Search

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 postoperative 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 FROM AUTHOR]

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 FROM AUTHOR]

Reduced prophylactic effect of tixagevimab-cilgavimab in patients with hematological malignancies and without antibody response after SARS-COV-2 vaccination The median value of the anti-SARS-CoV-2 spike protein IgG antibodies in blood samples (neutralizing antibody titer) collected after 1, 2, and 4 months from prophylaxis administration was 2500, 2047, and 1193 UI/mL, respectively. In the context of the COVID-19 pandemic, patients with hematological diseases are classified as "high risk patients" and, if infected with SARS-CoV-2, are at increased risk of morbidity and mortality.[1] It is also known that COVID-19 vaccine in this population lacks efficacy because hematological patients do produce less anti-spike antibodies after full vaccination, especially those treated with B-cell-depleting therapies.[[2], [4], [6]] In 2021, tixagevimab-cilgavimab, a monoclonal antibody combination, was approved as pre-exposure prophylaxis in patients who have an inadequate response to vaccines and received a recommendation for use in recent guidelines.[[1], [5], [7]] However, the emergence of new variants, like Omicron, has challenged the efficacy not only of vaccines, but also of this monoclonal antibodies combination, emphasizing that some sub-variants may have acquired immune escape abilities.[8] Data regarding tixagevimab-cilgavimab specific preventive effect in the hematological population during infection by SARS-CoV-2 Omicron variant are very limited. [Extracted from the article]

Background: Polymicrobial bloodstream infections (pBSI) occurring in hematological patients are still poorly understood, and specific information are very limited. Objectives and methods: In this epidemiologic survey, we describe clinical characteristics and outcome of 125 consecutive pBSI occurred in oncohematological patients. Polymicrobial bloodstream infections (pBSI) were defined with the isolation of 2 or more bacteria from blood culture specimens obtained within 72 h. Results: Over an 11-year period, we documented 500 bacterial bloodstream infections (BSI) in 4542 hospital admissions and 25% (125) of these were pBSI. Most common underlying hematological disease was acute myeloid leukemia and 89% of patients had severe neutropenia. Fifty pBSI (40%) occurred in patients undergoing a stem cell transplantation (SCT), mostly within 30 days from transplant (42/50–84%). Principal bacterial association was Gram-positive plus Gram-negative (57%). Resolution rate of pBSI was 82%, without differences between SCT and non-SCT cases. pBSI-related mortality was 15% (6% in SCT cases). Septic shock occurred in 16% of cases and septic shock–related mortality was 65% (75% in SCT cases and 63% in non-SCT cases; p = 0.6). Multidrug-resistant (MDR) bacteria were involved in 22% of pBSI and the MDR-pBSI–related mortality was significantly higher in SCT patients (p = 0.007). Conclusions: This observational study highlights that pBSI is not a rare bloodstream infectious complication in oncohematological patients. pBSI-related mortality is lower than 20%, but, if septic shock occurs, mortality reaches 65%. MDR bacteria were involved in 22% of cases and pBSI-MDR–related mortality was significantly higher in SCT patients. [ABSTRACT FROM AUTHOR]

The management of difficult-to-treat acute and chronic respiratory infections (infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised and mechanically ventilated patients) and difficult-to-treat pathogens (including multidrug-resistant strains) has become a challenge in clinical practice. The arsenal of conventional antibiotic drugs can be limited by tissue penetration, toxicities, or increasing antibiotic resistance. Inhaled antimicrobials are an interesting therapeutic approach for optimizing the management of respiratory infections. Due to extensive developments in liposome technology, a number of inhaled liposome-based antibiotic and antifungal formulations are available for human use and many products are undergoing clinical trials. Liposomes are biocompatible, biodegradable, and nontoxic vesicles able to encapsulate and carry antimicrobials, enhancing the therapeutic index of various agents and retention at the desired target within the lung. Liposomes reduce drug toxicity and improve tolerability, leading to better compliance and to decreased respiratory side effects. The aim of this article was to provide an up-to-date overview of nebulized liposomal antimicrobials for lung infections (with a special focus on liposomal amikacin, tobramycin, ciprofloxacin, and amphotericin B for inhalation), discussing the feasibility and therapeutic potential of these new strategies of preventing and treating bacteria, mycobacterial and fungal infections. [ABSTRACT FROM AUTHOR]

• Higher inflammatory markers best select tocilizumab treatment. • The ward based tocilizumab group showed better responses and less infections than ICU tocilizumab group. • The former group may be the best for evaluating anti-cytokine therapy in COVID-19. • Poor risk factors for COVID-19 were present in the TOCI treated rather than in the good prognosis standard of care group. Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key. [ABSTRACT FROM AUTHOR]

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  < .001), but the investigation conducted at 18 months showed a drastic drop in flu shot acceptance (30/166, 18.1%). On the other hand, a great increase in vaccinations against SARS-CoV-2 occurred after the introduction of Green Pass (26.7% vs 72.9%). The major drivers of flu vaccine skepticism were represented by the feeling of protection regardless of prevention and by concerns regarding vaccines safety and efficacy; conversely compulsory strategies seemed to play a secondary role, since only a minority of the participants identified in the restrictions induced by the certification the major incentive to get immunized against SARS-CoV-2. The focus on this peculiar historical period helps to take a step forward in the comprehension of the complexity and dynamicity of the vaccine hesitancy phenomenon. Future vaccination campaigns will need to consider the role of personal opinions and emotions, interpreted according to the social and political context.

Purpose of Review: Culturing preservation fluids of solid organs before transplantation is not a standardized procedure. In this review, we aim to describe the state-of-the-art of literature evidence in this debated setting with a special focus on Gram-negative bacteria (GNB)., Recent Findings: Contamination of preservation fluids is frequent, but preservation fluids related infections are rare and most commonly caused by high-risk pathogens, including GNB. GNB preservation fluids related infections are characterized by high morbidity and mortality. Recent studies showed improved outcomes in solid organ transplant recipients receiving antibiotic therapy tailored according to preservation fluids cultures especially when multidrug-resistant GNB are found. A robust procurement network is needed to alert recipients' centers in cases of positivity and the support of transplant infectious diseases specialists is essential to choose the best therapy., Summary: Culturing preservation fluids is a further step into preventing donor-derived infections. Interpreting and managing GNB positivity require a multidisciplinary team with specific skills. Standardized randomized trials are needed for insight into the real utility of preservation fluids cultures, the role of preservation fluids positivity, and the impact of antimicrobial therapy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Predicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization., Methods: We performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors., Results: Overall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020-2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12-30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16-11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94-26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization., Conclusions: We observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients., (© 2024. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grossi, Wolfe and Peghin.)

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., (© 2024. The Author(s).)

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients., Methods: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response., Results: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014)., Discussion: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Skin and soft tissue infections (SSTI) in solid organ transplant (SOT) recipients may be a great challenge for clinicians caring for SOT due to the involvement of both common and opportunistic pathogens associated with a blunted immune response. The purpose of this review is to outline current literature and describe open issues on the management of SSTI in this special population., Recent Findings: Clinical presentation in SOT recipients can manifest as isolated skin lesions after primary inoculation or be the sign of a disseminated infection. Tissue samples for microscopy and histopathology are crucial to making an accurate diagnosis given the nonspecific and heterogeneous appearance of skin lesions. Multidisciplinary teams are required for a comprehensive diagnosis and management., Summary: SSTI are frequent contributors to morbidity and mortality in SOT. Specific research focused on the clinical presentation, risk factors and management in this special population is needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT)., Recent Findings: Universal prophylaxis and preemptive therapy are the most adopted strategies for prevention of CMV disease globally. Prophylaxis with valganciclovir is the most widely used approach to CMV prevention, however leukopenia and late onset CMV disease after discontinuation of prophylaxis requires new strategies to prevent this complication. The use of assays detecting CMV-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Letermovir has been recently approved for prophylaxis in kidney transplant recipients. CMV-RNAemia used together with CMV-DNAemia in the viral surveillance of CMV infection provides accurate information on viral load kinetics, mostly in patients receiving letermovir prophylaxis/therapy. The development of refractory and resistant CMV infection remains a major challenge and a new treatment with maribavir is currently available. In the present paper we will review the most recent advances in prevention and treatment of CMV diseases in SOT recipients., Summary: Recent findings, summarized in the present paper, may be useful to optimize prevention and treatment of CMV infection in SOT., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs)., Methods: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method., Results: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies., (© 2024. The Author(s).)

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.

Objectives: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors., Methods: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools., Results: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels ( OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up., Conclusions: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.

Purpose of Review: The potential for transmission of donor-derived infections (DDIs) is impossible to eliminate, but a thoughtful and systematic approach to donor evaluation can mitigate the risk. Prevention is a key issue and clinicians must maintain a high index of suspicion and remain vigilant in staying up to date on emerging infections. COVID-19 and Monkeypox have represented a new challenge for infectious disease screening and recommendations have been evolving, as knowledge in the field has grown. Additional considerations for pretransplant deceased donor screening include testing for neglected and endemic infectious diseases such as strongyloidiasis and HTLV 1/2. Molecular diagnostic tests have improved awareness on pathogenicity of mollicutes and fungi in the setting of DDIs. The aim of this review is to provide an update on the most recent literature on DDI with a special focus on these emerging hot topics., Recent Findings: Donor screening for uncommon pathogens must be guided by knowledge of changing epidemiology of infectious disease and availability of new diagnostic methods., Summary: Appropriate screening, early recognition, timely reporting, close monitoring, and appropriate management are essential to help reducing the risk of emerging DDIs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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.

Purpose of Review: Recurrent cellulitis is a challenging clinical condition affecting up to 47% of patients after the first episode, especially those with predisposing risk factors. The purpose of this review is to describe the state of the art of literature evidence and to highlight recent developments in its management., Recent Findings: Recurrent cellulitis can occur after successful treatment of cellulitis. Conditions that commonly increase the risk of cellulitis include local and systemic modifiable and nonmodifiable factors. A rigorous approach to the management of risk factors and treatment of acute infection is important as the risk of recurrence rises with repeated episodes. Risk factors, if present, need to be targeted in association with antibiotic prophylaxis. Penicillin V is the preferred antibiotic for prevention but other antibiotics and new drugs can be considered in cases of β-lactam allergy, intolerance, or failure., Summary: Recurrent cellulitis is associated with short term and long-term morbidity as well as significant healthcare costs. Management of underlying predisposing conditions is crucial to prevent recurrence in addition with evaluation of pharmacological measures, but specialized and multidisciplinary skills are needed. More efforts are needed to prevent and treat this underestimated problem., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Accumulating evidence indicates that the COVID-19 pandemic carries risks to psychological health and represents a collective traumatic experience with consequences at the social, economic, and health levels. The primary aim of this study was to collect ongoing COVID-19 survivors’ pandemic-related experiences as expressed through the use of metaphors; the secondary aim was to explore socio-demographic variables associated with the metaphor orientation as negative, positive or neutral. An observational follow-up survey was conducted and reported according to the STROBE guidelines. Patients ≥ 18 years, who were treated for COVID-19 during the first wave (March/April 2020) and who were willing to participate in a telephone interview were involved and asked to summarize their COVID-19 experience as lived up to 6 and 12 months in a metaphor. A total of 339 patients participated in the first (6 months) and second (12 months) data collection. Patients were mainly female (51.9%), with an average age of 52.9 years (confidence interval, CI 95% 51.2−54.6). At 6 months, most participants (214; 63.1%) used a negative-oriented metaphor, further increasing at 12 months (266; 78.5%), when they used fewer neutral-/positive-oriented metaphors (p < 0.001). At the 6-month follow-up, only three individual variables (female gender, education, and experiencing symptoms at the COVID-19 onset) were significantly different across the possible metaphor orientation; at 12 months, no individual variables were significantly associated. This study suggests increasingly negative lived experiences over time and the need for personalized healthcare pathways to face the long-term traumatic consequences of COVID-19.

Introduction: Emerging evidence suggests that mental health symptoms in COVID-19 survivors are higher than expected, possibly indicating that such symptoms are more likely to develop post-infection than just persist as a residual component of the acute phase. It is thus imperative to investigate the potential development of a post-COVID mental health syndrome in the longer-term and identify its risk factors., Material and Methods: A prospective study investigated mental health symptoms associated with COVID-19 and its determinants over a 12-month period following the disease onset in all consecutive adult inpatients and outpatients with COVID-19 attending a tertiary referral hospital from March to May 2020., Results: A total of 479 patients (female, 52.6%) were followed-up for 12 months after COVID-19 onset. Of them, 47.2% were still presenting with at least one symptom. While most symptoms subsided as compared to COVID-19 onset (all p  < 0.001), a significant increase was observed only for symptoms of psychiatric disorders (10.2%) and lack of concentration and focus (20%; all p  < 0.001). Patients presenting with symptoms related to multiple body systems 12 months after contracting COVID-19 (all p  ≤ 0.034) were more likely to suffer from mental health domain-related symptoms at follow-up. Also, a higher risk of presenting with lack of concentration and focus 12 months post infection was found in those suffering of psychiatric symptoms at COVID-19 onset ( p  = 0.005)., Conclusions: Findings of this study may have important public health implications, as they underlie the increased need for mental health support in COVID-19 survivors., (© 2022 The Authors.)

Purpose of Review: Nosocomial infections caused by Acinetobacter baumannii currently represent a serious challenge for clinicians because treatment options are limited and frequently associated with significant toxicity. Cefiderocol is a first-in-class siderophore cephalosporin that has a proven efficacy for the treatment of multidrug-resistant Gram-negative infections, including carbapenem-resistant A. baumannii. The aim of this review is to evaluate the current evidence for the role of cefiderocol in the management of A. baumannii infections., Recent Findings: In this review, we briefly summarize the available data on the efficacy (from randomized controlled trials) and on effectiveness and cure rates (from observational studies), pertaining to the use of cefiderocol for treatment of serious A. baumannii infections., Summary: Cefiderocol represents a promising and safe antibiotic option for treating patients with carbapenem-resistant A. baumannii infections. Due to conflicting mortality data from available experience, well-designed future randomized controlled trials and real-life studies are needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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 < 0.001) and of 0.623 (p < 0.001), respectively, for IgM and IgG. In patients with a diagnosis of COVID-19, accordance between LFA and CLIA was maintained as a function of time from the onset of COVID-19 disease and the severity of disease both for qualitative and semi-quantitative assessments. RDT compared to the NAAT gold standard in 858 patients showed 78.5% sensitivity (95% CI 75.1%-81.7%) and 94.1% specificity (95% CI 90.4%-96.8%), with variable accordance depending on the timing from symptom onset., Conclusion: The RDT used in our study can be a non-invasive and reliable alternative to serological tests and facilitate both qualitative and a semi-quantitative antibody detection in COVID-19., (© 2022. The Author(s).)

The COVID-19 pandemic has significantly changed organ donation and transplantation worldwide. Since the beginning of the pandemic, the uncertainty regarding the potential route of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created tremendous pressures on transplantation communities, and international organisations have advised against using organs from deceased donors who have tested positive for SARS-CoV-2. The possibility of SARS-CoV-2 transmission through organ donation has only been reported for lung transplantation; hence, based on current experience, transplantation of non-lung organs from donors with active SARS-CoV-2 infection has been considered possible and safe, at least over short-term follow-up. As the evolving outbreak of SARS-CoV-2 continues, alongside the presence of vaccines and new treatment options, clinicians should consider transplanting organs from deceased donors with active SARS-CoV-2 infection to recipients with limited opportunities for transplantation and those with specific natural or vaccine-induced immunity. This article proffers an expert opinion on the use of organs from deceased donors with resolved or active SARS-CoV-2 infection in the absence of more definitive data and standardised acceptance patterns., Competing Interests: Conflict of interest PAG has the following conflict of interest: Consulting fees from Merck, Sharp & Dohme, Gilead Sciences, Takeda, Shionogi, Allovir; member of speakers bureau for Merck, Sharp & Dohme, Gilead Sciences, Takeda, Atara; MP has no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to describe the impact of vaccination and the role of humoral responses on post-COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2)., Methods: This prospective study was conducted through interviews to investigate post-COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March-May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed., Results: A total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post-COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post-COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR: 1.35; 95% CI, 1.11-1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7-37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4-31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs. 0.9-2500 U/mL; OR: 1.36; 95% CI, 0.62-3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451)., Discussion: The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU., Methods: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study., Results: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC., Conclusions: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment., (© 2022. The Author(s).)

As the at-risk population expands and new antifungal resistance patterns develop, it is critical to understand and recognize cutaneous manifestations of old and emerging fungal diseases., Purpose of Review: The aim of this review is to provide an overview of the most frequent and emerging deep cutaneous fungal infections following either primary inoculation or secondary spread after haematogenous seeding in disseminated infections in different geographical areas., Recent Findings: Fungal skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions based on the site of the infection, route of acquisition of the pathogen, epidemiological setting and the virulence of the fungus in relation to the host. The approach to a patient suspected of having a fungal SSTI is complex and usually poses a major diagnostic challenge. The treatment approach should include attempts at immune reconstitution, targeted antifungal therapy and/or aggressive surgical debridement., Summary: Fungal SSTIs can be an important cause of morbidity and mortality in both immunocompromised and immunocompetent patients and are being reported with increasing frequency worldwide., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of the study was to assess reinfection rates in relation to long-term antibody dynamics against SARS-CoV-2 after the first wave. A prospective longitudinal study with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. During the follow-up, reinfections were collected. A total of 546 unselected individuals with COVID-19 acquired from March to May 2020 were included (292 female, mean age 53 years). After a median follow-up of 10 months (IQR 6.2-10.4), reinfection occurred in 6 (1.1%) patients, median age of 44.5 years (IQR 33‒49). All had a previous history of mild COVID-19 (all were healthcare workers) and reinfection occurred a median of 9 months (IQR 8.2‒10.2) after the onset of the first episode. Patients with reinfection were either seronegative (2/56, n = 3.6%), seroreverted (2/137, 1.5%), or seropositive (2/353, 0.6%) (p = 0.085). All reinfections were mild (n = 5) or asymptomatic (n = 1). After reinfection, none of patients developed IgM response and only two had a transitory boosted IgG immunization response. In an unselected population after the first wave of COVID-19, after a prolonged observation period (mean 10 months), reinfection was very uncommon; occurred in patients with a previous history of mild infection, mostly with weak or absent serological response; and manifested with mild or asymptomatic clinical presentation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Poststernotomy mediastinitis (PSM) remains a serious infection and is significantly associated with high morbidity, short-term and long-term mortality. Gram-negative bacteria (GNB) are an underestimated cause of PSM, and there is little information on the risk factors, prevention, diagnosis and management of GNB PSM., Recent Findings: The pathogenesis of PSM is the result of a complex and multifactorial interplay between intraoperative wound contamination, host-related and surgical host factors but GNB are probably mostly translocated from other host site infections. GNB are frequent cause of PSM (18-38% of cases) and GNB PSM have shown to more frequently polymicrobial (20-44%). GNG PSM has shown to occur earlier than Gram-positive PSM. Early diagnosis is crucial to successful treatment. The management of PSM needs a combination of culture-directed antimicrobial therapy and an early extensive surgical debridement with either immediate or delayed closure of the sternal space. Antibiotic treatment choice and duration should be based on clinical evaluation, evolution of inflammatory markers, microbiological tests and imaging studies. Mortality has shown to be significantly higher with GNB PSM compared with other causes and the inappropriateness of initial antibiotic therapy may explain the worse outcome of GNB PSM., Summary: GNB PSM is usually undervalued in the setting of PSM and have shown to be a frequent cause of inappropriate treatment with adverse prognostic potential. There is a need for efforts to improve knowledge to prevent and adequately treat GNB PSM., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess the prevalence of and factors associated with post-coronavirus disease 2019 (COVID-19) syndrome 6 months after the onset., Methods: A bidirectional prospective study. Interviews investigated symptoms potentially associated with COVID-19 6 months after the disease onset of all consecutive adult inpatients and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. IgG antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were also evaluated 6 months after the onset of symptoms, at the time of the interview., Results: A total of 599 individuals were included (320 female, 53.4%; mean age 53 years, SD 15.8) and interviewed 187 days (22 SD) after onset. The prevalence of post-COVID-19 syndrome was 40.2% (241/599). The presence of IgG antibodies was significantly associated with the occurrence of post-COVID-19 syndrome (OR 2.56, 95% CI 1.48-4.38, p 0.001) and median SARS-CoV-2 IgG titres were significantly higher in patients with post-COVID-19 syndrome than in patients without symptoms (42.1, IQR 17.1-78.4 vs. 29.1, IQR 12.1-54.2 kAU/L, p 0.004). Female gender (OR 1.55, 95% CI 1.05-2.27), a proportional increase in the number of symptoms at the onset of COVID-19 (OR 1.81, 95% CI 1.59-2.05) and ICU admission OR 3.10, 95% CI 1.18-8.11) were all independent risk factors for post-COVID-19 syndrome. The same predictors also emerged in a subgroup of 231 patients with the serological follow-up available at the time of the interview alongside the proportional increase in anti-SARS-CoV-2 IgG (OR 1.01, 95% CI 1.00-1.02, p 0.04)., Discussion: Prospective follow-up could be offered to specific subgroups of COVID-10 patients, to identify typical symptoms and persistently high anti-SARS-CoV-2 IgG titres as a means of early detection of post-COVID-19 long-term sequelae., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known., Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness., Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness., Results: Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness., Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.

Introduction: Previous series on the use of daptomycin in enterococcal infective endocarditis (EIE) have shown various outcomes, including higher mortality rates. We analyzed the effectiveness of high-dose daptomycin for the treatment of EIE., Methods: We performed a prospective study from 2010 to 2018 in a referral center in patients with native (NVE) and prosthetic valve endocarditis (PVE) due to Enterococcus spp. The standard high-dose daptomycin at our institution is 10-12 mg/kg/day (CLCr > 30 ml/min). We compared the efficacy of a daptomycin-based regimen (DBR) versus daptomycin-sparing regimen (DSR) and daptomycin monotherapy versus combination therapy. Primary endpoints of the study were evaluation of risk factors associated with 30-day mortality and failure at end of therapy., Results: We collected 43 EIE cases; 29 were NVE (67.4%). Overall, 16 (37.2%) were treated with DBR, mainly with combination regimens (11, 68.7%), in the majority of cases in association with ß-lactam (7, 43.7%). The mean administered dose of daptomycin was 10.125 mg/kg/day (range 8-12 mg/kg/day). Overall, patients treated with DBR compared with patients treated with DSR had no higher mortality rates and/or failure at end of therapy (6.2% vs. 22. 2%; P 0.41 and MICs 0.25-2 mg/l, 6.2% vs. 3.7%; P 1.0). In the sub-group of patients with NVE and PVE treated with DBR and DSR, no difference was found regarding the primary endpoints on the single or combined use of daptomycin., Conclusion: Our findings suggest that high-dose daptomycin might be used as an alternative treatment regimen in EIE.

Background: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe., Methods: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU)., Results: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis., Conclusions: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Invasive aspergillosis (IA) is a serious opportunistic infection, which has increasingly been recognized as an emerging disease of non-neutropenic patients. In this group of patients, the diagnosis of IA can be challenging owing to the lack of specificity of symptoms, the difficulty in discriminating colonization from infection, and the lower sensitivity of microbiological and radiological tests compared with immunocompromised patients. The aim of this article is to present to clinicians a critical review on the management of IA in non-neutropenic patients.

Purpose: The aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality., Methods: A multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011-2013 was performed., Results: A total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C. albicans was the most common species (found in 131 episodes, 54.4%), followed by C. glabrata (35, 14.5%) and C. parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2-4.5) and septic shock (OR 3.2, 95% CI 1.7-6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3-0.9) was associated with survival benefit., Conclusions: A shift towards increasing prevalence of C. glabrata and C. parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.

Although the incidence of invasive aspergillosis has decreased in haematologic patients and solid organ transplant recipients due to the use of prophylaxis; aspergillosis has emerged in other populations undergoing immunosuppressive drugs where prophylaxis is not well defined presenting different clinical patterns. Voriconazole is the gold standard in the treatment of aspergillosis and probably combined therapy, with voriconazole plus anidulafungin, could have a role in the initial management of the infection.