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

Abstract

Objective: To study whether replacement of nosocomial ampicillin-resistant Enterococcus faecium (ARE) clones by vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineages, increases mortality in patients with E. faecium bacteremia, and to evaluate whether any such increase is mediated by a delay in appropriate antibiotic therapy. Design: Retrospective, matched-cohort study. Setting: The study included 20 Dutch and Danish hospitals from 2009 to 2014. Patients: Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed. Methods: The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors. Results: The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06–2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of 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.

Vancomycin-sensitive Enterococcus faecium bacteraemia – hospital transmission and mortality in a Danish University Hospital

“…We found that the overall 30 day mortality of VSEfm bacteraemia was 40 %, a result similar to another Danish–Dutch study, which found the 30 day mortality for VSEfm at 38 % and VREfm at 48 % [30]. This is a surprisingly high 30 day mortality compared to bacteraemia from S.…”

“…We found that the overall 30 day mortality of VSEfm bacteraemia was 40 %, a result similar to another Danish-Dutch study, which found the 30 day mortality for VSEfm at 38 % and VREfm at 48 % [30]. This is a surprisingly high 30 day mortality compared to bacteraemia from S. aureus and Escherichia coli with levels for meticillin-sensitive S. aureus (MSSA) at 18 %, and meticillinresistant S. aureus (MRSA) at 25 %, while Escherichia coli with an hospital-onset was found at 31 % [41,42].…”

“…Several studies have reported a high 30 day mortality of 24-66 % of E. faecium bacteraemia [26,27]. The reported 30 day mortality is different for VREfm (40-56 %) and VSEfm (29-32 %) bacteraemia, but both are correlated to severe underlying illness [28][29][30]. This points to these patients having a poor state of health before the onset of infection, which raises the questions of: it is the underlying disease and extensive use of antibiotics that facilitates the growth of E. faecium, and whether the patient dies of or with the E. faecium bacteraemia.…”

Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010–2019

“…In 2009, the 30-day mortality among Danish patients with E. faecium BSI was found to be very high compared with the mortality for E. faecalis BSI patients (38% vs. 20%) [ 10 ]. International meta-analyses [ 11–14 ], as well as later studies [ 15 ], including a combined case series from Denmark and the Netherlands [ 16 ], further suggest an association between VRE BSI and excess mortality and length of hospital stay. However, methodological biases such as patient selection and unmeasured confounding factors make interpretation difficult.…”

No Effect of Lactobacillus rhamnosus GG on Eradication of Colonization by Vancomycin-Resistant Enterococcus faecium or Microbiome Diversity in Hospitalized Adult Patients

“…In Denmark, the preferred antibiotic to treat invasive E. faecium infections is vancomycin, and therefore the increase in vancomycin-resistant E. faecium (VREfm) since 2013 has been a concern for the Danish health authorities ( 3 , 4 ). VREfm is endemic in hospital settings, and infections are associated with longer hospitalization and higher mortality than those with vancomycin-sensitive enterococci ( 5 , 6 ). In the United States, VREfm caused an estimated 54,500 infections among hospitalized patients in 2017 with an annual attributable health care cost of 539 million US dollars ( 7 ).…”