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Molecular epidemiology and drug-resistance mechanisms in carbapenem-resistant Klebsiella pneumoniae isolated in patients from a tertiary hospital in …
2020
Abstract Objectives The aim of this study has been to characterize carbapenem-resistant Klebsiella pneumoniae isolates and to determine the resistance mechanisms involved, the clonal relationship between strains and clinical and demographical data of the infected patients. Methods Clinical and demographical data from patients were collected and statistically analysed. Antimicrobial susceptibility testing was performed and resistance genes were detected both phenotypically and genotypically. Conjugation assays were performed to show horizontal transferability of resistance genes. Clonal relationship was also studied. Next-generation sequencing (NGS) was performed to obtain information regard…
The clinical impact of PCR‐based point‐of‐care diagnostic in respiratory tract infections in children
2020
Abstract Background Children are commonly affected by respiratory tract infections. Based on clinical symptoms, laboratory evaluation, and imaging, the causative pathogen often cannot be delineated. Point‐of‐care‐testing systems that provide an opportunity for fast detection of common viruses and some bacteria can therefore influence treatment's options. We aimed to examine whether the Biofire® FilmArray® has an effect on antibiotic treatment, duration of antibiotic therapy, and length of hospital stay within a pediatric cohort. Methods We included children who were admitted to inpatient treatment with an acute respiratory tract infection from 02/2017 to 04/2018 using the FA respiratory pan…
Molecular characterisation of quinolone-resistant Shigella strains isolated in Tehran, Iran.
2016
Over the past few years, the number of Shigella strains resistant to nalidixic acid has increased and has made the selection of effective antimicrobial therapy more difficult. The purpose of this study was to investigate the molecular mechanism of quinolone resistance in Shigella strains. Shigella strains isolated from 1100 diarrhoeal patients in Tehran, Iran, were assessed for their susceptibility to nalidixic acid prior to PCR-RFLP and sequence analysis of their quinolone resistance genes. Among 73 Shigella strains isolated, 23 (31.5%) were resistant to nalidixic acid. The most common Shigella spp. was Shigella sonnei (54; 74.0%). Of the 23 quinolone-resistant isolates, 4 (17.4%) (includi…
Long‐term treatment with the oncolytic ECHO‐7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a his…
2016
Oncolytic virotherapy is a recent addition to cancer treatment. Here, we describe positive treatment outcomes in three patients using Rigvir virotherapy. One of the patients is diagnosed with melanoma stage IV M1c, one with small cell lung cancer stage IIIA, and one with histiocytic sarcoma stage IV. The diagnoses of all patients are verified by histology or cytology. All patients started Rigvir treatment within a few months after being diagnosed and are currently continuing Rigvir treatment. The degree of regression of the disease has been determined by computed tomography. Safety assessment of adverse events graded according to NCI CTCAE did not show any value above grade 1 during Rigvir(…
Spread of Klebsiella pneumoniae ST395 non-susceptible to carbapenems and resistant to fluoroquinolones in North-Eastern France
2017
Abstract Objectives Fluoroquinolones (FQs) are a potential treatment for infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae that are susceptible to these agents. Methods Owing to increasing non-susceptibility to carbapenems among Enterobacteriaceae, in this study FQ resistance mechanisms were characterised in 36 ertapenem-non-susceptible Klebsiella pneumoniae isolated from North-Eastern France in 2012. The population structure was described by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Among the 36 isolates, 13 (36%) carried a carbapenemase encoding-gene. Decreased expression of the OmpK35-encoding gene might be…
Immunodominant Cytomegalovirus Epitopes Suppress Subdominant Epitopes in the Generation of High-Avidity CD8 T Cells
2021
CD8+ T-cell responses to pathogens are directed against infected cells that present pathogen-encoded peptides on MHC class-I molecules. Although natural responses are polyclonal, the spectrum of peptides that qualify for epitopes is remarkably small even for pathogens with high coding capacity. Among those few that are successful at all, a hierarchy exists in the magnitude of the response that they elicit in terms of numbers of CD8+ T cells generated. This led to a classification into immunodominant and non-immunodominant or subordinate epitopes, IDEs and non-IDEs, respectively. IDEs are favored in the design of vaccines and are chosen for CD8+ T-cell immunotherapy. Using murine cytomegalov…
Fast-Growing Alveolar Echinococcosis Following Lung Transplantation
2020
International audience; Alveolar echinococcosis is a rare but life-threatening infection caused by the parasiteEchinococcus multilocularis. Its natural history is characterized by a slow parasitic growth over several years. Increased incidence and shorter development delay have been reported in immune-compromised patients. We report the reactivation of aborted lesions within 12 months of lung transplantation leading to a fast-growing aggressive hepatic lesion. Timely identification of alveolar echninococcosis allowed prompt albendazole treatment and radical surgery leading to a favorable outcome 42 months after transplantation. However, close clinical, serological and radiological monitorin…
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
2019
Summary While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressi…
Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.
2016
Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGI…
The Mouse Cytomegalovirus Gene m42 Targets Surface Expression of the Protein Tyrosine Phosphatase CD45 in Infected Macrophages
2016
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264.7 macrophage cell line led to comparable regulation of CD45 expression. In immunocompetent mice infected with an m42 del…