Activity of Daptomycin or Linezolid in Combination with Rifampin or Gentamicin Against Biofilm-Forming Enterococcus faecalis or E. faecium in an In Vitro Pharmacodynamic Model Using Simulated Endocardial Vegetations and an In Vivo Survival Assay Using Galleria mellonella Larvae

Enterococci are the third most frequent cause of infective endocarditis. A high-inoculum stationary-phase in vitro pharmacodynamic model with simulated endocardial vegetations was used to simulate the human pharmacokinetics of daptomycin at 6 or 10 mg/kg of body weight/day or linezolid at 600 mg every 12 h (q12h), alone or in combination with gentamicin at 1.3 mg/kg q12h or rifampin at 300 mg q8h or 900 mg q24h. Biofilm-forming, vancomycin-susceptible Enterococcus faecalis and vancomycin-resistant Enterococcus faecium (vancomycin-resistant enterococcus [VRE]) strains were tested. At 24, 48, and 72 h, all daptomycin-containing regimens demonstrated significantly more activity (decline in CFU/g) than any linezolid-containing regimen against biofilm-forming E. faecalis. The addition of gentamicin to daptomycin (at 6 or 10 mg/kg) in the first 24 h significantly improved bactericidal activity. In contrast, the addition of rifampin delayed the bactericidal activity of daptomycin against E. faecalis, and the addition of rifampin antagonized the activities of all regimens against VRE at 24 h. Also, against VRE, the addition of gentamicin to linezolid at 72 h improved activity and was bactericidal. Rifampin significantly antagonized the activity of linezolid against VRE at 72 h. In in vivo Galleria mellonella survival assays, linezolid and daptomycin improved survival. Daptomycin at 10 mg/kg improved survival significantly over that with linezolid against E. faecalis. The addition of gentamicin improved the efficacy of daptomycin against E. faecalis and those of linezolid and daptomycin against VRE. We conclude that in enterococcal infection models, daptomycin has more activity than linezolid alone. Against biofilm-forming E. faecalis, the addition of gentamicin in the first 24 h causes the most rapid decline in CFU/g. Of interest, the addition of rifampin decreased the activity of daptomycin against both E. faecalis and VRE

The Impact of Antimicrobial Resistance and Aging in VAP Outcomes: Experience from a Large Tertiary Care Center

Background: Ventilator associated pneumonia (VAP) is a serious infection among patients in the intensive care unit (ICU). Methods: We reviewed the medical charts of all patients admitted to the adult intensive care units of the Massachusetts General Hospital that went on to develop VAP during a five year period. Results: 200 patients were included in the study of which 50 (25%) were infected with a multidrug resistant pathogen. Increased age, dialysis and late onset (≥5 days from admission) VAP were associated with increased incidence of resistance. Multidrug resistant bacteria (MDRB) isolation was associated with a significant increase in median length of ICU stay (19 vs. 16 days, p = 0.02) and prolonged duration of mechanical ventilation (18 vs. 14 days, p = 0.03), but did not impact overall mortality (HR 1.12, 95% CI 0.51–2.46, p = 0.77). However, age (HR 1.04 95% CI 1.01–1.07, p = 0.003) was an independent risk factor for mortality and age ≥65 years was associated with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections (OR 2.83, 95% CI 1.27–6.32, p = 0.01). Conclusions: MDRB-related VAP is associated with prolonged ICU stay and mechanical ventilation. Interestingly, age ≥ 65 years is associated with MRSA VAP

The Effects of Enterprise Systems on the Absorptive Capacity of Greek Firms

In the highly dynamic, competitive, complex and ‘knowledge intensive’ modern economy the exploitation and management of external knowledge has become of critical importance for the success of firms, and this has led to increasing interest of both researchers and practitioners in the concept of firm’s absorptive capacity (ACAP). It has been recognized that information and communication technologies (ICT) can be quite useful for the improvement of firms’ ACAP. Some empirical research has been conducted in this direction, which however has not examined the role from this perspective of the most important ICT investments of firms: the different types of enterprise systems (ES) implemented by firms increasingly, which become critical infrastructures of their operation. This paper contributes to filling this research gap, by presenting an empirical investigation of the effects of the five most important and widely used types of enterprise systems (ERP, CRM, SCM, business intelligence/business analytics and collaboration support systems) on the ACAP of Greek firms. It is based on data collected through a survey from 122 Greek firms from both manufacturing and services sectors, which are used for the estimation of regression models of firm’s ACAP. It has been concluded that the use of three of the above types of ES, the ERP, the CRM and the business intelligence/business analytics ones, have positive effects on firm’s ACAP, which concern mainly two of its dimensions: the internal diffusion and analysis of external knowledge, and also the assimilation/integration in the knowledge base of the firm

Nocardiosis of the Central Nervous System: Experience From a General Hospital and Review of 84 Cases From the Literature

Abstract Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Invertebrate models of fungal infection

AbstractThe morbidity, mortality and economic burden associated with fungal infections, together with the emergence of fungal strains resistant to current antimicrobial agents, necessitate broadening our understanding of fungal pathogenesis and discovering new agents to treat these infections. Using invertebrate hosts, especially the nematode Caenorhabditis elegans and the model insects Drosophila melanogaster and Galleria mellonella, could help achieve these goals. The evolutionary conservation of several aspects of the innate immune response between invertebrates and mammals makes the use of these simple hosts an effective and fast screening method for identifying fungal virulence factors and testing potential antifungal compounds. The purpose of this review is to compare several model hosts that have been used in experimental mycology to-date and to describe their different characteristics and contribution to the study of fungal virulence and the detection of compounds with antifungal properties. This article is part of a Special Issue entitled: Animal Models of Disease

Learning How to Learn in a Real-Life Context Insights from Expert Focus Groups on Narrowing the Soft-Skills Gap

The soft-skills gap the misalignment between the soft skills needed at the workplace and the soft skills possessed by the workforce is considered to be widening, especially after the COVID-19 pandemic. This paper presents evidence from two focus-group interviews conducted in May 2021 and May 2022 in Greece. We wanted to understand the factors influencing the soft-skills gap and possible ways to narrow it. Participants were experts on soft skills, involved in various ways and roles in the teaching, training, and evaluation of soft skills. They expressed their concerns about the soft-skills gap and identified aspects that involved employees, employers, the work environment, and the broader social environment. The idea of a constantly changing environment led to the conclusion that adaptability, taking the initiative, and metacognitive skills are most important for university graduates. This conclusion came with a caveat: Learning should take place in real-life contexts, and universities should find ways to embed educational practices in social and work interactions, both inside and outside universities, working closely with local communities

Learning How to Learn in a Real-Life Context Insights from Expert Focus Groups on Narrowing the Soft-Skills Gap

The soft-skills gap the misalignment between the soft skills needed at the workplace and the soft skills possessed by the workforce is considered to be widening, especially after the COVID-19 pandemic. This paper presents evidence from two focus-group interviews conducted in May 2021 and May 2022 in Greece. We wanted to understand the factors influencing the soft-skills gap and possible ways to narrow it. Participants were experts on soft skills, involved in various ways and roles in the teaching, training, and evaluation of soft skills. They expressed their concerns about the soft-skills gap and identified aspects that involved employees, employers, the work environment, and the broader social environment. The idea of a constantly changing environment led to the conclusion that adaptability, taking the initiative, and metacognitive skills are most important for university graduates. This conclusion came with a caveat: Learning should take place in real-life contexts, and universities should find ways to embed educational practices in social and work interactions, both inside and outside universities, working closely with local communities

VAP patients stratified by age.

<p>ARDS: Acute respiratory distress syndrome; ICU: intensive care unit; IQR: interquartile range; LOS: length of stay; MRSA: Methicillin-resistant <i>Staphylococcus aureus</i>; MV: mechanical ventilation; SAPS II: simplified acute physiology score II; VAP: ventilator associated pneumonia.</p><p>*Results shown are percentages of the 167 patients for whom a microbiological diagnosis of VAP was successful.</p><p>**Results shown are percentages of the 147 patients for whom data on antimicrobial sensitivities were available.</p

Etiologic diagnosis of VAP and resistance profiles.

<p>MDR: multidrug resistant; N/A: not applicable; VAP: ventilator associated pneumonia.</p