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UK Team Outlines Use of WGS to Assess MRSA Outbreak

NEW YORK (GenomeWeb News) – In a study appearing online today in The Lancet Infectious Diseases, a UK team describes the whole-genome sequencing approach it used to assess — and ultimately curtail — a methicillin-resistant Staphylococcus aureus outbreak first detected in an infant ward at one of the Cambridge University Hospitals.

"Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures," co-senior author Julian Parkhill, a researcher with the Wellcome Trust Sanger Institute, said in a statement.

The initial phase of the study focused on MRSA isolates collected from 17 infants at Addenbrooke's Hospital's special care baby unit, or SCBU, over six months in 2011. Through whole-genome sequencing-based analyses of the isolates — already tested with standard epidemiological infection control methods — researchers were able to better define the relationships between these strains, verifying that more than a dozen of the isolates were part of a single, multi-stage MRSA outbreak.

Moreover, the analysis offered new insights into the true extent of this outbreak, indicating that it had spread beyond the hospital and into the community at large.

During a resurgence of the MRSA outbreak in the hospital's SCBU around two months after the initial infections appeared to subside, genome sequence information contributed to the identification and treatment of an unsuspecting healthcare worker carrying the outbreak-associated strain. That prevented further spread of the infection, underscoring the notion that whole-genome sequencing can serve as a promising alternative to conventional MRSA testing and tracking methods.

Still, the team cautioned that challenges remain in routinely implementing such whole-genome sequencing approaches for MRSA control and prevention in health centers.

"Before this technology can be used in routine clinical practice, we will require automated tools that interpret sequence data and provide information to healthcare workers and people without specialist sequencing knowledge," co-senior author Sharon Peacock, a clinical microbiologist affiliated with the University of Cambridge, the Health Protection Agency, and the Wellcome Trust Sanger Institute said in statement.

Peacock noted that the team is currently working to come up with such a scheme. "If we have a robust system of this type in operation when the outbreaks occur," she said, "we predict that we will be able to stop them after the first few cases, as we will rapidly find clear connections."

The first phase of the team's current analysis centered on a set of MRSA infections in the SCBU that appeared potentially related to one another. But prior to the genome sequencing assessment, the associated MRSA isolates had not been confirmed to be part of the same outbreak.

Using the Illumina MiSeq, researchers sequenced the genomes of MRSA isolates from 17 infants from the hospital's SCBU. The resulting data verified that 14 of the infants were infected with genetically related MRSA strains representing a previously undetected MRSA sequence type called ST2371, consistent with the notion that they were part of an inter-connected outbreak. The other three isolates were classified as ST1, ST8, and ST22.

Through analyses of these and other MRSA samples collected through a related surveillance program, the team determined that the MRSA ST2371 outbreak affected at least 26 individuals — including not only infants in the SCBU, but also individuals from a post-natal ward for mothers and in the community outside of the hospital.

Using the genome sequence data, they also delineated transmission events that contributed to this outbreak.

When MRSA re-emerged in another infant 64 days after the initial outbreak, the researchers screened 154 healthcare workers connected to the SCBU ward. They subsequently verified by whole-genome sequencing that one of these staff members was asymptomatically carrying the same ST2371 MRSA sequence type associated with the original outbreak.

"Whole-genome sequencing data were used to propose and confirm that MRSA carriage by a staff member had allowed the outbreak to persist during periods without known infection on the SCBU and after a deep clean," the study's authors noted.

By identifying this individual, it was possible to curb further infection by removing the staff member from the ward until he or she had been successfully decolonized for MRSA.

"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," said co-author Nicholas Brown, a microbiology researcher and physician affiliated with the University of Cambridge and Cambridge University Hospitals National Health Service Foundation Trust.

Going forward, the team plans to continue studying MRSA infection dynamics at the same hospital, in others hospital nearby, and in the community at large over a full year.

In a commentary article accompanying the new Lancet Infectious Disease study, University of California at San Francisco infectious diseases researcher Binh An Diep explained that the application of whole-genome sequencing for infection surveillance and tracking during outbreaks could help in understanding pathogen biology and controlling these infections.

But he also cautioned that such analyses may not always be straightforward, particularly in the case of bugs that turn up in a significant proportion of asymptomatic carriers in the general population.

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