Evaluation of the Impact of an Antibiotic Time-out for Transition of IV Vancomycin to Oral Linezolid in Hospitalized Patients

Background: Oral linezolid is a broad-spectrum oxazolidinone antibiotic that offers advantages compared to intravenous (IV) vancomycin including no requirement for therapeutic drug monitoring, no need for home health or peripherally inserted central catheter (PICC) line placement, and opportunities for earlier hospital discharge due to the ease of continuing therapy outpatient. A medication use evaluation investigated if opportunities existed for oral linezolid over IV vancomycin among a randomized cohort of 100 patients initiated on IV vancomycin. Reviewers identified 15 patients who were candidates for transition to oral linezolid and calculated a potential cost avoidance of $125 per day of antibiotic therapy. The purpose of this study is to assess the feasibility of implementing an interdisciplinary approach for transitioning IV vancomycin to oral linezolid based on pharmacist-led transition criteria. Methods: This is an IRB-reviewed, single-center, quasi-experimental study at Baptist Hospital of Miami, a 900-bed tertiary community hospital. Included patients were \u3e18 years old, receiving IV vancomycin for \u3e48 hours, and admitted between January 10, 2023 and March 31, 2023. Patients were excluded if they had an active vasopressor order, were immunocompromised, or if the patient was receiving antibiotics for meningitis, endocarditis, febrile neutropenia, or surgical prophylaxis. A pharmacy resident was on-call to assess for oral linezolid candidates using antibiotic timeout criteria and intervened as appropriate. Continuous and categorical variables were evaluated using the Mann-Whitney U test and Fisher’s exact test, respectively. The primary outcome was total cost avoidance in patients transitioned from IV vancomycin to oral linezolid. Secondary outcomes included median hospital length of stay, median antibiotic treatment days, and incidence of thrombocytopenia and acute kidney injury, and pharmacist intervention acceptance rate. Results: Investigators screened 317 patients for study inclusion and 94 patients met criteria. 66 (70$5,538, with a total of $21 and$70 saved per inpatient and outpatient antibiotic treatment day, respectively. Median length of antibiotic treatment days was 6 days between both groups (p=0.3524). No statistically significant differences were observed between length of stay, length of antibiotic treatment days, or safety outcomes between the 2 groups. Acute kidney injury occurred in 1 patient receiving linezolid and 1 patient receiving IV vancomycin. Thrombocytopenia, defined as a \u3e50% drop in platelet count from baseline, occurred in 1 patient receiving provider-driven linezolid therapy. Conclusion: Pharmacist-driven transition criteria from IV vancomycin to linezolid therapy resulted in a positive cost avoidance strategy, with similar effect on hospital antibiotic treatment days and no difference in incidence of adverse effects. These results demonstrate the practicality of a pharmacist prospective antibiotic timeout and intervention strategy for patients receiving empiric or targeted Methicillin-resistant Staphylococcus aureus (MRSA) therapy

Assessment of a Pharmacist-Led Antibiotic Time-out for Transition of IV Vancomycin to Oral Linezolid

Introduction: Intravenous (IV) vancomycin requires therapeutic drug monitoring and line placement and may prolong hospital stay. Linezolid requires less monitoring, is orally bioavailable, and may expedite transitions of care. This study assessed the impact of a pharmacist-led antibiotic timeout for the transition from IV vancomycin to oral linezolid. Methods: This single-center, quasi-experimental study included admitted adult patients receiving IV vancomycin for over 48 hours. Patients receiving vasopressors, of immunocompromised status, or with specific antibiotic indications were excluded. The primary outcome was the pharmacist intervention acceptance rate. Secondary outcomes included median hospital length of stay, median antibiotic treatment days, and incidence of adverse effects. Results: Of the 317 screened patients, 94 were eligible for the antibiotic time-out assessment, of which 66 met the criteria for oral linezolid. Of those meeting the criteria, 27 interventions were made, of which 20 (74%) were accepted. The median length of antibiotic treatment days was six days between both groups (p = .352). No differences in safety outcomes were observed. Discussion: A pharmacist-led antibiotic timeout for IV vancomycin to oral linezolid resulted in a high intervention acceptance rate and increased oral linezolid use without impacting safety outcomes. These results support the use of this strategy for antimicrobial stewardship. Conclusion: This study illustrates the impact of a pharmacist-led antibiotic timeout for the transition from IV vancomycin to oral linezolid therapy as an antimicrobial stewardship tool

Simian Immunodeficiency Virus Infection Mediated Changes in Jejunum and Peripheral SARS-CoV-2 Receptor ACE2 and Associated Proteins or Genes in Rhesus Macaques

Angiotensin converting enzyme-2 (ACE2) and associated proteins play a pivotal role in various physiological and pathological events, such as immune activation, inflammation, gut barrier maintenance, intestinal stem cell proliferation, and apoptosis. Although many of these clinical events are quite significant in SIV/HIV infection, expression profiling of these proteins has not been well reported. Considering the different pathological consequences in the gut after HIV infection, we hypothesized that the expression of ACE2 and associated proteins of the Renin-angiotensin system (RAS) could be compromised after SIV/HIV infection. We quantified the gene expression of ACE2 as well as AGTR1/2, ADAM17, and TMPRSS2, and compared between SIV infected and uninfected rhesus macaques (Macaca mulatta; hereafter abbreviated RMs). The gene expression analysis revealed significant downregulation of ACE2 and upregulation of AGTR2 and inflammatory cytokine IL-6 in the gut of infected RMs. Protein expression profiling also revealed significant upregulation of AGTR2 after infection. The expression of ACE2 in protein level was also decreased, but not significantly, after infection. To understand the entirety of the process in newly regenerated epithelial cells, a global transcriptomic study of enteroids raised from intestinal stem cells was performed. Interestingly, most of the genes associated with the RAS, such as DPP4, MME, ANPEP, ACE2, ENPEP, were found to be downregulated in SIV infection. HNFA1 was found to be a key regulator of ACE2 and related protein expression. Jejunum CD4+ T cell depletion and increased IL-6 mRNA, MCP-1 and AGTR2 expression may signal inflammation, monocyte/macrophage accumulation and epithelial apoptosis in accelerating SIV pathogenesis. Overall, the findings in the study suggested a possible impact of SIV/HIV infection on expression of ACE2 and RAS-associated proteins resulting in the loss of gut homeostasis. In the context of the current COVID-19 pandemic, the outcome of SARS-CoV-2 and HIV co-infection remains uncertain and needs further investigation as the significance profile of ACE2, a viral entry receptor for SARS-CoV-2, and its expression in mRNA and protein varied in the current study. There is a concern of aggravated SARS-CoV-2 outcomes due to possible serious pathological events in the gut resulting from compromised expression of RAS- associated proteins in SIV/HIV infection

The Lick AGN Monitoring Project 2011: Dynamical Modeling of the Broad-Line Region

We present models of the H$\beta$-emitting broad-line region (BLR) in seven Seyfert 1 galaxies from the Lick AGN (Active Galactic Nucleus) Monitoring Project 2011 sample, drawing inferences on the BLR structure and dynamics as well as the mass of the central supermassive black hole. We find that the BLR is generally a thick disk, viewed close to face-on, with preferential emission back toward the ionizing source. The dynamics in our sample range from near-circular elliptical orbits to inflowing or outflowing trajectories. We measure black hole masses of $\log_{10}(M_{\rm BH}/M_\odot) = 6.48^{+0.21}_{-0.18}$ for PG 1310$-$108, $7.50^{+0.25}_{-0.18}$ for Mrk 50, $7.46^{+0.15}_{-0.21}$ for Mrk 141, $7.58^{+0.08}_{-0.08}$ for Mrk 279, $7.11^{+0.20}_{-0.17}$ for Mrk 1511, $6.65^{+0.27}_{-0.15}$ for NGC 4593, and $6.94^{+0.14}_{-0.14}$ for Zw 229$-$015. We use these black hole mass measurements along with cross-correlation time lags and line widths to recover the scale factor $f$ used in traditional reverberation mapping measurements. Combining our results with other studies that use this modeling technique, bringing our sample size to 16, we calculate a scale factor that can be used for measuring black hole masses in other reverberation mapping campaigns. When using the root-mean-square (rms) spectrum and using the line dispersion to measure the line width, we find $\log_{10}(f_{{\rm rms},\sigma})_{\rm pred} = 0.57 \pm 0.19$. Finally, we search for correlations between $f$ and other AGN and BLR parameters and find marginal evidence that $f$ is correlated with $M_{\rm BH}$ and the BLR inclination angle, but no significant evidence of a correlation with the AGN luminosity or Eddington ratio.Comment: 26 pages, 14 figures. Accepted for publication in Ap

L-Edge Spectroscopy of Dilute, Radiation-Sensitive Systems Using a Transition-Edge-Sensor Array

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by conventional grating-based spectrometers. These results show that soft X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.Comment: 19 pages, 4 figure

The apparent British sea slope is caused by systematic errors in the levelling-based vertical datum

The spirit-levelling–based British vertical datum (Ordnance Datum Newlyn) implies a south–north apparent slope in mean sea level of up to 53 mm deg–1 latitude, due to the datum falling on heading northwards. Although this apparent slope has been investigated since the 1960s, explanations of its origin have remained inconclusive. It has also been suggested that, rather than a slope, the British vertical datum includes a step of about 240 mm affecting all sites north of about 53°N. In either case, the British vertical datum may be of limited use for any study requiring accurate heights or changes in heights, such as testing geoid models, groundwater and hydrocarbon extraction, the calibration and validation of satellite-based digital terrain models, and the unification of vertical datums internationally. Within the last decade, however, based on an apparent reduction in the slope to only −12 mm deg–1 latitude with respect to recent geoid models, it has been claimed that the British vertical datum does provide a physically meaningful surface for use in scientific applications.In this paper, we reinvestigate the presence of apparent south–north sea slopes around Britain and reported slopes in the vertical datum, using the EGM2008 global gravitational model, together with mean sea level and GPS data from British tide gauges, GPS ellipsoidal heights of 178 fundamental benchmarks across mainland Britain, and vertical deflection observations at 192 stations. We demonstrate a south–north slope in the British vertical datum of −(20–25) mm deg–1 latitude with respect to both mean sea level (corrected for the ocean's mean dynamic topography and the inverse barometer response to atmospheric pressure loading) and the EGM2008 quasigeoid model, while EGM2008 is shown to exhibit a negligible slope of (2 ± 4) mm deg–1 with respect to mean sea level. It is clear, therefore, that the slope can only arise from systematic errors in the levelling, although we are unable to isolate their exact origin. Using an offset detection method based on a penalized likelihood maximization using the Schwarz Information Criterion, we do not detect a step in the vertical datum affecting all sites north of 53°N, but do identify regional distortions that we attribute to the inhomogeneity in both the levelling data used and the least squares adjustment procedures used to realize the datum. We conclude that the British vertical datum remains unsuitable for scientific purposes

Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.This work was supported by funding from the Intramural Research Program of the National Institute on Aging/NIH. Work in JMV laboratory was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) grant BFU2015-64630-R, Ministerio de Ciencia, Innovación y Universidades (MICIU) grant RTI2018-100695-B-I00, Spanish Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276, the FEDER Funding Program from the European Union, and Universidad de Córdoba. MCR was supported by a FPU fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (reference FPU14/06308). SRL held a FPI predoctoral contract funded by MINECO (reference BES-2016-078229).Peer reviewe