Increase of vancomycin-resistant Enterococcus faecium strain type ST117 CT71 at Charité - Universitätsmedizin Berlin, 2008 to 2018

Abstract

Background: In addition to an overall rise in vancomycin-resistant Enterococcus faecium (VREfm), an increase in certain strain types marked by sequence type (ST) and cluster type (CT) has been reported in Germany over the past few years. Outbreak analyses at Charité-Universitätsmedizin Berlin revealed the frequent occurrence of VREfm ST117 CT71 isolates in 2017 and 2018. To investigate whether ST117 CT71 have emerged in recent years or whether these strains have been circulating for a longer time, we retrospectively analyzed non-outbreak strains that occurred between 2008 and 2018 to identify frequent STs and CTs. Methods: In total, 120 VREfm isolates obtained from clinical and surveillance cultures from the years 2008, 2013, 2015, and 2018 were analyzed. Thirty isolates per year comprising the first 7-8 non-outbreak isolates of each quarter of the respective year were sequenced using whole genome sequencing. MLST and cgMLST were determined as well as resistance genes and virulence factors. Risk factors for VREfm ST117 were analyzed in a multivariable analysis with patient characteristics as possible confounders. Results: The percentage of VREfm of type ST117 increased from 17% in 2008 to 57% in 2018 (p = 0.012). In 2008, vanA genotype accounted for 80% of all ST117 isolates compared to 6% in 2018. VanB CT71 first appeared in 2018 and predominated over all other ST117 at 43% (p < 0.0001). The set of resistance genes (msrC, efmA, erm(B), dfrG, aac(6′)-Ii, gyrA, parC and pbp5) and virulence factors (acm, esp, hylEfm, ecbA and sgrA) in CT71 was also found in other ST117 non-CT71 strains, mainly in CT36. The study population did not differ among the different calendar years analyzed in terms of age, gender, length of stay, or ward type (each p > 0.2). Conclusion: This study revealed an increase in ST117 strains from 2008 to 2018, accompanied by a shift toward CT71 strains with the vanB genotype in 2018. We did not detect resistance or virulence traits in CT71 that could confer survival advantage compared to other CTs among ST117 strains. To date, it is not clear why ST117 and in particular strain type ST117 CT71 predominates over other strains.

Molecular Characterisation of Vancomycin-Resistant Enterococcus faecium Isolates Belonging to the Lineage ST117/CT24 Causing Hospital Outbreaks

“…Two of these genes, pilA and hyl , were carried on plasmids as described in the literature ( Freitas et al, 2018 ; Gao et al, 2018 ). Our data are in line with the observation that the pattern of virulence and resistance genes herewith detected is linked to “high risk” Enterococcus strains ( Weber et al, 2020 ) and is consistent with the classification within the major putative virulence markers typical of clade A1 as proposed by Freitas et al (2018) .…”

“…Here, we describe the genomic makeup of 39 VREfm strains isolated from 2011 until 2017, including two consecutive outbreak isolates sharing the same genetic background and compare them with VSEfm isolates. These isolates belonged to ST117, a lineage frequently associated with nosocomial outbreaks ( Papagiannitsis et al, 2017 ; Zhou et al, 2018 ; Abdelbary et al, 2019 ; Falgenhauer et al, 2019 ; Liese et al, 2019 ; Pinholt et al, 2019 ; Eisenberger et al, 2020 ; Weber et al, 2020 ) and classified as part of the hospital-associated clade A1 ( Lebreton et al, 2013 ). A previous study showed that strains belonging to this clade have a larger genome size suggesting that the acquisition of new traits occurred whilst persisting in the hospital environment.…”

Prevalence and risk factors of colonisation with vancomycin-resistant Enterococci faecium upon admission to Germany’s largest university hospital

“…The significantly higher VR E. faecium prevalence of 1.5 per 100 patients screened in 2015 compared to 0.8 in 2014 can be explained by the dynamics of VR E. faecium epidemiology in the last few years. As reported, at Charité University Hospital, the number of isolates representing the ST117 CT71 strain increased by 36.7% (p<0.001) [ 31 ]. German national nosocomial infection surveillance system (KISS) data confirms a trend of increasing VRE positivity in hospitalised patients between 2008 and 2016 that is in accordance with European surveillance data [ 3 ], [ 35 ].…”

“…One cause might be the regional emergence of specific VRE strains. In clinical and surveillance samples from different wards at Charité University Hospital from 2008 to 2018, a significant increase in VRE strain sequence type (ST)117 cluster type (CT)71 was reported [ 31 ]. Therefore, we can assume that the rising VRE prevalence at Charité University Hospital is due to strain ST177 CT71.…”

“…Based on data on antimicrobial use density in Germany, some federal states with high VRE prevalence shown an antimicrobial use density above the German mean. Other federal states did not [ 31 ], [ 32 ]. Thus, the regional differences in the rate of VRE or VR E. faecium prevalence in Germany cannot be explained by the nationwide distribution of antimicrobial use density.…”