The Hospital Antimicrobial Use Process: From Beginning to End

Hospital antimicrobial stewardship (AMS) programs are responsible for ensuring that all antimicrobials are utilized in the most appropriate and safe manner to improve patient outcomes, prevent adverse drug reactions, and prevent the development of antimicrobial resistance. This Perspectives article outlines the hospital antimicrobial use process (AUP), the foundational system that ensures that all antimicrobials are utilized in the most appropriate and safe manner. The AUP consists of the following steps: antimicrobial ordering, order verification, preparation and delivery, administration, monitoring, and discharge prescribing. AMS programs should determine how each step contributes to how an antimicrobial is used appropriately or inappropriately at their institution. Through this understanding, AMS programs can integrate stewardship activities at each step to ensure that every opportunity is taken to optimize antimicrobial use during a patient’s treatment course. Hence, approaching AMS through the framework of a hospital’s AUP is essential to improving appropriate antimicrobial use

A Nonrestrictive Approach to Fluoroquinolone Stewardship at Two Community Hospitals

Background Fluoroquinolones are one of the most prescribed antimicrobials in the United States and have been increasingly used in inpatient and outpatient settings to treat various infectious diseases syndromes. Due to the unwanted collateral effects on antibiotic resistance, poor susceptibility rates among Gram-negative pathogens, and adverse effects, fluoroquinolones are often targeted by hospital antimicrobial stewardship programs to prevent overutilization. This study describes the association of nonrestrictive antimicrobial stewardship interventions at 2 nonacademic community hospitals on levofloxacin utilization, prescribing patterns on alternative antibiotics, and Pseudomonas aeruginosa nonsusceptibility rates to levofloxacin. Methods Nonrestrictive antimicrobial stewardship interventions included monitoring and reporting of fluoroquinolone susceptibility trends to physician groups, performing medication use evaluations of levofloxacin accompanied with prescriber detailing, daily prospective audit and feedback, implementation of beta-lactam-based institutional guidelines for empiric therapy in various infectious disease syndromes, review and adjustment of electronic medical record order sets containing fluoroquinolones, and intensive prescriber education. No preauthorization of levofloxacin was used during this study period. Antibiotic utilization data were collected for the time periods of August 2015 through January 2021. Correlation between levofloxacin and other broad-spectrum antibiotc use was investigated as well as the impact on Pseudomonas aeruginosa levofloxacin nonsusceptibility rates. Results Both hospitals showed an overall downward trend in the prescribing of levofloxacin during the time period of August 2015 to January 2021. There was a significant negative correlation between monthly ceftriaxone and levofloxacin days of therapy for both hospitals (P \u3c .0001). There was a positive correlation between levofloxacin days of therapy and P aeruginosa nonsusceptibility (P \u3c .02 at both hospitals). Conclusions Our results demonstrate that a nonrestrictive approach to fluoroquinolone stewardship interventions had a significant impact on reducing levofloxacin utilization, increasing ceftriaxone utilization, and improving P aeruginosa levofloxacin susceptibility

The Antibiogram: Key Considerations for Its Development and Utilization

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We also stress the importance of easy accessibility and education on antibiogram use, to allow for prescribers to select the most optimal empirical treatment regimens and propose the creation of an abbreviated antibiogram for frontline users. Multidisciplinary antimicrobial stewardship programmes are vital to accomplishing these goals

Deep learning network to correct axial and coronal eye motion in 3D OCT retinal imaging

Optical Coherence Tomography (OCT) is one of the most important retinal imaging technique. However, involuntary motion artifacts still pose a major challenge in OCT imaging that compromises the quality of downstream analysis, such as retinal layer segmentation and OCT Angiography. We propose deep learning based neural networks to correct axial and coronal motion artifacts in OCT based on a single volumetric scan. The proposed method consists of two fully-convolutional neural networks that predict Z and X dimensional displacement maps sequentially in two stages. The experimental result shows that the proposed method can effectively correct motion artifacts and achieve smaller error than other methods. Specifically, the method can recover the overall curvature of the retina, and can be generalized well to various diseases and resolutions

PhOTO Zebrafish: A Transgenic Resource for In Vivo Lineage Tracing during Development and Regeneration

Background: Elucidating the complex cell dynamics (divisions, movement, morphological changes, etc.) underlying embryonic development and adult tissue regeneration requires an efficient means to track cells with high fidelity in space and time. To satisfy this criterion, we developed a transgenic zebrafish line, called PhOTO, that allows photoconvertible optical tracking of nuclear and membrane dynamics in vivo. Methodology: PhOTO zebrafish ubiquitously express targeted blue fluorescent protein (FP) Cerulean and photoconvertible FP Dendra2 fusions, allowing for instantaneous, precise targeting and tracking of any number of cells using Dendra2 photoconversion while simultaneously monitoring global cell behavior and morphology. Expression persists through adulthood, making the PhOTO zebrafish an excellent tool for studying tissue regeneration: after tail fin amputation and photoconversion of a ~100µm stripe along the cut area, marked differences seen in how cells contribute to the new tissue give detailed insight into the dynamic process of regeneration. Photoconverted cells that contributed to the regenerate were separated into three distinct populations corresponding to the extent of cell division 7 days after amputation, and a subset of cells that divided the least were organized into an evenly spaced, linear orientation along the length of the newly regenerating fin. Conclusions/Significance: PhOTO zebrafish have wide applicability for lineage tracing at the systems-level in the early embryo as well as in the adult, making them ideal candidate tools for future research in development, traumatic injury and regeneration, cancer progression, and stem cell behavior

X-ray metal line emission from the hot circumgalactic medium: probing the effects of supermassive black hole feedback

We derive predictions from state-of-the-art cosmological galaxy simulations for the spatial distribution of the hot circumgalactic medium (CGM, ${\rm [0.1-1]R_{200c}}$) through its emission lines in the X-ray soft band ($[0.3-1.3]$ keV). In particular, we compare IllustrisTNG, EAGLE, and SIMBA and focus on galaxies with stellar mass 10^{10-11.6}\, \MSUN at $z=0$. The three simulation models return significantly different surface brightness radial profiles of prominent emission lines from ionized metals such as OVII(f), OVIII, and FeXVII as a function of galaxy mass. Likewise, the three simulations predict varying azimuthal distributions of line emission with respect to the galactic stellar planes, with IllustrisTNG predicting the strongest angular modulation of CGM physical properties at radial range ${\gtrsim0.3-0.5\,R_{200c}}$. This anisotropic signal is more prominent for higher-energy lines, where it can manifest as X-ray eROSITA-like bubbles. Despite different models of stellar and supermassive black hole (SMBH) feedback, the three simulations consistently predict a dichotomy between star-forming and quiescent galaxies at the Milky-Way and Andromeda mass range, where the former are X-ray brighter than the latter. This is a signature of SMBH-driven outflows, which are responsible for quenching star formation. Finally, we explore the prospect of testing these predictions with a microcalorimeter-based X-ray mission concept with a large field-of-view. Such a mission would probe the extended hot CGM via soft X-ray line emission, determine the physical properties of the CGM, including temperature, from the measurement of line ratios, and provide critical constraints on the efficiency and impact of SMBH feedback on the CGM.Comment: 21 pages, 15 figures. Submitted to MNRAS and received a positive referee repor

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Public health triangulation: approach and application to synthesizing data to understand national and local HIV epidemics

<p>Abstract</p> <p>Background</p> <p>Public health triangulation is a process for reviewing, synthesising and interpreting secondary data from multiple sources that bear on the same question to make public health decisions. It can be used to understand the dynamics of HIV transmission and to measure the impact of public health programs. While traditional intervention research and metaanalysis would be ideal sources of information for public health decision making, they are infrequently available, and often decisions can be based only on surveillance and survey data.</p> <p>Methods</p> <p>The process involves examination of a wide variety of data sources and both biological, behavioral and program data and seeks input from stakeholders to formulate meaningful public health questions. Finally and most importantly, it uses the results to inform public health decision-making. There are 12 discrete steps in the triangulation process, which included identification and assessment of key questions, identification of data sources, refining questions, gathering data and reports, assessing the quality of those data and reports, formulating hypotheses to explain trends in the data, corroborating or refining working hypotheses, drawing conclusions, communicating results and recommendations and taking public health action.</p> <p>Results</p> <p>Triangulation can be limited by the quality of the original data, the potentials for ecological fallacy and "data dredging" and reproducibility of results.</p> <p>Conclusions</p> <p>Nonetheless, we believe that public health triangulation allows for the interpretation of data sets that cannot be analyzed using meta-analysis and can be a helpful adjunct to surveillance, to formal public health intervention research and to monitoring and evaluation, which in turn lead to improved national strategic planning and resource allocation.</p

Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p