Enterococcus Faecium Bloodstream Infections Research Articles

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

Cessation of Rectal Screening for Vancomycin-Resistant Enterococci: Experience from a Tertiary Care Hospital from Türkiye.

Here, we compared the impact of different polices on the epidemiology of Vancomycin-resistant Enterococcus faecium bloodstream infections (VRE-BSIs) in a tertiary care hospital including two hospital buildings (oncology and adult hospitals) in the same campus. All patients who were hospitalized in high-risk units were screened weekly for VRE colonization via rectal swab between January 2006 and January 2013. After January 2013, VRE screening was only performed in cases of suspicion of VRE outbreak and during point prevalence studies to evaluate the epidemiology of VRE colonization. Contact precautions were in place for all VRE-positive patients. The incidence density rates of hospital-acquired (HA)-VRE-BSIs were compared between two periods. While the rate of VRE colonization was higher in the second period (5% vs. 9.5% (p < 0.01) for the adult hospital, and 6.4% vs. 12% (p = 0.02 for the oncology hospital), there was no increase in the incidence rate HA-VRE BSIs after the cessation of routine rectal screening in either of the hospitals. Screening policies should be dynamic and individualized according to the epidemiology of VRE as well as the workforce and cost. Periodical rectal screening of VRE can be discontinued if suspicion of an outbreak can be carefully monitored.

Impact of vancomycin resistance in Enterococcus faecium bloodstream infection on mortality: A retrospective analysis of nationwide surveillance data

ObjectivesIt is unclear whether the poor outcome of patients with severe vancomycin-resistant enterococci (VRE) infection is attributable to vancomycin resistance or to Enterococcus faecium (Efm), which predominates among VRE. MethodsRetrospective study of a prospectively identified cohort from nationwide surveillance. A cohort of consecutive, nonduplicate episodes of monomicrobial bloodstream infections (BSIs) caused by Efm in 2016 was selected. The primary outcome was all-cause, 30-day, in-hospital mortality. Inverse probability weighting was applied using the propensity score for vancomycin-resistant Efm (VREfm) BSI. ResultsA total of 241 Efm BSI episodes were included, of which 59 (24.5%) were VREfm. Patients with VREfm BSI were younger but had similar comorbidities to those with vancomycin-sensitive Efm (VSEfm) BSI. Multivariable logistic regression revealed that younger age, previous piperacillin-tazobactam use, and steroid use were significant risk factors for VREfm BSI, but 30-day in-hospital mortality did not differ significantly between groups (35.6% and 23.6% for VREfm and VSEfm, respectively; odds ratio, 1.79; 95% confidence interval, 0.95-3.37; P = 0.101). However, Cox regression with inverse probability weighting revealed that vancomycin resistance was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.18; 95% confidence interval, 1.03-4.62; P = 0.041). ConclusionIn patients with Efm BSI, vancomycin resistance was independently associated with mortality.

The combination of daptomycin with β-lactam antibiotics is more effective than daptomycin alone for vancomycin-resistant Enterococcus faecium bloodstream infection

BackgroundThe treatment options for vancomycin-resistant Enterococcus (VRE) are limited. A combination of daptomycin (DAP) and β-lactam (BL) has been suggested; however clinical studies supporting this are lacking. MethodsPatients with VR E. faecium bacteremia who received ≥ 8 mg/kg daptomycin for ≥ 72 h and initiated ≤ 5 days of culture collection between 2010 and 2021 were included. DAP+BL was defined as receiving BL for ≥ 24 h and within 24 h of DAP initiation. The primary endpoint was a composite clinical success (neither 14-day mortality, microbiological failure, nor change in the anti-VRE regimen). Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW). ResultsA total of 430 patients were enrolled (DAP, n = 45; DAP+BL, n = 385). Clinical success was achieved in 19 (42.2%) patients in the DAP group and 244 (63.4%) in the DAP+BL group [adjusted odds ratio, 3.19; 95% confidence interval (CI) 1.61–6.33; P = 0.001]. Marginal analysis showed that the efficacy of DAP+BL was particularly significant with DAP dose ≥ 9 mg/kg and DAP minimum inhibitory concentration (MIC) ≥ 2 mg/L. With the balance of AIPW, standardized mean clinical success rates for DAP and DAP+BL 37.3% and 63.5%, respectively. The difference between DAP+BL and DAP was of 26.2% in favor of DAP+BL (95% CI, 10.0–42.3%; P = 0.001). ConclusionsDAP+BL was associated with a significantly higher rate of compositive clinical success than DAP for treatment of VR E. faecium bacteremia. The study suggested BL in combination with high-dose DAP for VR E. faecium bacteremia treatment, especially when VRE showed a high DAP MIC.

Influence of daptomycin doses on the outcomes of VRE bloodstream infection treated with high-dose daptomycin.

The CLSI recommended high-dose daptomycin (8-12 mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8 mg/kg. We conducted a multicentre prospective observational study of patients who received a ≥8 mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28 day mortality. A total of 661 patients were included. The 28 day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8 mg/kg; P < 0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR) = 0.85; 95% CI = 0.73-0.99; P = 0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11 mg/kg dose of daptomycin (P = 0.003). The 8 to <11 and ≥11 mg/kg doses of daptomycin differed in the 28 day mortality in the higher MIC group (≥2 mg/L) (49.4% versus 33.3%; P = 0.004), but not in the lower MIC group (≤1 mg/L) (29.3% versus 29.4%; P = 0.99). A dose of ≥11 mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000 U/L) compared with 1.1% with 8 to <11 mg/kg (P = 0.04). The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11 mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11 mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.

Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I).

BackgroundVancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking.MethodsThe Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with ≥1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing.ResultsForty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score ≥2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified.ConclusionsFailure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes.

PGP-006 - Impact of vancomycin resistance in Enterococcus faecium bloodstream infection on mortality: a retrospective analysis of nationwide surveillance data

PGP-006 - Impact of vancomycin resistance in Enterococcus faecium bloodstream infection on mortality: a retrospective analysis of nationwide surveillance data

Daptomycin versus Glycopeptides for the Treatment of Enterococcus faecium Bacteraemia: A Cohort Study.

Background: Ampicillin resistant and glycopeptide susceptible Enterococcus faecium bloodstream infection (GSEF-BSI) incidence has risen. However, the treatment of choice remains unknown. Daptomycin use for the treatment of enterococcal infections has increased, despite effectiveness and safety concerns. The objective was to compare the effectiveness and safety of daptomycin and glycopeptides in the treatment of GSEF-BSI. Methods: This was a single-centre, retrospective observational cohort study performed at Hospital del Mar (Barcelona, Spain), from January 2006–May 2018. The primary outcome was clinical cure at the end of the therapy, and secondary outcomes included 14-day, 30-day, in-hospital mortality, and length of stay. Results: From a total of 192 patients with GSEF-BSI, 54 (28.1%) were treated with glycopeptides and 17 (8.9%) with daptomycin. Patients treated with daptomycin presented a lower clinical cure than patients treated with glycopeptides (58.8% vs. 83.3%, RR 0.416 (95% CI 0.189–0.915)). After controlling for confounding variables by means of multivariate analysis the significative difference was confirmed (aOR 4.313, 95% CI, 1.053–17.660). The need for treatment discontinuation due to adverse events was similar. Conclusions: Patients with GSEF-BSI treated with glycopeptides showed a higher clinical cure than those treated with daptomycin.

Treatment and outcomes of Enterococcus faecium bloodstream infections in solid organ transplant recipients.

Optimal antimicrobial therapy for Enterococcus faecium bloodstream infection (EFBSI) in the solid organ transplant (SOT) population is not well defined. The purpose of this study was to describe the pharmacotherapy and outcomes of EFBSI in SOT patients. This was a single-center retrospective cohort of SOT patients with EFBSI from 2013 to 2019. Susceptibility testing was performed with Vitek® 2 or Etest. Estimates of optimal DAP pharmacokinetic/pharmacodynamic exposures (dose <10mg/kg, fAUC/MIC >27.4) were made from previously established literature and equations. Fifty-one unique cases were included in the analysis. The median age was 61years and liver (64%), intestinal (19%), and kidney (12%) were the most common organs transplanted. Most patients had indwelling central lines (75%) at the time of bacteremia; intra-abdominal abscesses/fluid collections were present in 44% of patients and 8% had endocarditis. Nineteen (37%) patients had polymicrobial infections. The most common definitive antimicrobial regimens were as follows: DAP plus beta-lactam (46%), DAP monotherapy (18%), and LZD (25%). Of the 33 patients that received DAP, 21% of Efaecium isolates developed DAP resistance. 30-day mortality was 25% overall but higher in patients who received an initial DAP dose <10mg/kg (43% vs 13%). Vancomycin-resistance, severity of illness, neutropenia, and source control were also associated with mortality. Inadequate DAP dosing for EFBSI may be associated with mortality in the SOT population. Larger, controlled analyses are necessary to determine the impact of optimized pharmacodynamics in this population.

1019. Treatment Outcomes for Enterococcus faecium Bacteremia in Solid-Organ Transplant Patients: Implications for Daptomycin

BackgroundOptimal antimicrobial therapy for Enterococcus faecium (EFM) bacteremia in the solid-organ transplant (SOT) population is not well defined. Antimicrobial resistance, immunosuppression, and high mortality associated with EFM infections all pose serious threats. The purpose of this study was to describe the pharmacotherapy and outcomes of EFM bacteremia in SOT patients.MethodsThis was a single-center retrospective cohort of SOT patients with EFM bloodstream infection from 2013 to 2018. Susceptibility of ampicillin (AMP), vancomycin (VAN), linezolid (LZD), and daptomycin (DAP) against EFM were reported as MIC90 when available. The primary outcome, 30-day all-cause mortality, was assessed in bivariate analysis to identify potential risk factors. Secondary outcomes included inpatient mortality and development of DAP nonsusceptibility (DNS).ResultsForty-four unique cases representing 40 patients were included in the analysis. The median age was 62.5 years and liver (65.9%), intestine (20.5%), and kidney (11.4%) were the most common organs transplanted. The MIC90 of VAN, DAP, and LZD of initial isolates collected were >32 mg/L, 4 mg/L, and 2 mg/L, respectively; all were AMP resistant. The median durations of hospitalization and intensive care stay were 29 days and 17.5 days, respectively. Most patients had indwelling central lines (81.8%) at the time of bacteremia; intra-abdominal abscesses/fluid collections were present in 45.5% of patients and 9.1% had endocarditis. The most common definitive antimicrobial regimens were DAP plus β-lactam (45.5%), DAP monotherapy (18.2%), and LZD 600 mg Q12H (25.0%). The mean initial and definitive DAP doses were 8.1 ± 1.6 and 8.9 ± 1.7 mg/kg actual body weight, respectively. Among subjects that received DAP, 21.9% developed DNS. Inpatient mortality was 39.5% and 30-day mortality was 27.3%. Mortality at 30-days was greater in patients with high-grade bacteremia (40.7 vs. 5.9%, P = 0.01) and receipt of DAP <10 mg/kg as the first active antibiotic (42.9 vs. 13.0%, P = 0.03).ConclusionInadequate DAP dosing for EFM bacteremia may be associated with mortality in the SOT population. Larger, matched analyses are necessary to determine the impact of optimized pharmacodynamics. Disclosures S. L. Davis, Achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. Nabriva: Scientific Advisor, Consulting fee. Zavante: Scientific Advisor, Consulting fee.

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia.

Vancomycin-resistant Enterococcus faecium bloodstream infections (VREF-BSI) cause significant mortality, highlighting the need to optimize their treatment. We compared the effectiveness and safety of daptomycin (DAP) and linezolid (LZD) as continuous or sequential therapy for VREF-BSI in a national, retrospective, propensity score (PS)-matched cohort study of hospitalized Veterans Affairs patients (2004 to 2014). We compared clinical outcomes and adverse events among patients treated with continuous LZD, continuous DAP, or sequential LZD followed by DAP (LZD-to-DAP). Secondarily, we analyzed the impact of infectious diseases (ID) consultation and source of VREF-BSI. A total of 2,630 patients were included in the effectiveness analysis (LZD [n = 1,348], DAP [n = 1,055], LZD-to-DAP [n = 227]). LZD was associated with increased 30-day mortality versus DAP (risk ratio [RR], 1.11; 95% confidence interval [CI], 1.01 to 1.22; P = 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26; P = 0.015). LZD-to-DAP switchers had lower mortality than those remaining on LZD (RR, 1.29; 95% CI, 1.03 to 1.63; P = 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a ≥50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11; P = 0.001). DAP was associated with lower mortality than was LZD in patients with endocarditis (RR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024); however, there was no statistically significant association between treatment group and mortality with regard to other sources of infection. Therefore, source of infection appears to be important in selection of patients most likely to benefit from DAP over LZD.

Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint?

Daptomycin has become a front-line antibiotic for multidrug-resistant Enterococcus faecium bloodstream infections (BSIs). We previously showed that E. faecium strains with daptomycin minimum inhibitory concentrations (MICs) in the higher end of susceptibility frequently harbor mutations associated with daptomycin resistance. We postulate that patients with E. faecium BSIs exhibiting daptomycin MICs of 3-4 µg/mL treated with daptomycin are more likely to have worse clinical outcomes than those exhibiting daptomycin MICs ≤2 µg/mL. We conducted a multicenter retrospective cohort study that included adult patients with E. faecium BSI for whom initial isolates, follow-up blood culture data, and daptomycin administration data were available. A central laboratory performed standardized daptomycin MIC testing for all isolates. The primary outcome was microbiologic failure, defined as clearance of bacteremia ≥4 days after the index blood culture. The secondary outcome was all-cause in-hospital mortality. A total of 62 patients were included. Thirty-one patients were infected with isolates that exhibited daptomycin MICs of 3-4 µg/mL. Overall, 34 patients had microbiologic failure and 25 died during hospitalization. In a multivariate logistic regression model, daptomycin MICs of 3-4 µg/mL (odds ratio [OR], 4.7 [1.37-16.12]; P = .014) and immunosuppression (OR, 5.32 [1.20-23.54]; P = .028) were significantly associated with microbiologic failure. Initial daptomycin dose of ≥8 mg/kg was not significantly associated with evaluated outcomes. Daptomycin MICs of 3-4 µg/mL in the initial E. faecium blood isolate predicted microbiological failure of daptomycin therapy, suggesting that modification in the daptomycin breakpoint for enterococci should be considered.

Dramatic increase in vancomycin-resistant enterococci in Germany

Among European countries, Germany has one of the highest proportions of vancomycin-resistant Enterococcus faecium bloodstream infections. The aim of this study was to investigate the development of vancomycin-resistant enterococci (VRE) in German hospitals and to consider the regional distribution of VRE in Germany. Data from three components of the German national nosocomial surveillance system (KISS) from the period 2007-12 were used for analysis: ICU-KISS data on nosocomial primary bloodstream infections and urinary tract infections from intensive care units (ICUs); OP-KISS data on surgical site infections from surgical departments; and Pathogen-KISS data concentrating on VRE cases (infections and colonizations) in ICUs. Trends over time were calculated and a map according to German federal states was prepared. Data from up to 645 ICUs and 681 surgical departments for 2 year periods from 2007 to 2012 were analysed. The proportion of VRE increased significantly for surgical site infections (526%; P < 0.01) and bloodstream infections (265%; P < 0.01) and non-significantly for urinary tract infections (278%; P = 0.07). A large subgroup of ICUs also reported VRE cases in the same period, with a significant increase of 282%. The mapping of federal states showed large variation in VRE proportions and incidence rates in a belt of states with significantly higher VRE proportions from west (North Rhine-Westphalia) to east (Saxony). The high overall VRE proportion in Germany is mainly due to the situation in four states. There is an urgent need to analyse the epidemiology of VRE in detail to develop appropriate infection control strategies.

Algorithm for pre-emptive glycopeptide treatment in patients with haematologic malignancies and an Enterococcus faecium bloodstream infection

IntroductionNowadays Enterococcus faecium has become one of the most emerging and challenging nosocomial pathogens. The aim of this study was to determine risk factors in haematology patients who are at risk of an Enterococcus faecium bloodstream infection (BSI) and should be considered for pre-emptive glycopeptide treatment. With these identified risk factors a prediction model can be developed for clinical use.MethodsRetrospectively clinical and microbiological data in 33 patients with an E. faecium BSI were compared to 66 control patients during a 5-year period at the haematology ward. Multivariate logistic regression was used to explore the independent risk factors and a prediction model was developed to determine the risk of an E. faecium BSI.ResultsE. faecium BSIs were found to be associated with high mortality rates. Independent risk factors for E. faecium BSI were colonization with E. faecium 30 days prior to blood culture (OR 5.71; CI 1.7-18.7), combination of neutropenia and abdominal focus (4.37; 1.4-13.4), age > 58 years (4.01; 1.3-12.5), hospital stay prior to blood culture > 14 days (3.55; 0.98-12.9) and CRP (C-reactive protein) level >125 mg/L (4.37; 1.1-10.2).ConclusionUsing data from this study, risk stratification for the development of an E. faecium BSI in patients with haematological malignancies is possible. Pre-emptive treatment should be considered in those patients who are at high risk. Using a prediction model as designed in this study, antibiotic stewardship in terms of prudent use of glycopeptides can be improved and might be helpful in controlling further spread of VRE (vancomycin resistant enterococci).

Algorithm for empirical glycopeptide treatment in patients with hematologic malignancies and enterococcus faecium blood stream infection

Enterococcus faecium has become a major cause of nosocomial infections especially in patients with hematologic malignancies. The aim of this study was to determine risk factors in those patients who are at risk of Enterococcus faecium blood stream infection (BSI) and should be considered for empirical treatment.

De Novo Daptomycin Nonsusceptibility in a Clinical Isolate

We report a case of non-daptomycin-susceptible Enterococcus faecium bloodstream infection in a patient with no previous exposure to daptomycin. To our knowledge, this is the first report of de novo resistance to daptomycin in a clinical isolate. An 84-year-old man was admitted to the hospital