The importance of adjusting for enterococcus species when assessing the burden of vancomycin resistance: a cohort study including over 1000 cases of enterococcal bloodstream infections

Infections caused by vancomycin-resistant enterococci (VRE) are on the rise worldwide. Few studies have tried to estimate the mortality burden as well as the financial burden of those infections and found that VRE are associated with increased mortality and higher hospital costs. However, it is unclear whether these worse outcomes are attributable to vancomycin resistance only or whether the enterococcal species ( or ) play an important role. We therefore aimed to determine the burden of enterococci infections attributable to vancomycin resistance and pathogen species ( and in cases of bloodstream infection (BSI). We conducted a retrospective cohort study on patients with BSI caused by or between 2008 and 2015 in three tertiary care hospitals. Data was collected on true hospital costs (in €), length of stay (LOS), basic demographic parameters, and underlying diseases including the results of the Charlson comorbidity index (CCI). We used univariate and multivariable regression analyses to compare risk factors for in-hospital mortality and length of stay (i) between vancomycin-susceptible (VSEm) and vancomycin-susceptible (VSEf) cases and (ii) between vancomycin-susceptible (VSEm) vancomycin-resistant (VREm). We calculated total hospital costs for VSEm, VSEf and VREm. Overall, we identified 1160 consecutive cases of BSI caused by enterococci: 596 (51.4%) cases of BSI and 564 (48.6%) cases of BSI. 103 cases of BSI (17.3%) and 1 case of BSI (0.2%) were infected by vancomycin-resistant isolates. Multivariable analyses revealed (i) that in addition to different underlying diseases was an independent risk factor for in-hospital mortality and prolonged hospital stay and (ii) that vancomycin-resistance did not further increase the risk for the described outcomes among -isolates. However, the overall hospital costs were significantly higher in VREm-BSI cases as compared to VSEm- and VSEf-BSI cases (80,465€ vs. 51,365€ vs. 31,122€