The underlying mechanisms by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect host resistance to Pseudomonas aeruginosa are unclear. The aim of this study was to determine ...their role on the kinetic of pro- and antiinflammatory response in lung infection. Mice fed either a control diet or a diet enriched with EPA and DHA were infected intratracheally and we studied lung expression of proinflammatory markers CXCL1, interleukin (IL)-6, tumor necrosis factor-α, antiinflammatory markers (IL-10, A20, and IκBα), and PPARα and PPARγ. The inflammatory response was assessed using recruitment of neutrophils and macrophages into bronchoalveolar lavage fluid, bacterial clearance from the lung, pulmonary injury, and 7-d survival rate. Compared with the control group, EPA and DHA delayed the expression of proinflammatory markers during the first 2 h (P < 0.05), upregulated proinflammatory marker expression (P < 0.05), and induced overexpression of antiinflammatory markers at 8 h (P < 0.05), enhanced recruitment of neutrophils at 16 h (P < 0.05), and induced PPARα and PPARγ overexpression at 4 and 8 h (P < 0.01), respectively. Pulmonary bacterial load decreased and pulmonary injury and mortality were reduced during the first 24 h (P < 0.05). In conclusion, EPA and DHA modulate the balance between pro- and antiinflammatory cytokines, alter the early response of the host to P. aeruginosa infection, and affect the early outcome of infection.
•HCoV−OC43 is involved in healthcare–associated infections.•HCoV−OC43 genotypes B, E, F and G are identified.•Asian and European strains of HCoV−OC43 circulate among patients.
While respiratory viral ...infections are recognized as a frequent cause of illness in hematopoietic stem cell transplantation (HSCT) recipients, HCoV−OC43 infections have rarely been investigated as healthcare-associated infections in this population.
In this report, HCoV−OC43 isolates collected from HSCT patients were retrospectively characterized to identify potential clusters of infection that may stand for a hospital transmission.
Whole-genome and S gene sequences were obtained from nasal swabs using next-generation sequencing and phylogenetic trees were constructed. Similar identity matrix and determination of the most common ancestor were used to compare clusters of patient’s sequences. Amino acids substitutions were analysed.
Genotypes B, E, F and G were identified. Two clusters of patients were defined from chronological data and phylogenetic trees. Analyses of amino acids substitutions of the S protein sequences identified substitutions specific for genotype F strains circulating among European people.
HCoV−OC43 may be implicated in healthcare-associated infections.
The magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to ...conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies.
DIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions.
A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database.
From January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%).
The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study.
Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies.
These results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.
Display omitted
•Difficulties to maintain prospective surveillance.•Added value of a free electronic tool for increasing the reliable knowledge of CDI.•An easy tool to include the surveillance of CDI into a daily monitoring.•A generation of data to be shared at national and international level.
Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and ...M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15
M-MDSCs) was associated with overall mortality (
= 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15
M-MDSCs was a good predictor of mortality (
= 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4-1.0) and 0.86 (0.62-1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.
‘In the name of common sense’ – Author's reply Meylan, Sylvain; Guery, Benoit
Clinical microbiology and infection,
December 2020, 2020-12-00, 20201201, Volume:
26, Issue:
12
Journal Article
Objective
To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin.
Methods
This ...prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients.
Results
At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported.
Conclusions
Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.
Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.
Objectives: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated diarrhea, often complicated by severe infection and recurrence with increased morbidity and ...mortality. Data from large cohorts in Switzerland are scarce. We aimed to describe diagnostic assays, treatment, outcomes, and risk factors for CDI in a large cohort of patients in Switzerland. Methods: We conducted a retrospective cohort study of CDI episodes diagnosed in patients from two tertiary care hospitals in Switzerland. During a 3-month follow-up, we used a composite outcome combining clinical cure at day 10, recurrence at week 8, or death, to evaluate a patient’s response. Unfavorable outcomes consisted in the occurrence of any of these events. Results: From January 2014 to December 2018, we included 826 hospitalized patients with documented CDI. Overall, 299 patients (36.2%) had a severe infection. Metronidazole was used in 566 patients (83.7%), compared to 82 patients (12.1%) treated with vancomycin and 28 patients (4.1%) treated with fidaxomicin. Overall mortality at week 8 was at 15.3% (112/733). Eighty-six patients (12.7%) presented with clinical failure at day 10, and 78 (14.9%) presented with recurrence within 8 weeks; 269 (39.8%) met the composite outcome of death, clinical failure, or recurrence. The Charlson Comorbidity Index score (p < 0.001), leukocytes > 15 G/L (p = 0.008), and the use of metronidazole (p = 0.012) or vancomycin (p = 0.049) were factors associated with the composite outcome. Conclusions: Our study provides valuable insights on CDI treatment and outcomes in Switzerland, highlights the heterogeneity in practices among centers, and underlines the need for the active monitoring of clinical practices and their impact on clinical outcomes through large multicentric cohorts.
Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational ...study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.
The pathogenesis and the outcome of Pseudomonas aeruginosa ventilator-acquired pneumonia depend on the virulence factors displayed by the bacteria as well as the host response. Thus, quorum sensing, ...lipopolysaccharide, and type 3 secretion system have each individually been shown to be important virulence systems in laboratory reference strains. However, the relative contribution of these three factors to the in vivo pathogenicity of clinically relevant strains has never been studied. We analyzed the virulence of 56 nonclonal Pseudomonas aeruginosa strains isolated from critically ill patients with ventilator-acquired pneumonia. To avoid the variation of human immune response, we used a murine model of pneumonia. The aim was to determine which virulence factor was the most important.
Research laboratory of a university.
Male adult BALB/c mice.
In vitro, the phenotype of each strain was established as to the expression of quorum sensing-regulated factors (elastase and pyocyanin), type 3 secretion system exotoxin secretion (Exotoxin U, S and/or T, or "nonsecreting"), and lipopolysaccharide O-antigen serotype. Strain pathogenicity was evaluated in vivo in a mouse model of acute pneumonia through lung injury assessment by measuring alveolar-capillary barrier permeability to proteins, lung wet/dry weight ratio, and bacterial dissemination. Associations were then sought between virulence system phenotypes and levels of lung injury.
In univariate analysis, elastase production, O11 serotype, and type 3 secretion system exotoxin secretion were associated with increased lung injury and exotoxin U was linked to an increase risk of bacteremia. In multivariate analysis, we observed that type 3 secretion system exotoxin secretion and to a lesser degree elastase production were associated with increased lung injury.
In a murine model of pneumonia, our data suggest that type 3 secretion system and elastase are the most important virulence factors in clinically relevant P. aeruginosa strains.
The murine norovirus (MNV) is a recently discovered mouse pathogen, representing the most common contaminant in laboratory mouse colonies. Nevertheless, the effects of MNV infection on biomedical ...research are still unclear. We tested the hypothesis that MNV infection could alter immune response in mice with acute lung infection. Here we report that co-infection with MNV increases survival of mice with Pseudomonas aeruginosa acute lung injury and decreases in vivo production of pro-inflammatory cytokines. Our results suggest that MNV infection can deeply modify the parameters studied in conventional models of infection and lead to false conclusions in experimental models.
PDF
