Vancomycin-resistant Enterococci Bloodstream Infections Research Articles

Epidemiological trends and susceptibility patterns of bloodstream infections caused by Enterococcus spp. in six German university hospitals: a prospectively evaluated multicentre cohort study from 2016 to 2020 of the R-Net study group.

To analyse recent epidemiological trends of bloodstream infections (BSI) caused by Enterococcus spp. In adult patients admitted to tertiary care centres in Germany. Epidemiological data from the multicentre R-NET study was analysed. Patients presenting with E. faecium or E. faecalis in blood cultures in six German tertiary care university hospitals between October 2016 and June 2020 were prospectively evaluated. In vancomycin-resistant enterococci (VRE), the presence of vanA/vanB was confirmed via molecular methods. In the 4-year study period, 3001 patients with BSI due to Enterococcus spp. were identified. E. faecium was detected in 1830 patients (61%) and E. faecalis in 1229 patients (41%). Most BSI occurred in (sub-) specialties of internal medicine. The pooled incidence density of enterococcal BSI increased significantly (4.0-4.5 cases per 10,000 patient days), which was primarily driven by VRE BSI (0.5 to 1.0 cases per 10,000 patient days). In 2020, the proportion of VRE BSI was > 12% in all study sites (range, 12.8-32.2%). Molecular detection of resistance in 363 VRE isolates showed a predominance of the vanB gene (77.1%). This large multicentre study highlights an increase of BSI due to E. faecium, which was primarily driven by VRE. The high rates of hospital- and ICU-acquired VRE BSI point towards an important role of prior antibiotic exposure and invasive procedures as risk factors. Due to limited treatment options and high mortality rates of VRE BSI, the increasing incidence of VRE BSI is of major concern.

The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea

There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with VRE because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). This retrospective quasi-experimental study was conducted at a tertiary care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the hematology unit before (phase 1) and after (phase 2) the policy change. At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval [CI]: -0.053 - 0.023, P = 0.45 and 0.000, 95% CI: -0.002 - 0.002, P = 0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the hematology unit (-0.285, 95% CI: -0.618 - 0.048, P = 0.09 and -0.018, 95% CI: -0.036 - 0.000, P = 0.054, respectively) did not change significantly across the two phases. Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the hematology unit. Horizontal intervention for multidrug-resistant organisms, including measures like enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

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.

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.

Therapeutics for Vancomycin-Resistant Enterococcal Bloodstream Infections.

Vancomycin-resistant enterococci (VRE) are common causes of bloodstream infections (BSIs) with high morbidity and mortality rates. They are pathogens of global concern with a limited treatment pipeline. Significant challenges exist in the management of VRE BSI, including drug dosing, the emergence of resistance, and the optimal treatment for persistent bacteremia and infective endocarditis. Therapeutic drug monitoring (TDM) for antimicrobial therapy is evolving for VRE-active agents; however, there are significant gaps in the literature for predicting antimicrobial efficacy for VRE BSIs. To date, TDM has the greatest evidence for predicting drug toxicity for the three main VRE-active antimicrobial agents daptomycin, linezolid, and teicoplanin. This article presents an overview of the treatment options for VRE BSIs, the role of antimicrobial dose optimization through TDM in supporting clinical infection management, and challenges and perspectives for the future.

Healthcare-associated infections and antimicrobial resistance in Canadian acute care hospitals, 2017-2021.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) continue to contribute to excess morbidity and mortality among Canadians. This report describes epidemiologic and laboratory characteristics and trends of HAIs and AMR from 2017 to 2021 (Candida auris 2012-2021) using surveillance and laboratory data submitted by hospitals to the Canadian Nosocomial Infection Surveillance Program (CNISP) and by provincial laboratories to the National Microbiology Laboratory (NML). Data collected from 88 Canadian sentinel acute care hospitals between January 1, 2017, and December 31, 2021, for Clostridioides difficile infections (CDI), carbapenemase-producing Enterobacterales (CPE), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) and vancomycin-resistant Enterococcus (VRE) BSIs. Candida auris (C. auris) surveillance was initiated in 2019 by CNISP and in 2012 by the NML. Case counts, rates, outcomes, molecular characterization and antimicrobial resistance profiles are presented. From 2017 to 2021, increased rates per 10,000 patient days were observed for MRSA BSIs (35%; 0.84-1.13), VRE BSIs (43%; 0.23-0.33) and CPE infections (166%, 0.03-0.08). CDI rates decreased 11% (5.68-5.05). Thirty-one C. auris isolates were identified in Canada from 2012 to 2021, with the majority from Western Canada (68%). From 2017 to 2021, the incidence of MRSA and VRE BSIs, and CPE infections increased in Canadian acute care hospitals participating in a national sentinel network (CNISP) while CDI decreased. Few C. auris isolates were identified from 2012 to 2021. Reporting standardized surveillance data and the consistent application of infection prevention and control practises in acute care hospitals are critical to help decrease the burden of HAIs and AMR in Canada.

Treatment decisions in VRE bacteraemia: a survey of infectious diseases pharmacists.

VRE infections increased in 2020. High-dose daptomycin (≥10 mg/kg) has shown mortality benefit over other regimens, though daptomycin resistance is increasing. Limited data exist on the practice patterns of ID pharmacists for VRE bloodstream infections (VRE BSIs). To describe practice patterns for VRE BSI in ID pharmacists. A 22-question REDCap survey was distributed to ID pharmacist members of the American College of Clinical Pharmacy (ACCP) Infectious Diseases Practice and Research Network (ID PRN) via e-mail listserv. The survey was distributed on 7 April 2022 and remained open for 4 weeks. Sixty-eight pharmacists responded. All pharmacists completed additional training or certification in infectious diseases past their PharmD, and most (70.5%) had been practising for 10 years or less. Pharmacists at academic medical centres (80.0%) were more likely (P = 0.001) to have implemented the updated CLSI breakpoints than pharmacists at other types of institutions (55.2%). Daptomycin was the preferred drug for VRE BSI (92.6%), with 10 mg/kg (72.1%) being the preferred dose. Adjusted body weight was the most common weight (61.2%) used for obese patients. Fourteen days (76.1%) was the most common treatment duration for VRE BSI. Pharmacists defined persistent VRE BSI as 5 days (68.7%) after first blood culture. ID pharmacists overwhelmingly selected high-dose daptomycin for VRE BSI. There were variations in practice and response rate when selecting combination therapy, managing persistent bacteraemia, and treating patients with high daptomycin MICs or previous exposure to daptomycin.

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.

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.

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.

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.

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&amp;lt; 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