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Team Uses Sequencing to Track MRSA in Resource-Limited Center with High Transmission Rates

NEW YORK (GenomeWeb) – A study appearing online today in Genome Research suggests genome sequencing can successfully untangle complicated transmission patterns for methicillin-resistant Staphylococcus aureus (MRSA), even in centers where the bug is relatively widespread.

Researchers from the UK, Australia, and Thailand used genome sequencing to assess 76 samples collected from symptom-free patients and staff — identified as MRSA carriers over a few months of screening — in intensive care wards at a hospital in northeast Thailand.

A phylogenetic analysis of the MRSA sequences suggested at least five clades from the same sequence type were circulating simultaneously in the adult and pediatric wards tested, while a look at isolates within these clades provided clues to the pathogen's genetic diversity and movement between individuals.

"Our long-term goal is to use such information to inform infection control practice," senior author Sharon Peacock, a researcher affiliated with the Wellcome Trust Sanger Institute and the University of Cambridge, said in a statement.

"The degree of transmission we demonstrated in our study has directly led to the prioritization of improved hand hygiene practices at the study hospital," Peacock added.

In the past, researchers have turned to whole-genome sequencing to resolve MRSA relationships and transmission patterns within centers where relatively aggressive screening and/or infection control practices are already being implemented, the researchers explained. But less is known about how the bug spreads in locations that may not have access to or sufficient financial resources for adequate infection control resources.

"Filling gaps in our understanding of how MRSA spreads in such settings is important, since this not only highlights the problem but also provides direction to interventions that tackle this and other hospital-based pathogens," Peacock said in a statement.

"The objective of this study was to use [whole-genome sequencing] to define phylogeny and transmission dynamics of MRSA in a hospital setting where MRSA transmission was common," she and her co-authors noted.

Over the course of three months in 2008, the researchers collected nasal swab and fingertip culture samples from 169 adult patients in an intensive care unit, 98 children from a pediatric ICU, and more than three-dozen nurses in the two wards.

Sixteen percent of patients from the adult ICU ward and just over one-third of the pediatric patients tested positive for MRSA during the screening period. One nurse from the adult ward and four nurses at the pediatric ICU also tested positive for MRSA carriage once over the three-month screening stretch.

All told, the team did genome sequencing on 76 MRSA isolates from 46 of the patients and five staff members. The isolates all belonged to the S. aureus sequence type ST 239 and could not be accurately distinguished from one another based on genotyping analyses.

After aligning the resulting sequences to the ST 239 reference genome, the researchers identified more than 1,500 SNPs that were subsequently used to put together a phylogenetic tree for the bugs.

By looking at the way these variants clustered with one another, they defined at least five MRSA clades that included 67 of the isolates circulating at the hospital within the three months in question.

Isolates from three of the clades were largely detected in patients and staff from the adult ICU, while those from the remaining two clades generally turned up in the pediatric ward.

Still, one staff member from each of the wards carried isolates that did not fit neatly into the five MRSA clade clusters but did resemble isolates identified in healthcare settings in 2006 or 2007, researchers reported, hinting that they may have picked up MRSA at another healthcare site.

Using the genome sequences, the team also tracked transmission patterns within and between the wards as well as the genetic diversity present in the isolates. The latter included differences in the presence or absence of plasmids containing genes implicated in antibiotic and/or antiseptic resistance. 

"A striking result from sequence data was the presence of multiple distinct clades, which suggests that several different variants of MRSA were circulating through the hospital at the same time," Peacock said in a statement. "We also confirmed numerous transmission events between patients after admission to the ICU, and identified a 'super-spreader' in each unit."

To track MRSA diversity over time, researchers went on to sequence multiple samples that had been collected from one of the super-spreaders over more than two months. The individual's samples displayed significant within-patient diversity. Moreover, the study's authors explained, results from the analysis support the notion that the adult patient "appeared to introduce clade 5 into the adult ICU where it predominated to the end of the study period."

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