Epidemic and nonepidemic multidrug-resistant Enterococcus faecium

Abstract

The epidemiology of vancomycin-resistant Entero- coccus 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.

Figure 1

Cluster analysis of vancomycin-susceptible Enterococcus faecium (VSEF) isolates originating from clinical infections and clinical and community surveys. VSEF (n=92) were genotyped by amplified fragment length polymorphism (AFLP). Grouping of AFLP patterns showed four different clusters with >65% similarity. Numbers on the horizontal axis indicate percentage similarity. Closed circles indicate presence of the esp gene and the purK-1 allele and also the source of the isolates. Open circles represent esp-negative strains and other purK alleles. Closed arrowheads indicate ampicillin resistance. The vertical dashed line indicates the level of 65% similarity. Horizontal dashed lines indicate the boundaries of the four different clusters.

Figure 2

Frequencies of the esp gene and ampicillin resistance among vancomycin-susceptible enterococci (VSE) and vancomycin-resistant enterococci (VRE) of different origin. Percentages of esp-positive (solid bars) and ampicillin-resistant (dotted bars) VRE and VSE isolates originating from four different sources have been indicated. Clin-Inf, clinical infectious; Clin-Surv, clinical survey; Comm-Surv, community survey.

Figure 3

Hypothetical evolutionary scheme for Enterococcus faecium genotypes and phenotypes from an ancestral E. faecium type. Open slices indicate esp-negative, ampicillin-susceptible, and vancomycin-susceptible. Closed slices indicate esp-positive, ampicillin-resistant, and vancomycin-resistant. Numbers indicate the number of strains. Arrows indicate the putative evolutionary direction. Clin-Inf, clinical infectious; Clin-Surv, clinical survey; Comm-Surv, community survey. ^a, dominant genogroup (A,C) for vancomycin-resistant enterococci and dominant cluster (2,3,4) for vancomycin-susceptible enterococci.
^b, clinical relevant strains (“yes”) are the total of epidemic and clinical infectious isolates, clinical nonrelevant strains (“no”) are the total of clinical and community survey isolates.