Exploiting the aggregation propensity of beta-lactamases to design inhibitors that induce enzyme misfolding.

There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have observed that certain beta-lactamases tend to aggregate, which persists throughout their evolution under the selective pressure of antibiotics on their active sites. Interestingly, we find that existing beta-lactamase active site inhibitors can act as molecular chaperones, promoting the proper folding of these resistance factors.

Cervicofacial actinomycosis following third molar removal: case-series and review.

Actinomycosis is an opportunistic infection caused by bacteria of the Actinomyces spp., commonly A. israelii.

Efficacy and safety of a Belgian tertiary care outpatient parenteral antimicrobial therapy (OPAT) program.

Purpose: Evidence supports the implementation of outpatient parenteral antimicrobial therapy (OPAT) as standard of care. Until 2015 the overall experience with OPAT in Belgium remained limited. The aim of this study was to evaluate the efficacy and safety of a Belgian 'OPAT at home' program, which was implemented in University Hospitals Leuven starting from January 2017.

Translating Data From an Electronic Prescribing and Medicines Administration System Into Knowledge: Application to Doctor-Nurse Time Discrepancy in Antibiotic Ordering and Administration.

Background: Electronic Prescribing and Medicines Administration (EPMA) systems are being widely implemented to facilitate medication safety improvement. However, translating the resulting big data into actionable knowledge has received relatively little attention.

Objective: The objective of this study was to use routinely collected EPMA data in the study of exact time discrepancy between physicians' order and nurses' administration of systemic antibiotics.

Supervised teaching and feedback improve physiotherapists' reporting of the International Classification of Functioning, Disability and Health in physiotherapeutic electronic patient records: A proof-of-concept randomized controlled trial.

Rationale, Aims, And Objectives: The International Classification of Functioning, Disability and Health (ICF) is a landmark for physiotherapy to describe the full spectrum of human functioning, but ICF patient record completion could improve. In this study, we examine the effect of supervised teaching and personalized feedback on physiotherapists' completion and reporting of ICF in electronic patient records.

Method: In this proof-of-concept randomized controlled trial, the intervention group (10 physiotherapists) received supervised teaching and four rounds of personalized feedback on reporting of ICF components in electronic patient records.

Frequency and Pattern of IgE-mediated Sensitization to Aero and Food Allergens in Ahvaz, Province of Khuzestan in Southwestern Iran.

Efficient diagnosis of allergy and proper treatment need identification of the causative allergens eliciting clinical symptoms. The present study was performed to identify the most common aero- and food allergens and determine the pattern of sensitization among people of Ahvaz (southwestern Iran), one of the most polluted cities worldwide. Based on the physical examination and medical records, patients were referred to the Allergy laboratory for "in vitro" IgE determination.

Compliance with evidence-based guidelines for the prevention of central line-associated bloodstream infections in a Belgian home care setting: An observational study.

This study assessed the compliance of Belgian home care nurses with good practice recommendations to prevent central line-associated bloodstream infections. The compliance to 3 care bundles was 0% (0 out of 7), 13.3% (2 out of 15), and 22.

Outpatient parenteral antimicrobial therapy and antibiotic stewardship: opponents or teammates?

Purpose: This narrative review aims to describe barriers of outpatient parenteral antimicrobial therapy at home (OPAT), potentially compromising general standards of antibiotic stewardship (ABS) and facilitators of OPAT for ABS.

Methods: After a literature review, five authors determined the barriers and facilitators to discuss in this review.

Results: Sixty-six publications were included in the narrative review and seven barriers and five facilitators are discussed in this article.

Ses proteins as possible targets for vaccine development against Staphylococcus epidermidis infections.

Objectives: The opportunistic pathogen Staphylococcus epidermidis is progressively involved in device-related infections. Since these infections involve biofilm formation, antibiotics are not effective. Conversely, a vaccine can be advantageous to prevent these infections.

Aggregating sequences that occur in many proteins constitute weak spots of bacterial proteostasis.

Aggregation is a sequence-specific process, nucleated by short aggregation-prone regions (APRs) that can be exploited to induce aggregation of proteins containing the same APR. Here, we find that most APRs are unique within a proteome, but that a small minority of APRs occur in many proteins. When aggregation is nucleated in bacteria by such frequently occurring APRs, it leads to massive and lethal inclusion body formation containing a large number of proteins.

Validation of the Child HCAHPS survey to measure pediatric inpatient experience of care in Flanders.

Unlabelled: The recently developed Child HCAHPS provides a standard to measure US hospitals' performance on pediatric inpatient experiences of care. We field-tested Child HCAHPS in Belgium to instigate international comparison. In the development stage, forward/backward translation was conducted and patients assessed content validity index as excellent.

De novo design of a biologically active amyloid.

Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction.

sesC as a genetic marker for easy identification of Staphylococcus epidermidis from other isolates.

Staphylococcus epidermidis is one of the major concerns with respect to hospital-acquired infections. Therefore, a rapid and easy method to identify at species level S. epidermidis isolates out of a broad range of bacteria is necessary.

The Possible Role of Staphylococcus epidermidis LPxTG Surface Protein SesC in Biofilm Formation.

Staphylococcus epidermidis is the most common cause of device-associated infections. It has been shown that active and passive immunization in an animal model against protein SesC significantly reduces S. epidermidis biofilm-associated infections.

Protein aggregation as an antibiotic design strategy.

Taking advantage of the xenobiotic nature of bacterial infections, we tested whether the cytotoxicity of protein aggregation can be targeted to bacterial pathogens without affecting their mammalian hosts. In particular, we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased in vitro screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin-resistant Staphylococcus aureus.

Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance.

Background And Aims: Community-acquired pneumonia (CAP) is a common infectious disease affecting children and adults of any age. Mycoplasma pneumoniae has emerged as leading causative agent of CAP in some region, and the abrupt increasing resistance to macrolide that widely used for management of M. pneumoniae has reached to the level that it often leads to treatment failures.

Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting.

Background: We verified the analytical performance of strip-based handheld glucose meters (GM) for prescription use, in a comparative split-sample protocol using blood gas samples from a surgical intensive care unit (ICU).

Methods: Freestyle Precision Pro (Abbott), StatStrip Connectivity Meter (Nova), ACCU-CHEK Inform II (Roche) were evaluated for recovery/linearity, imprecision/repeatability. The GMs and the ABL90 (Radiometer) blood gas analyzer (BGA) were tested for relative accuracy vs.

Novel LC-MS/MS method for plasma vancomycin: comparison with immunoassays and clinical impact.

Background: Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As literature suggests between-method differences, our first objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for total vancomycin in human plasma and to compare frequently used immunoassays with this method. Secondly, we investigated the clinical impact of between-method quantification differences.

Selectivity of aggregation-determining interactions.

Protein aggregation is sequence specific, favoring self-assembly over cross-seeding with non-homologous sequences. Still, as the majority of proteins in a proteome are aggregation prone, the high level of homogeneity of protein inclusions in vivo both during recombinant overexpression and in disease remains surprising. To investigate the selectivity of protein aggregation in a proteomic context, we here compared the selectivity of aggregation-determined interactions with antibody binding.

Non-typeable Haemophilus influenzae, an under-recognised pathogen.

Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk.

Protein aggregation in bacteria: the thin boundary between functionality and toxicity.

Misfolding and aggregation of proteins have a negative impact on all living organisms. In recent years, aggregation has been studied in detail due to its involvement in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, and type II diabetes--all associated with accumulation of amyloid fibrils. This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional.

Performance of cassette-based blood gas analyzers to monitor blood glucose and lactate levels in a surgical intensive care setting.

Background: With the use of a traditional blood gas analyzer (BGA) (ABL800 Radiometer) for blood glucose monitoring, tight glucose control (TGC) reduced in-hospital mortality and morbidity of surgical intensive care unit (ICU) adult and pediatric patients. Such BGAs are now superseded by cassette-based BGAs. We assessed the analytical reliability of cassette-based BGAs to monitor patient's metabolic status in an ICU setting.

Detection of Pseudomonas aeruginosa in sputum headspace through volatile organic compound analysis.

Introduction: Chronic pulmonary infection is the hallmark of cystic fibrosis lung disease. Searching for faster and easier screening may lead to faster diagnosis and treatment of Pseudomonas aeruginosa (P. aeruginosa).

Vaccination with SesC decreases Staphylococcus epidermidis biofilm formation.

The increased use of medical implants has resulted in a concomitant rise in device-related infections. The majority of these infections are caused by Staphylococcus epidermidis biofilms. Immunoprophylaxis and immunotherapy targeting in vivo-expressed, biofilm-associated, bacterial cell surface-exposed proteins are promising new approaches to prevent and treat biofilm-related infections, respectively.