Vancomycin-resistant Enterococci Bloodstream Infections Research Articles

650. LiaX as a Surrogate Marker of Daptomycin Susceptibility in Multidrug-Resistant Enterococcus faecium

Abstract Background Vancomycin-resistant Enterococcus faecium (VREfm) are important causes of bloodstream infections (BSI) in patients (pts) with cancer, liver disease, and foreign bodies. Daptomycin (DAP) is commonly used to treat VRE BSI, but DAP resistance (DAP-R) is increasing. Current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility. DAP triggers the LiaFSR cell membrane stress response pathway, resulting in the extracellular release of LiaX, a protein that functions as a sentinel molecule for DAP, and controls the cell membrane response. Methods We used 6 reference Efm isolates to optimize a whole-cell enzyme-linked immunosorbent assay (ELISA) method for LiaX detection. We then assessed 86 clinical Efm BSI isolates recovered from 3 hospitals in Houston and Detroit for DAP MICs and used whole genome sequencing to assess for substitutions in LiaFSR/LiaXYZ proteins. We collected patient and microbiological data by chart review. Results All DAP-R reference strains had increased detection of LiaX compared to DAP-S strains (p< 0.0001). Of the 86 pts with Efm BSI, 73.2% had malignancy, 9.3% had liver disease, and 76.7% had foreign bodies. The source of 52.3% of BSIs was determined to be gastrointestinal. Two of the 86 isolates were DAP-R by CLSI breakpoints. The LiaX test and DAP MICs had a categorical agreement in 62.8% of isolates. All isolates with discordant ELISA/MIC results had DAP-S MIC (median 2, IQR 1-3)but increased LiaX. Using the genomic information, we identified 41 sites of amino acid (AA) changes in the LiaFSR/XYZ proteins of the ELISA/MIC discordant isolates. The substitutions LiaR S19F and LiaS E153K/D251E were associated with discordancy (p=0.0036 and p=0.0018, respectively). Conclusion Detection of LiaX is likely to indicate activation of the DAP-mediated cell membrane response in Efm and may be an indicator of DAP-R. Important discrepancies between LiaX and standard DAP MIC determination were found, highlighting the limitation of MIC determination. Further characterization of the discrepant isolates by time-kill assays and evaluation of patient clinical outcomes are warranted to fully validate the performance and clinical utility of the LiaX ELISA. Disclosures Truc T. Tran, PharmD, Merck (Grant/Research Support) Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support)

Comparing Hospital Healthcare-Associated Infection Incidence During Pre-COVID-19 Pandemic and Pandemic Eras

Background: Diversion of resources from infection prevention activities, personal protective equipment supply shortages, conservation (extended use and reuse) or overuse with multiple gown and glove layers, and antimicrobial prescribing changes during the COVID-19 pandemic might increase healthcare-associated infection (HAI) incidence and antimicrobial resistance. We compared the incidences of Clostridioides difficile infection (CDI), methicillin-resistant Staphyloccocus aureus bloodstream infection (MRSA BSI), and vancomycin-resistant enterococci bloodstream infection (VRE BSI) reported by California hospitals during the COVID-19 pandemic with incidence data collected prior to the pandemic. Methods: Using data reported by hospitals to the California Department of Health via the NHSN, we compared incidences in the second and third quarters of 2020 (pandemic) to the second and third quarters of 2019 (before the pandemic). For CDI and MRSA BSI, we compared the standardized infection ratios (SIRs, based on the 2015 national baseline), and we calculated the P values. No adjustment model is available for VRE BSI; thus, we measured incidence via crude incidence rates (infections per 100,000 patient days). We calculated incidence rate ratio (IRR) with 95% CI for VRE BSI. To examine the possible effect of missing data during the pandemic, we performed a sensitivity analysis by excluding all facilities that had incomplete data reporting at any time during either analysis period. Results: Incidence measures and numbers of facilities contributing data in prepandemic and pandemic periods are shown in Table 1. There were no statistically significant changes in SIRs at P = .05 for either MRSA BSI or CDI between the prepandemic and pandemic periods (MRSA BSI P = .17; CDI P = .08). Crude VRE BSI incidence increased during the pandemic compared to the prepandemic period (IRR, 1.40; 95% CI, 1.16–1.70). Excluding facilities with incomplete data had minimal effect. Conclusions: We found insufficient evidence that MRSA BSI or CDI incidence changed in California hospitals during the pandemic relative to the prepandemic period; however, there was a significant increase in the crude incidence of VRE BSI. Next, we will include interrupted time series analyses to assess departure from long-term trends, including a risk-adjusted model for VRE BSI. Additionally, we will evaluate for changes in central-line–associated bloodstream infection incidence and antimicrobial resistance among HAI pathogens.Funding: NoDisclosures: None

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.

10. The Impact of the Verigene® Gram-positive Blood Culture Panel on the Management of Vancomycin Resistant enterococci Bloodstream Infections in a Multi-site Cohort Study

BackgroundVancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs) are associated with high morbidity and mortality. PCR-based rapid diagnostic tests provide prompt identification of infectious etiologies within hours. This study evaluated the impact of the Verigene® Gram-positive blood culture (GP-BC) panel on the outcomes on patients with VRE BSIs.MethodsA multi-center pre- and post-implementation retrospective cohort study was conducted at four large HCA Healthcare facilities. The implementation of Verigene® GP-BC and VigiLanz® surveillance software with real-time notifications to clinical pharmacists occurred in 2015. Adults > 18 years with VRE BSIs were evaluated over two time periods; pre-implementation (Pre; May 2011 - May 2013) and post-implementation (Post; May 2015 - May 2017). Patients were excluded if not admitted or were discharged/deceased before blood culture results. The primary outcome of this study was to compare time to optimal therapy (TOT). Secondary outcomes included hospital mortality, length of stay (LOS), and TOT comparing clinical pharmacy staffing models. Multivariable logistic regression models were used to identify independent predictors. Adjusted ORs (aOR) and their 95% CIs were reported.ResultsA total of 104 patients with VRE BSIs were included in the study; 50 and 54 in the pre- and post-implementation periods, respectively. There were no differences in baseline characteristics between the groups. TOT was significantly shorter in the post vs. pre group (29 hrs ± 36 vs. 67 hrs ± 124, p=0.03). There was significantly lower hospital mortality when comparing the pre- and post-implementation periods (32% vs. 11%, p< 0.01). After adjusting for age, sex, severity of illness, treatment/dose, the post implementation period was independently associated with reduced hospital mortality (aOR 0.21, CI 0.61–0.73, p=0.01). There were no significant differences in LOS or clinical pharmacy staffing models on TOT.Baseline Characteristics Primary and secondary outcomes data ConclusionThe implementation of the Verigene® BC-GP with VigiLanz® substantially decreased TOT for VRE BSIs and was associated with reduced hospital mortality. This study highlights the positive impact of RDTs on shorter TOT and associated clinical outcomes.Disclosures All Authors: No reported disclosures

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

1080. Changing Epidemiology and Long-Term Outcome of Bloodstream Infection Due to Enterococcus for Patients with Acute Leukemia: Impacts and Limitations on Strategy of Restricting Antibiotics

BackgroundGastrointestinal dysbiosis due to antibiotics and mucosal injury by intensive chemotherapy are important risk factors for Enterococcal infection in patients with acute leukemia. However, there is still disagreement about trends of incidence and outcome of bloodstream infection (BSI) due to Enterococcus species. This study aimed to identify the changes in the epidemiology of Enterococcal BSI and to estimate the long-term impact of Enterococcal BSI on outcome in an acute leukemia cohort.MethodsAll adult acute leukemia patients diagnosed with Enterococcal BSI (N = 512) between 2014 to 2018 at the Catholic Hematology Hospital were retrospectively reviewed. The incidence rate was compared with antibiotics use and multivariable models were used to estimate the impact of Enterococcal BSI on the outcome.ResultsOf 433 patients, 512 episodes of Enterococcal BSI occurred: 172 (33.6%) of 512 were vancomycin-resistant Enterococcus (VRE) and baseline characteristics were similar in comparison with vancomycin-susceptible Enterococcus (VSE) BSI. The incidence rate of VRE seemed to decrease for 6 months after a change in the strategy of restricting prophylactic use of fluoroquinolone and empirical use of carbapenem (39.2% vs 12.2%, Odds ratio [OR]=0.312, 95% confidence interval [CI], 0.116-0.843, p=0.018). However, overall Enterococcal BSI continued to increase with the rapidly increased use of unrestricted antibiotics. VRE BSI was associated with higher 100-day mortality than VSE BSI after adjusting for covariates (hazard ratio [HR]=1.477; 95% CI, 1.027-2.125, p=0.035), but there was no difference in long-term outcome at one year. In multivariable models, high-risk groups such as old age, advanced stage of disease, polymicrobial infection, high Pitt bacteremia score, and BSI complications after hematopoietic cell transplantation (HSCT) were strongly associated with worse long-term outcome (p< 0.05 for all variables).Table 1. Baseline characteristics of Enterococcal bloodstream infection (BSI) Figure 1. Incidence rate of Enterococcal BSI with changes of aggregated antibiotics utilization in acute leukemia cohort. Vertical black dash line is the time of new institutional strategy of restricting fluoroquinolone prophylaxis and use of carbapenem. Abbreviations: DDDs, defined daily doses; Q, quarter Figure 2. Multivariable analysis of risk factors for overall survival at one year. Abbreviations: HR, hazard ratio; CI, confidence interval; BSI, bloodstream infection; CR, complete remission; HSCT, hematopoietic stem cell transplantation; ALL, acute lymphocytic leukemia; VRE, vancomycin-resistant Enterococcus ConclusionThe effort to restrict the use of fluoroquinolone and carbapenem alone is insufficient to reduce Enterococcal BSI. To improve long-term outcomes, especially in high-risk patients, multidisciplinary interventions to reduce the overall use of antibiotics along with the total incidence of Enterococcal BSI are needed.Disclosures Sung-Yeon Cho, MD, Gilead (Grant/Research Support, Speaker’s Bureau)Merck Sharp & Dohme (Grant/Research Support, Speaker’s Bureau)Pfizer (Grant/Research Support, Speaker’s Bureau)

664. LiaX as a Surrogate Marker of Daptomycin Susceptibility in Multidrug-Resistant Enterococcus faecium Recovered from Cancer Patients

BackgroundVancomycin-resistant Enterococcus faecium (VREfm) are leading causes of bloodstream infections (BSI) in patients (pts) with hematological malignancies (HM). Daptomycin (DAP) is commonly used to treat VRE BSI, but DAP non-susceptibility (DAP-NS) in pts with HM is increasing. Current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility. DAP triggers the LiaFSR cell membrane stress response pathway, resulting in the extracellular release of the protein LiaX, a novel protein that functions as a regulator of the membrane response. We postulated that detection of extracellular LiaX correlates with DAP-NS in clinical strains of VREfm.MethodsWe used 6 well-characterized VREfm BSI isolates (2 DAP-S, 4 DAP-NS) as reference strains to optimize a whole-cell indirect enzyme-linked immunosorbent assay (ELISA) method for LiaX detection. We assessed limit of detection and reproducibility of the ELISA LiaX method. We then assessed 54 clinical VREfm BSI isolates from pts with cancer for validation. We determined DAP MICs by broth microdilution (BMD). We collected clinical and microbiological details by chart reviewResultsThe 6 reference strains showed high reproducibility with low coefficient of variation. All DAP-NS reference strains had increased detection of LiaX (p< 0.0001) compared to DAP-S reference strains. Of the 54 isolates from pts, most pts (83.3%) had HM. The source of 62.9% of VRE BSIs was determined to be gastrointestinal. Six of the 54 isolates were DAP-NS by BMD MIC. The LiaX test and MIC had categorical agreement on 56% of isolates. Of the isolates with disagreement, 19 isolates were susceptible by MIC (median 2 μg/ml) but non-susceptible by LiaX ELISA, and 5 isolates were non-susceptible by MIC (6, 8, 8, 8, and 16 μg/ml, respectively) but susceptible by LiaX ELISA.Whole-cell indirect LiaX ELISA A405nm of Efm reference strains shows ability to differentiate DAP susceptible MICs from DAP resistant MICs. DAP susceptible (MIC=2 μg/ml) Efm strains are shown in green and DAP resistant (MIC≥8 μg/ml) strains in red. DAP-S reference strains have no LiaFSR mutations. The dotted line indicates an example cutoff for DAP-S/R in this assay. *p<0.05, **p<0.0001 by unpaired t-test. Coefficieint of variance for each reference is <15%. ConclusionDetection of extracellular LiaX has important discrepancies with DAP MIC. Interestingly, LiaX may be a surrogate marker to detect strains with heightened DAP-mediated cell membrane response and potentially identify strains predisposed to DAP therapy failure. Further characterization of the discrepant isolates by genomic analyses and time-kill assays are warranted to fully validate the performance of LiaX ELISA.Disclosures Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

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.

Hospital-Acquired Bloodstream Infections With MRSA and VRE: Standardized Admission Screening Did Not Impact Rates

Background: Bloodstream infections (BSIs) are an important cause of morbidity and mortality in severely ill patients, contributing to increased length of stay and a higher cost of care. Surveillance of hospital-acquired (HA) BSI is considered a measure of quality of care and has been performed provincially in Alberta since 2011. Prior to October 2015, a nonstandardized, risk-factor–based VRE screening process was used. Screening practices for antibiotic-resistant organisms (AROs) were aligned in October 2015 with a provincially standardized admission screening tool to allow for early initiation of contact precautions for patients colonized or infected with MRSA or VRE. In this data review, we sought to determine whether this admission screening change influenced ARO infections through review of HA-BSI rates. Methods: Prospectively, we reviewed reports of all patients admitted to Alberta Health Services/Covenant Health acute-care and acute-/tertiary-care rehabilitation facilities who met inclusion criteria: (1) positive blood culture identified with MRSA or VRE; (2) new episode for the patient; and (3) positive result occurred on or after calendar day 3 of admission. Data are presented as quarterly rates. Screening practices for MRSA and VRE were standardized provincially in October 2015 to include screening for MRSA on admission for patients who had an inpatient admission, received hemodialysis, or was an inmate in a correctional facility in the past 6 months. We also screened for VRE patients admitted to a solid-organ transplant unit or a hematology unit, regardless of risk factors. Results: We detected no changes in the quarterly rates of HA-BSI with MRSA or VRE after admission screening was standardized. Prior to standardized screening, MRSA BSI rates ranged from 0.12 to 0.25 per 10,000 patient days, with an overall rate of 0.18 per 10,000 patient days. After standardization, rates ranged from 0.09 to 0.30 per 10,000 patient days, with an overall rate of 0.17 per 10,000 patient days (P = .46). VRE BSI rates prior to standardization ranged from 0.03 to 0.13 per 10,000 patient days, with an overall rate of 0.08 per 10,000 patient days, which increased slightly to 0.09 per 10,000 patient days after standardized screening, ranging between 0.04 and 0.16 per 10,000 patient days (P = .61). Conclusions: Following the implementation of standardized admission screening and the early initiation of contact precautions, no significant changes were observed in rates of either HA-BSI with MRSA or VRE. Further investigation is required to identify the most effective strategies to reduce HA-BSIs caused by MRSA and VRE.Funding: NoneDisclosures: None

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2014-2018.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose serious threats to the health of Canadians due to increased morbidity, mortality and healthcare costs. Epidemiologic and laboratory surveillance data, collected through the Canadian Nosocomial Infection Surveillance Program, are used to inform infection prevention and control and antimicrobial stewardship programs and policies. The objective of this study was to describe the epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2014 to 2018 using surveillance data provided by Canadian hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Data were collected from 70 Canadian sentinel hospitals between January 1, 2014 and December 31, 2018 for Clostridioides difficile infection (CDI), methicillin-resistant Staphylococcus aureus bloodstream infections, vancomycin-resistant Enterococci bloodstream infections and carbapenemase-producing Enterobacteriaceae. Case counts, rates, outcome data, molecular characterization and antimicrobial resistance profiles are presented. Additionally, hospital-level Escherichia coli antibiogram data were collected and are described. Increases in rates per 10,000 patient-days were observed for methicillin-resistant S. aureus bloodstream infections (59%; 0.66-1.05, p=0.023) and vancomycin-resistant Enterococci bloodstream infections (143%; 0.14-0.34, p=0.023). However, CDI rates decreased by 12.5% between 2015 and 2018 (from 6.16-5.39, p=0.042). Carbapenemase-producing Enterobacteriaceae infection rates remained low and stable whereas colonization increased by 375% (0.04-0.19; p=0.014). Ongoing efforts to prevent HAIs and reduce AMR in Canada require consistent, standardized surveillance data from acute care hospitals. Increased collaboration with provincial, territorial and international partners in infection prevention and control, as well as antimicrobial stewardship, will be essential in reducing the burden of observed HAIs (including antimicrobial resistant organisms).

Epidemiology, treatment and outcomes of bloodstream infection due to vancomycin-resistant enterococci in cancer patients in a vanB endemic setting

BackgroundVancomycin-resistant enterococcus (VRE) is an important cause of infection in immunocompromised populations. Few studies have described the characteristics of vanB VRE infection. We sought to describe the epidemiology, treatment and outcomes of VRE bloodstream infections (BSI) in a vanB predominant setting in malignant hematology and oncology patients.MethodsA retrospective review was performed at two large Australian centres and spanning a 6-year period (2008–2014). Evaluable outcomes were intensive care admission (ICU) within 48 h of BSI, all-cause mortality (7 and 30 days) and length of admission.ResultsOverall, 106 BSI episodes were observed in 96 patients, predominantly Enterococcus faecium vanB (105/106, 99%). Antibiotics were administered for a median of 17 days prior to BSI, and 76/96 (79%) were neutropenic at BSI onset. Of patients screened before BSI onset, 49/72 (68%) were found to be colonised. Treatment included teicoplanin (59), linezolid (6), daptomycin (2) and sequential/multiple agents (21). Mortality at 30-days was 31%. On multivariable analysis, teicoplanin was not associated with mortality at 30 days.ConclusionsVRE BSI in a vanB endemic setting occurred in the context of substantive prior antibiotic use and was associated with high 30-day mortality. Targeted screening identified 68% to be colonised prior to BSI. Teicoplanin therapy was not associated with poorer outcomes and warrants further study for vanB VRE BSI in cancer populations.

Management of Antimicrobial Agents in Abdominal Organ Transplant Patients in Intensive Care Unit.

Purpose of ReviewEarly diagnosis of infections and immediate initiation of appropriate antimicrobials are crucial in the management of patients before and after organ transplantation. We reviewed the most recent literature and guidelines in this field and organized the current recommendations for healthcare professionals caring for critically ill organ transplant recipients.Recent FindingsThe incidence of multidrug-resistant organisms is increasing. Multidrug-resistant Gram-negative bacteria comprise about 14% of organisms. Vancomycin-resistant enterococci bloodstream infections are also on the rise, as 20.5% of nosocomial enterococci are now vancomycin-resistant, changing empiric antibiotic selection. Fluconazole-resistant Candida species comprise up to 46% of cases of candidemia in hospitalized patients. Consequently, new guidelines recommend primary use of echinocandins in patients with candidemia who have moderate-to-severe disease. Finally, the incidence of emergence of ganciclovir-resistant cytomegalovirus infection in patients is 5–12%, requiring early recognition and change to alternative regimens in the case of poor response to therapy.SummaryBloodstream infections are a major cause of mortality and morbidity in solid organ transplantation. Mortality as high as 24% and 50% have been reported with sepsis and septic shock respectively. As such, bloodstream infections should be diagnosed rapidly and intravenous antibiotics should be started immediately. Appropriate resuscitation should be initiated and the number and/or dose of immunosuppressive drugs should be reduced. Proper source control must also be achieved with radiologic drainage or surgical intervention as appropriate. Initial antibiotic treatment of these patients should cover both Gram-positive organisms, especially in the presence of intravascular catheters, and Gram-negative bacteria. Echinocandins like caspofungin should also be considered especially in critically ill patients, particularly if a patient has been on total parenteral nutrition or broad-spectrum antibiotics.

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.

1017. Impact of Enterococcal Bloodstream Infection on Mortality in Patients With Acute Myelogenous Leukemia

BackgroundThough enterococcal bloodstream infection (EBSI) is common in patients with acute myelogenous leukemia (AML), its impact on mortality requires further elucidation. Our objectives were to: (1) determine attributable mortality to EBSI and (2) compare overall, 1-year, relapse-related mortality (RRM), and treatment-related mortality (TRM) between AML patients with and without EBSI.MethodsThis was a retrospective cohort receiving intensive chemotherapy for AML from 2010 to 2015. EBSI was defined by _1 positive blood culture for E. faecium or faecalis and fever, hypotension, or chills. Attributable mortality to EBSI was defined by failure to achieve BSI Clearance (_1 negative culture _24 hr after last positive culture and defervescence) by the date of death. Student’s t-test was used to compare continuous variables, and C2 test was used for categorical variables. Kaplan–Meier was used for survival analyses (unadjusted), and P-values were computed by log-rank.ResultsThree hundred eight patients were identified during the study period: 80 with EBSI and 228 without EBSI. 5/80 patients died with EBSI (6%) although 4/5 patients had concurrent infections at the time of death (Clostridium difficile colitis, candidemia, proven invasive aspergillosis, and probable invasive fungal disease, respectively). There were no significant differences between overall and 1-year mortality (Table 1). In the survival analyses, EBSI did not significantly impact overall survival, 1-year mortality, RRM, and TRM (Figure 1). However, patients with vancomycin-resistant EBSI (VRE) trended toward increased overall mortality.ConclusionAttributable mortality to EBSI is uncommon (6%) in AML. Additionally, EBSI does not significantly impact mortality in this vulnerable patient population that already has very high rates of RRM and TRM. However, as EBSI inflicted 26% of patients over the course of this study period, further investigation is needed to elucidate the morbidity suffered from this common infection and identify potentially modifiable risk factors.Table 1.EBSIN = 80 (26%)No EBSIN = 228 (74%) P Age AML diagnosis (median years, IQR)63(51–69)61(50–69)0.93Overall mortality (%)63/73 (86)154/198 (77)0.12Time AML diagnosis to death (median years, IQR)220 (67–541)273 (62–582)0.16 Disclosures A. Sung, Merck: Grant Investigator, Grant recipient. Enterome: Grant Investigator, Grant recipient.

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.

Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated With the Rate of Bacterial Clearance.

Vancomycin-resistant enterococci are important pathogens for healthcare-associated infections. Although linezolid is bacteriostatic and daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in vitro, it is not clear whether they differ in their effect on bacterial clearance in patients with vancomycin-resistant enterococci bloodstream infections. Prospective observational study. Two university hospitals and research laboratory. Patients with vancomycin-resistant enterococci bloodstream infection proven by blood cultures were prospectively enrolled from January 2010 to July 2015. Sequential blood samples were collected. Real-time quantitative polymerase chain reaction was used to monitor bacterial loads. One hundred eight patients with vancomycin-resistant enterococci bloodstream infection were enrolled. Quantitative polymerase chain reaction assays were performed on 465 blood isolates. We found this method to be closely correlated with colony-forming units and more sensitive than culture. Sixty-three patients (58.3%) received "conventional dose" daptomycin (6-9 mg/kg), 15 (13.9%) received high-dose daptomycin (≥ 9 mg/kg), and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents. The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to survival. Survivors had a more rapid early bacterial clearance than nonsurvivors (Δ log10 copies/mL/d; -0.16 vs 0.31; p = 0.02). Multivariable logistic regression showed that a slower early bacterial clearance independently predicted increased mortality (odds ratio, 3.21; 95% CI, 1.03-10.02; p = 0.045). Conventional dose daptomycin was associated with a significantly slower rate of bacterial clearance than high-dose daptomycin (Δ log10 copies/mL/d; -0.04 vs -0.41; p < 0.001) and linezolid (-0.04 vs -0.56; p = 0.043). We found that survivors of vancomycin-resistant enterococci bloodstream infection had a significantly more rapid early bacterial clearance by quantitative polymerase chain reaction than nonsurvivors. High-dose daptomycin and linezolid were associated with more rapid bacterial clearance than conventional dose daptomycin. These results support recommendations that conventional dose daptomycin not be used for the treatment of patients with vancomycin-resistant enterococci bloodstream infection.