273 research outputs found

    Rationale and clinical application of antimicrobial stewardship principles in the intensive care unit: a multidisciplinary statement

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    Abstract Background Antimicrobial resistance represents a major critical issue for the management of the critically ill patients hospitalized in the intensive care unit (ICU), since infections by multidrug-resistant bacteria are characterized by high morbidity and mortality, high rates of treatment failure, and increased healthcare costs worldwide. It is also well known that antimicrobial resistance can emerge as a result of inadequate antimicrobial therapy, in terms of drug selection and/or treatment duration. The application of antimicrobial stewardship principles in ICUs improves the quality of antimicrobial therapy management. However, it needs specific considerations related to the critical setting. Methods The aim of this consensus document gathering a multidisciplinary panel of experts was to discuss principles of antimicrobial stewardship in ICU and to produce statements that facilitate their clinical application and optimize their effectiveness. The methodology used was a modified nominal group discussion. Conclusion The final set of statements underlined the importance of the specific interpretation of antimicrobial stewardship’s principles in critically ill patient management, quasi-targeted therapy, the use of rapid diagnostic methods, the personalization of antimicrobial therapies’ duration, obtaining microbiological surveillance data, the use of PK/PD targets, and the use of specific indicators in antimicrobial stewardship programs

    Ten golden rules for optimal antibiotic use in hospital settings : the WARNING call to action

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    Abstract: Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

    Advanced Cutaneous Squamous Cell Carcinoma: Italian Multicentric Retrospective Analysis of Patient Profiles and Therapeutic Approaches

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    Background: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). Objectives: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. Methods: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018-May 31, 2020. Patients aged >= 18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients' characteristics and treatment strategies was performed. Results: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients' clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72-86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced >= 1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. Conclusions: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population

    Ceftazidime/Avibactam and Meropenem/Vaborbactam for the Management of Enterobacterales Infections: A Narrative Review, Clinical Considerations, and Expert Opinion

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    : This comprehensive review examines the unique attributes, distinctions, and clinical implications of ceftazidime-avibactam (CAZ-AVI) and meropenem-vaborbactam (MEM-VAB) against difficult-to-treat Enterobacterales infections. Our manuscript explores these antibiotics' pharmacokinetic and pharmacodynamic properties, antimicrobial activities, in vitro susceptibility testing, and clinical data. Moreover, it includes a meticulous examination of comparative clinical and microbiological studies, assessed and presented to provide clarity in making informed treatment choices for clinicians. Finally, we propose an expert opinion from a microbiological and a clinical point of view about their use in appropriate clinical settings. This is the first review aiming to provide healthcare professionals with valuable insights for making informed treatment decisions when combating carbapenem-resistant pathogens

    Impaired respiratory function reduces haemoglobin oxygen affinity in COVID-19

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    ZnS Filters radiation test report

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    The present document reports the tests performed on a representative set of dichroic samples of the MAJIS (Moons And Jupiter Imaging Spectrometer) instrument which is part of JUICE (Jupiter Icy Moons Explorer) ESA mission. The dichroic shall withstands the Jupiter and the icy moons electron radiation environment without any permanent degradation at the end of the mission. To verify the effect of the electron flux on the optical performances of the dichroic, transmittance and reflectance measurements have been repeated after each irradiation test performed

    MAJIS Shutter QM and FM Thermo-vacuum Test Report

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    This test report provides a summary of the Thermo-Vacuum Test results on the QM and FM shutter units, a mechanical part of the spectrometer MAJIS (Moon And Jupiter Imaging Spectrometer), a payload instrument on board of the JUCE (JUpiter ICy moons Explorer) mission. The shutter actuator is composed by an electromagnetic brushless actuator mounted with an aluminium blade. The aims of the actuator are to maintain the blade in two stable positions (open and closed), to rotate the blade from one position to other in a time less than 300ms and a low power consumption. These tests have been conducted to demonstrate the capability of the shutter to operate according to requirements in vacuum at predefined temperature conditions. The target temperatures for the QM model are Top-Min = 100K and Top-Max = 165K and pressures less than 1 mbar. A total number of thermo-vacuum cycles of 42 are requested, including an extra hot point at 337K but only for the first cycle at the beginning. A slope of 2.7K/min has been agreed and planned for all the cycles. For the life test, performed only on the QM1, selected as reference, a total number of 1500 cycles at the same conditions of T and P are requested. For what concerns the test performed on the FM model, the target temperature is Top-Min = 105K and Top-Max = 160K. A total number of thermo-vacuum cycles of 4 are requested, including an extra hot point at 337K but only for the first cycle at the beginning. A slope of 2.7K/min has been agreed and planned for all the cycles

    Al Huwaysah 010: The most reduced brachinite, so far

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    Al Huwaysah 010 is an ungrouped achondrite meteorite, recently referred to as abrachinite-like meteorite. This meteorite, showing a fine-grained assemblage of low-Ca pyroxene and opaque phases, is strongly reduced in comparison to other reduced brachinites. The occurrence of some tiny plates of graphite and oldhamite in this meteorite suggests that a partial melt residue has experienced a further reduction process. Olivine, the most abundant phase, is compositionally homogeneous (Fo83.3) as well as the clinopyroxene (En45.5Fs10.8Wo43.7) and the plagioclase (Ab69.5). Orthopyroxene (En85.4Fs13.9Wo0.7) also occurs but only in a fine intergrowth. Other accessory phases are Fe metal grains (Ni-free or Cr-bearing Fe-Ni alloy), troilite, chlorapatite, pentlandite (as inclusions in chromite). The sample shows two different closure temperatures: the highest (‚Čą900¬įC) is determined via the olivine‚Äďchromite intercrystalline geothermometer and the lowest temperature (‚Čą520¬įC) is determined via the pyroxene-based intracrystalline geothermometer. These temperatures may represent, respectively, the closure temperature associated with the formation and a subsequent impact event excavating the sample from the parental body. The visible to near-infrared (VNIR)reflectance spectra of Al Huwaysah 010 exhibit low reflectance, consistent with the presence of darkening components, and weak absorptions indicative of olivine and pyroxene. Comparing the spectral parameters of Al Huwaysah 010 to potential parent bodies characterized by olivine‚Äďpyroxene mineralogy, we find that it falls within the field previously attributed to the SIII type asteroids. These results lead us to classify the Al Huwaysah 010 meteorite as the most reduced brachinite, whose VNIR spectral features show strong affinities with those of SIII asteroids

    New Antimicrobial Resistance Strategies: An Adaptive Resistance Network Conferring Reduced Glycopeptide Susceptibility in VISA

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    Background: Vancomycin-intermediate Staphylococcus aureus (VISA) emerges typically in the healthcare-associated methicillin-resistant S. aureus and more rarely in community-acquired S. aureus (CA-MRSA). VISA is a serious concern for public health due to its association with persistent infections, the failure of vancomycin treatment, and poor clinical outcomes. Currently, the burden of VISA is somewhat high, even though vancomycin is the mainstay treatment for severe MRSA infections. The molecular mechanisms of reduced glycopeptide susceptibility in S. aureus are constantly under investigation but have still not yet been fully characterized. Methods: Our goal was to investigate the reduced glycopeptide susceptibility mechanisms emerging in a VISA CA-MRSA versus its vancomycin-susceptible (VSSA) CA-MRSA parents in a hospitalized patient undergoing glycopeptide treatment. Comparative integrated omics, Illumina MiSeq whole-genome sequencing (WGS), RNA-Seq, and bioinformatics were performed. Results: Through a comparison of VISA CA-MRSA vs. its VSSA CA-MRSA parent, mutational and transcriptomic adaptations were found in a pool of genes involved, directly or indirectly, in the biosynthesis of the glycopeptide target conferring or supporting the VISA phenotype, and its cross-resistance with daptomycin. This pool included key genes responsible for the biosynthesis of the peptidoglycan precursors, i.e., D-Ala, the D-Ala-D-Ala dipeptide termini of the pentapeptide, and its incorporation in the nascent pentapeptide, as key targets of the glycopeptide resistance. Furthermore, accessory glycopeptide-target genes involved in the pathways corroborated the key adaptations, and thus, supported the acquisition of the VISA phenotype i.e., transporters, nucleotide metabolism genes, and transcriptional regulators. Finally, transcriptional changes were also found in computationally predicted cis-acting small antisense RNA triggering genes related both to the key or accessory adaptive pathways. Conclusion: Our investigation describes an adaptive resistance pathway acquired under antimicrobial therapy conferring reduced glycopeptide susceptibility in a VISA CA-MRSA due to a comprehensive network of mutational and transcriptional adaptations in genes involved in pathways responsible for the biosynthesis of glycopeptide’s target or supporters of the key resistance path
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