Vancomycin-susceptible E. Faecium Research Articles

The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones.

Between 2010 and 2015 the incidence of vancomycin-resistant Enterococcus faecium (VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010-15; n=239) and (2) Norwegian vancomycin-susceptible E. faecium (VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global E. faecium strains from the National Center for Biotechnology Information (NCBI) (1946-2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin-antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as Enterococcus lactis, harboured fewer VFs than E. faecium in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian E. faecium isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.

Genomic investigation of the emergence of vanD vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus (VRE) is an increasingly identified cause of human disease, with most infections resulting from the vanA and vanB genotypes; less is known about other clinically relevant genotypes. Here we report a genomic exploration of a vanD VRE faecium (VREfm), which arose de novo during a single infectious episode. The genomes of the vancomycin-susceptible E. faecium (VSEfm) recipient and resulting VREfm were subjected to long-read sequencing and closed, with whole-genome alignments, cross-mapping and orthologue clustering used to identify genomic variation. Three key differences were identified. (i) The VREfm chromosome gained a 142.6 kb integrative conjugative element (ICE) harbouring the vanD locus. (ii) The native ligase (ddl) was disrupted by an ISEfm1 insertion. (iii) A large 1.74 Mb chromosomal inversion of unknown consequence occurred. Alignment and phylogenetic-based comparisons of the VREfm with a global collection of vanD-harbouring genomes identified strong similarities in the 120-160 kb genomic region surrounding vanD, suggestive of a common mobile element and integration site, irrespective of the diverse taxonomic, geographical and host origins of the isolates. This isolate diversity revealed that this putative ICE (and its source) is globally disseminated and is capable of being acquired by different genera. Although the incidence of vanD VREfm is low, understanding its emergence and potential for spread is crucial for the ongoing efforts to reduce antimicrobial resistance.

Occult Vancomycin-Resistant Enterococcus faecium ST117 Displaying a Highly Mutated vanB2 Operon

Rare information is available on clinical Enterococcus faecium encountered in Sardinia, Italy. This study investigated the antimicrobial susceptibility profiles and genotypic characteristics of E. faecium isolated at the University Hospital of Sassari, Italy, using the Vitek2 system and PCR, MLST, or WGS. Vitek2 revealed two VanB-type vancomycin-resistant Enterococcus faecium (VREfm) isolates (MICs mg/L = 8 and ≥32) but failed to detect vancomycin resistance in one isolate (MIC mg/L ≤ 1) despite positive genotypic confirmation of vanB gene, which proved to be vancomycin resistant by additional phenotypic methods (MICs mg/L = 8). This vanB isolate was able to increase its vancomycin MIC after exposure to vancomycin, unlike the "classic" occult vanB-carrying E. faecium, becoming detectable by Vitek 2 (MICs mg/L ≥ 32). All three E. faecium had highly mutated vanB2 operons, as part of a chromosomally integrated Tn1549 transposon, with common missense mutations in VanH and VanB2 resistance proteins and specific missense mutations in the VanW accessory protein. There were additional missense mutations in VanS, VanH, and VanB proteins in the vanB2-carrying VREfm isolates compared to Vitek2. The molecular typing revealed a polyclonal hospital-associated E. faecium population from Clade A1, and that vanB2-VREfm, and nearly half of vancomycin-susceptible E. faecium (VSEfm) analyzed, belonged to ST117. Based on core genome-MLST, ST117 strains had different clonal types (CT), excluding nosocomial transmission of specific CT. Detecting vanB2-carrying VREfm isolates by Vitek2 may be problematic, and alternative methods are needed to prevent therapeutic failure and spread.

Survival of hospital- and community-associated Enterococcus faecium following exposure to in-use concentrations of the biocide sodium dichloroisocyanurate (NaDCC)

Hospital-associated infections with vancomycin-resistant Enterococcus faecium (VREfm) have increased dramatically in Denmark. A cornerstone in infection control is effective cleaning and disinfection. This study investigated the survival and resuscitation/growth of clinical isolates of E. faecium exposed to the chlorine-releasing disinfectant, sodium dichloroisocyanurate plus detergent (NaDCC Plus). To assess biocide efficacy, we modified a method developed to characterise the dose-time-response of bacteria to antibiotics. E. faecium isolates (n=59) were screened in 96-well plates containing 50-1400 ppm free available chlorine. Bacteria were exposed for 10 min, after which the biocide was inactivated with a neutralizer. Cells were collected by centrifugation, new broth added, and after 20-22 h, viability was recorded as growth/no growth. For a subset of strains the impact of shorter biocide exposure times were examined, as was the influence of longer incubation times. E. faecium survived exposure to relatively high concentrations of NaDCC Plus, average 415 ppm of free available chlorine (SD ± 78 ppm), compared to recommended in-use concentration (1000 ppm). "Outbreak" clones did not prove more tolerant to NaDCC Plus compared to other VREfm clones, hospital-associated vancomycin-susceptible E. faecium (VSEfm) or community-associated VSEfm. Shorter exposure time and extended incubation time in broth both significantly increased the concentration needed to eradicate E. faecium, with some isolates surviving higher concentrations than the recommended in-use concentration. Our results indicate that if an exposure time of 10 min is not achieved, the efficacy of the disinfectant will not be sufficient.

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

Background: Vancomycin-resistant Enterococcus faecium (VREfm) is a successful nosocomial pathogen. The current molecular method recommended in the Netherlands for VREfm typing is based on core genome Multilocus sequence typing (cgMLST), however, the rapid emergence of specific VREfm lineages challenges distinguishing outbreak isolates solely based on their core genome. Here, we explored if a detailed molecular characterisation of mobile genetic elements (MGEs) and accessory genes could support and expand the current molecular typing of VREfm isolates sharing the same genetic background, enhancing the discriminatory power of the analysis. Materials/Methods: The genomes of 39 VREfm and three vancomycin-susceptible E. faecium (VSEfm) isolates belonging to ST117/CT24, as assessed by cgMLST, were retrospectively analysed. The isolates were collected from patients and environmental samples from 2011 to 2017, and their genomes were analysed using short-read sequencing. Pangenome analysis was performed on de novo assemblies, which were also screened for known predicted virulence factors, antimicrobial resistance genes, bacteriocins, and prophages. Two representative isolates were also sequenced using long-read sequencing, which allowed a detailed analysis of their plasmid content. Results: The cgMLST analysis showed that the isolates were closely related, with a minimal allelic difference of 10 between each cluster’s closest related isolates. The vanB-carrying transposon Tn1549 was present in all VREfm isolates. However, in our data, we observed independent acquisitions of this transposon. The pangenome analysis revealed differences in the accessory genes related to prophages and bacteriocins content, whilst a similar profile was observed for known predicted virulence and resistance genes. Conclusion: In the case of closely related isolates sharing a similar genetic background, a detailed analysis of MGEs and the integration point of the vanB-carrying transposon allow to increase the discriminatory power compared to the use of cgMLST alone. Thus, enabling the identification of epidemiological links amongst hospitalised patients.

Characterization of a vancomycin-resistant Enterococcus faecium isolate and a vancomycin-susceptible E. faecium isolate from the same blood culture.

To characterize two Enterococcus faecium isolates with different resistance phenotypes obtained from the same blood culture. The isolates were identified by MALDI-TOF MS and antimicrobial susceptibility testing (AST) was performed using a VITEK® 2 AST P592 card and Etest. WGS was performed on the MiSeq and MinION sequencer platforms. Core-genome MLST (cgMLST) and seven-loci MLST were performed. Plasmid analysis was performed using S1-PFGE followed by Southern-blot hybridization. Both E. faecium isolates were ST203. AST revealed that one was a vancomycin-resistant E. faecium (VREfm) isolate and the other was a vancomycin-susceptible E. faecium (VSEfm) isolate. The VREfm isolate harboured the vanA gene cluster as part of a Tn1546-type transposon encoded on a 49 kb multireplicon (rep1, rep2 and rep7a) plasmid (pAML0157.1). On the same plasmid, ant(6)-Ia, cat-like and erm(B) were encoded. The VSEfm isolate harboured a rep2 plasmid (pAML0158.1), 12 kb in size, which was present in full length as part of pAML0157.1 from the VREfm isolate. The vanA-encoding pAML0157.1 was a chimera of the rep2 pAML0158.1 and a second DNA segment harbouring vanA, ant(6)-Ia, erm(B) and cat-like, as well as the replicons rep1 and rep7a. By cgMLST analysis, the VREfm and VSEfm isolates were identical. Our results demonstrate that the VREfm and VSEfm blood culture isolates represented ST203 and were identical. The investigated heterogeneous resistance phenotypes resulted from the acquisition or loss of plasmid segments in the enterococcal isolates. These data illustrate that mobile genetic elements may contribute to the spread of vancomycin resistance among enterococci and to the genotypic and phenotypic variation within clonal isolates.

Long-Lasting Decrease of the Acquisition of Enterococcus faecium and Gram-Negative Bacteria Producing Extended Spectrum Beta-Lactamase (ESBL) by Transient Application of Probiotics.

Previously it was shown that application of probiotics stopped the acquisition of vancomycin-resistant Enterococcus faecium (VRE) by patients in an early rehabilitation ward. Once the application of probiotics ended, we examined whether acquisition of VRE reoccurred. Furthermore, we examined whether probiotics altered prevalence of vancomycin-susceptible E. faecium (VSE) and Gram-negative bacteria, which produce extended spectrum beta-lactamase (ESBL). Although probiotic application ceased in April 2018, VRE-colonized patients rarely presented on that ward until 2019. Probiotic treatment also resulted in a decreased number of patients with VSE and ESBL. While decreased incidence of VRE occurred immediately, decreased VSE and ESBL numbers occurred months later. A probiotic-mediated decrease of VSE and ESBL incidence cannot be explained when assuming bacterial transmission exclusively as a linear cause and effect event. The decrease is better understood by considering bacterial transmissions to be stochastic events, which depend on various driving forces similar to an electric current. We hypothesize that VRE, VSE and ESBL uptake by patients and by staff members mutually reinforced each other, leading staff members to form a bacterial reservoir, similar to a condenser that stores electrical energy. Probiotic treatment then inhibited regeneration of that store, resulting in a breakdown of the driving force.

WGS of 1058 Enterococcus faecium from Copenhagen, Denmark, reveals rapid clonal expansion of vancomycin-resistant clone ST80 combined with widespread dissemination of a vanA-containing plasmid and acquisition of a heterogeneous accessory genome.

From 2012 to 2015, a sudden significant increase in vancomycin-resistant (vanA) Enterococcus faecium (VREfm) was observed in the Capital Region of Denmark. Clonal relatedness of VREfm and vancomycin-susceptible E. faecium (VSEfm) was investigated, transmission events between hospitals were identified and the pan-genome and plasmids from the largest VREfm clonal group were characterized. WGS of 1058 E. faecium isolates was carried out on the Illumina platform to perform SNP analysis and to identify the pan-genome. One isolate was also sequenced on the PacBio platform to close the genome. Epidemiological data were collected from laboratory information systems. Phylogeny of 892 VREfm and 166 VSEfm revealed a polyclonal structure, with a single clonal group (ST80) accounting for 40% of the VREfm isolates. VREfm and VSEfm co-occurred within many clonal groups; however, no VSEfm were related to the dominant VREfm group. A similar vanA plasmid was identified in ≥99% of isolates belonging to the dominant group and 69% of the remaining VREfm. Ten plasmids were identified in the completed genome, and ∼29% of this genome consisted of dispensable accessory genes. The size of the pan-genome among isolates in the dominant group was 5905 genes. Most probably, VREfm emerged owing to importation of a successful VREfm clone which rapidly transmitted to the majority of hospitals in the region whilst simultaneously disseminating a vanA plasmid to pre-existing VSEfm. Acquisition of a heterogeneous accessory genome may account for the success of this clone by facilitating adaptation to new environmental challenges.

Comparison of antibiotic resistance and virulence in vancomycin-susceptible and vancomycin-resistant Enterococcus faecium strains

Aim. Today, infections caused by vancomycin-resistant Enterococcus faecium (VRE) are a major problem in the healthcare system. The aim of this study was to compare the antibiotic resistance and virulence traits between vancomycin-susceptible E. faecium (VSE) and VRE clinical isolates.Material and Methods. Studies were performed on 66 E. faecium (32 VRE and 34 VSE) strains. Susceptibility testing and identification were performed, and strains were examined for ß-lactamase, hemolysin and biofilm production. Isolates were tested for the presence of 5 van genes, 8 virulence genes and 6 aminoglycoside-modifying enzyme (AME) genes. Obtained amplicons were subjected to electrophoretical separation and DNA sequencing.Results. Among 32 VRE isolates, 28 were found to have the VanA phenotype, and 4 the VanB. The most frequent resistance and virulence profile among VRE strains was resistance to ampicillin, imipenem, gentamicin, streptomycin, teicoplanin, and vancomycin with enterococcal surface protein (esp), endocarditis antigen (efaA), collagen adhesin (acm), and hialuronidase (hyl) genes; among VSE: resistance to ampicillin, imipenem, gentamicin, streptomycin with esp, efaA, acm, and hyl genes. Conclusions. Our findings prove that both VRE and VSE strains were well equipped with virulence and resistance genes, although VRE strains were characterized by a greater variety and a higher number of these genes. However, statistical analysis revealed no significant differences between VSE and VRE strains (p > 0.05). Nevertheless, our results suggest that VRE strains may slowly acquire and incorporate resistance and virulence genes, due to their ability to survive in a hospital environment for a long time.

Comparison of Enterococcus faecium Bacteremic Isolates from Hematologic and Non-hematologic Patients: Differences in Antimicrobial Resistance and Molecular Characteristics.

BackgroundEnterococcus faecium, especially vancomycin-resistant E. faecium (VREfm), is a major concern for patients with hematologic diseases. Exposure to antibiotics including fluoroquinolone, which is used as a routine prophylaxis for patients with hematologic (MH) diseases, has been reported to be a risk factor for infection with vancomycin-resistant eneterocci. We compared the characteristics of E. faecium isolates according to their vancomycin susceptibility and patient group (MH vs non-MH patients).MethodsA total of 120 E. faecium bacteremic isolates (84 from MH and 36 from non-MH patients) were collected consecutively, and their characteristics (susceptibility, multilocus sequence type [MLST], Tn1546 type, and the presence of virulence genes and plasmids) were determined.ResultsAmong the vancomycin-susceptible E. faecium (VSEfm) isolates, resistance to ampicillin (97.6% vs 61.1%) and high-level gentamicin (71.4% vs 38.9%) was significantly higher in isolates from MH patients than in those from non-MH patients. Notably, hyl, esp, and pEF1071 were present only in isolates with ampicillin resistance. Among the VREfm isolates, ST230 (33.3%) and ST17 (26.2%) were predominant in MH patients, while ST17 (61.1%) was predominant in non-MH patients. Plasmid pLG1 was more prevalent in E. faecium isolates from MH patients than in those from non-MH patients, regardless of vancomycin resistance. Transposon analysis revealed five types across all VREfm isolates.ConclusionsThe antimicrobial resistance profiles and molecular characteristics of E. faecium isolates differed according to the underlying diseases of patients within the same hospital. We hypothesize that the prophylactic use of fluoroquinolone might have an effect on these differences.

Multilevel population genetic analysis of vanA and vanB Enterococcus faecium causing nosocomial outbreaks in 27 countries (1986-2012).

Vancomycin-resistant Enterococcus faecium (VREfm) have been increasingly reported since the 1980s. Despite the high number of published studies about VRE epidemiology, the dynamics and evolvability of these microorganisms are still not fully understood. A multilevel population genetic analysis of VREfm outbreak strains since 1986, representing the first comprehensive characterization of plasmid content in E. faecium, was performed to provide a detailed view of potential transmissible units. From a comprehensive MeSH search, we identified VREfm strains causing hospital outbreaks (1986-2012). In total, 53 VanA and 18 VanB isolates (27 countries, 5 continents) were analysed and 82 vancomycin-susceptible E. faecium (VSEfm) were included for comparison. Clonal relatedness was established by PFGE and MLST (goeBURST/Bayesian Analysis of Population Structure, BAPS). Characterization of van transposons (PCR mapping, RFLP, sequencing), plasmids (transfer, ClaI-RFLP, PCR typing of relaxases, replication-initiation proteins and toxin-antitoxin systems, hybridization, sequencing), bacteriocins and virulence determinants (PCR, hybridization, sequencing) was performed. VREfm were mainly associated with major human lineages ST17, ST18 and ST78. VREfm and VSEfm harboured plasmids of different families [RCR, small theta plasmids, RepA_N (pRUM/pLG1) and Inc18] able to yield mosaic elements. Tn1546-vanA was mainly located on pRUM/Axe-Txe (USA) and Inc18-pIP186 (Europe) plasmids. The VanB2 type (Tn5382/Tn1549) was predominant among VanB strains (chromosome and plasmids). Both strains and plasmids contributed to the spread and persistence of vancomycin resistance among E. faecium. Horizontal gene transfer events among genetic elements from different clonal lineages (same or different species) result in chimeras with different stability and host range, complicating the surveillance of epidemic plasmids.

Structure and transfer of the vanA cluster in vanA-positive, vancomycin-susceptible Enterococcus faecium, and its revertant mutant

Of 18 vanA-positive vancomycin-susceptible Enterococcus faecium isolates, vanRS in the vanA cluster was detected in all isolates, while vanHAX was detected in only 2 isolates. Following exposure to glycopeptides, 22.2% of vancomycin-susceptible E. faecium (VSE) converted into vancomycin-resistant E. faecium. The vanA cluster of the revertant mutant was transferred to the VSE isolates.

Molecular characterization of Enterococcus faecium isolated from hospitalized patients in Korea

Multilocus sequence typing (MLST) was performed for vancomycin-resistant Enterococcus faecium (VREF) from diverse geographical areas in Korea to obtain insights into the genetic relationships with other molecular profiles. To understand the diversity of lineages, vancomycin-susceptible E. faecium (VSEF) were included. A total of 60 E. faecium isolates were analysed by MLST and esp profile. Molecular typing of Tn1546 of 30 VREF strains was evaluated by overlapping PCR of Tn1546 and DNA sequencing. Seven sequence types (ST) were found among 30 VSEF isolates, and four STs were found among 30 VREF isolates. The types most frequently encountered were ST 78 (26 isolates) and ST 203 (16 isolates). Of the 60 E. faecium isolates, 35 isolates were positive for the esp gene. On molecular typing of Tn1546, all VREF isolates were divided into four main types. Strains with the same ST showed divergence in Tn1546 types and strains with the same Tn1546 type represented different STs. An association between Tn1546 typing and MLST was not found. These results suggest that the horizontal spread of Tn1546 between strains plays a major role in the dissemination of vancomycin resistance in Korea.

Epidemic and Nonepidemic Multidrug-ResistantEnterococcus faecium

The epidemiology of vancomycin-resistant Enterococcus faecium (VREF) in Europe is characterized by a large community reservoir. In contrast, nosocomial outbreaks and infections (without a community reservoir) characterize VREF in the United States. Previous studies demonstrated host-specific genogroups and a distinct genetic lineage of VREF associated with hospital outbreaks, characterized by the variant esp-gene and a specific allele-type of the purK housekeeping gene (purK1). We investigated the genetic relatedness of vanA VREF (n=108) and vancomycin-susceptible E. faecium (VSEF) (n=92) from different epidemiologic sources by genotyping, susceptibility testing for ampicillin, sequencing of purK1, and testing for presence of esp. Clusters of VSEF fit well into previously described VREF genogroups, and strong associations were found between VSEF and VREF isolates with resistance to ampicillin, presence of esp, and purK1. Genotypes characterized by presence of esp, purK1, and ampicillin resistance were most frequent among outbreak-associated isolates and almost absent among community surveillance isolates. Vancomycin-resistance was not specifically linked to genogroups. VREF and VSEF from different epidemiologic sources are genetically related; evidence exists for nosocomial selection of a subtype of E. faecium, which has acquired vancomycin-resistance through horizontal transfer.

Selection of a teicoplanin-resistant Enterococcus faecium mutant during an outbreak caused by vancomycin-resistant enterococci with the vanB phenotype.

Vancomycin-resistant enterococci (VRE) have recently become an increasing problem in hospitals in Poland, being responsible for a growing number of nosocomial outbreaks. In this work, we have analyzed the second outbreak of VRE with the VanB phenotype to be identified in the country. It was caused by clonal dissemination of a single strain of vancomycin-resistant Enterococcus faecalis (VRES) and horizontal transmission of vancomycin resistance genes among several vancomycin-resistant Enterococcus faecium (VREM) strains. Two similar restriction fragment length polymorphism types of the vanB gene cluster characterized VRES and VREM isolates, and they both contained the same vanB2 variant of the vanB gene. Two vancomycin-susceptible E. faecium (VSEM) isolates, recovered from the same wards during the outbreak, proved to be related to certain VREM isolates and could represent endemic strains that had acquired vancomycin resistance. One VSEM and four VREM isolates, all identified in the same patient, belonged to a single clone, although they revealed remarkable diversity in terms of susceptibility, PFGE patterns, plasmid content, and number of vanB gene cluster copies. Most probably they reflected the dynamic evolution of an E. faecium strain in the course of infection of a single patient. One of the VREM isolates turned out to be resistant to teicoplanin, which coincided with the use of this antibiotic in the patient's therapy. Its vanB gene variant differed by a single mutation from that found in other isolates; however, it also lacked a large part of the vanB gene cluster, including the regulatory genes vanR(B) and -S(B), and the vancomycin-inducible promoter P(YB). Expression of the resistance genes vanH(B), -B, and -X(B) was constitutive in the mutant, and this phenomenon was responsible for its unusual phenotype.

Enterococcus faecium bacteremia: does vancomycin resistance make a difference?

Enterococcus faecium has received increased attention, primarily due to the emergence of vancomycin resistance. The purpose of this investigation was to study the epidemiological characteristics of vancomycin-resistant E faecium (VRE) bacteremia and to determine the clinical impact of vancomycin resistance on the outcome of patients with this infection. We retrospectively analyzed the clinical features and outcome of 53 patients with E faecium bacteremia. From January 1992 until December 1995, there were 32 episodes of bacteremia caused by vancomycin-susceptible E faecium (VSE) and 21 caused by VRE. An intra-abdominal site was the most common source of bacteremia in both groups. All of the VRE and 78% of VSE bacteremia cases were nosocomially acquired. Previous administration of vancomycin was associated with VRE bacteremia (P<.001), as were indwelling bladder catheters (P=.01). Fifty-nine percent of the patients with VSE bacteremia survived vs 24% with VRE (P=.009), despite similar severity-of-illness scores. In 62% of the patients with VRE sepsis, death was related to the bacteremia (P=.01). Patients infected with VRE had longer hospitalizations than those with VSE (34.8 vs 16.7 days, respectively) (P=.004), were more likely to be on the medical service (P=.03), and on the average, had hospitalization costs of more than $27,000 per episode than did patients with VSE bloodstream infection ($83,897 vs $56,707, respectively) (P=.04). Vancomycin-resistant E faecium bacteremia is a complication of prolonged hospitalization in debilitated patients. Vancomycin resistance has a negative impact on survival in patients with E faecium bacteremia and leads to higher health care costs.