Vancomycin-resistant Enterococci Bloodstream Research Articles

Calprotectin, a Promising Serological Biomarker for the Early Diagnosis of Superinfections with Multidrug-Resistant Bacteria in Patients with COVID-19.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

High Serum S100A12 as a Diagnostic and Prognostic Biomarker for Severity, Multidrug-Resistant Bacteria Superinfection and Herpes Simplex Virus Reactivation in COVID-19.

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.

Vancomycin-resistant enterococcus bloodstream infection successfully managed with oritavancin and fosfomycin as sequential treatment

Bloodstream infections caused by vancomycin-resistant enterococci are increasingly reported and a consensus therapy does not exist. Oritavancin has shown good antimicrobial activity against VRE, but its use is mainly limited to skin, soft tissue, and/or bone infections. Fosfomycin is increasingly used for enterococcal infections (including bloodstream infections and endocarditis) as a partner drug given its anti-biofilm and synergistic properties. Recently in vitro and in vivo synergism between oritavancin and fosfomycin against VRE isolates has been demonstrated. Herein we report the case of a hematologic patient with a VRE bloodstream infection successfully treated with oritavancin and fosfomycin as sequential treatment.

Risk factors for mortality after linezolid treatment of vancomycin-resistant Enterococcus bloodstream infection

ObjectivesWe analyzed the risk factors affecting linezolid treatment outcome in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). MethodsWe conducted a multicenter observational study of patients who received linezolid 600 mg every 12 hours for VRE BSI. The primary outcome was 28-day mortality. The estimated area under the concentration-time curve and trough concentration were calculated. Multivariable logistic regression was used for the outcome analysis. ResultsA total of 170 patients were included: 114 (67.1%) survived and 56 (32.9%) did not. A total of 26 (18.2%) isolates showed a linezolid minimum inhibitory concentration (MIC) of ≤1 mg/l, 113 (79.0%) of 2 mg/l, and 4 (2.8%) of 4 mg/l. The univariable analysis showed that the linezolid MIC and concentration-time curve/MIC were not associated with mortality (P = 0.95 and P = 0.42, respectively). After adjusting for underlying comorbidity and disease severity, the linezolid dose per body weight (LDBW), body height, and interaction between them were independent risks for mortality. Marginal analysis showed that increasing the LDBW was protective in patients with a body height <160 cm. A trough concentration of >12.2 mg/l was a risk factor for thrombocytopenia. ConclusionThe LDBW and body height were interactively associated with clinical outcomes of linezolid treatment for VRE BSI.

Molecular Rapid Diagnostics Improve Time to Effective Therapy and Survival in Patients with Vancomycin-Resistant Enterococcus Bloodstream Infections.

Delays in appropriate antibiotic therapy are a key determinant for deleterious outcomes among patients with vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs). This was a multi-center pre/post-implementation study, assessing the impact of a molecular rapid diagnostic test (Verigene® GP-BC, Luminex Corporation, Northbrook, IL, USA) on outcomes of adult patients with VRE BSIs. The primary outcome was time to optimal therapy (TOT). Multivariable logistic and Cox proportional hazard regression models were used to determine the independent associations of post-implementation, TOT, early vs. delayed therapy, and mortality. A total of 104 patients with VRE BSIs were included: 50 and 54 in the pre- and post-implementation periods, respectively. The post- vs. pre-implementation group was associated with a 1.8-fold faster rate to optimized therapy (adjusted risk ratio, 1.841 [95% CI 1.234-2.746]), 6-fold higher likelihood to receive early effective therapy (<24 h, adjusted odds ratio, 6.031 [2.526-14.401]), and a 67% lower hazards for 30-day in-hospital mortality (adjusted hazard ratio, 0.322 [0.124-1.831]), after adjusting for age, sex, and severity scores. Inversely, delayed therapy was associated with a 10-fold higher risk of in-hospital mortality (aOR 10.488, [2.497-44.050]). Reduced TOT and in-hospital mortality were also observed in subgroups of immunosuppressed patients in post-implementation. These findings demonstrate that the addition of molecular rapid diagnostic tests (mRDT) to clinical microbiology and antimicrobial stewardship practices are associated with a clinically significant reduction in TOT, which is associated with lower mortality for patients with VRE BSIs, underscoring the importance of mRDTs in the management of VRE infections.

The Combination of Daptomycin with Fosfomycin is More Effective than Daptomycin Alone in Reducing Mortality of Vancomycin-Resistant Enterococcal Bloodstream Infections: A Retrospective, Comparative Cohort Study.

High-dose daptomycin-based combinations are recommended for vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI). Preclinical data have shown a synergistic effect of daptomycin/fosfomycin combinations against VRE. However, clinical studies comparing daptomycin monotherapy with daptomycin/fosfomycin combinations are unavailable. An observational study of VRE-BSI was performed between 2010-2021 on patients receiving daptomycin monotherapy (≥ 8mg/kg) or daptomycin combined with intravenous fosfomycin. Patients treated with concomitant β-lactam combinations were excluded. The primary outcome was in-hospital mortality. Outcomes were analyzed using multivariable logistic regression and augmented inverse probability weighting (AIPW) analyses. Among 224 patients, 176 received daptomycin monotherapy, and 48 received fosfomycin combinations. The median daptomycin and fosfomycin doses were 9.8mg/kg and 12g/day, respectively. In-hospital mortality was 77.3% and 47.9% in the daptomycin monotherapy and fosfomycin combination groups (P < 0.001), respectively. Multivariable logistic regression analysis predicted lower mortality with fosfomycin combination treatment (adjusted odds ratio, 0.35; 95% confidence interval (CI), 0.17-0.73; P = 0.005). AIPW demonstrated a 17.8% reduced mortality with fosfomycin combinations (95% CI, - 30.6- - 4.9%; P = 0.007). The survival benefit was significant, especially among patients with a lower Pitt bacteremia score or fosfomycin minimum inhibitory concentration (MIC) ≤ 64mg/l. Fosfomycin combination resulted in higher hypernatremia (10.4% vs. 2.8%, P = 0.04) and hypokalemia (33.3% vs. 15.3%, P = 0.009) compared to daptomycin monotherapy. The combination of high-dose daptomycin with fosfomycin improved the survival rate of patients with VRE-BSI compared to daptomycin alone. The benefit of the combination was most pronounced for VRE with fosfomycin MIC ≤ 64mg/l and for patients with a low Pitt bacteremia score.

Risk factors and outcomes associated with persistent vancomycin resistant Enterococcal Bacteremia

BackgroundPrior studies have identified that vancomycin resistant enterococcus (VRE) bacteremia that persists for four days or more is an independent predictor of mortality. Despite this, there is no published data to identify those patients at highest risk of developing persistent VRE bacteremia.MethodsThis was a single center, retrospective, case-control study of adult patients with a VRE bloodstream infection (BSI). Case patients were those with persistent bacteremia (≥ 4 days despite VRE-directed therapy) and control patients were those with non-persistent bacteremia. Logistic regression was used to assess risk factors associated with persistent VRE BSIs. Secondary outcomes included in-hospital mortality, recurrent bacteremia, and breakthrough bacteremia.ResultsDuring the study period, 24/108 (22%) patients had persistently positive blood cultures. Risk factors for persistent bacteremia included severe neutropenia (OR 2.13), 4 out of 4 positive index blood cultures (OR 11.29) and lack of source control (OR 11.88). In an unadjusted analysis, no statistically significant differences in in-hospital mortality (58% versus 40%; p = 0.121), recurrent bacteremia (17% versus 6%; p = 0.090), or breakthrough bacteremia (13% versus 7%; p = 0.402) were observed between groups.ConclusionPatients with severe neutropenia, 4 out of 4 positive index blood culture bottles, and lack of source control were more likely to develop persistent VRE bacteremia despite directed antibiotic treatment.

The associated impact of standardized admission screening on vancomycin-resistant Enterococci bloodstream infections.

To determine whether discontinuing active screening for vancomycin-resistant Enterococcus (VRE) in Alberta, Canada, acute-care facilities had an associated impact on the rate of rise of hospital-acquired (HA) VRE bloodstream infection (VRE-BSI). Acute-care facilities in Alberta, Canada. All patients who were admitted to Alberta Health Services or Covenant Health acute-care facilities between January 1, 2013, and March 31, 2020, and who met the definition for hospital-acquired VRE-BSI were included in the analyses. An intervention time-series Poisson regression was used to determine the slope change in VRE incidence between the pre- and postintervention (screening) periods. The patient population was separated into 3 cohorts: group 1 (low risk, VRE screening stopped), group 2 (high risk, VRE screening stopped), and group 3 (high risk, VRE screening continued). For all groups, a level- and slope-change model was used. We did not find a statistically significant difference in the slope change or rate of rise in VRE-BSI before and after the intervention, with incidence rate ratio (IRRs) of 1.015 (95% confidence interval [CI], 0.982-1.049), 1.025 (95% CI, 0.967-1.086), and 0.989 (95% CI, 0.924-1.059) for groups 1, 2 and 3, respectively. In Alberta, the rate of HA VRE-BSI has remained consistent, and our findings indicate that there has been no increase in the rate of rise of HA VRE-BSI in sites or units that discontinued screening for VRE, regardless of patient risk group.

Daptomycin area under the curve to minimum inhibitory concentration ratio by broth microdilution for predicting the outcome of vancomycin-resistant Enterococcus bloodstream infection

ObjectivesDifferent methods are used to determine the minimum inhibitory concentration (MIC) for daptomycin. The threshold is unknown for the free drug area under the concentration–time curve to MIC ratio (fAUC/MIC) of daptomycin using broth microdilution (BMD) to predict outcome of vancomycin-resistant enterococcus (VRE) bacteremia. The MIC testing method which is best for predicting the outcome remains unclear. MethodsThis is a retrospective cohort study. The inclusion criterion was VRE bacteremia treated with ≥ 8 mg/kg of daptomycin. As we aimed to compare different daptomycin MIC testing methods for predicting the clinical outcome of VRE bacteremia, the inclusion criteria included the availability of MIC values for BMD, Etest, and automated antimicrobial susceptibility testing (AST). The primary end point was 28-day mortality. The fAUC/MIC was dichotomized using classification and regression tree analysis for predicting survival. ResultsA total of 393 patients were included; 215 survived and 178 died. In the multivariable logistic model for predicting mortality, the dichotomized fAUC/MICs for Etest and AST were 0.508 and 0.065 times as probable, respectively, as that for BMD to minimize information loss. An fAUC/MIC > 75.07 for BMD significantly predicted lower mortality (adjusted odds ratio, 0.53, 95% confidence interval, 0.30–0.95; P = 0.03) after adjusting for underlying disease and bacteremia severity. Using Monte Carlo simulation, none of the doses had a probability of target attainment of ≥ 50% with an MIC of ≥ 2 mg/L. ConclusionThe dichotomized threshold for fAUC/MIC for BMD was the best predictor of mortality. An fAUC/MIC > 75.07 for BMD independently predicted better survival.

Molecular Epidemiology of Vancomycin-Resistant Enterococci Bloodstream Infections in Germany: A Population-Based Prospective Longitudinal Study.

Vancomycin-resistant enterococci (VRE) pose a public health challenge worldwide. While VRE bloodstream infections (VREBI) increase in Germany and Europe, population-based molecular data are scarce. We aimed to analyze the molecular epidemiology, demographic aspects, and geographical distribution of VREBI in the German Federal State of North-Rhine–Westphalia (NRW), located in the German–Dutch–Belgian border area, representing over 20% of Germany’s population. VREBI isolates were collected from hospitals across NRW between 2016 and 2019. Demographic data were gathered and anonymized upon sample collection. Multilocus sequence typing (MLST) and identification of glycopeptide resistance were carried out. Epidemiological analysis and geographical mapping were performed. Single VREBI isolates from 755 patients were analyzed. In total, 38.9% were female, and 80.0% were aged ≥ 60 years. The VREBI incidence per 100,000 inhabitants nearly tripled, from 0.52 (2016) to 1.48 (2019), particularly in male patients aged ≥ 50 years. The proportion of vanB reached 83% (n = 202/243) in 2018, overtaking vanA as the predominant glycopeptide resistance determinant, detected in close relation with ST117 isolates. The proportion of MLST sequence type (ST) 117 peaked in 2018, at 78.2% (n = 190/243). The major role of these emerging strains in invasive infections in central Europe requires novel strategies for their diagnosis, treatment, and prevention.

Favorable Outcome in Patients with Pre-Transplant Gut Colonization with Intrinsically Vancomycin-Resistant Enterococci

IntroductionGut colonization with vancomycin-resistantenterococci (VRE) (specifically, Enterococcus faecium and E. fecalis) is common both before and after allogeneic hematopoietic cell transplantation (allo-HCT), and has been variably associated with VRE bloodstream infections. Clinical infections with intrinsically low-level VRE(E. gallinarum and E. casseliflavus), which have the chromosomally encoded vanC gene, are rare. Additionally, the clinical impact of pre-HCT gut colonization with these bacteria is unknown. In this study, we evaluated the outcome significance of pre-HCT colonization with E. gallinarum and E. casseliflavus, collectively named “intrinsics” herein.MethodsWe retrospectively reviewed the medical records of all adult and pediatric (>1 year old) allo-HCT recipients with available pre-HCT rectal swab or stool culture results at our institution (2011-2017). Second transplant recipients were excluded. SpectraTM VRE chromogenic agar medium (ThermoFisher Scientific) was used for species-level identification, and vancomycin E-test was used for MIC determination. Cases with ≥1 positive pre-HCT result for E. gallinarum or E. casseliflavus and no positive test for VRE or vancomycin-intermediate enterococci (VIE) were defined as intrinsics. Patients with no previous positive test for intrinsics or VRE/VIE, and with at least 2 negative tests for all these, were defined as controls. Due to the rare occurrence of colonization with intrinsics and the preponderance of pediatric patients with this condition, we used a matched-pairs design. Each intrinsic case was matched to a control using the following hierarchical criteria: (i) Diagnosis (malignant vs. non-malignant), (ii) disease risk (standard vs. high vs. non-malignant), (iii) donor type (matched sibling vs. matched unrelated donor vs. cord blood), (iv) conditioning intensity (myeloablative vs. reduced-intensity), and (v) age (± 10 years). The Prentice-Wilcoxon test was used to evaluate the matched pairs on the primary endpoints of overall survival (OS). For relapse and RFS, we excluded patients with non-malignant disorders.ResultsTable 1 shows the characteristics of the control group and intrinsics (n = 18 in each group). The groups were similar in all studied variables. The median follow up was 15 months. The intrinsic group showed a significantly higher 2-year OS of 86 [52-96]% vs. controls with OS of 35 [8-65]% at 2 years (P < 0.01, Figure 1). This remarkable difference in OS was due to a significantly lower NRM in the intrinsic group (0% vs. 36 [8-65]%, P= 0.01). Other transplant outcomes (GVHD and relapse) in each group were similar. Both deaths in the intrinsic group were due to relapse. In contrast, deaths in the control group were due to organ failure in 45%, relapse in 33%, infection in 11%, and GVHD in 11%.ConclusionsIn matched-pair analysis of intrinsically vancomycin-resistantenterococcivs. controls, we observed a remarkably lower NRM among patients colonized pre-HCT with E. gallinarum or E. casseliflavus .The mechanisms for this finding remain to be further explored. We hypothesize that in addition to vanC, these organisms have other genes that collectively contribute to establishment of a protective microbiome against various etiologies of early post-transplant NRM. This may occur as a result of beneficial microbial secondary metabolites that modulate the host immune system, or be consequent to colonization resistance against pathogenic organisms. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia

BackgroundIn-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI.MethodsIRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if < 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach.ResultsA total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075).Table 1: Patient Characteristics Table 2. Primary and Secondary Outcomes ConclusionWe did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings.Disclosures All Authors: No reported disclosures

VanA rectal swab screening as a predictor of subsequent vancomycin-resistant enterococcal bloodstream infection in critically ill adults.

To evaluate whether vanA rectal screening for vancomycin-resistant Enterococcus (VRE) predicts vancomycin resistance for patients with enterococcal bloodstream infection (BSI). A retrospective cohort study. Large academic medical center. The predictive performance of a vanA rectal swab was evaluated in 161 critically ill adults with an enterococcal BSI from January 1, 2007, to September 1, 2014, and who had a vanA rectal swab screening obtained within 14 days prior to blood culture. Of the patients meeting inclusion criteria, 83 (51.6%) were vanA swab positive. Rectal-swab-positive patients were more likely to be younger, to be immunocompromised, to have an indwelling central vascular catheter, and to have a history of MDR bacteria. The vanA rectal swab had sensitivity and negative predictive values of 83.6% and 85.9%, respectively, and specificity and positive predictive values of 71.3% and 67.5%, respectively, for predicting a vancomycin-resistant enterococcal BSI in critically ill adults. VanA rectal swabs may be useful for antimicrobial stewardship at institutions with VRE screening already in place for infection control purposes. A higher PPV would be warranted to implement a universal vanA screen on all ICU patients.

Discontinuing Contact Precautions for Vancomycin-Resistant Enterococcus (VRE) Is Associated With Rising VRE Bloodstream Infection Rates in Ontario Hospitals, 2009-2018: A Quasi-experimental Study.

In Ontario, Canada, since 2012, some hospitals discontinued contact precautions for vancomycin-resistant Enterococcus (VRE). Between 2009 and 2018, there was an associated rise in VRE bloodstream infections in hospitals where contact precautions were discontinued but not in hospitals that maintained contact precautions. These data suggest contact precautions are important for hospital VRE control programs.

634. Incidence of vanC-Mediated Vancomycin-Resistant Enterococcus Bloodstream Infections at Children’s Hospital of Colorado and Implications for Empiric Enterococcal Therapy

BackgroundThe most well-known Enterococcal species, E. faecium and E. faecalis, can harbor high-level vancomycin resistance mediated by acquired vanA and vanB operons. However, other Enterococcal species such as E. gallinarum and E. casseliflavus (VCE), harbor intrinsic low-level vancomycin resistance mediated by an intrinsic vanC operon, and the incidence of these pathogens among pediatric patients is not clear. As the antibiotic resistance pattern of VCE is different than E. faecium and E. faecalis, a high prevalence of VCE may have implications for antibiotic therapy. We describe the incidence and susceptibility of VCE bloodstream infections at a large children’s hospital and compare to E. faecalis and E. faecium.MethodsPositive blood culture results from 2013 to 2018 were obtained from the Children’s Hospital of Colorado data warehouse. All first-time positive cultures for Enterococcus were analyzed for species, susceptibility, and hospital unit location. First-time positive was defined as being at least 2 weeks after any previous positive Enterococcus blood culture. Susceptibilities were categorized by clinical laboratories standards institute (CLSI) guidelines.ResultsOf 240 positive isolates, 7% were ampicillin susceptible and vancomycin nonsusceptible (resistant or intermediate), vs. 6% that were ampicillin resistant and vancomycin susceptible. An additional 3% of isolates were not susceptible to either antibiotic; all of these were E. faecium. VCE accounted for 12% of our isolates while E. faecalis and E. faecium accounted for 66% and 16%, respectively. All VCE were susceptible to ampicillin, but 52% were nonsusceptible to vancomycin. VCE incidence, ampicillin resistance, and vancomycin nonsusceptibility were most prevalent in our hematology, oncology, and bone marrow transplant (BMT) units.ConclusionAt our institution, an as yet unspeciated Enterococcus is equally likely to be ampicillin susceptible and vancomycin nonsusceptible as ampicillin resistant and vancomycin susceptible. This is driven by a significant incidence of VCE, especially on our hematology, oncology, and BMT units. Therefore, vancomycin may not provide adequate empiric Enterococcal coverage on these units, and the addition of ampicillin will be recommended. Disclosures All authors: No reported disclosures.

Risk Factors and Outcomes of Vancomycin-Resistant Versus Vancomycin-Sensitive Enterococcal Bloodstream Infections in Patients With Acute Myeloid Leukemia

Background Studies have shown increased mortality from vancomycin-resistant enterococcal (VRE) bloodstream infections (BSI) in neutropenic patients. Whether these mortality differences pertain to acute myeloid leukemia (AML) patients is unknown. We compared risk factors and outcomes between VRE and vancomycin-sensitive enterococcal (VSE) BSIs in AML patients. Methods We conducted a single-center, 5-year, retrospective cohort study of AML patients with enterococcal BSI. Neutropenia duration, Enterococcus species, vancomycin exposure, VRE colonization, 7- and 30-day mortality, age, sex, length of stay, and central line status were compared and analyzed. Results There were a total of 77 AML patients with enterococcal BSI, 54.5% had VRE. Enterococcus faecalis and Enterococcus faecium accounted for 28.5% and 62.3% of BSI, respectively. The E. faecalis isolates were more likely to be VSE (91% vs 9%, P &lt; 0.001) and E. faecium isolates to be VRE (71% vs 29%, P &lt; 0.001). Duration of neutropenia was significantly longer (27.3 days vs 2.7 days, P &lt; 0.005) among VRE patients. Recent vancomycin use and VRE colonization were associated with VRE BSI. There were no differences in bacteremia duration, length of stay, or 7- and 30-day mortality between VRE and VSE BSI. Conclusion Enterococcal infections among AML patients are more likely to be caused by vancomycin-resistant E. faecium. The risk is increased by VRE colonization and vancomycin exposure. In a relatively homogenous group of patients, treatment-related factors may affect outcome more than species type or susceptibility of bacterial isolates. This finding is important for future development of patient education, preventive, and treatment protocols.

Bloodstream Infection Due to Vancomycin-resistant Enterococcus Is Associated With Increased Mortality After Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndrome: A Multicenter, Retrospective Cohort Study.

We examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database. Adult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups-VRE BSI, non-VRE BSI, without BSI-according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year. Of 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI], 2.2-3.7) and increased NRM (RR, 4.7; 99% CI, 3.6-6.2) (P < .0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, - mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P < .001 for all variables). VRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT.

2444. Incidence of Daptomycin Toxicity Among Patients With Vancomycin-Resistant Enterococcus Blood Stream Infections

BackgroundDaptomycin (DAP) is a lipopeptide antibiotic and is first-line treatment for infections caused by Vancomycin-resistant Enterococcus (VRE). DAP is considered a safe antimicrobial agent, most commonly causing elevation of CPK. The historical incidence of DAP toxicity reported in the literature is low, ranging between 3 to 9%. We aim to describe the incidence of DAP toxicity among patients with VRE blood stream infection (BSI).MethodsThis is a retrospective cohort study conducted in a tertiary hospital in Cleveland, Ohio. We included all consecutive adult patients diagnosed with VRE BSI treated with DAP between November 2011 and January 2015. Patients were grouped based on dose of DAP received (Group 1: ≤6 mg/kg and Group 2 ≥ 8 mg/kg). Patient data were obtained from the microbiology department database, pharmacy information technology services and electronic medical records (EMR) (Table 1).ResultsDuring the study period, a total of 217 patients with VRE BSI were treated with DAP. (Table 1) The number of patients that received DAP dose of ≤6 mg/kg was 192 (88%), compared with 25 patients that received a DAP dose of ≥8 mg/kg (12%). The total incidence of DAP toxicity was present in only 3 patients (1.4%); and of those, only 2 patients developed CPK elevation leading to rhabdomyolysis requiring discontinuation of DAP (Maximum CPK value was 3142 U/L and 987 U/L for each case). The other patient developed a rash thought to be secondary to DAP. Of note, all 3 patients that developed DAP toxicity, received doses of ≤6 mg/kg.ConclusionIn this retrospective cohort study of patients with VRE BSI treated with DAP, the incidence of DAP toxicity was only 3 cases out of 217 patients. All of these patients received doses of ≤6 mg/kg of DAP. This is lower than what is reported in the literature. DAP was well tolerated and the development of side effects did not seem to be related to the dose. Disclosures S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant.

1255. First Outbreak Due to Vancomycin-Resistant Enterococcus Epidemic Clone ST796 in Europe

BackgroundA large outbreak with different clones of vancomycin-resistant enterococci (VRE) affected the Bern University Hospital group for several months. The aim of this study was to describe the extent of the outbreak, using whole-genome sequencing (WGS).MethodsTriggered by two cases of VRE bloodstream infections on our hemato-oncology ward, an outbreak investigation was started. Microbiological diagnosis of VRE was obtained by culture and PCR. Epidemiological links were assessed by meticulous chart review and supplemented with WGS analyses. Multiple infection control measures were implemented to avoid further transmissions.ResultsBetween December 2017 and April 2018, 2,877 screening samples were obtained from 1,200 patients. Three out of six hospitals within the Bern University Hospital group were affected. Eighty-three patients (6.9%) were colonized with VR Enterococcus faecium. Of those, 76 (91.6%) had a strain carrying vanB, with 70 (84%) isolates virtually identical (separated by up to two alleles) by cgMLST and identified as MLST type ST796 (figure). The remaining seven patients (8.4%) were colonized with vanA carrying strains from five different STs. Five patients (7%) developed an invasive infection with VRE ST796. Temporo-spatial links were found in most patients carrying the outbreak strain. In order to control the outbreak, extensive infection control measures were implemented. By April 2018 the outbreak was contained with these specific measures.ConclusionThis VRE outbreak was characterized by a rapid intra- and inter-institutional spread of the emergent clone ST796. This clone was recently described in Australia and New Zealand but never before in Europe.1,2 A multi-faceted infection control led to the containment of the outbreak.

What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream Infections?

What Is the Best Treatment for Vancomycin-Resistant Enterococcal Bloodstream Infections?