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To investigate the dynamic evolution of vaccine hesitancy toward both COVID-19 and influenza in a context characterized by the compresence of SARS-CoV-2 pandemic and seasonal flu epidemics, a two times repeated cross-sectional exploratory design was performed at Udine Hospital (Italy) following a cohort of 479 adult patients with a previous history of SARS-CoV-2 infection in 2020. Vaccine attitude was assessed through standardized telephone interviews performed at 12 and 18 months after the acute illness. The first interview reported the success of the 2020/21 seasonal influenza immunization with 46.8% (224/479) of the participants showing a positive attitude, especially the elderly and people with comorbidities (p

SARS-CoV-2 infection represents a new challenge for solid organ transplantation (SOT) with evolving recommendations. A cross-sectional survey was performed (February–June 2024) to describe practices among Member States of the Council of Europe (COE) on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection. Overall, 32 out of 47 Member States with a transplant program participated in the study. Four (12.5%) countries did not use organs from deceased donors either with resolved or with active SARS-CoV-2 infection and 8 (25%) countries accepted organs only from deceased donors with resolved SARS-CoV-2 infection. Donor evaluation for SARS-CoV-2 included universal screening with standard PCR testing on respiratory specimens generally (61.4%) performed within 24 h prior to organ recovery. Further microbiological, immunological and radiological investigations varied. Most waitlisted patients receiving organs from a deceased donor with active (94.5%) or resolved (61.5%) SARS-CoV-2 infection were preferred to have natural, vaccine-induced or hybrid SARS-CoV-2 immunity. Most countries did not require recipients to undergo specific anti-SARS-CoV-2 treatment as pre-exposure (0%), post-exposure prophylaxis (15.4%) or modification of immunosuppression regimen (24%). This study highlights similarities and heterogeneities in the management of SARS-CoV-2 positive donors between COE countries, and a potential to safely expand donors’ pool.

Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Perioperative antibiotic prophylaxis (PAP) in lung transplant recipients (LuTRs) has high heterogeneity between centers. Our aim was to investigate retrospectively the approach to PAP in our center over a 20-year period (2002–2023), and its impact on early post-operative infections (EPOIs) after lung transplantation (LuT). Primary endpoint was diagnosis of EPOI, defined as any bacterial infection including donor-derived events diagnosed within 30 days from LuT. Main exposure variables were type of PAP (combination vs. monotherapy) and PAP duration. We enrolled 111 LuTRs. PAP consisted of single-agent or combination regimens in 26 (25.2%) and 85 (74.8%) LuTR. Median PAP duration was 10 days (IQR 6–13) days. Piperacillin/tazobactam was the most common agent used either as monotherapy (n = 21, 80.7%) or as combination with levofloxacin (n = 79, 92.9%). EPOIs were diagnosed in 30 (27%) patients. At multivariable analysis no advantages were found for combination regimens compared to single-agent PAP in preventing EPOI (OR: 1.57, 95% CI: 0.488–5.068, p:0.448). The impact of PAP duration on EPOIs development was investigated including duration of PAP ≤6 days as main exposure variables, without finding a significantly impact (OR:2.165, 95% CI: 0.596–7.863, p: 0.240). Our results suggest no advantages for combination regimens PAP in preventing EPOI in LuTR.

Abstract Background Several scientific contributions have summarized the “lessons learnt” during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years. Methods A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final “lessons learnt” has been agreed by all members, as described in a detailed fashion. Results Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies. Conclusions The multidisciplinary approach, which also included patients’ perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies.

Abstract Background: There is limited information to compare the qualitative and semi-quantitative performance of rapid diagnostic tests (RDT) and serology for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the objective of the study was (a) to compare the efficacy of SARS-CoV-2 antibody detection between RDT and laboratory serology, trying to identify appropriate semi-quantitative cut-offs for RDT in relation with quantitative serology values and to (b) evaluate diagnostic accuracy of RDT compared to the NAAT gold standard in an unselected adult population. Methods: SARS-CoV-2 antibodies were simultaneously measured with lateral flow immunochromatographic assays (LFA), the Cellex qSARS-CoV-2 IgG/IgM Rapid Test (by capillary blood), the iFlash-SARS-CoV-2 IgG/IgM chemiluminescent immunoassay (CLIA) (by venous blood) and the nucleic acid amplification test (NAAT) in samples from in- and out-patients with confirmed, suspected and negative diagnosis of coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) (March-May 2020). Interpretation of RDT was qualitative (positive/negative) and semi-quantitative based on a chromatographic intensity scale (negative, weak positive, positive). Results: Overall, 720 paired antibody measures were performed on 858 patients. The qualitative and semiquantitative agreement analysis performed in the whole sample between LFA and CLIA provided a Kendall’s tau of 0.578 (p

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed (p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22–8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40–7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12–2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.

IntroductionStress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19.MethodsIn a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission.ResultsPatients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078–6.012) and death (OR 2.281; CI 1.049–7.369) independently of diabetes and other major confounders.ConclusionsIn patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use.

ABSTRACT We sought to assess the characteristics and outcomes of neutropenic hematologic patients with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) treated with ceftolozane-tazobactam (C/T). We conducted a multicenter, international, matched-cohort study of PA BSI episodes in neutropenic hematologic patients who received C/T. Controls were patients with PA BSI treated with other antibiotics. Risk factors for overall 7-day and 30-day case fatality rates were analyzed. We compared 44 cases with 88 controls. Overall, 91% of episodes were caused by multidrug-resistant (MDR) strains. An endogenous source was the most frequent BSI origin (35.6%), followed by pneumonia (25.8%). There were no significant differences in patient characteristics between groups. C/T was given empirically in 11 patients and as definitive therapy in 41 patients. Treatment with C/T was associated with less need for mechanical ventilation (13.6% versus 33.3%; P = 0.021) and reduced 7-day (6.8% versus 34.1%; P = 0.001) and 30-day (22.7% versus 48.9%; P = 0.005) mortality. In the multivariate analysis, pneumonia, profound neutropenia, and persistent BSI were independent risk factors for 30-day mortality, whereas lower mortality was found among patients treated with C/T (adjusted OR [aOR] of 0.19; confidence interval [CI] 95% of 0.07 to 0.55; P = 0.002). Therapy with C/T was associated with less need for mechanical ventilation and reduced 7-day and 30-day case fatality rates compared to alternative agents in neutropenic hematologic patients with PA BSI. IMPORTANCE Ceftolozane-tazobactam (C/T) has been shown to be a safe and effective alternative for the treatment of difficult to treat infections due to Pseudomonas aeruginosa (PA) in the general nonimmunocompromised population. However, the experience of this agent in immunosuppressed neutropenic patients is very limited. Our study is unique because it is focused on extremely immunosuppressed hematological patients with neutropenia and bloodstream infection (BSI) due to PA (mainly multidrug resistant [MDR]), a scenario which is often associated with very high mortality rates. In our study, we found that the use of C/T for the treatment of MDR PA BSI in hematological neutropenic patients was significantly associated with improved outcomes, and, in addition, it was found to be an independent risk factor associated with increased survival. To date, this is the largest series involving neutropenic hematologic patients with PA BSI treated with C/T.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection is being one of the most significant challenges of health care systems worldwide. Bacterial and fungal infections in hospitalized patients with coronavirus disease 2019 (COVID-19) are uncommon but consumption of antibiotics and antifungals has increased dramatically during the ongoing pandemic resulting in increased selective pressure for global antimicrobial resistance. Nosocomial bacterial superinfections appear to be more frequent than community-acquired coinfections, particularly among patients admitted to the intensive care unit (ICU) and those receiving immunosuppressive treatment. Fungal infections associated with COVID-19 might be missed or misdiagnosed. Existing and new antimicrobial stewardship (AMS) programmes can be utilized directly in COVID-19 pandemic and are urgently needed to contain the high rates of misdiagnosis and antimicrobial prescription. The aim of this review is to describe the role of bacterial and fungal infections and possible strategies of AMS to use in daily practice for optimal management of COVID-19.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006–May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

The coronavirus disease 2019 (COVID-19) pandemic has posed significant global challenges for solid organ transplant (SOT) recipients. Mortality rates of COVID-19 in this patient population remain high, despite new available therapeutic options and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination. Priority access to SARS-CoV-2 vaccination for waitlisted candidates and for SOT patients and their family members is recommended since the advantage from vaccination reduces the risk of COVID-19-related complications. However, immunogenicity and efficacy of COVID-19 vaccines are lower in waitlisted candidates and SOT recipients than in the general population. Routine systematic assessment of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, although highly recommended for investigation and improvement of knowledge. SOT recipients should continue to adhere to preventive protective measures despite vaccination and may undergo passive antibody prophylaxis. This article seeks to provide an update on SARS-CoV-2 vaccination and preventive measures in SOT recipients based on existing literature and international guidelines.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006–2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01–2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27–0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76–2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.