Faecium Bloodstream Infections Research Articles

Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010–2019

ABSTRACT The emergence of bloodstream infections (BSI) caused by vancomycin-resistant Enterococci (VRE) has caused concern. Nonetheless, it remains unclear whether these types are associated with an excess risk of severe outcomes when compared with infections caused by vancomycin-susceptible Enterococci (VSE). This cohort study included hospitalized patients in Denmark with Enterococcus faecium-positive blood cultures collected between 2010 and 2019 identified in the Danish Microbiology Database. We estimated 30-day hazard ratio (HR) of death or discharge among VRE compared to VSE patients adjusted for age, sex, and comorbidity. The cohort included 6071 patients with E. faecium BSI (335 VRE, 5736 VSE) among whom VRE increased (2010–13, 2.6%; 2014–16, 6.3%; 2017–19; 9.4%). Mortality (HR 1.08, 95%CI 0.90–1.29; 126 VRE, 37.6%; 2223 VSE, 37.0%) or discharge (HR 0.89, 95%CI 0.75–1.06; 126 VRE, 37.6%; 2386 VSE, 41.6%) was not different between VRE and VSE except in 2014 (HR 1.87, 95% CI 1.18–2.96). There was no interaction between time from admission to BSI (1–2, 3–14, and >14 days) and HR of death (P = 0.14) or discharge (P = 0.45) after VRE compared to VSE, despite longer time for VRE patients (17 vs. 10 days for VSE, P < 0.0001). In conclusion, VRE BSI was not associated with excess morbidity and mortality. The excess mortality in 2014 only may be attributed to improved diagnostic- and patient-management practices after 2014, reducing time to appropriate antibiotic therapy. The high level of mortality after E. faecium BSI warrants further study.

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.

1825. Comparative Effectiveness of Ampicillin versus Vancomycin or Daptomycin for the Treatment of Ampicillin-Susceptible Enterococcus spp. Bloodstream Infections

Abstract Background Treatment options against Enterococcus spp., a common nosocomial pathogen, are limited due to intrinsic resistance to multiple antibiotics. Ampicillin is considered drug of choice if susceptible, but data comparing outcomes between ampicillin, daptomycin, and vancomycin for ampicillin-sensitive Enterococcus spp. bacteremia are limited. Methods This was a single-center retrospective cohort study of adults with confirmed ampicillin-sensitive Enterococcus spp. bloodstream infection (BSI) who received definitive treatment with intravenous ampicillin, daptomycin, or vancomycin from January 2013 to December 2021. Polymicrobial BSI were excluded. Definitive treatment was defined as the active antibiotic used for more than 50% of the total treatment duration following availability of susceptibility results. The primary outcome was 28-day all-cause hospital mortality; secondary outcomes were 90-day readmission due to microbiological recurrence and all-cause hospital mortality. Multivariate Cox regression analysis was performed to identify independent risk factors for 28-day hospital mortality. Results A total of 199 patients (ampicillin, n = 141; daptomycin, n = 17; vancomycin, n = 41) were evaluated. Overall in-hospital all-cause mortality was 15.1% (n = 30). Twenty-eight-day hospital mortality was numerically lower with ampicillin and daptomycin compared to vancomycin (9.2%, 11.8%, and 22%, respectively; p = 0.088). Ninety-day readmission due to microbiological recurrence (4.3%, 5.9%, and 7.3%; p = 0.722) and all-cause hospital mortality (12.8%, 17.6%, and 22%; p = 0.335) were not significantly different between treatment groups. Independent risk factors for 28-day hospital mortality included age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02 to 1.09; p = 0.003), E. faecium BSI (HR 3.94, 95% CI 1.39 to 11.1; p = 0.010), and definitive treatment with vancomycin (HR 2.54, 95% CI 1.04 to 6.21; p = 0.040). Conclusion Vancomycin used as definitive therapy for ampicillin-sensitive Enterococcus spp. bacteremia was found to be an independent risk factor for 28-day mortality. Further studies evaluating the role of daptomycin in this setting are warranted. Disclosures All Authors: No reported disclosures.

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.

Bloodstream Infections in Patients with Hematologic Diseases: Causative Organisms and Factors Associated with Resistance.

BackgroundPatients with hematologic diseases are at high risk of bloodstream infections (BSIs). This study aimed to analyze clinical features and distributions of microorganisms in patients with hematologic diseases presenting at a tertiary care university-affiliated hospital in Korea.Materials and MethodsWe retrospectively reviewed all BSI episodes recorded in patient medical records at two hematologic wards of the Catholic Hematology Hospital from January to December 2020. Our aim was to analyze demographic and clinical characteristics relevant to BSIs. We also described the antimicrobial resistance patterns of the major pathogens identified in this study, and evaluated risk factors for extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae isolates and for vancomycin resistance in enterococcal isolates.ResultsA total of 380 BSI episodes were identified in 334 patients over the course of 1 year (monomicrobial BSI episodes, 86.1%; polymicrobial BSI episodes, 13.9%). Gram-negative bacteria accounted for 242 isolates (54.8%). The most frequently isolated Gram-negative bacteria isolates were Escherichia coli (107 [24.2%]) followed by Klebsiella spp. (72 [16.3%]), Pseudomonas spp. (21 [4.8%]), and Enterobacter spp. (12 [2.7%]). The most commonly identified Gram-positive bacteria were Enterococcus spp. (72 [16.3%]) followed by viridans streptococci (54 [12.2%]), coagulase-negative staphylococci (CoNS) (24 [5.4%]), and Corynebacterium spp. (22 [5.0%]). ESBL-producing Enterobacteriaceae accounted for 25.1% of the total distribution. Among 54 Enterococcus faecium isolates, 100.0% were resistant to ampicillin and 55.6% showed resistance to vancomycin, while 100.0% (n = 12) of Enterococcus faecalis isolates were susceptible to ampicillin and vancomycin, respectively. Use of ciprofloxacin prophylaxis (odds ratio: 5.20; 95% confidence interval: 1.11 - 24.34; P = 0.04) was an independent risk factor for ESBL production in Enterobacteriaceae BSIs.ConclusionCompared with the results of a previous study conducted at the same institution, our findings demonstrated that Gram-negative bacteria remained dominant pathogens in BSIs occurring in patients with hematologic diseases. Our findings also demonstrated a comparatively decreased prevalence of ESBL-producing Enterobacteriaceae in the evaluated BSIs. However, the prevalence of enterococcal BSIs had not decreased, and the proportion of vancomycin-resistant Enterococcus isolates from E. faecium BSIs had increased. In addition, we found that ciprofloxacin prophylaxis was statistically significantly associated with ESBL production in Enterobacteriaceae BSIs. We conclude that, in order to avoid critical complications and to reduce the burden of antimicrobial-resistant organisms in patients with hematologic diseases, it is necessary to conduct periodic examinations evaluating changes in BSI epidemiology within a single medical center.

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.

1221. Genomic Factors Affecting the Efficacy of Antimicrobial Therapy in Daptomycin-, Linezolid-, Vancomycin-Resistant Enterococcus faecium (DLVRE)

BackgroundNosocomial acquisition of vancomycin-resistant Enterococcus (VRE) is one of the most challenging problems in healthcare. As Enterococcus isolates are increasingly resistant to vancomycin, clinicians now rely on alternative antimicrobial therapies including linezolid and daptomycin (DAP) to treat infections. For multidrug-resistant (MDR) VRE, combination therapy with beta-lactams and daptomycin has been shown to be effective. MethodsFollowing initiation of empiric DAP and ceftaroline (CPT) for an MDR E. faecium bloodstream infection (VRE_001), we aimed to determine if there existed in vitro synergy between both agents that supported their clinical use. Combination synergy testing was performed using E-test strips and minimal inhibitory concentrations (MICs) were read at 24 hours. For whole genome sequence-based analysis (WGS), genomic DNA from VRE_001 was used for both short read (Illumina MiSeq) and long-read sequencing (MinION, Nanopore). The complete genome was assembled and the NCBI AMRFinderPlus program used to identify known resistance mechanisms. ResultsOriginal MICs of VRE_001 from the clinical microbiology laboratory at Northwestern Memorial revealed an MDR E. faecium (Table 1). Combination synergy testing in the experimental laboratory revealed only modest amounts of synergy between CPT and DAP (Table 2). Following WGS, VRE_001 was identified as an ST-584 E. faecium with a 3.2 Mbp genome, including a single chromosome and five plasmids. WGS analysis revealed several mechanisms of antimicrobial resistance (Table 3) genetically supporting the observed MDR-DLVRE phenotype. ConclusionOur investigational antimicrobial testing allowed for real-time in vitro analysis of synergistic MICs in a case of DLVRE bacteremia. Despite the fact that in vitro testing of CPT and DAP did not support the clinical usage of combination antimicrobial therapy, the patient cleared their blood cultures. WGS of VRE_001 revealed a plethora of antimicrobial resistance mechanisms including three mutations that explain high levels of DAP resistance. Synergy testing is not routinely available in most clinical laboratories, but rapid implementation of investigational MIC testing paired with genomic analysis may one day successfully support real-time clinical decision making.Disclosures All Authors: No reported disclosures

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

The Timing and Epidemiology of Enterococcus Faecium and E. Faecalis Bloodstream Infections (BSI) in Patients with Acute Leukemia Receiving Chemotherapy

Enterococcal BSI occurs frequently in patients with acute leukemia and causes significant morbidity and mortality. Daptomycin non-susceptible Enterococcus (DNSE) infection has emerged as a threat that has limited treatment options. However, the timing of enterococcal BSI in relationship to chemotherapy is unknown. In addition, previous studies have focused on the epidemiology of vancomycin-resistant E. faecium (VRE) BSI. The present study investigates the timing of enterococcal BSI in relationship to chemotherapy and the epidemiology of both E. faecium and E. faecalis BSI in patients with acute leukemia. We hypothesize that most BSIs are gut derived, mucosal barrier injury infections that occur in patients who undergo intensive chemotherapy that causes prolonged neutropenia and chemotherapy-induced mucositis leading to febrile neutropenia and antimicrobial-induced gut dysbiosis.We conducted a retrospective cohort study of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) admitted to Duke University for infusional chemotherapy from 2010-15. BSI was adjudicated by CDC criteria. Appropriate enterococcal therapy was defined as receipt of an antibiotic with in vitro activity against the BSI isolate. BSI clearance was defined by negative follow-up blood cultures obtained within 72 hours after positive blood cultures. Recurrent BSI was defined by positive blood cultures for Enterococcus after BSI clearance. Bivariate analysis was performed using chi-squared test.Three hundred twelve patients were evaluated for this study, 83 of whom had enterococcal BSI during the study period (27%; Table 1). Eight-seven percent had BSI due to E. faecium while 13% had BSI due to E. faecalis . Most were febrile (82%) and neutropenic (96%) on broad-spectrum antimicrobials at the time of BSI. All patients had an indwelling central line and had received intensive chemotherapy prior to BSI. Median time from acute leukemia diagnosis to BSI was 30 days. BSI occurred most frequently during the first cycle of induction chemotherapy (47%), but a combined 52% of BSIs occurred during the 2nd-5rd cycles of induction chemotherapy. Sixty-six percent of BSIs qualified as mucosal barrier injury infections. Only 2 patients had metastatic sites of infection: 1 with empyema and 1 with CNS infection, both due to VRE. In terms of clinical response to therapy, 61% of patients achieved cure, and 10% died with BSI. Twenty-eight percent suffered recurrent BSI, and 29% of these patients had DNSE BSI after previous daptomycin exposure. Fifty-one percent of patients underwent central line removal for BSI. Failure to remove the central line for BSI did not increase risk of recurrent BSI (p=0.38).Enterococcal BSI typically occurs as a mucosal barrier injury infection in febrile neutropenic patients with acute leukemia receiving intensive chemotherapy. Many cases take place during re-induction chemotherapy in patients with relapsed or refractory disease. VRE is the most common infecting pathogen, but E. faecalis is not an insignificant cause of BSI (13%). In addition, some E. faecium isolates maintain ampicillin or vancomycin susceptibility. These results support empiric anti-VRE therapy with daptomycin upon initial suspicion for enterococcal BSI, but this therapy could be switched to ampicillin or vancomycin depending on isolate susceptibility to conserve daptomycin susceptibility. The risk of recurrent enterococcal BSI is notable as is the emergence of DNSE following daptomycin therapy. However, failure to remove the central line does not appear to be associated with recurrent BSI. Future study of changes to the gut enterococcal microbiome over the course of chemotherapy for acute leukemia will be critical in ultimately preventing enterococcal BSI. [Display omitted] DisclosuresSung:Cellective: Research Funding; Novartis: Research Funding; Merck: Research Funding.

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.

Increasing Rates of Intensive Care Unit Bloodstream Infections During the Second COVID-19 Pandemic Wave, Particularly Primary Endogenous &lt;i&gt;Enterococcus faecium&lt;/i&gt;, with High Crude Mortality and Associated with Introduction of Immunomodulatory Therapy

Background: Reports indicate that COVID-19 patients have more bloodstream infections (BSI) on the intensive care unit (ICU) potentially due to lapses in infection control practice or other factors.Methods: Retrospective single-site study of ICU-BSIs in mechanically ventilated (MV) COVID-19 patients during the first pandemic year. Clinical, demographic and laboratory data including targeted pathogen genome sequencing was analysed during first (March 13th - May 31st 2020) and second (October 1st 2020 - March 15th 2021) pandemic waves.Findings: There were 305 MV-ICU patients in wave one and 440 in wave two with peak occupancy of 113 and 155 patients, respectively. The BSI rate was higher during both waves than pre-pandemic, but more in wave-two than wave-one, particularly during the first 28 days on ICU (14.1 vs. 9.4/1000 bed days; p=0.03) and with E. faecium (3.57 vs. 0.47/1000 bed days; p=0.0067). 22/28 (77%) of E. faecium BSIs had no microbiologically definable focus and the high wave-two rate could not be explained by transmission. Wave-two BSI-patients received more corticosteroids and tocilizumab and had higher crude hospital mortality compared with non-BSI patients (41% vs. 21% pInterpretation: MV-COVID-19 patients had a greater BSI-burden in wave two associated with the emergence of primary endogenous E. faecium. Identifying mechanisms and causal links between admission COVID-19 disease severity, immunomodulation, BSI and death could help identify new approaches to improving outcomes for COVID-19 patients.

Enterococcal bloodstream infections in critically ill patients with COVID-19: a case series

Background An unexpected high prevalence of enterococcal bloodstream infection (BSI) has been observed in critically ill patients with COVID-19 in the intensive care unit (ICU). Materials and methods The primary objective was to describe the characteristics of ICU-acquired enterococcal BSI in critically ill patients with COVID-19. A secondary objective was to exploratorily assess the predictors of 30-day mortality in critically ill COVID-19 patients with ICU-acquired enterococcal BSI. Results During the study period, 223 patients with COVID-19 were admitted to COVID-19-dedicated ICUs in our centre. Overall, 51 episodes of enterococcal BSI, occurring in 43 patients, were registered. 29 (56.9%) and 22 (43.1%) BSI were caused by Enterococcus faecalis and Enterococcus faecium, respectively. The cumulative incidence of ICU-acquired enterococcal BSI was of 229 episodes per 1000 ICU admissions (95% mid-p confidence interval [CI] 172–298). Most patients received an empirical therapy with at least one agent showing in vitro activity against the blood isolate (38/43, 88%). The crude 30-day mortality was 42% (18/43) and 57% (4/7) in the entire series and in patients with vancomycin-resistant E. faecium BSI, respectively. The sequential organ failure assessment (SOFA) score showed an independent association with increased mortality (odds ratio 1.32 per one-point increase, with 95% confidence interval 1.04–1.66, p = .021). Conclusions The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. Our results suggest a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome. KEY MESSAGES The cumulative incidence of enterococcal BSI is high in critically ill patients with COVID-19. The crude 30-day mortality of enterococcal BSI in critically ill patients with COVID-19 may be higher than 40%. There could be a crucial role of the severity of the acute clinical conditions, to which both the underlying viral pneumonia and the enterococcal BSI may contribute, in majorly influencing the outcome.

Occurrence and determinants of enterococcal bloodstream infections: a population-based study

Background: Although enterococci are common causes of bloodstream infections (BSIs), few studies have examined their epidemiology in non-selected populations.Objective: To examine the incidence and risk factors for development of enterococcal BSI.Methods: Surveillance for incident enterococcal BSI was conducted among all residents of the western interior of British Columbia, Canada during 2011–2018.Results: The overall annual incidence was 10.0 per 100,000 and was 6.6 and 2.7 per 100,000 for E. faecalis and E. faecium, respectively. Among the overall cohort of 145 incident cases of enterococcal BSI, 22 (15.2%) were community-associated, 63 (43.5%) were healthcare associated and 60 (41.4%) were hospital-onset. Enterococcal BSI was predominantly a disease of older adults with rare cases occurring among those aged less than 40 years. Males showed significantly increased risk compared to females (14.3 vs. 5.6 per 100,000; incidence rate ratio; IRR; 2.6; 95% confidence interval; CI; 1.8–3.8; p < .0001) and this was most pronounced with advanced age. Several co-morbid illnesses were associated with increased risk (IRR; 95% CI) for development of enterococcal BSI most importantly cancer (8.8; 6.0–12.9; p < .0001), congestive heart failure (5.7; 3.1–9.7; p < .0001), diabetes mellitus (4.4; 3.0–6.3; p < .0001) and stroke (3.7; 1.9–6.5; .0001). As compared to patients with E. faecalis, patients with E. faecium BSI were more likely to be of hospital-onset, more likely to have an intra-abdominal/pelvic focus, and trended towards higher 30-day case-fatality rate.Conclusions: Enterococci are relatively common causes of BSI. Although E faecalis and E faecium share commonalities they are epidemiologically distinguishable on several criteria.

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.

Impact of improved observed hand hygiene on bloodstream infection rates in Ireland. A prospective segmented regression analysis, 2009-2016.

Participation in European surveillance for bloodstream infection (BSI) commenced in Ireland in 1999 with all laboratories (n = 39) participating by 2014. Observational hand hygiene auditing (OHHA) was implemented in 2011. The aim of this study was to evaluate the impact of OHHA on hand hygiene compliance, alcohol hand rub (AHR) procurement and the incidence of sensitive and resistant Staphylococcus aureus and Enterococcus faecium and faecalis BSI. A prospective segmented regression analysis was performed to determine the temporal association between OHHA and outcomes. Observed hand hygiene improved from 74.7% (73.7-75.6) in 2011 to 90.8% (90.1-91.3) in 2016. AHR procurement increased from 20.1 l/1000 bed days used (BDU) in 2009 to 33.2 l/1000 BDU in 2016. A pre-intervention reduction of 2% per quarter in the ratio of methicillin sensitive Staphylococcus aureus BSI/BDU stabilized in the time period after the intervention (P < 0.01). The ratio of Methicillin resistant Staphylococcus aureus (MRSA) BSI/BDU was decreasing by 5% per quarter pre-intervention, this slowed to 2% per quarter post intervention, (P < 0.01). There was no significant change in the ratio of vancomycin sensitive (P = 0.49) or vancomycin resistant (P = 0.90) Enterococcus sp. BSI/BDU post intervention. This study shows national OHHA increased observed hand hygiene compliance and AHR procurement, however there was no associated reduction in BSI.

573. Enterococcal Bacteremia in a Tertiary Care Center in Mexico: A Retrospective Analysis Focus on Vancomycin-Resistant E. faecium and Ampicillin-Resistant E. faecalis

BackgroundThe primary pathogens in genera enterococcus are E. faecalis and E. faecium, increasing acquired resistance to glycopeptides and β lactamic has done the management more challenging. We aimed to describe the risk factors for acquisition of bacteremia for vancomycin-resistant E. faecium (VRE) and ampicillin-resistant E. faecalis (ARE) and the 30-day mortality in comparison to susceptible enterococcal bloodstream infection (BSI)MethodsFrom 2007- 2017 medical records of all BSI for E. faecalis and E. faecium were evaluated. Risk factor for acquisition of VRE and ARE as well as the significant variables associated with 30-day mortality for enterococcal BSI were determined by univariate and multivariate analysis. The molecular mechanism of VRE was performed by PCRResultsThere were 192 patients with E. faecium BSI of which 107(56%) patients had VRE BSI with 94% VRE strains expressing vanA gene. The index bacteremic episodes were classified as nosocomial o healthcare associated in 99%, 102(95%) had hospitalization 1 year before and 101(94%) history of use of antibiotics 3 months earlier, the multivariate analysis showed duration of the previous hospitalization >10 days (OR, 80.18; 95% CI, 1.81–634), use of central venous catheter [OR, 11.15; 95% CI, 2.48–50.2), and endotracheal cannula [OR, 17.91; 95% CI, 1.22–262) as significant associated variables. The mortality for VRE was greater than susceptible E. faecium (60% vs. 24%, P < 0.001). The only factors for 30-day mortality for E. faecium BSI in the multivariate analysis was APACHE ll score [OR,1.45; 95% CI, 1.26–1.66) and patients with chemotherapy of cancer. (OR, 3.52; 95% CI, 1.09–11.39). 147 patients had E. faecalis BSI of which 18 (11%) patients had ARE, we did not find relevant clinical differences of ARE in comparison with ampicillin-susceptible E. faecalis, neither in risk factors for acquisition of ARE nor 30-day mortality [7(39%) vs. 38(29%), P = 0.58] in uni and multivariate analysisConclusionOur evaluation showed in a period of 10 years that VRE expressing vanA gene had a strong association with patients with previous nosocomial exposure. Severely ill patients and cancer patients on chemotherapy during the bacteremic episode were the variables more associated with 30-day mortality. ARE is yet of low prevalence and less known, constant surveillance about it is warrantedDisclosures All authors: No reported disclosures.