The rise in multidrug resistant bacteria is an area of growing concern and it is essential to identify new biocidal agents. Cationic grafted compounds were investigated for their antimicrobial ...properties using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Synergy testing was carried out using the compounds in the presence of ultraviolet (UV). Fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) tests were carried out using the cationic molecules in conjunction with metal ion solutions of gold, silver, palladium, platinum, rhodium, titanium, tin, vanadium and molybdenum. Individually, the cationic compounds containing quaternary amines, polyphenylene vinylene (PPV) with long polyacrylate grafts (
PPV-
g
-PMETAC
(HMw)), polyphenylene ethylene (PPE) with long polyacrylate grafts (
PPE-
g
-PMETAC
(HMw)), polyphenylene vinylene (PPV) with short polyacrylate grafts (
PPV-
g
-PMETAC
(LMw)) and polyphenylene ethylene (PPE) with short polyacrylate grafts (
PPE-
g
-PMETAC
(LMw)) were effective against
Enterococcus faecium
. The most successful compound under UV was
PPV-
g
-PMETAC
(HMw). Following the FICs, palladium and rhodium ion solutions caused a synergistic reaction with all four tested compounds. The presence of conjugated bonds in the cationic molecules increased its antimicrobial activity. These results suggest that the chemical backbone of the compounds, alongside the chain lengths and chain attachment affect the antimicrobial efficacy of a compound. These factors should be taken into consideration when formulating new biocidal combinations.
The rise in multidrug resistant bacteria is an area of growing concern and it is essential to identify new biocidal agents.
Tixagevimab-cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab-cilgavimab versus ...placebo, in patients receiving remdesivir and other standard care.
In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg-cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab-cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing.
From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab-cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab-cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio RRR 1·08 95% CI 0·97-1·20; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 0·97-1·34; p=0·13). Mortality was lower in the tixagevimab-cilgavimab group (61 9%) versus placebo group (86 12%; hazard ratio HR 0·70 95% CI 0·50-0·97; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab-cilgavimab and 212 (30%) placebo group participants (HR 0·83 0·68-1·01; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab-cilgavimab group and 38 (5%) in the placebo group.
Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab-cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower.
US National Institutes of Health (NIH) and Operation Warp Speed.
The article reports on the case of a 39-year-old woman with rapidly progressive respiratory failure. She was found to have adenovirus infection, disseminated. The different treatment methodologies ...and management strategies for adenovirus infection are highlighted.
Background: Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated ...with filter clotting during continuous renal replacement therapy (CRRT). The incidence, clinical features, and treatment strategies to address severe filter clotting in patients with COVID-19 is unknown.
Aim: We aimed to characterize the burden of CRRT filter clotting in patients with COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing.
Methods: Consecutive patients with confirmed COVID-19 infection admitted between March 16, 2020 and April 27, 2020 who required CRRT were included in this multi-center retrospective study. Severe clotting was defined as >2 filter losses in 48 hours or one filter loss <8 hours into CRRT. Primary outcome was time to CRRT filter loss. Due to the unreliability of PTT levels in patients with COVID-19, a COVID-specific CRRT anticoagulation protocol (referred to as protocol henceforth) which dosed systemic unfractionated heparin (UFH) by anti-factor Xa levels was piloted at one center starting April 13, 2020.
Given that there was no difference in the treatment plan from CRRT initiation to first filter loss between the two anticoagulation approaches, this period served as a run-in period. Time from first to second filter loss (where protocol patients were exposed to low systemic UFH dosing) and time from second to third filter loss (where protocol patients were exposed to high systemic UFH dosing) were analyzed with a log-rank test.
Results: Sixty-five patients were analyzed, with 17 using the anti-factor Xa protocol to guide systemic heparin dosing whereas 48 were treated with standard of care anticoagulation dosed by PTT . There were no major differences between groups in age, sex, race, ethnicity, body mass index, or baseline medications. Fifty-seven out of 65 patients (88%) initiated CRRT for AKI, whereas 8/65 patients (12%) had end stage renal disease. At the time of CRRT initiation, 64/65 patients (98%) were mechanically ventilated, 22/65 patients (34%) required prone ventilation, and 59/65 patients (91%) were on intravenous vasopressors. Patients spent a median of 6 2, 13 days on CRRT.
Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 2.5, 33.5 hours. There was no difference between groups in percentage who lost their first filter (88% vs. 81%), or second filter (73% vs. 72%). However, fewer patients in the protocol group lost their third filter (55% vs. 93%) resulting in a longer median third filter survival time (24 15.1, 54.2 vs. 17.3 9.5, 35.1 hours, p = 0.04), Figure 1.
Conclusions: The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is a reasonable approach to anticoagulation in this population.
Display omitted
Rosovsky:Bristol-Myers Squibb: Consultancy, Research Funding; Portola: Consultancy; Janssen: Consultancy, Research Funding; Dova: Consultancy. Sise:EMD-Serono: Research Funding; Abbvie: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Bioporto: Consultancy. Steele:HealthReveal: Consultancy; Blackstone Life Sciences: Consultancy. Czarnecki:Alexion: Consultancy; Reata: Consultancy. Allegretti:Mallinckrodt Pharmaceuticals: Consultancy.
Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might ...represent a novel pathologic entity.
How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza?
We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients.
In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients.
DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.
PDF
