Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals

Hegstad, Kristin; Longva, Jørn-Åge; R, Hide; Aasnæs, Bettina; Lunde, Tracy Tamara Munthali; Simonsen, Gunnar Skov

doi:10.3109/00365548.2014.923107

Cited by 16 publications

(7 citation statements)

References 27 publications

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“…as well as an increase in ST117 in Germany in recent years [8]. An occurrence of ST117 strains was also observed in other European countries such as Denmark [23], Switzerland [24], Norway [25], the Netherlands [26,27], and Spain [28].…”

Section: Discussionmentioning

confidence: 94%

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

Weber

Maechler

Schwab

et al. 2020

Antimicrob Resist Infect Control

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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.

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Section: Discussionmentioning

confidence: 94%

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

Weber

Maechler

Schwab

et al. 2020

Antimicrob Resist Infect Control

View full text Add to dashboard Cite

show abstract

“…Thus, an overall increase of VRE may not be the only explanation for the rise of ST117/CT71. An occurrence of ST117 strains was also observed in other European countries such as Denmark (24), Switzerland (25), Norway (26), the Netherlands (27,28), and Spain (29).…”

Section: Discussionmentioning

confidence: 57%

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

Weber

Maechler

Schwab

et al. 2020

Preprint

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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, ermB, 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.

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“…Assembly of the raw WGS data followed by filtering of low length contigs gave a total of 172 scaffolds (range: 310-137, 266 bp; N50: 41,930 bp; L50: 18; mean coverage: 92X). E. faecium E35048 was assigned to ST117, a globally disseminated hospital-adapted clone ( Hegstad et al, 2014 ; Tedim et al, 2017 ). Resistome analysis revealed the presence of six acquired resistance genes in addition to the previously described optrA and cfr genes: erm (B) (resistance to macrolides, lincosamides and group B streptogramins), msr (C) (resistance to macrolides and group B streptogramins), tet (M) (resistance to tetracycline), aphA and aadE (resistance to aminoglycosides), and sat4 (resistance to streptothricin).…”

Section: Resultsmentioning

confidence: 99%

“…Distinctive findings of the optrA - and cfr -carrying plasmid pE35048-oc are its relation to the well-known enterococcal plasmid pRE25, shared with plasmid pEF12-0805 ( Lazaris et al, 2017 ); a unique optrA context, that has never been described before; and the fact that both the optrA and cfr contexts are capable of excising to form minicircles. This, in addition to the belonging of E. faecium E35048 to ST117, a globally disseminated clone recovered in many European health institutions ( Hegstad et al, 2014 ; Tedim et al, 2017 ), might favor the spread of optrA and cfr in the hospital setting. Under this respect, the in vitro non-transferability of pE35048-oc is someway reassuring, although transfer in vivo cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

et al. 2018

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Enterococcus faecium E35048, a bloodstream isolate from Italy, was the first strain where the oxazolidinone resistance gene optrA was detected outside China. The strain was also positive for the oxazolidinone resistance gene cfr. WGS analysis revealed that the two genes were linked (23.1 kb apart), being co-carried by a 41,816-bp plasmid that was named pE35048-oc. This plasmid also carried the macrolide resistance gene erm(B) and a backbone related to that of the well-known Enterococcus faecalis plasmid pRE25 (identity 96%, coverage 65%). The optrA gene context was original, optrA being part of a composite transposon, named Tn6628, which was integrated into the gene encoding for the ζ toxin protein (orf19 of pRE25). The cfr gene was flanked by two ISEnfa5 insertion sequences and the element was inserted into an lnu(E) gene. Both optrA and cfr contexts were excisable. pE35048-oc could not be transferred to enterococcal recipients by conjugation or transformation. A plasmid-cured derivative of E. faecium E35048 was obtained following growth at 42°C, and the complete loss of pE35048-oc was confirmed by WGS. pE35048-oc exhibited some similarity but also notable differences from pEF12-0805, a recently described enterococcal plasmid from human E. faecium also co-carrying optrA and cfr; conversely it was completely unrelated to other optrA- and cfr-carrying plasmids from Staphylococcus sciuri. The optrA-cfr linkage is a matter of concern since it could herald the possibility of a co-spread of the two genes, both involved in resistance to last resort agents such as the oxazolidinones.

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Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals

Cited by 16 publications

References 27 publications

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

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

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

Characterization of a Multiresistance Plasmid Carrying the optrA and cfr Resistance Genes From an Enterococcus faecium Clinical Isolate

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