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

Abstract

BackgroundInfections 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 (Enterococcus faecium or Enterococcus faecalis) play an important role. We therefore aimed to determine the burden of enterococci infections attributable to vancomycin resistance and pathogen species (E. faecium and E. faecalis) in cases of bloodstream infection (BSI).MethodsWe conducted a retrospective cohort study on patients with BSI caused by Enterococcus faecium or Enterococcus faecalis 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 E. faecium- (VSEm) and vancomycin-susceptible E. faecalis- (VSEf) cases and (ii) between vancomycin-susceptible E. faecium- (VSEm) and vancomycin-resistant E. faecium-cases (VREm). We calculated total hospital costs for VSEm, VSEf and VREm.ResultsOverall, we identified 1160 consecutive cases of BSI caused by enterococci: 596 (51.4%) cases of E. faecium BSI and 564 (48.6%) cases of E. faecalis BSI. 103 cases of E. faecium BSI (17.3%) and 1 case of E. faecalis BSI (0.2%) were infected by vancomycin-resistant isolates. Multivariable analyses revealed (i) that in addition to different underlying diseases E. faecium 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 E. faecium-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€ p < 0.001).ConclusionOur data indicates that in-hospital mortality and infection-attributed hospital stay in enterococci BSI might rather be influenced by Enterococcus species and underlying diseases than by vancomycin resistance. Therefore, future studies should consider adjusting for Enterococcus species in addition to vancomycin resistance in order to provide a conservative estimate for the burden of VRE infections.Electronic supplementary materialThe online version of this article (10.1186/s13756-018-0419-9) contains supplementary material, which is available to authorized users.

Prevalence of Vancomycin resistant enterococci (VRE) in Ethiopia: a systematic review and meta-analysis

“…In contrast, higher rates of VRE was observed in our study than reports from Singapore (9.3%) [55], Germany (9.8%) [49], Iran (9.4%) [56] and United Kingdom (9.2%) [57]. Different factors were identified as risk factors for acquiring VRE infections including previous hospitalization, patient transfer, urinary catheters, critical illnesses, underlying diseases, contact with VRE patients and inappropriate use of antibiotics [54,55,58,59]; all of which could contribute for the high prevalence of VRE in Ethiopia.…”

“…Determining the prevalence of antibiotic resistance is an important step in the formulation of interventions to control emergence and transmission of resistant pathogens. In recent years, an increase in invasive VRE infections have been reported elsewhere in the worldwide [13,17,25,49]. Although antimicrobial resistance surveillance centers were established and priority surveillance pathogens were identified to prevent the spread of drug resistance in Ethiopia, VRE were not included in the lists of priority pathogens.…”

Vancomycin-Resistant Enterococci (VRE) in Nigeria: The First Systematic Review and Meta-Analysis

“…This indirectly indicates the potential existence of VRE, not only in health care settings but in in the environment as well as animals in Nigeria, and its likely spread to communities unless properly contained. Our estimate is comparable with reports from Malaysia 25% [ 37 ] but higher than those reported in Ethiopia 14.8% [ 16 ], Iran 14%, 18.75% [ 38 , 39 ], North America (21%), Asia (24%), Europe (20%) [ 40 ], Germany (9.8%) [ 41 ], Iran (9.4%) [ 42 ], the United Kingdom (9.2%) [ 43 ], and Singapore (9.3%) [ 44 ]. Our estimate was probably higher because our studies included animal and environmental sources in addition to clinical settings unlike all the studies listed above where they largely centred on clinical settings.…”

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study

“…This issue implicates a relevant risk of bias due to varying pathogenicity [34,35] and virulence of E. faecium and E. faecalis and even other enterococcal species. A German study [36] reported increased in-hospital mortality in patients with E. faecium compared to E. faecalis BSI even after adjusting for underlying disease and vancomycin resistance. Similarly, even after adjustment for effective antibiotic treatment, Hayakawa et al [37] observed impaired outcome following BSI due to vancomycinresistant E. faecium compared to vancomycin-resistant E. faecalis strains.…”