Background: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics. Methods: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020–July 2020) and 2nd (August 2020–January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected. Results: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students (p < 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%. Conclusions: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Introduction: The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics. Case Presentation: We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime. Discussion: IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a wide range of clinical manifestations modulated by genetic factors. The aim of this study was to identify genetic determinants of severe COVID-19 affecting protein sequence to gain insight into disease pathogenesis. Variants prioritized in two patients requiring lung transplant were tested in the Milan FOGS cohort (487/869 cases/controls), highlighting an independent association between the p.F8S low-frequency variant of interferon alpha receptor 2 gene (IFNAR2) and severe disease (OR = 1.73 [1.24–2.42], p = 0.001), replicated in the COVID-19 Host Genetics Initiative cohort (26,167/2,061,934 cases/controls). In the FOGS cohort, the p.F8S variant was linked to higher circulating IL-6 levels. In keeping, bulk transcriptomic analysis in PBMCs at the peak of infection (n = 57) showed that carriers of the p.F8S variant had upregulation of immune signaling and pathogens response (p < 0.05). Functional flow cytometry experiments in healthy donors (n = 12) revealed that membrane IFNAR2 protein expression was reduced in B lymphocytes, but higher in dendritic cells (p < 0.05). Finally, by interrogating a public scRNAseq resource of PBMC of people with COVID-19, we showed that p.F8S carriers had upregulation of immune pathways specifically in dendritic cells (p < 0.05). These results suggest that the p.F8S variant may influence COVID-19 severity by enhancing adaptive immune response, thereby favoring inflammation.

Background/Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa pneumonia and bloodstream infections (BSI) remain challenging because of their severity, limited therapeutic options, and high mortality, despite the availability of novel β-lactam-based agents. We aimed to describe real-world treatment patterns, characteristics associated with treatment and infusion-strategy selection, and the association of these strategies with clinical outcomes in the retrospective, multicentre Italian SUSANA cohort, an observational study evaluating the use, safety, and outcomes of novel antibiotics in hospitalized patients. Methods: Adults with MDR P. aeruginosa pneumonia and/or BSI treated with novel antipseudomonal agents for ≥72 h were included. Treatment was classified as monotherapy or combination therapy, and infusion strategy as prolonged/continuous or standard. The primary outcome was 28-day all-cause mortality. A multivariable Cox regression analysis was performed. Results: Among 173 patients, pneumonia was the most frequent clinical presentation (74.0%). Monotherapy was used in 111 patients (64.2%), combination therapy in 62 (35.8%), and prolonged/continuous infusion in 120 (69.4%). Ceftolozane–tazobactam (CT) (64.7%) and ceftazidime–avibactam (CZA) (20.2%) were the most prescribed agents. Patients receiving prolonged/continuous infusion, regardless of monotherapy or combination therapy, had greater baseline clinical severity than those receiving standard infusion. Overall, 28-day mortality was 23.7%. In the multivariable analysis, neither combination therapy nor prolonged/continuous infusion was independently associated with reduced mortality, whereas septic shock (aHR 4.10, 95% CI 1.01–16.66) and ICU admission (aHR 2.53, 95% CI 1.06–6.08) increased mortality risk. Conclusions: In this multicentre real-world cohort, treatment strategies for MDR P. aeruginosa pneumonia and BSI appeared to be influenced by baseline severity and patient-related factors. Mortality was more strongly associated with markers of severe illness, including ICU admission and septic shock. No independent association with improved survival was observed for combination therapy compared with monotherapy or for prolonged/continuous compared with standard infusion. These findings highlight the prognostic role of baseline clinical severity and support the need for prospective, randomized, pharmacokinetic/pharmacodynamic (PK/PD)-guided studies to identify patients who may benefit from these strategies.