Relentless spread and adaptation of non-typeable vanA vancomycin-resistant Enterococcus faecium: a genome-wide investigation

Abstract

These findings confirmed the evolution, emergence and dissemination of non-typeable vanA E. faecium. This study has highlighted the utility of WGS when attempting to describe accurately the hospital-based pathogen epidemiology, which in turn will continue to inform optimal infection control measures necessary to halt the spread of this important nosocomial organism.

Emergence of an Australian-like pstS-null vancomycin resistant Enterococcus faecium clone in Scotland

“…Most of the Australian pstS -null genomes we analysed were ST1421 (Fig. 1C), in agreement with recent data showing that ST1421 is the most common and widespread pstS -null VRE strain in Australia, accounting for more than 70% of the cases [25,26]. Since both Australian [8] and Scottish (this study) VREfm pstS -null strains were found in different hospitals (Fig.…”

“…We then performed a phylogenetic comparison of VREF001-5 genomes with other known VREfm genomes reported to have a missing pstS locus; these included: 14 (out of 66 reported) Australian strains isolated from 9 different hospitals between 2014 and 2015 [8], 5 Australian strains (out of 202 reported within 6 local health districts) isolated from 2 different local health districts (LHD-1 and LHD-2) in New South Wales during 2016 [25], and all 5 English pstS -null E. faecium strains isolated from a single hospital (Kathy Raven, personal communication) in 2005 [7]. In our phylogenetic analysis we also included: 5 hospital-associated isolates of different MLST sequence type each, 3 isolates (BM4538, UAA1025 and E2883) previously reported to have an insertion in the tetM -locus [16] and the first complete E. faecium genome, Aus0004 [9].…”

“…Non-typeable VREfm strains have recently emerged and have been shown to be very rare in the UK: in a study encompassing whole genome sequencing of nearly 500 E. faecium healthcare-associated isolates from 2001-2011 in the UK and Ireland, there were only 5 cases of pstS -null VRE strains, all of which were isolated from a single English hospital, between 2004 and 2005 [7]. The emergence of such strains was even more recent in Australia: the first two strains were isolated in 2013, but numbers increased rapidly to a total of 89 cases, by the end of 2015 [8,29,30] and to about 300 cases, by the end of 2016 [25,30,31].…”

“…For the above reasons VRE infections may spread over long periods and across long distances. Indeed, our phylogenetic analysis is indicative of an inter-continental spread between Australia and Scotland: the closest phylogenetic relationships were identified among Australian and Scottish ST1424 clones; such 6-locus sequence type has been identified in 28.7% (58/202) of the recently sequenced pstS -null VREfm strains from New South Wales, Australia [25]. In addition, the spread of such strains in all health districts of New South Wales is also suggestive of inter-hospital transmission for this VREfm clone [25].…”

Genomic interrogation of the burden and transmission of multidrug-resistant pathogens within and across hospital networks

“…In Australia, as in Europe, the major pathogen surveillance programs such as Australian Group for Antimicrobial Resistance (AGAR) and the Victorian Hospital Pathogens Surveillance System (VHPSS) [11, 12] focus on isolates from bacteremic patients, meaning the true burden of MDROs, many of which lead to colonization or non-bacteremic infection, is undefined and poorly understood [9, 11]. Australia has one the highest rates of VRE in the world (47.0% in 2017 [13]), having been dominated by vanB until the last five years, when vanA VRE has emerged rapidly across multiple states [14]. Whilst the patient risk factors of MDRO acquisition are well understood for most of these organisms [15-22], further analysis using whole genome sequencing has the potential to add further insights, particularly defining the relatedness of isolates by genomics (and hence putative transmission when combined with epidemiologic data), which to date has only just started to be applied in a clinical setting [23, 24].…”