Transmission dynamics of a linear vanA-plasmid during a nosocomial multiclonal outbreak of vancomycin-resistant enterococci in a non-endemic area, Japan

Yoshihiro Fujiya,Yoshihiro Tsujimoto,Nobuhiro Tanimura,Hiroshi Kakeya,Yukihiro Akeda,Yo Sugawara,Shigeyuki Hamada,Kazunori Tomono,Masako Yasuda,Isao Nishi,Ryuji Kawahara,Wataru Shibata,Tetsuya Harada,Junichi Hayashi,Takahiro Yamaguchi,Ayako Masumi

doi:10.1038/s41598-021-94213-5

Abstract

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings. A large-scale multiclonal VRE outbreak has rarely been reported in Japan due to low VRE prevalence. We evaluated the transmission of vancomycin resistance in a multiclonal VRE outbreak, conducted biological and genomic analyses of VRE isolates, and assessed the implemented infection control measures. In total, 149 patients harboring VanA-type VRE were identified from April 2017 to October 2019, with 153 vancomycin-resistant Enterococcus faecium isolated being grouped into 31 pulsotypes using pulsed-field gel electrophoresis, wherein six sequence types belonged to clonal complex 17. Epidemic clones varied throughout the outbreak; however, they all carried vanA-plasmids (pIHVA). pIHVA is a linear plasmid, carrying a unique structural Tn1546 containing vanA; it moves between different Enterococcus spp. by genetic rearrangements. VRE infection incidence among patients in the “hot spot” ward correlated with the local VRE colonization prevalence. Local prevalence also correlated with vancomycin usage in the ward. Transmission of a novel transferrable vanA-plasmid among Enterococcus spp. resulted in genomic diversity in VRE in a non-endemic setting. The prevalence of VRE colonization and vancomycin usage at the ward level may serve as VRE cross-transmission indicators in non-intensive care units for outbreak control.

Highlights

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings
One hundred and sixteen (78%) patients had a history of prior admission to the hospital, of which 112 (97%), including those who were VRE-positive at admission, had stayed in ward A
We provide an overview of a multiclonal VanA-type VRE outbreak in a hospital specializing in dialysis therapy in a non-endemic area

Summary

Introduction

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings. A large-scale multiclonal VRE outbreak has rarely been reported in Japan due to low VRE prevalence. We evaluated the transmission of vancomycin resistance in a multiclonal VRE outbreak, conducted biological and genomic analyses of VRE isolates, and assessed the implemented infection control measures. PIHVA is a linear plasmid, carrying a unique structural Tn1546 containing vanA; it moves between different Enterococcus spp. by genetic rearrangements. VRE infection incidence among patients in the “hot spot” ward correlated with the local VRE colonization prevalence. The prevalence of VRE colonization and vancomycin usage at the ward level may serve as VRE crosstransmission indicators in non-intensive care units for outbreak control. VRE outbreaks have been occasionally reported in Japan[6,7], the Japan Nosocomial Infections Surveillance (https://janis.mhlw.go.jp/english/report/index.html) reported only 0.9% vancomycin resistance in all clinical isolates of E. faecium in 2018. Conjugative plasmid transfer is responsible for the widespread VanA-type vancomycin resistance among enterococcal populations[1,9,13]

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