Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case-control study over 5 years.

Purpose: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed.

Methods: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital.

FAT10 localises in dendritic cell aggresome-like induced structures and contributes to their disassembly.

Dendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS.

The role of mechanotransduction in heart failure pathobiology-a concise review.

This review evaluates the role of mechanotransduction (MT) in heart failure (HF) pathobiology. Cardiac functional and structural modifications are regulated by biomechanical forces. Exposing cardiomyocytes and the myocardial tissue to altered biomechanical stress precipitates changes in the end-diastolic wall stress (EDWS).

Distinct CCR7 glycosylation pattern shapes receptor signaling and endocytosis to modulate chemotactic responses.

The homeostatic chemokines CCL19 and CCL21 and their common cognate chemokine receptor CCR7 orchestrate immune cell trafficking by eliciting distinct signaling pathways. Here, we demonstrate that human CCR7 is N-glycosylated on 2 specific residues in the N terminus and the third extracellular loop. Conceptually, CCR7 glycosylation adds steric hindrance to the receptor N terminus and extracellular loop 3, acting as a "swinging door" to regulate receptor sensitivity and cell migration.

Inflammation-Induced CCR7 Oligomers Form Scaffolds to Integrate Distinct Signaling Pathways for Efficient Cell Migration.

Host defense depends on orchestrated cell migration guided by chemokines that elicit selective but biased signaling pathways to control chemotaxis. Here, we showed that different inflammatory stimuli provoked oligomerization of the chemokine receptor CCR7, enabling human dendritic cells and T cell subpopulations to process guidance cues not only through classical G protein-dependent signaling but also by integrating an oligomer-dependent Src kinase signaling pathway. Efficient CCR7-driven migration depends on a hydrophobic oligomerization interface near the conserved NPXXY motif of G protein-coupled receptors as shown by mutagenesis screen and a CCR7-SNP demonstrating super-oligomer characteristics leading to enhanced Src activity and superior chemotaxis.

Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old, and very old critically ill patients*.

Objective: We investigated the epidemiology of ventilator-associated pneumonia in elderly ICU patients. More precisely, we assessed prevalence, risk factors, signs and symptoms, causative bacterial pathogens, and associated outcomes.

Design: Secondary analysis of a multicenter prospective cohort (EU-VAP project).

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies.

Background: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention.

Methods: We identified relevant studies through systematic review.

Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study.

Purpose: The recent increase in drug-resistant micro-organisms complicates the management of hospital-acquired bloodstream infections (HA-BSIs). We investigated the epidemiology of HA-BSI and evaluated the impact of drug resistance on outcomes of critically ill patients, controlling for patient characteristics and infection management.

Methods: A prospective, multicentre non-representative cohort study was conducted in 162 intensive care units (ICUs) in 24 countries.

Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units.

Objectives: Information on clinical practice regarding the diagnosis of pneumonia in European intensive care units is limited. The aim of this study was to describe the spectrum of actual diagnostic practices in a large sample of European intensive care units.

Design: Prospective, observational, multicenter study.

Local anesthetics time-dependently inhibit staphylococcus aureus phagocytosis, oxidative burst and CD11b expression by human neutrophils.

Background And Objectives: Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S.

Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells.

Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming inflammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhesion molecules on tumor necrosis factor-alpha (TNF-alpha) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under flow in vitro. TNF-alpha stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-di-chloro-phenyl)-3-pyrazolidone.

Treatment with tigecycline of recurrent urosepsis caused by extended-spectrum-beta-lactamase-producing Escherichia coli.

A 25-year-old female was admitted to our intensive care unit with septic shock and multiorgan failure caused by extended-spectrum beta-lactamase-producing Escherichia coli originating from the right renal pelvis. A 16-day course of treatment with meropenem reversed the septic condition, but the infection recurred thereafter. The patient recovered fully after therapy was changed to tigecycline.

Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role.

Continuous infusion of beta-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of beta-lactam antibiotics when administered by continuous infusion.

Ventilator-associated pneumonia.

Ventilator-associated pneumonia is the most serious infectious complication in critically ill patients, associated with increased length of intensive care unit treatment and high mortality rates. Investigations focused on outcome variables have improved the database to estimate diagnostic and therapeutic management strategies. This knowledge has diminished the importance of the discussion on how to diagnose the pneumonia.

Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance.

Objective: To assess the distribution of bacterial species and antimicrobial resistance in an ICU during long-term use of selective digestive decontamination (SDD) in the context of national reference data.

Design And Setting: Five-year prospective observational study in a 24-bed interdisciplinary surgical ICU of a university hospital (study ICU) participating in the project "Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units" (SARI; reference ICUs).

Patients: Resistance data were obtained from all patients; patients intubated for at least 2 days received SDD (colistin, tobramycin, amphotericin B).

Selective decontamination of the digestive tract: cumulating evidence, at last?

Selective decontamination of the digestive tract (SDD), an infection-control strategy designed to prevent nosocomial pneumonia in mechanically ventilated patients, has been implemented in numerous studies for more than 2 decades, but its role remains controversial. Sentinel studies in the 1960s and 1970s identified a link between colonization of the upper respiratory tract and subsequent increased risk of developing nosocomial pneumonia in critically ill patients. Studies in the 1980s found that prophylaxis with topical and systemic antibiotics to decontamination of the upper respiratory tract and gastrointestinal tract (particularly depleting gram-negative aerobic bacteria) was associated with lower rates of infections.

Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus.

Objective: Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused by Staphylococcus aureus. Although various immunomodulatory effects of barbiturates have been described in vitro, their influence on the phagocytosis of viable S.

Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers.

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.

Rationale for the development of immunotherapy regimens against enterococcal infections.

Enterococci are the third most common pathogen isolated in bloodstream infections. Increasing resistance against multiple antimicrobial agents has left few treatment options for enterococcal infections, and alternative therapeutic approaches are needed. Although a variety of virulence factors have been described for Enterococcus faecalis, only aggregation substance (AS) and a teichoic acid-like capsular polysaccharide have been evaluated for their potential for vaccine development.

Treatment of meningitis due to methicillin-resistant Staphylococcus epidermidis with linezolid.

Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response.

Assessment of the role of antibiotics and enterococcal virulence factors in a mouse model of extraintestinal translocation.

Objective: To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs.

Design: Prospective controlled animal study.

Setting: Animal experimental laboratory at a university medical center.

Correlation of meropenem plasma levels with pharmacodynamic requirements in critically ill patients receiving continuous veno-venous hemofiltration.

Background: In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements.

Methods: Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h.

Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to Staphylococcus aureus.

Background: With invasion of bacteria, the host defense system is activated by a complex cascade of various mechanisms. Local anesthetics previously were shown to interact with diverse components of the immune response, such as leukocyte adherence on endothelial monolayers, oxidative burst, or crosstalk within lymphocyte subset populations. However, effects of newer local anesthetics like bupivacaine and ropivacaine on antibacterial host defense-primarily phagocytosis activity, oxidative burst, or CD11b expression-still remain unclear.