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Genome Sequences Show How Hospital-Acquired Bloodstream Infections Are Transmitted

NEW YORK (GenomeWeb) – A new study supports the notion that genome sequencing can offer insights into potential infection sources and transmission patterns for infectious microbes such as vancomycin-resistant Enterococcus faecium, a bug implicated in hospital-acquired or nosocomial infections.

As part of a retrospective analysis published in Clinical Infectious Diseases yesterday, the researchers used genome sequencing to profile nearly 300 isolates — including 200 vancomycin-resistant and 93 vancomycin-susceptible E. faecium representatives — collected from individuals diagnosed with bloodstream infections at a hospital in the UK over several years.

With a phylogenetic analysis of the isolates, alongside sequences from E. faecium isolates associated with bloodstream infections at other sites around the world, the team attributed all but two of the original cases to isolates from a clade of hospital- or healthcare-associated E. faecium strains. It also untangled transmission patterns in half a dozen E. faecium sub-clusters, including isolates involved in 93 bloodstream infection cases.

"These findings provide important insights for infection control practice and signpost areas for interventions," senior author Sharon Peacock, a researcher affiliated with the University of Cambridge, the London School of Hygiene and Tropical Medicine, and the Wellcome Trust Sanger Institute, and her co-authors wrote. "We conclude that sequencing represents a powerful tool for the enhanced surveillance and control of nosocomial E. faecium transmission and infection."

Starting from 342 E. faecium bloodstream infection cases at Cambridge University Hospitals NHS Foundation Trust, the researchers got ahold of 293 archived E. faecium isolates — a set that included 197 vancomycin-resistant isolates carrying the vanA resistance gene, three resistant isolates with vanB, a single resistant isolate with both vanA and vanB, and 93 E. faecium isolates that were susceptible to vancomycin.

The team used the Illumina HiSeq2000 to do whole-genome sequencing on the isolates, as well as hundreds more E. faecium isolates from the UK and beyond. A phylogenetic analysis that included the UK hospital isolates and 73 global isolates, indicated that 291 of the Cambridge University Hospital isolates fell into a clade of hospital-acquired strains.

Of those, 284 isolates belonged to an inter-related clonal expansion cluster with high genetic diversity, perhaps reflecting multiple introductions of these bugs, coupled with ongoing transmission and expansion within the hospital, the researchers reported.

With a more in-depth transmission analysis, hinging on SNP and recombination patterns in six E. faecium sub-clusters, they teased out examples of within-hospital ward E. faecium transmission and infections involving genetically similar isolates at other hospitals in the UK.

Finally, the team saw signs of fluidity when it came to vancomycin susceptibility and resistance, with resistance arising on multiple occasions in strains that were previously vulnerable to the antibiotic.

Based on their findings, the authors called for active E. faecium screening as a strategy for reducing transmission of the bug from asymptomatic carriers in the hospital setting. 

They also argued that "the scope of infection control investigations for suspected [vancomycin-resistant E. faecium] outbreaks requires the inclusion of multiple wards and specialties, the potential complexity of which could be simplified by bacterial sequencing."

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