Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone

Abstract

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand.

Methods: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796.

Results: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed.

Conclusions: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

Keywords: Infection control; Molecular epidemiology; Outbreak; VRE; Whole genome sequencing.

Fig. 1

Source of 131 ST796 E. faecium isolates from seven hospitals across Australia and New Zealand

Fig. 2

Rates of VRE E. faecium bacteremia by ST over 17 years at Austin Health, Melbourne. We have observed two recent outbreaks of VRE bacteremia, the first with ST203 which has now been almost completely replaced by ST796. *One isolate from 2010 was not typed

Fig. 3

Maximum likelihood phylogenomic tree of 131 ST796 isolates. The tree was constructed from non-recombinogenic core SNPs and branches with less than 70% bootstrap support (500 replicates) were collapsed. The VSE, vanA and vanB isolates formed distinct and robust phylogroups. The single vanA + vanB isolate clustered within the vanB phylogroup. Branch lengths are proportional to core SNP differences with the scale as indicated. The inferred occurrences of intra-hospital evolution among the vanB isolates are labelled (brackets). The phylogenomic position of the ST796 most recent common ancestor (MRCA) in the ST796 tree was identified by using Enterococcus hirae (hirae_ATCC_9790, GenBank accession no. CP003504) as an outgroup. A = Alfred Health, Melbourne; B = Auckland City Hospital; C = Austin Health, Melbourne; D = John Hunter Hospital, Newcastle; E = other Auckland hospital; F = Monash Health, Melbourne; G = Royal Adelaide Hospital

Fig. 4

Pairwise comparisons of non-recombinogenic core SNP differences according to institution of origin. Overall, intra-hospital diversity is equal to or greater than inter-hospital diversity, indicating that there is substantial ST genomic admixture within each hospital. Comparisons are ordered according to increasing means. A = Alfred Health, Melbourne; B = Auckland City Hospital; C = Austin Health, Melbourne; D = John Hunter Hospital, Newcastle; E = other Auckland hospital; F = Monash Health, Melbourne; G = Royal Adelaide Hospital