Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: a matched cohort study

Background: In many European hospitals, ampicillin-resistant Enterococcus faecium (ARE) is endemic, while outbreaks of vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineage, are increasingly reported. We studied the attributable mortality due to vancomycin resistance in patients with E. faecium bacteremia and evaluated whether this is mediated by a delay in appropriate antibiotic therapy. Methods: In a retrospective matched cohort study, patients with VRE bacteremia occurring between 2009 and 2014 in 20 Dutch and Danish hospitals were matched to patients with ARE bacteremia, on hospital, ward, length of hospital stay prior to bacteremia, and age. The risk ratio (RR) for 30-day mortality contrasting VRE with ARE was estimated with further analytic control for confounding factors. Results: In all, 63 VRE and 234 ARE episodes were matched (36 and 130 for the Netherlands and 27 and 104 for Denmark). Crude 30-day mortality was 27% and 38% for ARE in the Netherlands and Denmark, respectively, and 33% and 48% for VRE in the respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval (CI) 1.06-2.25). Although appropriate therapy was initiated later for VRE than for ARE bacteremia, this did not appear to mediate the increased mortality risk. Conclusions: Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.