Impact of rapid susceptibility testing on antimicrobial therapy and clinical outcomes in Gram-negative bloodstream infections.

BACKGROUND: Rapid antimicrobial susceptibility testing (rAST) has the potential to improve care of bloodstream infections. OBJECTIVES: The aim of this service evaluation was to assess the impact of rAST on antimicrobial therapy and clinical outcomes in patients with Gram-negative bloodstream infection. METHODS: A prospective service evaluation was conducted from March 2018 to December 2018. A rAST system (Alfred 60AST) was run Monday-Friday before midday and results were communicated to clinicians on the same day as positive blood culture, with subsequent conventional AST performed. Times to antibiotic therapy and clinical outcomes were compared between rAST and conventional AST. RESULTS: One hundred and ninety-one patients with Gram-negative bacteraemia were included (93 in the rapid group and 98 in the conventional group). Aminoglycoside combination therapy was stopped earlier in the rapid group [32 h (0-795) versus 54 h (4-216), P = 0.002]. The median time to optimal antibiotic based on AST results was significantly shorter than that in the conventional group [50 h (10-339) versus 69.5 h (20-872), P = 0.034]. In the subgroup of patients on ineffective empirical antibiotic, time to effective antibiotic was shorter in the rapid group [39.5 h (32-97) versus 57 h (49-83), P = 0.036]. No differences were found in 28 day mortality or length of stay. CONCLUSIONS: Rapid susceptibility testing resulted in faster discontinuation of aminoglycosides and a shorter time to starting effective and optimal antibiotic when compared with conventional AST results. rAST has potential clinical benefits and points to the need for larger future studies in areas of high antibiotic resistance

National action plans for antimicrobial resistance and variations in surveillance data platforms

Objective To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization’s (WHO’s) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO’s Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control’s (ECDC’s) network and Pfizer’s Antimicrobial Testing Leadership and Surveillance database. Using Bland–Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer’s database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO’s and Pfizer’s platforms for organism–country susceptibility data ranged from −26% to 35%. While mean susceptibilities of WHO’s and ECDC‘s platforms did not differ (bias: 0%, 95% confidence interval: −2 to 2), concordance between organism–country susceptibility was low (limits of agreement −18 to 18%). Significant differences exist in isolate numbers reported between WHO–Pfizer (mean of difference: 674, P-value: < 0.001 and WHO–ECDC (mean of difference: 192, P value: 0.04) platforms. Conclusion The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and address surveillance platform variability and its underlying mechanisms

Freestanding n-Doped Graphene via Intercalation of Calcium and Magnesium into the Buffer Layer - SiC(0001) Interface

The intercalation of epitaxial graphene on SiC(0001) with Ca has been studied extensively, yet precisely where the Ca resides remains elusive. Furthermore, the intercalation of Mg underneath epitaxial graphene on SiC(0001) has not been reported. Here, we use low energy electron diffraction, x-ray photoelectron spectroscopy, secondary electron cut-off photoemission and scanning tunneling microscopy to elucidate the physical and electronic structure of both Ca- and Mg-intercalated epitaxial graphene on 6H-SiC(0001). We find that Ca intercalates underneath the buffer layer and bonds to the Si-terminated SiC surface, breaking the C-Si bonds of the buffer layer i.e. 'freestanding' the buffer layer to form Ca-intercalated quasi-freestanding bilayer graphene (Ca-QFSBLG). The situation is similar for the Mg-intercalation of epitaxial graphene on SiC(0001), where an ordered Mg-terminated reconstruction at the SiC surface and Mg bonds to the Si-terminated SiC surface are formed, resulting in Mg-intercalated quasi-freestanding bilayer graphene (Mg-QFSBLG). Ca-intercalation underneath the buffer layer has not been considered in previous studies of Ca-intercalated epitaxial graphene. Furthermore, we find no evidence that either Ca or Mg intercalates between graphene layers. However, we do find that both Ca-QFSBLG and Mg-QFSBLG exhibit very low workfunctions of 3.68 and 3.78 eV, respectively, indicating high n-type doping. Upon exposure to ambient conditions, we find Ca-QFSBLG degrades rapidly, whereas Mg-QFSBLG remains remarkably stable.Comment: 58 pages, 10 figures, 4 tables. Revised text and figure

Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study.

OBJECTIVES: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). METHODS: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). RESULTS: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. CONCLUSION: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms

Collaborative database to track Mass Mortality Events in the Mediterranean Sea

Anthropogenic climate change, and global warming in particular, has strong and increasing impacts on marine ecosystems (Poloczanska et al., 2013; Halpern et al., 2015; Smale et al., 2019). The Mediterranean Sea is considered a marine biodiversity hotspot contributing to more than 7% of world\u2019s marine biodiversity including a high percentage of endemic species (Coll et al., 2010). The Mediterranean region is a climate change hotspot, where the respective impacts of warming are very pronounced and relatively well documented (Cramer et al., 2018). One of the major impacts of sea surface temperature rise in the marine coastal ecosystems is the occurrence of mass mortality events (MMEs). The first evidences of this phenomenon dated from the first half of \u201980 years affecting the Western Mediterranean and the Aegean Sea (Harmelin, 1984; Bavestrello and Boero, 1986; Gaino and Pronzato, 1989; Voultsiadou et al., 2011). The most impressive phenomenon happened in 1999 when an unprecedented large scale MME impacted populations of more than 30 species from different phyla along the French and Italian coasts (Cerrano et al., 2000; Perez et al., 2000). Following this event, several other large scale MMEs have been reported, along with numerous other minor ones, which are usually more restricted in geographic extend and/or number of affected species (Garrabou et al., 2009; Rivetti et al., 2014; Marb\ue0 et al., 2015; Rubio-Portillo et al., 2016, authors\u2019 personal observations). These events have generally been associated with strong and recurrent marine heat waves (Crisci et al., 2011; Kersting et al., 2013; Turicchia et al., 2018; Bensoussan et al., 2019) which are becoming more frequent globally (Smale et al., 2019). Both field observations and future projections using Regional Coupled Models (Adloff et al., 2015; Darmaraki et al., 2019) show the increase in Mediterranean sea surface temperature, with more frequent occurrence of extreme ocean warming events. As a result, new MMEs are expected during the coming years. To date, despite the efforts, neither updated nor comprehensive information can support scientific analysis of mortality events at a Mediterranean regional scale. Such information is vital to guide management and conservation strategies that can then inform adaptive management schemes that aim to face the impacts of climate change

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta