The ongoing challenge of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis in Europe: an epidemiological analysis of bloodstream infections

Abstract

Vancomycin-resistant enterococci infections are of great public health significance due to limited therapeutic options. We investigated epidemiological trends and risk factors of vancomycin resistance in enterococci isolates from patients with bloodstream infections in the EU/EEA from 2012 to 2018. Routine vancomycin susceptibility data of clinical E. faecium (n = 67,022) and E. faecalis (n = 103,112) blood isolates from the European Antimicrobial Resistance Surveillance Network were analysed using descriptive statistics and multivariable regression analyses. In Europe, proportions of vancomycin-resistant E. faecium (VREFm) increased from 8.1% (95%CI 6.7-9.7%) in 2012 to 19.0% (95%CI 16.8-21.5%) in 2018. Rising VREFm proportions were observed across all European regions, both genders and all age groups except children and adolescents (1-19 years). Adults (20-59 years) and elderly (≥60 years) had an increased likelihood of VREFm compared to children and adolescents (1-19 years) (OR: 1.99 [95%CI 1.42-2.79, p < 0.001] and OR: 1.56 [95%CI 1.09-2.23, p = 0.014], respectively). Inpatients hospital units, including internal medicine and ICUs, were associated with an increased likelihood of VREFm (OR: 2.29 (95%CI 1.58-3.32, p < 0.001) compared to the emergency department which reflects patients with community origin of E. faecium infections. The mean proportion of vancomycin-resistant E. faecalis in Europe was found to be low (1.1% [95%CI 0.9-1.4%]). Local and regional authorities should intensify efforts directed at diagnostic and antimicrobial stewardship for vancomycin and all last resort drugs for the management of VREFm, particularly for hospitalized elderly patients.

Keywords: VRE; VREF; Vancomycin-resistant Enterococcus faecium; vancomycin-resistant Enterococcus faecalis; vancomycin-resistant enterococci.

Figure 1.

Time trend of vancomycin-resistant E. faecium from blood isolates in the EU/EEA. Time trend of vancomycin-resistant Enterococcus faecium in (A) 30 countries of the European Union, European Economic Area and the United Kingdom, and in (B) major regions within Europe. Vancomycin resistance proportions are expressed as population-weighted mean proportions (%) among all Enterococcus faecium blood isolates, with corresponding 95% confidence intervals.

Figure 2.

Vancomycin-resistant E. faecium from blood isolates stratified into age. (A) Vancomycin-resistant Enterococcus faecium stratified into age, expressed as population-weighted mean proportions (%) among all Enterococcus faecium blood isolates, with corresponding 95% confidence intervals. (B) Time trends of vancomycin-resistant Enterococcus faecium in different age groups.

Figure 3.

Vancomycin-resistant E. faecium from blood isolates stratified into hospital units. (A) Vancomycin-resistant Enterococcus faecium stratified into hospital units, expressed as population-weighted mean proportions (%) among all Enterococcus faecium blood isolates, with corresponding 95% confidence intervals. (B) Time trends of vancomycin-resistant Enterococcus faecium in blood isolates from the emgercency department and inpatient hospital units (internal medicine, surgical units, intensive care unit, onocology and other hospital units).

Additional Figure 1.

Vancomycin-resistant E. faecium blood isolates in the EU/EEA. (A) Relative changes (in %) of proportions of vancomycin-resistant Enterococcus faecium (VREFm) among all E. faecium blood isolates between 2012/2013 (aggregated) and 2018* in European Union (EU) and Euroepan Economic Area (EEA). (B) Absolute VREFm proportions in 2018 (in %, VREFm isolates among all Enterococcus faecium blood isolates) in EU/EEA countries. * Since for Slovenia no data for 2018 were available, 2017 data were used. AT: Austria, BE: Belgium, BG: Bulgaria, CY: Cyprus, CZ: Czech Republic, DE: Germany, DK: Denmark, EE: Estonia, ES: Spain, FI: Finland, FR: France, GR: Greece, HR: Croatia, HU: Hungary, IE: Irleland, IS: Iceland, IT: Italia, LT: Lithunia, LU: Luxembourg, LV: Latvia, MT: Malta, NL: Netherlands, NO: Norway, PL: Poland, PT: Portugal, RO: Romania, SK: Slovakia, SL: Slovenia, UK: United Kingdom.

Additional Figure 2.

Vancomycin-resistant E. faecalis blood isolates in the EU/EAA. (A) Time trend of vancomycin-resistant Enterococcus faecalis in 30 countries of the European Union, Euroepan Economic Area and the United Kingdom, expressed as population-weighted mean proportions (%) among all Enterococcus faecalis blood isolates, with corresponding 95% confidence intervals. (B) Proportions of vancomycin-resistant Enterococcus faecalis in major regions of Europe.