Vancomycin-resistant Enterococcus faecium in Japan, 2007–2015: a molecular epidemiology analysis focused on examining strain characteristics over time

Abstract

Vancomycin-resistant enterococci (VRE) are a significant cause of healthcare-associated infections. In Japan, the estimated isolation rate of VRE is approximately 0.2%; however, sporadic outbreaks continue to occur in healthcare facilities. Despite sporadic cases of VRE at our hospital since the 2007 outbreak, it is unclear whether the same strains from 2007 were still prevalent. Therefore, we performed whole-genome sequencing of stored VRE strains at our hospital and assessed their potential utility as an alternative to pulsed-field gel electrophoresis (PFGE) for infection control. In contrast to previous studies, our analysis focused on examining strain characteristics over time. The results of taxonomic characterization using average nucleotide identity (ANI) values and multilocus sequence typing (MLST) showed good agreement with the PFGE analysis, indicating that ANI values and MLST were viable potential alternatives to PFGE. Notably, many of the strains isolated in 2010 belonged to ST1421. The first reported VRE outbreak in Japan, caused by pstS -null VRE ST1421, occurred in Aomori in 2018. However, the present study demonstrated, for the first time, that the ST1421 strain existed in Japan as early as 2010. In the time series analysis, the observed PFGE pattern did not correlate with the time of strain isolation, particularly for isolates collected after 2012. We also observed cases where isolates sharing the same Tn1546 variant were found on distinct clonal backgrounds. While ANI and MLST may serve as suitable alternatives to PFGE for short-term outbreak evaluations, a plasmid analysis may prove useful for long-term assessments. Our study emphasizes the efficacy of whole-genome sequencing (WGS) in addressing outbreaks of vancomycin-resistant enterococci. WGS enables the identification and tracking of resistant bacterial strains, early detection and management of novel infectious disease outbreaks, and the appropriate selection and use of antibiotics. Furthermore, our approach deepens our understanding of how resistant bacteria transfer genes and adapt to their environments or hosts. For modern medicine, these insights have significant implications for controlling infections and effectively managing antibiotic use in the current era, where antibiotic resistance is progressing.