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Abstract After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria. We investigated the changes in gut microbiota composition in allo-HSCT, aiming at investigating if the acquisition of ESBL colonization may affect gut microbiome diversity during allo-HSCT. This was a single-center prospective pilot study. All patients consecutively admitted to the Haematological Unit of the City of Health and Science, Molinette Hospital in Turin, Italy, and undergoing allo-HSCT between August 2017 to August 2020 were enrolled in the study. Microbiome analysis on fecal samples were collected every 7 days from hospital admission to discharge and until 1 year after HSCT. 48 patients were enrolled in the study. At baseline 14 patients (29.16%) were colonized by MDR bacteria, mostly extended-spectrum beta-lactamase (ESBL)-producing gram negatives (N = 11; 78.57%). During allo-HSCT, one patient had a positive rectal swab for a carbapenemase-producing Klebsiella pneumoniae and eight patients lost the colonization during the hospital stay. Microbiota composition was compared between patients colonized by ESBL at baseline and non-colonized patients. Patients colonized by ESBL had a greater abundances of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus Mogibacteriaceae, Peptostreptococceae and Oscillospira, while non-colonized ESBL patients had a greater abundance of Actinomycetales, Staphylococcus and Sutterella. Moreover, microbiota composition of colonized by ESBL that retained colonization after HSCT showed an increased in abundances of Akkermansia, Dialister, Erysipelotrichaceae and Methanobrevibacter when compared with patients that become negative at rectal swabs. From a clinical perspective, the evolution of this prospective pilot study will be to investigate markers of gut barrier functions, SCFA productions and to correlate the predictivity of these parameters with risk of invasive infections and clinical outcomes in allo-HSCT population.

Abstract Introduction Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe. Methods A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed. Results Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2–66.5%) for primary treatment and 73.5% (95% CI, 62.7–81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy. Conclusions This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.

Objectives: Acinetobacter baumannii (A. baumannii) nosocomial infections represent a serious hazard to public health, given high mortality rates and rapid spread of multidrug-resistance. The primary outcome of this study was to evaluate predictors of 14- and 30-d mortality in bloodstream infections (BSIs) due to both carbapenem-resistant and carbapenem-sensitive Acinetobacter. Secondary end points were to identify risk factors for BSIs due to carbapenem-resistant A. baumannii (CRAB) and to develop a predictive model for mortality in CRAB-related BSIs. Methods: Between 2019 and 2023, all consecutive hospitalized adult patients with bacteraemia due to A. baumannii were retrospectively enrolled at a single-centre. Results: One hundred twenty-six episodes of BSI caused by A. baumannii were recorded, 89.7% of which were due to CRAB. Recent burn injuries, older age, previous CRAB colonization, and antibiotics exposure were identified as risk factors for acquiring CRAB BSI. Overall, 14-d mortality was observed in 26.1% of the patients and 30-d mortality in 30.9% of the patients. On multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score was associated with both 14- and 30-d mortality, whereas burn injuries correlated with 30-d survival. Concurrent coronavirus disease (COVID) was associated with mortality, although not reaching statistical figures. No major impact of receiving appropriate treatment was observed. Based on these findings, a multivariable model to predict mortality among patients with CRAB BSI was built and internally validated. Conclusions: A. baumannii BSIs are characterized by poor outcomes and limited therapeutic options. This study aimed to assist physicians in prompt identification of patients who are at greater risk of death, contributing to more informed clinical decision making.

Herein, a large‐area nanofabrication process is proposed for flexible, ultrathin, and ultrasmooth gold films with extraordinary electro‐optical performance, making them competitive as transparent conductive electrodes (TCEs). The approach circumvents the thermodynamic constraints associated with the physical deposition of thin film electrodes, where 3D growth and metal dewetting delay stable percolation until the deposited film thickness exceeds 8–10 nm. It is demonstrated that a postgrowth ion irradiation procedure of compact gold films with Ar+ beam at very low energies, around 100 eV, predominantly induces ballistic smoothing and grain boundary restructuring. This process finally leads to the formation of ultrasmooth and ultrathin gold films that remain compact even at a thickness of 4 nm, with a sheet resistance in the range of 60 Ω sq−1 and an optical transparency around 80%. Remarkably, the films remain percolated even at thicknesses as low as 3 nm, with a transparency exceeding 90% and a sheet resistance of 190 Ω sq−1. These figures are comparable to those of commercial TCEs and enable simple, scalable, all‐metal transparent contacts on both rigid and flexible substrates, with significant potential for optoelectronic applications.

We explore patterns, regularities, and correlations in the evolving landscape of Ethereum-based tokens, both ERC-20 (fungible) and ERC-721 (non-fungible) to understand the factors contributing to the rise in certain tokens over others. By applying network science methodologies, minimum spanning trees, econometric autoregressive–moving-average (ARMA) models, and the study of accumulation processes, we are able to highlight a rising centralisation process. Not only do “rich” tokens get richer, but past transactions also emerge as more reliable predictors of new transactions. Our findings are validated across different samples of tokens.

As queer and trans scientists, we face varied and systemic barriers to our professional success, resulting in our relative absence from faculty ranks at many institutions. In this Perspective, we call for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

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.

Abstract Background In the region of Piedmont, in Northern Italy, formal monitoring of antimicrobial stewardship (AMS) programs has been in place since 2012. The objective of our study was to provide an updated assessment of AMS programs operating in our region, and to assess the impact of the COVID-19 pandemic on stewardship activities. Methods A retrospective observational study was conducted to investigate AMS programs implemented in acute-care trusts participating in a broader healthcare-associated infections and antimicrobial resistance (AMR) prevention and control program, promoted by the regional health department. Within this program, structure, process, and outcome indicators of AMS programs were investigated, using a previously developed scoring system. Differences between scores prior to (2019) and during the pandemic (2021) were assessed. Linear regression was used to assess whether the 5-year trends (2017–2021) in outcome measures in relation to structure and process scores were statistically significant. Compound annual growth rates (CAGR) for each outcome were calculated to illustrate changes in outcome rates over time. Results All public trusts in the Region (20) and a small number of private institutions (3) provided data for this study. A modest, non-significant improvement was found for 2021 structure, process, and total scores compared to respective 2019 scores. A significant improvement was found concerning the definition of a formal mission statement, whereas significantly less trusts included monitoring adherence to antimicrobial policy or treatment guidelines in their programs. Overall consumption of antibiotics for systemic use saw an increase in 2021, with 2021 recording the highest median overall consumption compared to all previous years considered in this study. Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) rates decreased over the 5-year period. Significant downwards trends in MRSA rates were identified for high-outlier structure and process groups. Conclusions Results of this study suggest AMS programs in Piedmont were not set back following the pandemic. This outcome was possible thanks to well-established programs, coordinated within a regional framework. Continued efforts should be dedicated to supporting AMS programs and contrasting AMR, even when the focus is shifted towards other public health emergencies.

Abstract Background The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. Material and Methods We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the “Città della Salute e della Scienza” University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). Results We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7–11 vs. 10, IQR: 8–13, p

Abstract Background In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. Methods A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. Results The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. Conclusions Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

Objectives: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. Methods: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. Results: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. Conclusion: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.

BackgroundAcute graft pyelonephritis (AGPN) is a relatively common complication in kidney transplants (KTs); however, the effects on allograft function, diagnostic criteria, and risk factors are not well established.MethodsRetrospective analysis of all consecutive adult KTs was performed between 01 January 2011 and 31 December 2018 (follow-up ended on 31 December 2019) to examine the association between the diagnosis of AGPN (confirmed with magnetic resonance imaging [MRI]) during the first post-transplantation year and graft outcomes.ResultsAmong the 939 consecutive KTs (≈50% with donors ≥60 years), we identified 130 MRI-confirmed AGPN episodes, with a documented association with recurrent and multidrug-resistant bacterial urinary tract infections (UTIs) (p

Introduction: Patients with hematologic malignancies are more likely to develop severe and prolonged SARS-CoV-2 infection, often showing viral persistence despite the use of authorized antivirals. Herein, we report the cases of four patients who received rituximab for different conditions and developed persistent COVID-19 treated with an extended course of dual antivirals, Nirmatrelvir/Ritonavir and Remdesivir. Moreover, we describe the pharmacokinetics and pharmacogenetics (PK/PG) characteristics of Nirmatrelvir/Ritonavir and Remdesivir treatment in two of these patients. Methods: Plasma specimens for evaluation of trough concentrations (Ctrough) were collected 10 min before the daily dose administration, in addition to 3 h (Cmax), 4 h (C4h), 6 h (C6h) and 1 h (Cmax) after the administration of Nirmatrelvir/Ritonavir and Remdesivir, respectively. The following gene single-nucleotide polymorphisms (SNPs) were investigated: ABCB1 3435 (rs1045642) C > T, ABCB1 1236 (rs1128503) C > T, PXR 63396 (rs2472667) T > C, CYP2D6 (rs1135840) G > C, and CYP3A4*1B (rs2740574) G > A. Results: Double antiviral treatment was successful in terms of symptoms resolution, whereas three out of four patients achieved microbiological eradication. Based on our results, concentrations of Nirmatrelvir ranging from 50 to 5000 ng/mL were effective, whereas a higher concentration (range 1068–3377 ng/mL), compared to that previously reported in patients with similar weight and BMI, was evidenced for Ritonavir. Considering the genetic variant analysis, ABCB1 3435 CT and 1236 CT genotypes were found in patient 1; and ABCB1 3435 CC and 1236 CC in patient 2. In conclusion, this real-life study supports the usefulness of TDM and genetics in immunocompromised patients with persistent SARS-CoV-2 infection, a challenging setting for clinicians in which personalized medicine may improve outcome.

Herpes zoster ophthalmicus results from the reactivation of the latent varicella zoster virus, affecting the first branch of the trigeminal nerve. In 20–70% of cases, Zoster Ophthalmicus can lead to ocular involvement, affecting various orbital structures. Orbital myositis is a rare but severe complication of herpes zoster ophthalmicus. We present a case of a 52-year-old man with no significant medical history who developed zoster-associated right ocular myositis and dacryocystitis. He was treated with intravenous acyclovir and oral steroids. A review of the literature identified 29 patients across 19 studies. The median age was 61 years, with a slight female predominance. In 55% of cases, the patients had no notable medical history. The most common presentation of myositis involved all oculomotor muscles. There were 22 cases who were treated with intravenous antiviral therapy and 19 received steroids. A full resolution of symptoms was achieved in 51.7% of patients. Zoster-related orbital myositis is a rare complication that should be considered even in immunocompetent individuals. It may occur either before or after the appearance of a vesicular rash. Magnetic resonance imaging is the preferred radiological exam for assessing orbital involvement. Intravenous antiviral therapy should be started within 72 h of symptom onset, and its combination with systemic corticosteroids appears to be an effective treatment for zoster-related ocular myositis.

Objectives: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. Methods: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). Results: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). Conclusion: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors.

Karst aquifers are characterized by different types of groundwater flow, related to different types of permeability due to the simultaneous presence of matrix, fractures and conduits. The presence of a well-developed karst conduit system leads to a rapid circulation of groundwater within the aquifer and a pulse-type response of the spring flow to the rainfall inputs, with a potential fast transport of contaminants from the hydrogeological basin surface to the discharge zones. Supported by hydro chemical analyses of spring water samples and single discharge measurements, it was possible to develop specific mass balance models, correlating ion content to spring flowrates. Specifically, Mg2+ content revealed a reliable application for spring baseflow separation in karst settings. Once the local model has been set, its conservative behaviour, in mostly limestone-dominant aquifers, allows using Mg2+ as a natural tracer of groundwater flow, distinguishing conduit flow (overflow) and diffuse flow (baseflow) occurrence in the spring outlet, without additional discharge measurements. In karst settings, the difficulty in continuously monitoring the spring discharge values makes this application interesting for exploitation management. This study shows the results obtained for two springs located in Central Italy, confirming that monitoring groundwater quality in karst environments is often the key for successfully characterizing springs and assessing the total yield when direct measurements are not available.

Recent developments in modeling and analysis of nanostructures are illustrated and discussed in this paper. Starting with the early theories of nonlocal elastic continua, a thorough investigation of continuum nano-mechanics is provided. Two-phase local/nonlocal models are shown as possible theories to recover consistency of the strain-driven purely integral theory, provided that the mixture parameter is not vanishing. Ground-breaking nonlocal methodologies based on the well-posed stress-driven formulation are shown and commented upon as effective strategies to capture scale-dependent mechanical behaviors. Static and dynamic problems of nanostructures are investigated, ranging from higher-order and curved nanobeams to nanoplates. Geometrically nonlinear problems of small-scale inflected structures undergoing large configuration changes are addressed in the framework of integral elasticity. Nonlocal methodologies for modeling and analysis of structural assemblages as well as of nanobeams laying on nanofoundations are illustrated along with benchmark applicative examples.

Key points FMECA is a proactive risk assessment tool that has proved useful in identifying potential failures in the process of prescribing and administering cancer treatments, which is a high-risk process. The analysis evidenced 22 failures modes, distributed over the various phases of the process. In order to reduce the likelihood of the cause, or to improve the chances of a failure mode being detected, this work identified a number of recommendations to be adopted in the administration of cancer treatment in an outpatient setting.

Abstract Background The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. Methods To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. Results 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. Conclusions Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020

ABSTRACT Microbiology conferences can be powerful places to build collaborations and exchange ideas, but for queer and transgender (trans) scientists, they can also become sources of alienation and isolation. Many conference organizers would like to create welcoming and inclusive events but feel ill-equipped to make this vision a reality, and a historical lack of representation of queer and trans folks in microbiology means we rarely occupy these key leadership roles ourselves. Looking more broadly, queer and trans scientists are systematically marginalized across scientific fields, leading to disparities in career outcomes, professional networks, and opportunities, as well as the loss of unique scientific perspectives at all levels. For queer and trans folks with multiple, intersecting, marginalized identities, these barriers often become even more severe. Here, we draw from our experiences as early-career microbiologists to provide concrete, practical advice to help conference organizers across research communities design inclusive, safe, and welcoming conferences, where queer and trans scientists can flourish.

Submarine caves are important biodiversity reservoirs, but there is little information about the biota of marine caves in the Southwestern Atlantic. Here, we describe three submarine cavities and their sponge communities on the Fernando de Noronha Archipelago, Northeast Brazil. The underwater cavities were explored and collections were made through scuba diving from 5 to 18 m depths. Sapata Cave has a wide semi-dark zone near the entrance, a narrow transition zone, and a dark chimney, which is closed at the top. Ilha do Meio Cave is narrower and shallower than Sapata Cave, but has a long passage that leads to two completely dark rooms. Pedras Secas Tunnel has only a semi-dark zone with high water movement. The sponge communities in the semi-dark zones of the three cavities are rich and dominated by the classes Demospongiae and Homoscleromorpha, but Calcarea are also common. The transition zones of both caves are dominated by a desma-bearing sponge, thinly encrusting spirastrellids, and small Homoscleromopha and Calcarea. The dark zone in Ilha do Meio Cave is almost azoic, with only three species. This study has increased the number of sponge species known in submarine cavities on Fernando de Noronha from 29 to 69, highlighting the great richness of the sponge communities in these cryptic environments.

Ceftobiprole is a fifth-generation cephalosporin approved by European and American regulatory agencies for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Ceftobiprole administration is useful in severe CAP as well as HAP where the potential is to save other β-lactams including carbapenems or linezolid/vancomycin in clinical practice. The aim of this study was to report the real-world evidence of ceftobiprole in patients with CAP and HAP in a single center. In this retrospective study, we included 159 patients with CAP or HAP: 105 (66%) had CAP and 54 (34%) had HAP. The median age was 70 years (IQR 60–77), the median Charlson Comorbidity Index was 5 (IQR 3–7.5) and baseline INCREMENT ESBL score was 8 (IQR 6–11). Ceftobiprole was mostly given as a combination treatment (77%) or as a carbapenem-sparing strategy (44%). There were no differences in mortality between shorter and longer duration of treatment (p = 0.93) or between first-line (HR 1.00, C.I. 0.46–2.17, p = 0.989) and second-line therapy. Ceftobiprole use in CAP or HAP in the real world is effective as a first- and second-line treatment as well as a carbapenem-sparing strategy. Further studies are needed to explore the full potential of ceftobiprole, including its real-world use in antimicrobial stewardship programs.

Background and Objectives: the principal purpose of this literature review is to cluster adults with hematological malignancies after treatment or on maintenance with obinutuzumab who experienced disseminated EV infection to understand clinical characteristics and outcome of this rare condition in these patients. We report the first clinical case of a male affected by follicular lymphoma treated with immune-chemotherapy including obinutuzumab who was affected by disseminated EV infection with cardiovascular involvement. Materials and Methods: this narrative review summarizes all the research about disseminated EV infection in immunosuppressed adult patients treated with obinutuzumab from January 2000 to January 2024 using the Scale for the Assessment of Narrative Review Articles (SANRA) flow-chart. We performed a descriptive statistic using the standard statistical measures for quantitative data. Results: we included six studies, five case reports, and one case report with literature analysis. We collected a total of seven patients, all female, with disseminated EV infection. The most common signs and clinical presentations of EV infection were fever and encephalitis symptoms (N = 6, 85.7%), followed by hepatitis/acute liver failure (N = 5, 71.4%). Conclusions: onco-hematological patients who receive immune-chemotherapy with a combination of treatments which depress adaptative immunity, which includes the antiCD20 obinutuzumab, could be at higher risk of disseminated EV infection, including CNS and cardiac involvement.

Left ventricular assist devices (LVADs) have been increasingly used as a valid option to improve the prognosis and reduce the symptoms of end-stage heart failure. However, long-term complications, mostly infections and coagulation disorders, are frequent. We described the epidemiology and risk factors for nosocomial infections (NIs) in a cohort of adult patients who underwent continuous-flow LVAD implant between January 2010 and December 2017 in Turin, Italy. Secondary outcomes were the prevalence of multidrug-resistant (MDR) bacteria and mortality. Results: Overall, 64 LVADs were implanted. A total of 32 (50%) patients experienced at least one episode of NI, with a total of 46 infectious events. VAD-related infections occurred in 22 patients (68.8%). Non VAD-related NIs occurred in 12 patients (37.5%), mainly low respiratory tract infections. Length of intensive care unit admission was a risk factor for NI (OR 1.224, 95%CI; 1.049, 1.429). Gram-negative bacilli were responsible for 58.8% of VAD-related infections and 79.5% of non-VAD related infections. In sixteen patients (50%), at least one episode of infection was related to an MDR strain. INTERMACS class and length of MV were independent risk factors for NIs by MDR strains (respectively, OR 2.12, 95%CI: 1.08, 6.80; p = 0.02 and OR 1.46, 95%CI: 1.07, 5.52, p = 0.047). In-hospital mortality was 6.3%. No differences in mortality were observed between infected and non-infected patients (p = 0.61) even when caused by MDR strains (p = 0.143). Conclusion: the rate of nosocomial infections in LVAD patients is associated with the length of ICU admission, and the etiology of nosocomial infection after LVAD implant is mainly due to GNB, including a high rate of MDR strains, especially KPC-KP and MDR PA.

Objectives: To date limited information about cefiderocol use is provided by real life studies. Our aim is to evaluate characteristics and outcome of patients with Gram-negative infections with limited therapeutic options treated with cefiderocol in combination or monotherapy. Methods: We retrospectively collected data on demographical, clinical characteristics and clinical cure, in-hospital and 30-days mortality, microbiological failure and Clostridioides difficile infections of all patients ≥ 18 years old treated with cefiderocol for ≥ 48 h. Results: There were 18 patients of which 14 (77.8%) treated with cefiderocol in combination and 4 (22.2%) with monotherapy. Median age was 54.5 (IQR 35.25–65.75) vs 70.5 (IQR 57.5–78.25) years old, respectively and ward of admission was the ICU in the 78.57% vs 100% of cases. In the 50% vs 100% of cases infections were VAP with concomitant bloodstream infections. Median SOFA score was 10 (IQR 4.5–12.5) vs 5 (IQR 4–6) and APACHE II score was 13.5 (IQR 7.5–18) vs 16 (IQR 8.5–23.5), respectively. Isolated pathogen was carbapenems-resistant Acinetobacter baumannii in 78.57% vs 100% of cases. Median duration of cefiderocol treatment was 9.5 (IQR 7–13.25) vs 9 days (IQR 5.5–12.5) and in 77.8% patients it was used in combination therapy, of which 57.1% were colistin-spairing regimens. Clinical cure was achieved in 64.29% for combination therapy vs 75% of monotherapy treated patients, 30-days mortality rate was 28.57% vs 25% and 30-day ICU admission rate was 14.29% vs 50%, respectively. No statistically significant differences were observed between combination therapy and monotherapy treated patients. Conclusions: To date, no differences have been demonstrated between cefiderocol monotherapy or combination. Further studies are required to understand whether cefiderocol combination therapy could provide an advantage in outcome in seriously-ill patients.

Abstract Eight hot topics regarding the diagnosis and management of bacterial skin infections were selected and reviewed by five experts from different European countries, chosen based on their expertise in microbiology, infectious diseases, and dermatology. As noninfectious skin diseases/conditions such as atopic dermatitis can be complicated by infections, including Acute Bacterial Skin and Skin Structure Infections (ABSSSI), a collaboration between dermatologists and infectious disease specialists can promote a rational approach to diagnosis and a more functional treatment approach, especially for complicated infections. In addition, an important role would be played by microbiologists as they are crucial for the isolation and classification of the bacterial pathogen to guide clinicians toward the most effective antibiotic therapy. Although there are many therapeutic options for the treatment of bacterial skin infections, including those due to methicillin‐resistant Staphylococcus aureus, these drugs often require multiple daily administrations leading to patient noncompliance and are associated with gastrointestinal adverse events and drug resistance. With their characteristics of being long‐acting, safety and single‐dose regimens, long‐acting antibiotics, such as dalbavancin and oritavancin, represent an effective alternative that could change the management of these infections with a considerable reduction of hospitalisation costs and risks.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Abstract Background Women with female genital mutilation/cutting are known to have psychological sequelae from the cutting and other traumatic experiences. However, very few studies report immediate psychological sequelae of genital reconstructive surgery in this population. The present case is the first to our knowledge to report post-traumatic stress disorder symptoms immediately following defibulation, a procedure common in women with female genital mutilation/cutting type III. Case presentation We present the case of a 31-year-old Sudanese nulliparous woman in the second trimester of pregnancy with female genital mutilation/cutting type IIIa who was referred for antepartum defibulation to facilitate a vaginal birth. Immediately after an uncomplicated surgery under local anesthesia and just before the first micturition, she developed post-traumatic stress disorder symptoms and suddenly recalled the traumatic experience of her first micturition after female genital mutilation/cutting when she was a child in Sudan. The woman was offered psychiatric follow-up with psychotherapy for 4 months and a short course of benzodiazepines. She had fully recovered by the time of delivery, 4 months after surgery. Conclusions We discuss the possibility of recall of a past traumatic experience of female genital mutilation/cutting during defibulation or other genital surgeries. We review the benefits and risks of defibulation, the impact of this procedure, and the setting and timing in which it is performed, focusing on women’s mental health and psychological support.

As queer and trans scientists, we face varied and systemic barriers to our professional success, resulting in our relative absence from faculty ranks at many institutions. In this Perspective, we call for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process. Queer and trans scientists face varied and systemic barriers to their professional success, resulting in a relative absence from faculty ranks at many institutions. This Perspective calls for a change in faculty hiring practices and present concrete guidance to make it a more inclusive process. [ABSTRACT FROM AUTHOR]

Background and Objectives: Stenotrophomonas maltophilia is a ubiquitous, aerobic, Gram-negative bacillus causing increasing concern in patients affected by haematological malignancies. Materials and Methods: We report a case series from two centres in Northern Italy to describe the characteristics, outcome and microbiological response of S. maltophilia infections in patients with haematological malignancies and/or allogenic hematopoietic stem cell transplantation (aHSCT). Results: Ten patients were included. The median age was 67 years, and seven patients (70%) were males. The median Charlson Comorbidity Index was 6 (IQR: 4–8). The most frequent haematological comorbidities were acute myeloid leukaemia (AML; n = 3; 30%) and non-Hodgkin’s lymphoma (n = 3; 30%). Three (30%) patients underwent aHSCT before infection, all for AML. All the patients had undergone a recent antibiotics course and had an indwelling central venous catheter before infection. The main clinical presentations were nosocomial pneumonia, with (2; 20%) or without (4; 40%) secondary bloodstream infection and CRBSI (3; 30%). Four patients were treated with cefiderocol in monotherapy or combinations therapy with cotrimoxazole. The rest of the patients were treated with cotrimoxazole or levofloxacin in monotherapy. Conclusions: Despite a high rate of clinical improvement (90%) after starting antimicrobial therapy, we faced high 30-day mortality (30%) and in-hospital mortality (50%) rates in a highly comorbid population.

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018–2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of Pantoea species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, Pantoea species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among Pantoea species isolates, P. agglomerans was the most frequently detected (45%; n = 9) followed by P. eucrina (30%; n = 6) and P. septica (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of Pantoea species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, Pantoea species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of Pantoea species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the Pantoea species in the onset of the disease, warranting further studies defining their pathogenic potential.