ABSTRACTNosocomial outbreaks of vancomycin-resistantEnterococcus faecium(VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology ofE. faeciumwithin a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61E. faecium(36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on fivevanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of thevanBgene, which contains the Tn1549transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicatingde novogeneration of VREfm rather than cross-transmission. Furthermore, Tn1549sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549sequence from one of the gut anaerobes. National and international comparatorE. faeciumisolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptibleE. faeciumrather than just VREfm.IMPORTANCEEnterococcus faeciumis an increasingly important human pathogen causing predominantly antibiotic-resistant infections in hospitalized patients. Large amounts of health care funding are spent trying to control antibiotic-resistant bacteria in hospitals globally, yet in many institutions around the world, vancomycin-resistantE. faecium(VREfm) infections continue to rise. The new findings from this study help explain the failures of our current approaches to controllingvanBVREfm in health care institutions. Given the importance of this bacterium as a cause of hospital-acquired infections and the difficulties faced by infection control units in trying to prevent colonization in their institutions, the novel findings from this study provide evidence that a new approach to controlling VREfm in hospitals is required. In particular, more attention should be given to understanding the epidemiology of hospital-adapted vancomycin-susceptibleE. faecium, and patients at higher risk forde novogeneration of VREfm need to be identified and optimally managed.
Complete Genome Sequences of Four Isolates of Vancomycin-Resistant Enterococcus faecium with the vanA Gene and Two Daptomycin Resistance Mutations, Obtained from Two Inpatients with Prolonged Bacteremia
