This study identified Enterococcus faecium as a gut bacterium with anti-obesity activity, which alleviated adipocyte hypertrophy, dyslipidemia, and hepatic steatosis by converting leucine into leucic...

AbstractEnterococcal bacteremia and endovascular infections remain difficult to treat because of intrinsic antimicrobial tolerance, increasing resistance, and frequent involvement of high-inoculum or deep-seated infection. While β-lactams generally demonstrate limited bacterial killing activity against enterococci when used alone, accumulating experimental and clinical data suggest that selected β-lactams may enhance the activity of companion agents, particularly daptomycin. This narrative review summarizes the mechanistic rationale, preclinical evidence, and available clinical data supporting adjunctive β-lactams for enterococcal bacteremia and endovascular infections. The strongest clinical evidence supports ampicillin plus ceftriaxone for Enterococcus faecalis infective endocarditis, whereas emerging data suggest that selected β-lactams may potentiate high-dose daptomycin against vancomycin-resistant Enterococcus faecium. Proposed mechanisms include complementary penicillin-binding protein inhibition, alterations in cell envelope physiology, increased antimicrobial binding, and suppression of resistance emergence. However, available clinical data are derived largely from retrospective studies and remain heterogenous with respect to patient populations, infectious syndromes, β-lactam selection, dosing strategies, and treatment duration. Current evidence favors a phenotype-directed approach rather than routine combination therapy for all enterococcal bloodstream infections. Adjunctive β-lactams appear most justifiable in patients with persistent bacteremia, endovascular infection, high-inoculum disease, elevated daptomycin minimum inhibitory concentrations, prosthetic material, or other features associated with microbiologic failure or relapse, whereas uncomplicated bacteremia may derive limited benefit. Important questions remain regarding optimal patient selection, β-lactam choice, and duration of therapy. Given the practical and financial barriers to conducting randomized trials in this population, mechanistic, translational, and observational studies will likely remain the foundation of real-world clinical decision-making.

Enterococcal bacteremia and endovascular infections remain difficult to treat because of intrinsic antimicrobial tolerance, increasing resistance, and frequent ...

An increasing proportion of the population receives immunosuppressive treatment. There is a lack of guidelines for bloodstream infections (BSIs) in this group. This study aims to provide a comprehensive analysis of the etiology and outcomes in BSI associated with underlying immunosuppression.MethodsThis population-based laboratory surveillance study included all positive blood cultures in southern Sweden, from 2013 through 2023. Immunosuppression was defined using diagnostic codes, medications, and laboratory data. We defined 6 categories of immunosuppression: antineoplastic treatment, neutropenia, immunosuppressant medication, organ transplants, primary immunodeficiency, and human immunodeficiency virus infection.ResultsIn total, 8058 of 47 552 (16.9%) BSI episodes were associated with underlying immunosuppression. This proportion increased over time (rate ratio, 1.019 per year [95% confidence interval {CI}, 1.012–1.027], P < .001). Immunosuppression was associated with a higher degree of Enterococcus faecium (odds ratio [OR], 3.16 [95% CI, 2.63–3.78]) and Pseudomonas spp (OR, 2.51 [95% CI, 2.16–2.91]) etiology. Intrinsic cephalosporin resistance was more frequent in BSI episodes with underlying immunosuppression (OR, 1.45 [95% CI, 1.36–1.55]). The 30-day mortality rate was higher in BSI episodes with underlying immunosuppression, at 17.9% (1439/8044), compared to 12.5% (4880/39 089) in episodes without immunosuppression (OR, 1.54 [95% CI, 1.45–1.64]).ConclusionsThis study provides an updated summary of etiology and outcomes in BSI associated with immunosuppression. Underlying immunosuppression is increasingly prevalent among patients with BSI and is associated with resistance to cephalosporins and increased short-term mortality. Clinical guidelines for the management of BSI in immunosuppressed patients are warranted.

Vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infection (BSI) represents a growing challenge in hematology-oncology settings. This study aimed to characterize the epidemiology, risk factors, and prognostic impact of VREfm BSI within a mixed adult hematology-oncology and transplant unit.MethodsWe conducted a retrospective matched case-control study (2014–2024). Multivariable conditional logistic regression identified factors associated with VREfm BSI, and restricted cubic spline (RCS) models assessed nonlinear exposure-response relationships between antimicrobial classes and VREfm BSI. Survival was analyzed using Kaplan–Meier curves and Cox proportional hazards regression.ResultsVREfm BSI incidence rose from 0.02 to 0.07 per 1000 person-days (2014–2018 vs 2019–2024). A high-risk composite comprising recipients of allogeneic stem cell transplant and/or AML (adjusted OR [aOR], 3.90; 95% CI, 1.87–8.15; P < .001) and ICU admission (aOR, 5.63; 95% CI, 2.15–14.78; P < .001), were independently associated with VREfm BSI. Cumulative days of carbapenems (aOR, 1.09/day; 95% CI, 1.02–1.17; P = .013), beta-lactam/beta-lactamase inhibitors (aOR, 1.09/day; 95% CI, 1.02–1.16; P = .006), and systemic antifungals (aOR, 1.12/day; 95% CI, 1.03–1.22; P = .009) exhibited duration-dependent associations. RCS models demonstrated a nonlinear, duration-dependent association with cumulative antibiotic exposure, including antianaerobic agents (P < .001). VREfm BSI was associated with increased mortality (adjusted hazard ratio, 2.09; 95% CI, 1.63–2.66; P < .001).ConclusionsVREfm BSI reflects the interplay between host susceptibility and nonlinear, duration- and spectrum-dependent antibiotic exposure pressure. This underscores the importance of antimicrobial stewardship strategies as a potential intervention to mitigate risk.

A landmark meta-analysis of nearly 700 studies reveals that vancomycin-resistant E. faecium now infects roughly one in three isolates worldwide, with environmental reservoirs playing a critical role