Enterococcal Bloodstream Infections Research Articles

Erratum for Rothe et al., "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".

Erratum for Rothe et al., "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".

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.

Characteristics of Enterococcus species bloodstream infections among adults with and without onco-hematological malignancies: Experiences from the national center of Hungary.

Over the past decade, enterococcal bloodstream infection (BSI) shows increasing incidence globally among the elderly and in patients with comorbidities. In this study, we aimed to assess microbiological and clinical characteristics and long-term outcomes of BSIs caused by Enterococcus spp. in adult patients with and without active onco-hematological malignancies hospitalized at a national referral institute. A prospective analysis of consecutive enterococcal BSI cases was conducted in the National Institute of Hematology and Infectious Diseases (Budapest, Hungary) between December 2019 and April 2022. We compared characteristics and outcomes at 30-days and 1 year afterdiagnosis among patients with and without onco-hematological malignancies. In total, 141patients were included (median age 68 ± 21 years, female sex 36.9%), 37% (52/141) had active onco-hematological malignancies. The distribution of species was as follows: 50.4% Enterococcus faecalis, 46.1% Enterococcus faecium, 1.4% Enterococcus avium and Enterococcus gallinarum, and 0.7% Enterococcus raffinosus. No statistically significant differences in all-cause mortality rates were observed between patient subgroups at 30 days (32.7 vs. 28.1%; P = 0.57) and 1 year (75.0 vs. 60.7%; P = 0.09). Enterococcal bloodstream infections yielded a relevant burden of morbidity, but with nostatistical difference in long-term outcomes of adult patients with and without active onco-hematological malignancies.

Epidemiology and outcomes associated with enterococcal blood stream infection among liver and kidney transplant recipients.

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n=54; 10.3%). Cases were mostly liver transplant recipients (n=20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p<.05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p<.0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n=23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.

Characterization of Prescribing Practices for Uncomplicated Streptococcal and Enterococcal Bacteremias: The NARRATE Study.

Bloodstream infections (BSIs) rank among the top causes of death in North America. Despite the prevalence of these infections, there remain significant practice variations in the prescribing of antibiotics. To investigate current prescribing practices for management of uncomplicated streptococcal and enterococcal BSIs. A retrospective cohort study was conducted using charts for patients admitted to an acute care centre in British Columbia between November 16, 2019, and October 20, 2020. Adult patients (≥ 18 years of age) with a diagnosis of uncomplicated streptococcal or enterococcal BSI were included. Patients were excluded if they had polymicrobial bacteremia or deep-seated infection or had been admitted for no more than 48 hours. The primary outcomes were duration of antibiotic therapy (IV and oral) and time to appropriate oral therapy for treatment of BSI. The secondary outcomes were observed rates of re-initiation of antibiotics and readmission with recurrent BSI. Descriptive statistics were calculated and regression analysis was performed for the primary and secondary outcomes. A total of 96 patients met the inclusion criteria. The median total duration of therapy for uncomplicated streptococcal and enterococcal BSI was about 2 weeks. Streptococcus pneumoniae BSIs were associated with a significantly shorter duration of IV therapy and were more likely to be associated with transition to oral antibiotics. No recurrent BSIs were observed in patients for whom therapy was transitioned to oral antibiotics. Further study is warranted to explore shorter duration of antibiotic therapy and transition to oral therapy as treatment approaches for uncomplicated streptococcal and enterococcal BSI. Other outcomes of interest for future research include determining the optimal time for transition to oral therapy.

1032. Are enterococcal blood stream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness? - The Munich Multi-Centric Enterococci cohort

Abstract Background To assess the long-term survival of patients with enterococcal bloodstream infections (BSI), encompassing various species and resistance patterns, in comparison to Escherichia coli (E. coli) BSI. Recruitment process Graphical Abstract Methods Between 2010 and 2019, 3,290 enterococcal and 3,415 E. coli BSI were retrospectively screened in seven hospitals in Munich, Germany. All vancomycin (VRE), vancomycin/linezolid (LVRE), and linezolid (LRE) resistant Enterococcus faecium (ECFM) BSI were included. Enterococcus faecalis (ECFA), vancomycin/Linezolid-susceptible ECFM, and E. coli BSI were randomly assigned. Cox-regression models were used to assess survival as the primary endpoint and were adjusted for limiting prognostic factors, which were measured for their importance using a random forest model (RFM). Results 952 patients with 916 episodes of enterococcal BSI and 193 E. coli BSI episodes were analysed. RFM identified multimorbidity and markers for disease severity as most indicative of low survival in enterococcal BSI. The 5-year survival was significantly lower for enterococcal BSI than for E. coli BSI (23.9% vs. 42.3%; p&amp;lt; 0.001). This difference remained significant in the Cox-regression analysis after adjusting for 17 prognostic factors and excluding patients with limited life expectancy (metastatic tumour disease, Charlson comorbidity index ≥5). Adjusted 5-year survival between E. coli and ECFA was similar but significantly different between ECFA and ECFM BSI (29.2% vs. 21.7%; p=0.002). The analysis conducted on monomicrobial ECFM and VRE BSI indicated that their respective 5-year survival was similar (19.6% vs. 21.2%; p=0.753). Conclusion ECFM BSI seems to be an independent risk factor for poor long-term survival. However, additional vancomycin resistance does not appear to be a contributing factor. Disclosures Jochen Schneider, MD, JS reports grants, personal fees, and nonfinancial support from AbbVie, Gilead Sciences, Janssen-Cilag, GSK/ViiV Healthcare, and MSD, Dr. Falk Pharma: Grant/Research Support Karl Dichtl, MD, KD reports grants from Euroimmun Medizinische Labordiagnostika and Fujifilm Wako Chemicals Europe outside of this study.: Advisor/Consultant Ulrich Seybold, MD, reports personal fees and nonfinancial support from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, Falk Foundation, Sanofi-Aventis.: Advisor/Consultant Christoph Spinner, MD, AbbVie, Gilead Sciences, Janssen-C,MSD, Cepheid, GSK, ViiV Healthcare, AstraZeneca, Apeiron, Braun, Pfizer, Novartis, Lilly, Biontech…: Advisor/Consultant|AbbVie, Gilead Sciences, Janssen-C,MSD, Cepheid, GSK, ViiV Healthcare, AstraZeneca, Apeiron, Braun, Pfizer, Novartis, Lilly, Biontech…: Board Member|AbbVie, Gilead Sciences, Janssen-C,MSD, Cepheid, GSK, ViiV Healthcare, AstraZeneca, Apeiron, Braun, Pfizer, Novartis, Lilly, Biontech…: Grant/Research Support|CDS reports grants and personal fees from AbbVie, grants, fees and non-financial support from Gilead Sciences, grants and personal fees from Janssen-C: Advisor/Consultant|CDS reports grants and personal fees from AbbVie, grants, fees and non-financial support from Gilead Sciences, grants and personal fees from Janssen-C: Board Member|CDS reports grants and personal fees from AbbVie, grants, fees and non-financial support from Gilead Sciences, grants and personal fees from Janssen-C: Grant/Research Support

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.

Reliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008-2017.

Serum procalcitonin is often ordered at admission for patients with suspected sepsis and bloodstream infections (BSIs), although its performance characteristics in this setting remain contested. This study aimed to evaluate use patterns and performance characteristics of procalcitonin-on-admission in patients with suspected BSI, with or without sepsis. Retrospective cohort study. Cerner HealthFacts Database (2008-2017). Adult inpatients (≥ 18 yr) who had blood cultures and procalcitonin drawn within 24 hours of admission. None. Testing frequency of procalcitonin was determined. Sensitivity of procalcitonin-on-admission for detecting BSI due to different pathogens was calculated. Area under the receiver operating characteristic curve (AUC) was calculated to assess discrimination by procalcitonin-on-admission for BSI in patients with and without fever/hypothermia, ICU admission and sepsis defined by Centers for Disease Control and Prevention Adult Sepsis Event criteria. AUCs were compared using Wald test and p values were adjusted for multiple comparisons. At 65 procalcitonin-reporting hospitals, 74,958 of 739,130 patients (10.1%) who had admission blood cultures also had admission procalcitonin testing. Most patients (83%) who had admission day procalcitonin testing did not have a repeat procalcitonin test. Median procalcitonin varied considerably by pathogen, BSI source, and acute illness severity. At a greater than or equal to 0.5 ng/mL cutoff, sensitivity for BSI detection was 68.2% overall, ranging between 58.0% for enterococcal BSI without sepsis and 96.4% for pneumococcal sepsis. Procalcitonin-on-admission displayed moderate discrimination at best for overall BSI (AUC, 0.73; 95% CI, 0.72-0.73) and showed no additional utility in key subgroups. Empiric antibiotic use proportions were not different between blood culture sampled patients with a positive procalcitonin (39.7%) and negative procalcitonin (38.4%) at admission. At 65 study hospitals, procalcitonin-on-admission demonstrated poor sensitivity in ruling out BSI, moderate-to-poor discrimination for both bacteremic sepsis and occult BSI and did not appear to meaningfully alter empiric antibiotic usage. Diagnostic stewardship of procalcitonin-on-admission and risk assessment of admission procalcitonin-guided clinical decisions is warranted.

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.

2107. Epidemiology and Outcomes Associated with Enterococcal Blood Stream Infection among Abdominal Solid Organ Transplant Recipients

Abstract Background Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus is an important cause of nosocomial BSI, accounting for up to 20% of BSIs in this population, with Vancomycin-resistant enterococcus (VRE) posing a particular risk. This study aims to characterize the epidemiology and outcomes of enterococcal BSIs in abdominal SOTs. Methods A retrospective, single-center, case-control study of adult abdominal organ transplant (kidney transplant (KT), liver transplant (LT), simultaneous liver-kidney transplant (SLK), pancreas transplant, or simultaneous pancreas-kidney transplant) recipients between 01/01/2016 - 07/30/2021 was conducted at Beth Israel Deaconess Medical Center. Subjects were identified and reviewed using the Organ Transplant Tracking Record, their online medical record, and Vigilanz. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. Results We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.2%). Cases were mostly LT recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14 - 43). Controls included 8 LT recipients (29%), 14 KT recipients (50%), and 6 SLK recipients (21.4%). Groups differed significantly (all p&amp;lt; 0.05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Most cases (n = 16; 62%) and 11 controls (39%) had received antibiotics within the month prior to transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p &amp;lt; 0.0001) (Figure 1). There were no differences in 1-year mortality (Figure 2) between the groups. E. faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. The VRE rate was 80.8% among cases, 38.9% among all BSIs, and 4.0% among all transplants. Table 1:Demographic, Surgical, Hospitalization, and Antimicrobial Data. Baseline demographic and clinical characteristics of enterococcal BSI cases and non-enterococcal BSI controls are compared, along with transplant characteristics, transfusion requirements, surgical risk factors, hospitalization data, outcomes, and antibiotic exposures. Microbiological and resistance data are also presented. Enterococcal BSIs had lower odds of being a kidney transplant and having CKD or CKD on RRT; they had higher odds of being a liver transplant and having prior immunosuppression, steroid induction alone, reoperations, and macrolide exposure. Enterococcal BSIs had lower KDPIs, higher transfusion requirements, lower cold ischemia times, more procedures, and a shorter time to BSI (Chi-square and Fischer exact tests for categorical variables; Mann-Whitney tests for continuous variables). **Liver and simultaneous liver-kidney transplants; ***Kidney and simultaneous liver-kidney transplants; ****Reoperation within two weeks of primary closure; *****Biopsy proven acute antibody or cellular rejection within 6 months of transplant; ******ERCP stenting compared to IR stenting, among those with biliary complication. BSI – bloodstream infection; CKD – chronic kidney disease; HIV – human immunodeficiency virus; MELD – model of end stage liver disease; KDPI – kidney donor profile index; CMV – cytomegalovirus; pRBC – packed red blood cells; ERCP – endoscopic retrograde cholangiopancreatography; RRT – renal replacement therapy. Figure 1:Time to Bloodstream InfectionProbability of BSI-free survival illustrated, with enterococcal BSIs occurring significantly earlier than non-enterococcal BSIs post-transplantation (Kaplan-Meier survival analysis). BSI – bloodstream infection.Figure 2:MortalityProbability of survival, without significant difference between enterococcal and non-enterococcal BSIs. Data censored at one year of follow-up. BSI – bloodstream infection. Conclusion In our abdominal organ SOTs, enterococcal BSIs occurred early among LT recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period. Disclosures Carolyn D. Alonso, MD, Cidara Therapeutics: Advisor/Consultant|Merck: Advisor/Consultant.

1826. Comparative Use of Vancomycin versus Ampicillin for Blood Stream Infections Caused by Ampicillin-susceptible Enterococcus faecalis

Abstract Background Available studies assessing the efficacy of beta-lactam antibiotics compared to vancomycin (VAN) in the treatment of Enterococcal blood stream infections (BSI) have varying results and have not assessed the impact of rapid diagnostic testing. We aimed to compare clinical outcomes of ampicillin (AMP) vs. VAN for E. faecalis BSI treatment. Methods A multisite, retrospective evaluation of adults with E. faecalis BSI between 2017 to 2021 was performed. Patients who received at least four days of AMP or VAN as definitive therapy were analyzed; only initial episodes were included. All positive blood cultures underwent multiplex polymerase chain reaction blood culture identification (BCID). Patients with polymicrobial BSI were excluded, or if they received ≥ 50% concomitant use of AMP and VAN. The primary outcome was 30-day all-cause mortality. Secondary objectives included 90-day all-cause mortality, hospital length of stay, incidence of treatment failure, persistent BSI, change from initial definitive therapy, and adverse drug reactions (ADRs). Other microbiology endpoints included time to active treatment, BCID, beta-lactam coverage, definitive therapy, and culture clearance. A sample size of 208 patients was estimated to provide a 15% mortality difference with 80% power. Results In total, 123 patients with E. faecalis BSI were analyzed (AMP, n = 92; VAN, n = 31). Baseline characteristics were similar among both groups except gender and baseline penicillin allergy (p &amp;lt; 0.001) (Table 1). All-cause 30-day mortality was not significantly different between patients treated with AMP and VAN (10.8% vs. 22.6%, p = 0.130). No difference was found in secondary objectives except time to definitive therapy was longer for the AMP treatment arm (56.7 hours vs. 15.8 hours, p &amp;lt; 0.001) (Table 2). The incidence of ADRs were similar between the two groups (Table 3). Conclusion No difference in mortality was observed in the treatment with AMP or VAN for patients with E. faecalis BSI, but the study was not sufficiently powered. Despite the use of rapid BCID testing, earlier initiation of AMP was not observed. AMP or VAN may be reasonable options for treatment of E. faecalis BSI, but further research is warranted. Disclosures All Authors: No reported disclosures.

1521. Non-faecium Non-faecalis enterococcal bloodstream infections in patients with cancer

Abstract Background Non-E. faecium non-E. faecalis (NFF) enterococci are a heterogeneous group of organisms consisting of enterococci with intrinsic low-level vancomycin resistance as well as several other species known to infect humans. Patients with cancer are at increased risk for bloodstream infections (BSIs) with NFF enterococci, but their optimal treatment and outcomes have not been extensively described. Methods We conducted a retrospective review of patients (pts) with blood cultures positive for all NFF by searching the microbiology database at a major cancer center in Houston, TX from 2016 to 2021. Patients were included if they were ≥ 18 years old, had ≥ 1 blood culture with NFF enterococci, and had a repeat blood culture within 7 days (d) of the index culture, to permit outcome analysis. Outcomes were a) in-hospital mortality, b) microbiological failure (blood culture clearance &amp;gt;4 d after index culture), and c) recurrence of bacteremia (new positive blood culture &amp;lt; 14 d after eradication). Results Sixty-two unique pts had NFF enterococcal BSI. Patients with hematological malignancy made up 53.2% of the cohort (78% had leukemia). The majority (83%) of solid malignancies were pancreatic, biliary, or intestinal in origin. In the 30 d preceding NFF enterococcal BSI, 79% of pts had exposure to antibiotics. The NFF species isolated were E. gallinarum (50%), E. casseliflavus (30.6%), E. avium (11.3%), E. raffinosus (3.2%), E. hirae (3.2%), and E. durans (1.6%). Only 23.3% of NFF enterococci were susceptible to vancomycin, and 53.8% were susceptible to linezolid. Most (62.9%) pts received combination therapy; the most frequent was daptomycin plus a beta-lactam (33.9%). Bacteremia recurred in 8.1% of pts, 27.4% had in-hospital mortality, and 4.8% had microbiological failure. Conclusion This retrospective review provides preliminary insight into the treatments, and outcomes of cancer pts with NFF enterococcal BSIs. The NFF enterococci isolates in this study had a higher rate of linezolid non-susceptibility than previously reported. Molecular investigation of these NFF enterococcal isolates is needed to elucidate the mechanisms and transmission of antibiotic resistance. Comparison of BSIs caused by NFF enterococci to E. faecium/E. faecalis will provide insight to physicians caring for these pts. Disclosures Cesar A. Arias, MD, PhD, Entasis: Grant/Research Support|MeMed Diagnostics Ltd: Grant/Research Support|Merck: Grant/Research Support.

Implementing Alfred60AST in a clinical lab: Clinical impact on the management of septic patients and financial analysis

Sepsis is an important cause of morbidity and mortality. An accelerated microbiology diagnosis is crucial in order to reduce the time to initiate targeted antibiotic therapy. The Alfred60AST system is able to provide phenotypic Antimicrobial Susceptibility Testing (AST) results within hours. This study has two objectives: assess the clinical impact of this technology and determine its cost-effectiveness. During a ten-week period, all new enterobacterial or enterococcal bloodstream infection was analyzed with the Alfred60AST system, in parallel with routine methods. Its impact on the clinician's therapeutic strategy was studied. In order to assess the financial and practical aspects of the method, an analysis of the extracosts and a survey of the technical staff were conducted. Fifty-three cases of bacteriemia were included. For the Enterobacteriaceae bacteriemias, a clinical impact was shown in 18.9% of the cases (e.g, treatment modification). The financial analysis highlighted an increase in costs (+38% for Enterobacteriaceae, +50% for Enterococci), compared to the theoretical costs reported by the firm, due to the workflow and the volumes of samples used. Finally, results of the technical staff survey were favorable in terms of ease of use of the system. In addition to its ease of use, the Alfred60AST system is able to provide an AST in a record time. This study shows a real interest of the technique in the therapeutic management of patients with enterobacterial sepsis. However, its routine implementation requires an increase of the analyzed volumes as well as a 24/7 organization of the laboratory in order to be profitable.

Time to Effective Therapy Is an Important Determinant of Survival in Bloodstream Infections Caused by Vancomycin-Resistant Enterococcus spp.

Enterococcal bloodstream infections (EBSI) caused by vancomycin-resistant enterococci (VRE) are associated with a significant rate of unfavorable outcomes. No definitive data have been reported about the association between delayed antibiotic therapy and mortality. In this prospective observational study in three large hospitals in Italy (from August 2016 to April 2021), all consecutive hospitalized patients with a confirmed diagnosis of hospital-acquired monomicrobial BSI caused by VRE—with no evidence of endocarditis—were analyzed. Cox regression analysis showed that risk factors independently associated with 30-day mortality were age (HR 2.98, CI95% 1.44–6.81, p = 0.002), chronic kidney disease (HR 5.21, CI95% 1.48–22.23, p = 0.001), oncologic disease (HR 2.81, CI95% 1.45–19.8, p = 0.005), and intensive care unit admission (HR 3.71, CI95% 2.23–7.99, p < 0.001). Conversely, early effective therapy was associated with survival (HR 0.32, CI95% 0.38–0.76, p < 0.001). The administration of early effective antibiotic therapy within 48 h from blood culture collection was associated with 30-day mortality rates lower than 33%. Time from blood culture collection to appropriate therapy was an independent predictor of 30-day mortality in patients with EBSI caused by VRE. Based on these data, clinicians should start effective antibiotic therapy as soon as possible, preferably within the first 48 h from blood culture collection. Treatment strategies allowing the early delivery of in vitro active antibiotics are urgently needed, especially in critically ill patients at risk of VRE bacteremia.

Epidemiology, microbiological and clinical characteristics of Enterococcus species bloodstream infections: A 10-year retrospective cohort study from Qatar

Background and objectiveEnterococcus species is one of the leading causes of community and healthcare-associated infections resulting in significant morbidity and mortality. In this study, we aim to evaluate the epidemiology, microbiological and clinical characteristics of Enterococcus Blood Stream Infections (BSIs) over 10 years period in a national secondary care setting. MethodsA retrospective cohort study was conducted on verified cases of enterococcal BSIs in adults from January 2009–December 2018 from specialized care hospitals at Hamad Medical Corporation, Qatar. Epidemiological, microbiological and clinical data were reported and analyzed. ResultsA total of 263 enterococcus BSIs cases were identified, predominant were males (65%) with a median age of 63 (IQR 48–74). E. faecalis and E. faecium were predominate at 93.5% (73.38% and 20.15% respectively). Diabetes was the commonest premorbid condition (54.3%) followed by chronic kidney disease (36.5%). Central lines and genitourinary were the most common sources (18.25%, 14.83% respectively) while no identified source was reported in 45.25% of cases. Ampicillin susceptibility was 82.51% while vancomycin resistance was reported in 10.6% of isolates. Successful bacteremia clearance was achieved in 81.37% of cases at a mean of 4 days (Range 2–5 days) while metastatic complications occurred in 5.3% of cases. Univariate mortality risk analysis was associated with ICU admission, low level of consciousness, high bacteremia scores, and presence of catheters. The 30 days mortality was high at 66.54% with CKD and cancer patients at the highest mortality risks (OR 16.334 (CI 4.2–62.4) and 16 (CI 3–84) respectively. ConclusionSignificant mortality was associated with enterococcus BSI despite low rates for ampicillin and vancomycin resistance necessitating early identification of susceptible patients to instigate suitable preventive measures.

A Proof of Concept of the Usefulness of a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series of Patients with Enterococcal Bloodstream Infections and/or Endocarditis.

(1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fCss) was calculated according to a plasma protein binding of 20%. The fCss/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by >50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections.

Treatment duration for central line-associated infection caused by Enterococcus spp.: a retrospective evaluation of a multicenter cohort.

Objective of this study was to assess the appropriate treatment duration for enterococcal central line-associated bloodstream infections (CLABSIs). This observational, retrospective, multicenter study conducted between 2011 and 2019 enrolled all hospitalized patients with monomicrobial enterococcal CLABSI. Those with infective endocarditis and non-survivors at least 7days from index blood culture (BC)were excluded. Primary endpoint was 30-day mortality. We enrolled 113 patients, of whom 59% were male, median age was 64 (SD ± 15) and median Charlson's index score 5 (IQR 3-8). Enterococcus faecalis and Enterococcus faecium were found in 51% and 44% of cases, respectively. Median treatment duration was 11days (IQR 6-17), and 32% of patients (n = 36) received ≤ 7days. Characteristics of patients receiving more or less than 7days of treatment were similar. Central line was removed in 82% (n = 93) of cases within a median of 3days (1-8). At both uni- and multivariate analysis, duration of antibiotic treatment > 7days was not associated with 30-day mortality [HR 0.41 (95% CI, 0.13-1.24), p = 0.12] even after adjustment with propensity score [HR 0.47 (95% CI 0.17-1.26), p = 0.13]. A 7-day treatment course appears to be safe in non-complicated enterococcal CLABSIs.

Pediatric Enterococcal Bacteremia: A 12-Year Retrospective Study in a French Pediatric Center.

Enterococcal bloodstream infections (EBSIs) are rare infections in children associated with 5%-10% of mortality in previous studies. The recent evolution of antimicrobial resistance and therapies require updated data. We conducted an observational retrospective study between January 2008 and December 2019 describing the characteristics of children with EBSI in a French pediatric hospital. All positive Enterococcus spp. blood cultures associated with sepsis symptoms were analyzed. We also compared characteristics of healthcare-associated infections (HAIs) and community-acquired infections (CAIs) and described antimicrobial resistance evolution during this period. In total 74 EBSI were included. Enterococcus faecalis was the most common pathogen (n = 60/74, 81%) followed by Enterococcus faecium (n = 18, 24%), including 4 enterococcal coinfections. EBSIs were mainly associated with central-line associated infection (38%), surgical site infection (14%) or urinary tract infection (11%). An underlying disease was present in 95.9%. However, 4 patients died in the month following the EBSI resulting in a 5.4%, 30-day mortality. All were HAI. HAI (84% of EBSI) was associated with longer bacteremia [31% persistent bacteremia (more than 3 days) versus 0% for CAI; P = 0.029] and more antimicrobial resistance. Amoxicillin resistance is increasing since 2013 in E. faecium (63% in 2013-2019), although high-level gentamicin resistance is stable (19%). Only 1 EBSI due to vancomycin-resistant Enterococcus was described in our cohort, who died. EBSIs are rare infections in children mostly described in children with underlying disease. Healthcare-associated bacteremia is associated with higher rates of resistance and poorer prognosis, requiring the involvement of pediatric infectious disease specialists to improve management.

Daptomycin susceptibility testing and therapeutic use in enterococcal bloodstream infection (EBSI) in a setting with high rates of vancomycin-resistant Enterococcus faecium (VREfm).

There is in vitro and clinical evidence to suggest daptomycin has good activity against Enterococcus. In 2019, CLSI produced clinical breakpoints for Enterococcus spp. To describe the distribution of MICs of daptomycin for enterococcal bloodstream infection (EBSI) isolates in a large Scottish health board, the indications for local daptomycin susceptibility testing and daptomycin doses used in vancomycin-resistant Enterococcus faecium (VREfm) infection. We investigated all EBSIs over a 21 month period and identified isolates tested against daptomycin. We recorded the distribution of MICs, as well as indications for daptomycin susceptibility testing and information on daptomycin dosing, where it was used. There were 293 blood culture isolates of Enterococcus spp., of which 37 had daptomycin susceptibility testing performed, from 31 individual patients. Of the 293 isolates, 103 were E. faecium, of which 63 were VREfm. Daptomycin testing was indicated by vancomycin resistance in 24/37 isolates. All E. faecium isolates tested were in the CLSI 'susceptible dose-dependent (SDD)' range of MICs. All other Enterococcus spp. tested were in the 'susceptible' range. Twelve patients received daptomycin, and dosing information was recovered for 10. Nine of these patients received 8-12 mg/kg/day dosing. There were no recorded adverse drug reactions. Ten of 12 patients were alive at the time of data collection. Daptomycin MIC distribution for EBSI isolates suggests a high local rate of susceptibility, according to CLSI breakpoints, in a population with high rates of VREfm. CLSI-recommended doses of daptomycin were used, with encouraging survival outcomes.

Clinical and microbiological characteristics of bloodstream infections caused by Enterococcus spp. within internal medicine wards: a two-year single-centre experience.

Enterococcal bloodstream infections (E-BSI) constitute the second cause of Gram-positive bacterial BSI in Europe with a high rate of in-hospital mortality. Furthermore, E-BSI treatment is still challenging because of intrinsic and acquired antibiotic resistances. We conducted a retrospective, 2-year, observational, single-centre study to evaluate clinical outcome and risk factors for E-BSI mortality in internal medicine wards. 201patients with E-BSI were included in the analysis. Infection rate was 2.4/1000 days of hospital admission. Most E-BSI were hospital acquired (78.1%). The median age was 68 years. Charlson Comorbidity Index, adjusted for age, was 5 (range 4–6). Patients with E-BSI frequently had at least one invasive device, predominantly a central venous (73%) or a bladder catheter (61.7%). Enterococcus faecium accounted for 47.94% of E-BSI (resistance rate to ampicillin or vancomycin was 22.2 and 23.3%, respectively) and Enterococcus faecalis for 52.08% (resistance rate to ampicillin or vancomycin was 3.1 and 2.2%, respectively). Among all E-BSI, 25% of patients received appropriate therapy. In total, 59% of E-BSI underwent echocardiography. At the multivariate analysis, resistance to vancomycin (OR 2.09, p = 0.025), sepsis (OR 2.57, p = 0.003) and septic shock (OR 3.82, p = 0.004) was a predictor of mortality. No difference in 28-day survival was observed between appropriate or inappropriate treatment, except for endocarditis. However, E-BSI sources in clinical practices are not always properly investigated, including the rule-out of intracardiac vegetations. We did not demonstrate a difference in mortality for inappropriate therapy in the absence of endocarditis in comorbid patients with a long history of medicalization.