A whiff of C-diff::using scent detection to diagnose Clostridium difficile infection

Smulders, Y.M. [Promotor]Vandenbroucke-Grauls, C.M.J.E. [Promotor]Agtmael, M.A. van [Copromotor

An Outbreak of Clostridium difficile Ribotype 027 Associated with Length of Stay in the Intensive Care Unit and Use of Selective Decontamination of the Digestive Tract: A Case Control Study

Clinical epidemiolog

Third-generation cephalosporin resistant gram-negative bacteraemia in patients with haematological malignancy; an 11-year multi-centre retrospective study

Objectives Among patients with haematological malignancy, bacteraemia is a common complication during chemotherapy-induced neutropenia. Resistance of gram-negative bacteria (GNB) to third-generation cephalosporins (3GC) is increasing. In order to explore the value of using surveillance cultures to guide empirical treatment e.g. choosing between carbapenem versus ceftazidime- we aimed to assess the distribution of pathogens causing bacteraemia in patients with haematological malignancy, and the proportion of 3GC-resistant GNB (3GC-R GNB) bacteraemia that was preceded by 3GC-R GNB colonization. Methods Using 11 years of data (2008-2018) from the Dutch national antimicrobial resistance surveillance system, we assessed the prevalence of 3GC-R GNB in episodes of bacteraemia, and the proportion of 3GC-R GNB bacteraemia that was preceded by 3GC-R GNB colonization. Colonization was defined as availability of any GNB surveillance isolate in the year before, independent of the causative micro-organism (time-paired isolates). Results We included 3887 patients, representing 4142 episodes of bacteraemia. GNB were identified in 715/4142 (17.3%), of which 221 (30.9%) were 3GC-R GNB. In 139 of these 221 patients a time-paired surveillance culture was available. In 76.2% (106/139) of patients these surveillance cultures already showed 3GC-R GNB isolates in the year prior to the culture date of the 3GC-R GNB positive blood isolate. Conclusions This multi-centre study shows that in patients with haematological malignancy, the majority of 3GC-R GNB bacteraemia is preceded by 3GC-R GNB colonization. Prospective clinical studies are needed to assess the safety and benefits of the use of surveillance-cultures to guide empirical therapy to restrict the empirical use of carbapenems in this population.Immunogenetics and cellular immunology of bacterial infectious disease

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees

Background Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced Fc gamma RIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. Methods Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Findings Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen -experienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen -experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 expression in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose. Interpretation Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence