Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted a retrospective cohort study (2014–2021) including all hospitalized adult patients with at least one blood culture positive for Enterococcus faecalis or Enterococcus faecium. We included 584 patients with enterococcal BSI: 93 were attributed to vancomycin-resistant E. faecium. The overall 30-day mortality was 27.5%; higher in cases of BSI due to vancomycin-resistant E. faecium (36.6%) and vancomycin-sensitive E. faecium (31.8%) compared to E. faecalis BSIs (23.2%) (p = 0.016). This result was confirmed by multivariable Cox analysis. Independent predictors of increased mortality included the PITT score, complicated bacteremia, and age (HR = 1.269, p < 0.001; HR = 1.818, p < 0.001; HR = 1.022, p = 0.005, respectively). Conversely, male gender, consultation with infectious disease (ID) specialists, and appropriate treatment were associated with reduced mortality (HR = 0.666, p = 0.014; HR = 0.504, p < 0.001; HR = 0.682, p = 0.026, respectively). In conclusion, vancomycin-resistant E. faecium bacteremia is independently associated with a higher risk of 30-day mortality.

This study explores the impact of antiretroviral administration on the expression of human endogenous retroviruses (HERVs), cell growth, and invasive capability of human melanoma cell lines in culture. We investigated three antiretrovirals—lamivudine, doravirine, and cabotegravir—in A375, FO-1, and SK-Mel-28, BRAF-mutated, and in MeWo, P53-mutated, melanoma cell lines. The findings indicate a general capability of these drugs to downregulate the expression of HERV-K Pol and Env genes and hinder cell viability, mobility, and colony formation capacity of melanoma cells. The antiretroviral drugs also demonstrate selectivity against malignant cells, sparing normal human epithelial melanocytes. The study reveals that the integrase inhibitor cabotegravir is particularly effective in inhibiting cell growth and invasion across different cell lines in comparison with lamivudine and doravirine, which are inhibitors of the viral reverse transcriptase enzyme. The investigation further delves into the molecular mechanisms underlying the observed effects, highlighting the potential induction of ferroptosis, apoptosis, and alterations in cell cycle regulatory proteins. Our findings showed cytostatic effects principally revealed in A375, and SK-Mel-28 cell lines through a downregulation of retinoblastoma protein phosphorylation and/or cyclin D1 expression. Signs of ferroptosis were detected in both A375 cells and FO-1 cells by a decrease in glutathione peroxidase 4 and ferritin expression, as well as by an increase in transferrin protein levels. Apoptosis was also detected in FO-1 and SK-Mel-28, but only with cabotegravir treatment. Moreover, we explored the expression and activity of the stimulator of interferon genes (STING) protein and its correlation with programmed death-ligand 1 (PD-L1) expression. Both the STING activity and PD-L1 expression were decreased, suggesting that the antiretroviral treatments may counteract the detrimental effects of PD-L1 expression activation through the STING/interferon pathway triggered by HERV-K. Finally, this study underscores the potential therapeutic significance of cabotegravir in melanoma treatment. The findings also raise the prospect of using antiretroviral drugs to downregulate PD-L1 expression, potentially enhancing the therapeutic responses of immune checkpoint inhibitors.

Purpose: To evaluate clinical outcomes, safety, patient-reported satisfaction, and cost-effectiveness of elastomeric pump-based Outpatient Parenteral Antimicrobial Therapy (OPAT) over six years at an Italian tertiary center. Methods: This retrospective single-center study included 76 adult patients treated with continuous-infusion OPAT via elastomeric pumps between 2019 and 2024 at the University Hospital of Trieste, Italy. Results: A total of 1,934 elastomeric pump-based OPAT days were delivered (median duration of 22.9 days). Clinical cure was achieved in 85.5% of patients; recurrence and failure occurred in 6.2% and 7.9%, respectively. Most frequent indications were skin/soft tissue and surgical site infections (25.9%), complicated urinary tract infections (22.4%), and bone/joint infections (16.4%). Pathogens were mainly Gram-negative (70.7%), including Enterobacterales (40.2%, 57.6% ESBL-producing), Pseudomonas aeruginosa (26.8%), and Staphylococcus aureus (17.1%, 28.6% methicillin-resistant S. aureus ). The most used antibiotics were piperacillin/tazobactam (51.3%), cefepime (12.5%) and ceftolozane/tazobactam (7.5%). Adverse events were observed in 13.75% of treatments, primarily vascular access-related (5.7 events/1,000 OPAT-days); drug-related adverse events occurred in 7.8% of patients (3.1 events/1,000 OPAT-days). Among contacted patients (75% response rate), 83.7% expressed willingness to reuse the pump. Total OPAT costs were €62,190.64 compared to an estimated €773,600.00 for inpatient care, yielding a 92% cost reduction (€711,409 saved). Conclusion: Elastomeric pump-based OPAT is a clinically effective, well-tolerated, and economically advantageous option for selected infections. Its integration into stewardship programs supports broader implementation within modern, sustainable infectious disease care models.

Tuberculosis is recognized as a great imitator and certain atypical presentations may be misdiagnosed as other diseases. Only a limited number of cases of isolated anterior mediastinal tuberculosis have been documented in the literature, particularly among immunocompetent patients.