High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages

Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. Here, we provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. We show that early-phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific immunoglobulin G (IgG) in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. We identified that this excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19. First, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease. Second, we found that anti-spike IgG from patients with severe COVID-19 is intrinsically more proinflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Low fucosylation of anti-spike IgG was normalized in a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. We identified Fc gamma receptor (Fc gamma R) Ila and FeyRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, we show that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Last, we demonstrate that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small-molecule inhibitor of Syk kinase.Proteomic

Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers.

The percentage of faecal samples containing resistant Echerichia coli and the proportion of resistant faecal E. coli were determined in three poultry populations: broilers and turkeys commonly given antibiotics, and laying hens treated with antibiotics relatively infrequently. Faecal samples of five human populations were also examined: turkey farmers, broiler farmers, laying-hen farmers, broiler slaughterers and turkey slaughterers. The MICs of antibiotics commonly used in poultry medicine were also determined. Ciprofloxacin-resistant isolates from these eight populations and from turkey meat were genotyped by pulsed-field gel electrophoresis (PFGE) after SmaI digestion. The proportion of samples containing resistant E. coli and the percentages of resistant E. coli were significantly higher in turkeys and broilers than in the laying-hen population. Resistance to nearly all antibiotics in faecal E. coli of turkey and broiler farmers, and of turkey and broiler slaughterers, was higher than in laying-hen farmers. Multiresistant isolates were common in turkey and broiler farmers but absent in laying-hen farmers. The same resistance patterns were found in turkeys, turkey farmers and turkey slaughterers and in broiler, broiler farmers and broiler slaughterers. The PFGE patterns of the isolates from the eight populations were quite heterogeneous, but E. coli with an identical PFGE pattern were isolated at two farms from a turkey and the farmer, and also from a broiler and a broiler farmer from different farms. Moreover, three E. coli isolates from turkey meat were identical to faecal isolates from turkeys. The results of this study strongly indicate that transmission of resistant clones and resistance plasmids of E. coli from poultry to humans commonly occurs

Antibiotic use and the prevalence of antibiotic resistance in bacteria from healthy volunteers in the dutch community.

Item does not contain fulltextBACKGROUND: Although most antibiotics are consumed in the community (80%), the relation of antibiotic consumption and resistance in the community has not been thoroughly studied. MATERIALS AND METHODS: In the present study, antibiotic use was related to the prevalence of antibiotic resistance of Escherichia coli and enterococci isolated from healthy volunteers living in the southern part of the Netherlands in 1996 and 1999. RESULTS: No change in the total antibiotic use in the Dutch community was observed between 1996 and 1999 (3542 and 3598 defined daily doses [DDD] per 1000 inhabitants/year). However, the increased fluoroquinolone use (+ 18%) and the increased prevalence of ciprofloxacin resistance from 0 to 2% is a point of concern, especially since this was accompanied by a significant shift towards higher minimum inhibitory concentration (MIC) values (p < 0.05). A significant decrease in the prevalence of vancomycin-resistant enterococci (p < 0.05) was found in addition to a significant shift towards lower MIC valued for avoparcin, a glycopeptide previously used as growth promoter in animal husbandry (p < 0.05). This was very likely due to the banning of avoparcin for this purpose from April 1997 onwards. CONCLUSION: In order to maintain the low level of antibiotic use and resistance in The Netherlands, surveillance of antibiotic resistance in nonclinical isolates in relation to antibiotic use is very important

Influence of population density on antibiotic resistance

Antibiotic consumption and population density as a measure of crowding in the community were related to the prevalence of antibiotic resistance of three cities in three different countries: St Johns in Newfoundland (Canada), Athens in Greece and Groningen in The Netherlands. Antibiotic consumption was expressed in DDD (defined daily dose), as DID (DDD/1000 inhabitants/day) and as DSD (DDD/km2). The prevalence of antibiotic-resistant Escherichia coli and enterococci was determined in faecal samples of healthy volunteers. In both Newfoundland (28 DID) and Greece (29 DID) the overall consumption of antibiotics was more than three times higher compared with that of The Netherlands (9 DID). The lowest prevalence of resistant E. coli against the majority of antibiotics tested was found for the samples from Newfoundland and was significant (P&amp;lt; 0.05) for cefazolin, oxytetracycline and trimethoprim. A poor correlation between the number of DID and the prevalence of resistance was observed [the Pearson correlation coefficient (Pcc) ranged between -0.93 and 0.87]. However, when population density was taken into consideration and antibiotic consumption was expressed in DSD, a strong correlation was observed (and Pcc ranged between 0.86 and 1.00). This study suggests that population density is an important factor in the development of antibiotic resistance and warrants special attention as a factor in resistance epidemiology

Maastrichtse Sociale Netwerk Analyse voor mensen met een verstandelijke beperking (MSNA-VB). Handleiding

Deze handleiding is onderdeel van de training "Werken met sociale netwerken van mensen met een verstandelijke beperking" (zie link 2) en heeft tot doel om begeleiders en studenten te leren werken met het instrument MSNA-VB. Met dit instrument kan het sociale netwerk van mensen met een lichte verstandelijke beperking in kaart worden gebracht. Deze training maakt deel uit van het trainingspakket: Ondersteuning aan mensen met een verstandelijke beperking: 4 trainingen in werken met sociale netwerken en aansluiten bij cliënten en hun ouders. Dit trainingspakket is ontwikkeld door het lectoraat Zorg voor Mensen met een Verstandelijke Beperking van de Hogeschool van Arnhem en Nijmegen. Bijbehorende materialen: Bestand 1: Handleiding MSNA-VB Bestand 2: MSNA-VB instrument: werkmaterialen voor het werken met het MSNA-VB instrument (MSNA-VB kaart 1-2-3, Ecogram, Trap van Vijf,Wensenformulier). Bij deze handleiding hoort tevens een trainingsfilm met handleiding, getiteld: Afname van de Maastrichtse Sociale Netwerk Analyse voor mensen met een Verstandelijke Beperking (MSNA-VB). Voor de handleiding bij de trainingsfilm zie link 1. Via deze link is tevens de trainingsfilm beschikbaar. Inhoudelijke informatie: De MSNA is een instrument waarmee het sociale netwerk van personen in kaart wordt gebracht. De MSNA biedt een samenhangend geheel van nauwkeurige informatie over de kwaliteit van het sociale netwerk van een persoon en maakt zichtbaar in welke mate er sprake is van sociale integratie dan wel van sociaal isolement. De MSNA is ontwikkeld aan de Universiteit Maastricht. Aanvankelijk werd de MSNA toegepast bij psychiatrische patiënten. Later werd het instrument ook bij andere doelgroepen gebruikt, zoals cliënten van de reclassering waaronder brandstichters en drugsverslaafden, maar ook bij fybromyalgie patiënten, Keniaase straatkinderen en mensen met een verstandelijke beperking. Voor deze laatste doelgroep is de MSNA aangepast. De MSNA-VB ontstond: de MSNA,aangepast voor afname bij mensen met een verstandelijke beperking. In de MSNA-VB is meer gebruik gemaakt van visualisatie, de woordkeuze bij de vraagstelling is aangepast en er zijn enkele vragen toegevoegd. Er bestond reeds een handleiding voor de MSNA in het algemeen (Baars, 1997), maar gezien de wijzigingen aan het instrument om deze te kunnen gebruiken bij mensen met een verstandelijke beperking, was een specifieke handleiding voor deze doelgroep wenselijk

Resistência a antimicrobianos de Escherichia coli isolada de dejetos suínos em esterqueiras Antibiotic-resistance of Escherichia coli isolates from stored pig slurry

<abstract language="eng">The antimicrobial resistance of 96 Escherichia coli strains isolated from a stabilization pond system on a pig-breeding farm was evaluated. Strains were tested for their resistance against 14 antimicrobial using the agar diffusion method. E. coli strains showed resistance to tetracycline (82.3%), nalidixic acid (64%), ampicilin (41%), sulfamethoxazole/trimethoprin (36%), sulfonamide (34%), cloranphenicol (274%), ciprofloxacin (19%), cefaclor (16%), streptomicyn (7.3%), neomicyn (1%), amoxacilin/ clavulanic acid (1%), and amikacin (1%). No resistance was observed to gentamicin and tobramycin, and 37.5% of E. coli strains were resistant to four or more antimicrobials. The multiresistance pattern was found in strains isolated during all sampled period. Strains showed a high variability in the antimicrobial resistance pattern