Prevalence of vancomycin-variable Enterococcus faecium (VVE) among vanA-positive sterile site isolates and patient factors associated with VVE bacteremia

PLoS One. 2018 Mar 22;13(3):e0193926. doi: 10.1371/journal.pone.0193926. eCollection 2018.

Abstract

Vancomycin-variable enterococci (VVE) are vanA-positive, vancomycin-susceptible enterococci with the ability to revert to a vancomycin-resistant phenotype on exposure to vancomycin. We sought to assess the prevalence of VVE and to determine clinical characteristics of patients infected with VVE. We prospectively collected Enterococcus faecium sterile site isolates from Toronto Invasive Bacterial Diseases Network hospitals from January 2015 to June 2016 and calculated VVE (defined as vanA-positive, vancomycin-susceptible isolates) prevalence among vanA-containing isolates. We performed chart reviews of VVE and vancomycin-resistant E. faecium (VRE) bacteremias identified from January 2012 to June 2016, and on a random sample of patients with bacteremia due to vanA/vanB-negative, vancomycin-susceptible enterococci (VSE) from January 2015 to June 2016. Clinical characteristics were compared and factors associated with mortality assessed. Because of the potential reversion from VVE to VRE, pulsed-field gel electrophoresis (PFGE) was performed for strains causing breakthrough bacteremia in order to identify relatedness among strains with different phenotypic resistance within the same patient. VVE comprised 47% (18/38) of vanA-positive isolates. The charts of 36 VRE, 25 VVE, and 79 VSE patients were reviewed. Central venous catheter associated bacteremia was more common in VVE (44%) and VRE patients (57%) than in VSE patients (28%) (P = 0.01). The Pitt bacteremia (OR 1.3, P = 0.002) and the Charlson score (OR 1.2, P = 0.008) were the only independent mortality predictors. PFGE of strains causing breakthrough bacteremia showed high within-patient clonality, irrespective of vanA-positivity or vancomycin-susceptibility. A substantial proportion of vanA-positive isolates are VVE and are therefore not detected with conventional selective culture methods. Bacteremia sources of patients with VVE are similar to those infected with VRE. We detected no association between VVE and 30-day mortality or breakthrough bacteremia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy
  • Bacteremia / microbiology*
  • Bacterial Proteins / genetics
  • Enterococcus faecium / drug effects*
  • Enterococcus faecium / genetics*
  • Genetic Variation / genetics*
  • Genotype
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / epidemiology
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests / methods
  • Middle Aged
  • Phenotype
  • Prevalence
  • Vancomycin / therapeutic use*
  • Vancomycin Resistance / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Vancomycin

Associated data

  • Dryad/10.5061/dryad.8pt2c

Grants and funding

This work was supported by the Swiss National Science Foundation Fellowship (158728 to P.K.), and internal funding from Public Health Ontario Laboratories and the Toronto Invasive Bacterial Diseases Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.