Daniela Francisci

New beta-lactam/beta-lactamase inhibitor combinations (BL/BLICs) are licensed for Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. However, data regarding their efficacy against bacterial biofilms and the potential of synergistic combinations remain limited. This study evaluated their efficacy on planktonic and biofilm forms of KPC-Kp isolated from catheter-related bloodstream infections (CRBSIs), correlating findings with genomic and clinical data. Twelve KPC-3-harboring isolates (ST512, n = 7; ST307, n = 3; ST101, n = 2) were characterized via whole-genome sequencing. Ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MEM/VAB), and imipenem/relebactam (IMI/REL) were tested alone or combined with fosfomycin (FOS), cefepime (FEP), meropenem (MEM), or imipenem (IMI) using checkerboard assays. All BL/BLICs alone showed significant, comparable efficacy against biofilm-producing strains. However, combination testing revealed heterogeneous synergistic profiles. CAZ/AVI combined with MEM, IMI, or FEP achieved 100% synergy in both planktonic and biofilm states. MEM/VAB-based combinations demonstrated consistent synergy (50–100%), whereas IMI/REL showed higher synergistic rates in biofilm than in planktonic forms. Conversely, FOS-based regimens were significantly less effective against biofilms. These findings provide a clinical rationale for selecting optimized dual regimens to eradicate biofilms, offering a critical therapeutic strategy to preserve vascular devices when catheter removal is unfeasible.

Objective: Assessment of real-life effectiveness of an intervention for smoking cessation in people living with HIV (PLWH) in long-term follow-up. Setting: Multicenter cohort prospective study, involving PLWH from Italian Infectious Disease Centers. Methods: During routine HIV care, clinicians usually promote smoking cessation implementing the European AIDS Clinical Society guidelines. We analyzed smoking cessation for 9 years of follow-up. The brief counseling intervention was defined “standard” when delivered in at least half follow-up visits, “soft” if less than half. We excluded from the analysis 85 patients lost at follow-up. The main outcome was definitive smoking interruption at the last follow-up visit (smoking abstinence for >6 months and no recurrence). Abstinence predictors were evaluated using a Cox-proportional hazard regression model [adjusted hazard ratio (aHR), and 95% confidence interval (CI)]. Results: Out of 1002 PLWH with prolonged follow-up, 510 were current smokers at baseline (median observation time was 7.4 years, interquartile range 6.9–8.0). The standard intervention was performed in 340 smokers (66.7%) and soft intervention in the remaining 170 (33.3%). At the last visit, 66 (12.9%) PLWH achieved self-reported definitive smoking cessation, 59 (17.4%) in standard and 7 (4.1%) in soft intervention. At the multivariate analysis, Fagerström score (by −1, aHR 1.16, 95% CI: 1.05 to 1.29), stage of change (preparation/action aHR 3.33, 95% CI: 1.81 to 6.12), and standard intervention (aHR 2.45, 95% CI: 1.08 to 5.58) were predictors of smoking cessation. Conclusions: The brief intervention led to self-reported definite smoking cessation in 12.9% of PLWH. The standard intervention was more effective: thus, adherence to intervention emerged as a critical factor for the effectiveness.

Infective endocarditis (IE) due to methicillin-susceptible Staphylococcus aureus (MSSA) still represents a clinical and therapeutic issue. Discrepancies between guidelines, clinical studies and clinical practice have already been highlighted, especially regarding daptomycin use in MSSA cases. The aim of this study was to evaluate daptomycin’s impact on outcomes in this setting. This was a retrospective observational study. We enrolled all patients with MSSA IE admitted from 2015 to 2023. Patients were divided into two groups according to daptomycin administration. We enrolled 76 patients, with 49 in group A (standard treatment) and 27 in group B (treated with daptomycin). The in-hospital crude mortality was 14.3% and 29.6% in group A and B, respectively (p = 0.191). Only heart failure was significantly associated with negative outcome in the univariate and multivariate analyses (OR 6.424, 95% CI, 1.680–24.559; p = 0.007). In this study population, daptomycin treatment for IE due to MSSA was not associated with a reduced mortality rate. Heart failure was the only independent risk factor associated with in-hospital mortality.

Introduction: Mpox virus (MpoxV), an emerging zoonotic pathogen, has recently caused global concern due to increasing outbreaks beyond its traditional endemic regions. While transmission primarily occurs via close contact, fomites are also suspected of contributing. This study aims to evaluate the effectiveness of UV-C irradiation on MpoxV-contaminated surfaces. Methods: the virucidal activity of UV-C (254 nm) irradiation on MpoxV applied to plastic, glass, and stainless-steel surfaces was assessed. Using a viral stock of 2.49 × 10⁵ TCID₅₀/mL, the samples were exposed to increasing UV-C doses. Viral titers were quantified through TCID₅₀ and plaque assays. Results: A UV-C dose of 6.34 mJ/cm² achieved a >2-log reduction of viral load, below the detection limit (31.6 TCID50/mL), on all tested surfaces. EC₉₀ values were determined as 3.33 mJ/cm² (plastic), 0.81 mJ/cm² (stainless steel), and 1.98 mJ/cm² (glass). No viable virus was detectable post-treatment at these doses on plastic and stainless steel while the titer was significantly reduced on glass. Conclusions: UV-C irradiation at low doses effectively inactivated MpoxV on various fomites. These findings support UV-C as a rapid and effective environmental disinfection strategy in healthcare and community settings to prevent indirect transmission of MpoxV.

Background: Intra-abdominal infection (IAI) is a challenging condition that needs both medical and surgical treatment and it is still associated with high morbidity and mortality rates. Fosfomycin is approved for use in combination therapy for IAIs. The aim of this study was to evaluate the impact of intravenous fosfomycin addition in a combination regimen for IAI treatment in an intensive care setting. Methods: We performed a retrospective, observational, monocentric study. We enrolled patients admitted to the ICU with IAIs from April 2022 to June 2024. Patients were divided into two groups: Group A, standard treatment; and Group B, combination therapy including fosfomycin. Primary endpoints were clinical response at 7 days and in-hospital mortality; moreover, a risk factor analysis for mortality was also performed. Results: In total, 104 patients were enrolled, 85 in Group A, and 19 in Group B. Groups were homogenous in regard to demographics, but clinical condition was slightly worst in Group B. Source control < 24 h was performed in 69.6% and 33.3% cases in Group A and Group B, respectively (p = 0.017). Clinical response on day 7 (81.2% vs. 73.7%, p = 0.675) and in-hospital mortality (27.1% vs. 47.2%, p = 0.145) were comparable. Univariate and multivariate analysis highlighted Charlson Comorbidity Index (CCI) (p = 0.04) and septic shock (p = 0.029) as risk factors, and effective empirical therapy (p = 0.04) as the protective factor; fosfomycin was not directly associated with outcome improvement. Conclusions: The outcome was comparable between groups; clinicians preferred to administer a combination regimen including fosfomycin in patients with statistically significant greater severity of illness and without early source control.

Background: The 2023 European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE) highlighted the essential role of multimodal imaging in the diagnostic algorithm of IE and its complications. Methods: We hereby report a case series of IE in which the diagnosis was confirmed or excluded by the use of multimodal imaging during the period between January 2024 and July 2024 at the Infectious Diseases Clinic, Perugia Hospital, Italy. Results: Six patients were retrospectively included. Prosthetic valve endocarditis (PVE) was suspected in four patients and native valve endocarditis (NVE) in two cases. In patients with prosthetic valves, 18F FDG-PET/CT was performed, except in one case (P1) where cardiac CTA was performed for suspicion of perigraft aneurysm. Patients underwent transesophageal echocardiography (TOE), which was diagnostic in two cases and inconclusive in the remaining cases. In case of inconclusive TOE, the use of multimodal imaging added a major criterion and allowed us to consider (from ‘rejected’ to ‘possible’) or confirm (from ‘possible’ to ‘definite’) the diagnosis of EI based on the 2023 Duke–ESC Criteria. In one case (P6), it was possible to exclude the diagnosis. For patients with diagnostic TOE, 18F FDG-PET/CT allowed for the enhancement of diagnostic accuracy, identifying the site of valve involvement and the extension of the infection to the device (cases P3 and P5, respectively). Conclusions: In clinical practice, the use of cardiac CTA and/or 18F FDG-PET/CT based on the latest ESC guidelines demonstrated a significant impact on the diagnosis and therapeutic management of IE.

Background. Urinary tract infections (UTIs) and asymptomatic bacteriurias (ABU) represent a large field of interest for antimicrobial stewardship programmes especially after 2020 EUCAST update in antimicrobial susceptibility testing interpretation and the possible related increase in carbapenems’ prescription rate. The aim of this study was to evaluate the impact of the 2020 EUCAST update on antibiotic prescription in UTI due to Pseudomonas aeruginosa organism and their characteristics. Methods. A retrospective observational study. We enrolled all the patients with P. aeruginosa isolation from urine, admitted to our hospital from 2018 to 2021. We compared demographic, clinical, and microbiological characteristics and treatment between cases before 2020 EUCAST update (period A, 2018–2019) and after it (period B, 2020–2021). Results. A total of 643 cases was analysed, 278 in period A and 365 in period B; 65% were ABU. Carbapenems’ prescription rate significantly increased in period B when considering ABU alone (21.4% vs. 41%, p = 0.016) and all the treated cases (treated ABU and UTI; 27.8% vs. 41.4%, p = 0.013); anti-Pseudomonas cephalosporins prescription significantly decreased in period B when considering ABU alone (15.7% vs. 3.6%, p = 0.021), UTI alone (20.7% vs. 5.9%, p = 0.009) and all the treated cases (18.5% vs. 5.9%, p = 0.001). Conclusions. The 2020 EUCAST update could have contributed to an increase in carbapenem prescriptions. UTI and ABU represent a large field of interest for stewardship interventions both from a diagnostic and therapeutic point of view.

Background. Pseudomonas aeruginosa is one of the major concerns among bacterial diseases even when it shows a wild-type susceptibility pattern. In 2020, EUCAST reconsidered antibiogram interpretation shifting “I” from “intermediate” to “sensible, increased exposure” with possible significant impact on antibiotic prescription. The aim of this study was to evaluate mortality in patients with P. aeruginosa bloodstream infections treated with antipseudomonal penicillins or cephalosporins vs. carbapenems and ceftazidime/avibactam. Methods. This is a retrospective observational study. All the patients with a bloodstream infection due to P. aeruginosa admitted to our hospital were enrolled. Exclusion criteria were as follows: extremely critical conditions, age 0.1). In group A, in-hospital BSI-related mortality was 23.2% (13/56), while it was 14.3% (3/21) in group B (p > 0.1). After multivariate analysis, only the PITT score represented a risk factor for BSI-related mortality (OR 2.917, 95% CI 1.381–6.163). Conclusions. Both all-cause and BSI-related mortality were comparable between the two groups. Treatment with carbapenem or ceftazidime/avibactam did not represent a protective factor for mortality in wild-type P. aeruginosa BSI.

Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.

Purpose: Daptomycin-induced eosinophilic pneumonia (DIEP) is a rare yet severe adverse event that requires rapid recognition and management. Diagnosing a definite case is challenging and involves meeting the American Thoracic Society (ATS) criteria, although alternative criteria have been suggested. This study aims to conduct a systematic review of literature and includes a case series. Methods: Six cases of DIEP identified at Perugia Hospital, Perugia, Italy have been described. A systematic review was carried out adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement guidelines. Results: a total of 74 cases of DIEP were analysed. Using ATS clinical criteria, 15 were classified as definite (20.3%), 54 as probable (73.0%), and 5 as possible (6.8%). Phillips criteria and the Lyon Algorithm identified 43/74 (58.2%) and 64/67 (95.5%) cases as definite, respectively. Bronchoalveolar lavage (BAL) was performed in 43 cases, revealing an average eosinophil count of 28.6% (SD 24.4). Radiological findings highlighted recurring features like bilateral opacities (68.1%), ground-glass opacities (41.7%), patchy infiltrates (30.6%), and peripheral predominance (19.4%). Upon suspicion, daptomycin was discontinued; 20 cases required no additional treatment, 38 received corticosteroids, and 12 received both corticosteroids and antibiotics. Recovery rates were high across all treatment types (≥ 73.7%). Most reports described rapid improvement post-withdrawal (within 96 h). Conclusions: DIEP is a rare, fast-progressing condition where early diagnosis and prompt treatment are vital. Diagnosis relies on clinical, laboratory, and radiological evaluations. Stopping daptomycin is essential, with corticosteroids often necessary. Further research is needed to enhance diagnostic accuracy for this disease.