Dalbavancin represents a promising treatment for cardiovascular prosthetic infections due to its prolonged half-life, bactericidal activity, large spectrum of activity, and excellent biofilm penetration. However, the use of dalbavancin in this setting is limited, and only a few cases have performed therapeutic drug monitoring (TDM) analysis to optimize dosage in suppressive treatments longer than 4 weeks. Our retrospective case series reports the use of dalbavancin in a small cohort of patients with cardiovascular prosthetic infections (cardiac implantable electronic device infections (CEDIs), prosthetic valve endocarditis (PVE), prosthetic vascular graft infections (PVGIs)) treated with dalbavancin as sequential therapy. From May 2019 to May 2023, 14 patients were included: eight cases of PVE (57.1%), seven cases of PVGI (50%), three cases of CEDI (21.4%), and four cases with overlap of infection sites (28.6%). The main pathogen was Staphylococcus aureus (35.7%). Prosthesis replacement was obtained in four patients (28.6%). The median time between symptom onset and the end of treatment was 15 weeks (IQR 7–53), with a median duration of dalbavancin therapy of 8 weeks (IQR 1 to 45 weeks) and 3.5 doses per patient. Among patients managed with TDM-guided strategy, dalbavancin infusion intervals ranged from 4 to 9 weeks. The median length of follow-up was 65 weeks (IQR 23 to 144 weeks). Clinical success was achieved in 10 cases (76.9%); all clinical failures occurred in patients with the implant retained. Among patients monitored by TDM, clinical success was 87.5% vs. 60% in patients treated without TDM. Because of pharmacokinetic individual variability, dalbavancin TDM-guided administration could improve clinical outcomes by individualizing dosing and selecting dosing intervals. This case series seems to suggest a promising role of long-term suppressive dalbavancin treatment for difficult-to-treat cardiovascular prosthesis infection, also with limited surgical indications.

Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors.

Background: Conflicting results exist about mortality risk of infections caused by vancomycin-susceptible Enterococcus faecium (VSEfm) and vancomycin-resistant Enterococcus faecium (VREfm). Our aim was to compare risk factors and clinical outcomes among patients with VSEfm and VREfm bloodstream infections (BSIs). Methods: A retrospective, multicentre, cohort study enrolled consecutive adult patients with VSEfm and VREfm BSI diagnosis between 2018–2022. Primary outcomes were 30-day-attributable and 30-day-overall mortality. Multivariable analysis propensity-weighted adjusted for timing to active therapy, Pitt Bacteremia Score (PBS) and Charlson Comorbidity Index (CCI) were performed to identify variables independently associated with 30-day mortality. Results: Overall, 446 patients were enrolled: 140 (31.4%) VREfm and 306 (68.6%) VSEfm. Comparatively, VREfm patients more frequently received inappropriate antibiotic therapy, had higher sequential organ failure assessment, PBS and BSI relapses. 30-day-attributable and 30-day-overall mortality did not differ significantly between the two groups. Independent risk factors for 30-day attributable mortality were age (HR 1.04, CI95%, 1.00–1.08, P = 0.022), corticosteroid therapy (HR 3.05, CI95%, 1.24–7.47, P = 0.014) and septic shock (HR 9.10, CI95%, 3.80–21.79, P≤0.001), and overall mortality were age (HR 1.04, CI95%, 1.02–1.05, P≤0.001.), chronic liver failure (HR 1.67, CI95%, 1.02–2.75, P = 0.04) and haematological disease (HR 2.25, CI95%, 1.28–3.94, P = 0.005). Vancomycin resistance is not an independent risk factor for mortality when data are adjusted for confounding factors. Conclusions: Adjusted analyses for time to active antibiotic therapy suggest that vancomycin resistance is not an independent risk factor for overall or attributable mortality among patients with Enterococcus faecium BSI. Independent risk factors identified in this study were exclusively comorbidities, severity and corticosteroids use.

Background: Our aim was to compare epidemiological, clinical and treatment characteristics, and outcomes between patients with diagnoses of coronavirus disease 2019–associated pulmonary aspergillosis (CAPA) or putative invasive pulmonary aspergillosis (PIPA), without hematological cancers. Methods: Retrospective, monocentric comparative observational cohort study, including nonhematological patients treated for invasive pulmonary aspergillosis between 2018 and 2022. Primary study end points were risk factors for 30-day mortality and clinical failure. To account for the imbalance in antifungal treatment allocation, a propensity score weighting approach was adopted. Results: A total of 209 patients were included, 93 (44.5%) with CAPA and 116 (55.5%) with PIPA; 144 (68.9%) we admitted to the intensive care unit. Patients with PIPA had higher Charlson Comorbidity Index values (mean [SD], 5.8 [2.6]; range, 0–14) and higher prevalences of chronic obstructive pulmonary disease (30.7%), solid cancer (36.8%), liver cirrhosis (12.3%), and concomitant immunosuppressive therapies (26.1%). Patients with CAPA received more invasive mechanical ventilation (70.5%) and corticosteroids (90.1%), more frequently had positive galactomannan (GM) results with bronchoalveolar lavage (80.5%), and had longer mean hospital stays (62.7 [SD, 52.1; range, 8–276] days) and intensive care unit stays (36 [30.7; 2–168] days). No differences in clinical cure or mortality rates were observed between groups. In multivariable analysis, isavuconazole was the only independent factor for clinical cure, reported also in the propensity score matching analysis (odds ratio, 0.41 [95% confidence interval, .16–1.03]; P = .06). A positive serum GM result was independently associated with 30-day mortality (hazard ratio, 1.78 [95% confidence interval, 1.02–3.10]; P = .04). Conclusions: Patients with CAPA have fewer comorbid conditions and higher fungal burden than those with PIPA, but clinical outcomes are similar between groups. Isavuconazole was an independent predictor for clinical cure, and serum GM positivity an independent predictor for 30-day mortality.

Objectives: To assess whether an electronic Clinical Decision Support System (eCDSS), embedded within a hospital-wide antimicrobial stewardship (AMS) programme, can meaningfully reduce antimicrobial use and improve prescribing quality in routine clinical practice. Methods: We conducted a prospective quasi-experimental interrupted time-series study in a 1200-bed tertiary-care hospital in Italy (April 2022–April 2024). The eCDSS, integrated into computerized order entry and linked to pharmacy data, triggered real-time identification of high-impact antimicrobial prescriptions and enabled infectious diseases (IDs)-led prospective audit and feedback. Primary outcomes were overall antibiotic use and carbapenem consumption; secondary outcomes included guideline adherence, stewardship intensity, antimicrobial duration and costs. Results: Across 5890 prescriptions in 2604 patients (9336 ID evaluations), the intervention was associated with a significant and sustained reduction in overall antibiotic consumption (CL: −3.27 DDD/100 patient-days, 95% CI −6.06 to −0.47; CT: −0.25 DDD/100 patient-days/month, 95% CI −0.44 to −0.07). Carbapenem use showed a parallel significant decline across both DDD and DOT metrics. In contrast, no significant reductions were observed for other monitored antibiotics or antifungals. Prescribing quality improved over time, with increasing adherence to local guidelines (CT: +1.59%/month; P = 0.001). Despite high-intensity stewardship activity (mean 1.6 ID interventions per prescription), antimicrobial expenditures remained stable, although a downward trend was observed. Conclusions: An eCDSS integrated into a human-led AMS programme was associated with a significant reduction in overall antibiotic and carbapenem use and improved prescribing quality. These findings demonstrate that digital stewardship tools do not replace but amplify ID expertise and pharmacy collaboration, enabling sustained optimization of antimicrobial use.

Usutu virus (USUV) is a neurotropic flavivirus, phylogenetically related to West Nile virus (WNV), maintained in the environment through a bird‐to‐mosquito transmission cycle, with humans and other animals occasionally becoming infected. In recent years, different cases of human infections have been reported concomitantly with increased viral circulation in several European countries. Most USUV infections in humans remain asymptomatic; however, neuroinvasive disease has been reported, mainly in the elderly and the immunocompromised but also in healthy individuals. Herein, we report a case of severe USUV meningoencephalitis in an elderly patient treated with a short course of dexamethasone and discuss the potential role of steroids in light of the most recent literature on the pathogenetic mechanisms of arboviral encephalitis.