Resistance Mechanisms, Epidemiology, and Approaches to Screening for Vancomycin-Resistant Enterococcus in the Health Care Setting

Abstract

Infections attributable to vancomycin-resistant Enterococcus (VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.

FIG 1

Vancomycin acts by binding to d-Ala-d-Ala pentapeptides blocking cell wall biosynthesis. Resistance to vancomycin is conferred by the van operon, which consists of a two-component regulatory system (vanS-vanR) that responds to either vancomycin, disruption at the cell membrane, or both. Detection of stimulus then activates downstream genes vanH, vanA or vanB and vanX. VanX is a d,d-dipeptidase that cleaves d-Ala-d-Ala repeats, both depleting the pool of d-Ala-d-Ala and supplying the bacteria with a free d-Ala for Van(A/B). VanH is a d-hydroxyacid dehydrogenase that reduces pyruvate to d-Lac for the ligase Van(A/B). Van(A/B) then ligates d-Ala-d-Lac, allowing for the production of d-Ala-d-Lac pentapeptides that have low affinity for vancomycin. In addition, VanY is a d,d-carboxypeptidase that cleaves the d-Ala terminal peptide to further reduce pools of pentapeptides that have high affinity to vancomycin. Finally, VanZ, which is present on vanA-carrying strains, confers modest resistance to teicoplanin through an unknown mechanism. Differences in the level of resistance are likely a result of pentapeptide composition, as the ratio between pentapeptides consisting of high affinity to low affinity to vancomycin correlate with the isolate MICs. High-level resistance (HLR) occurs when pentapeptides are mostly composed of low-affinity molecules, and moderate-level resistance (MLR) involves more-heterogeneous pools of high- and low-affinity pentapeptides.