harm to patients and potentially saving the hospital money.

“Our study indicates the considerable potential of sequencing for the rapid identification of MRSA outbreaks,” said Professor Sharon Peacock, lead author from the University of Cambridge and clinical specialist at the Health Protection Agency. "What we need before this can be introduced into routine care is automated tools that interpret sequence data and provide readily understandable information to healthcare workers. We are currently working on such a system.

“If we have a robust system of this type in operation when the outbreaks occur, we predict that we will be able to stop them after the first few cases, as we will rapidly find clear connections.”

In their next step, the team will study all MRSA carriers and infected patients over the next year in Addenbrooke’s Hospital and surrounding hospitals and the community to understand transmission events with the aim of improving infection management.

Sir Mark Walport, director of the Wellcome Trust, says: “This is a dramatic demonstration that medical genomics is no longer a technology of the future - it is a technology of the here and now. By collaborating with NHS doctors, geneticists have shown that sequencing can have extremely important applications in healthcare today, halting an outbreak of a potentially deadly disease.”


Reference

Harris SR et al. Using whole genome sequencing to dissect the cause and effect of a meticillin-resistant Staphylococcus aureus outbreak: a descriptive study. Lancet Infect Dis 2012 (epub ahead of print).