Evaluation of in vitro pharmacodynamic drug interactions of ceftazidime-avibactam with tigecycline in ESBL- and carbapenemase producing Escherichia coli and Klebsiella pneumoniae.

Background: Combination therapy offers a promising option to enhance efficacy and prevent resistance. A comprehensive and quantitative assessment of the last-resort combination of ceftazidime/avibactam and tigecycline is not available.

Objective: This study systematically investigated the pharmacodynamic interaction between ceftazidime/avibactam and tigecycline in clinical and isogenic Escherichia coli and Klebsiella pneumoniae strains harbouring genes that encode various carbapenemases or ESBLs.

Femtosecond laser writing of robust waveguides in optical fibers with enhanced photosensitivity.

We report the femtosecond laser writing of meter-long optical waveguides inscribed through the coating of specifically designed optical fibers. In order to improve the material photosensitivity and to ensure non-guiding optical fibers for subsequent laser processing of the waveguiding core, a depressed refractive index core design is implemented by co-doping a large portion of the optical fiber with germanium oxide and fluorine. The enhanced photosensitivity provided by further deuterium loading these fibers allows laser-writing of large refractive index contrast waveguides over wide cross sections.

In vitro efficacy of combinations of antibiotics used in clinical practice on clinical isolates of Helicobacter pylori.

Background: The main antibiotics used against Helicobacter pylori have been chosen empirically over time, with few preclinical studies to provide support. The rise in resistance to some of these antibiotics is prompting a reassessment of their use. This work aimed to evaluate the in vitro efficacy of 2 × 2 combinations of the most widely used antibiotics against H.

Pharmacokinetic/pharmacodynamic analysis of ceftazidime/avibactam and fosfomycin combinations in an hollow fiber infection model against multidrug-resistant .

Mechanistic understanding of pharmacodynamic interactions is key for the development of rational antibiotic combination therapies to increase efficacy and suppress the development of resistances. Potent tools to provide those insights into pharmacodynamic drug interactions are semi-mechanistic modeling and simulation techniques. This study uses those techniques to provide a detailed understanding with regard to the direction and strength of the synergy of ceftazidime-avibactam and ceftazidime-fosfomycin in a clinical isolate expressing extended spectrum beta-lactamase (CTX-M-15 and TEM-4) and carbapenemase (OXA-244) genes.

Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.

Background: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear.

Methods: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up.

Physician perspectives on chronic pain management: barriers and the use of eHealth in the COVID-19 era.

Background: Chronic pain is a highly prevalent and disabling condition which is often undertreated and poorly managed in the community. The emergence of COVID-19 has further complicated pain care, with an increased prevalence of chronic pain and mental health comorbidities, and burnout among physicians. While the pandemic has led to a dramatic increase in virtual health care visits, the uptake of a broader range of eHealth technologies remains unclear.

Characterization of resistance to ceftolozane-tazobactam due to and/or mutations observed during treatment using semi-mechanistic PKPD modeling.

A double (AmpC) and (AmpD) genes mutations have been identified by whole genome sequencing in a (PaS) that became resistant (PaR) in a patient treated by ceftolozane/tazobactam (C/T). To precisely characterize the respective contributions of these mutations on the decreased susceptibility to C/T and on the parallel increased susceptibility to imipenem (IMI), mutants were generated by homologous recombination in PAO1 reference strain (PAO1- AmpC, PAO1-AmpD, PAO1-AmpC/AmpD) and in PaR (PaR-AmpC/AmpD). Sequential time-kill curve experiments were conducted on all strains and analyzed by semi-mechanistic PKPD modeling.

Evaluation of in vitro pharmacodynamic drug interactions of ceftazidime/avibactam and fosfomycin in Escherichia coli.

Background: Combination therapy can increase efficacy of antibiotics and prevent emergence of resistance. Ceftazidime/avibactam and fosfomycin may be empirically combined for this purpose, but a systematic and quantitative evaluation of this combination is needed.

Objectives: In this study, a systematic analysis of the pharmacodynamic interactions of ceftazidime/avibactam and fosfomycin in clinical and isogenic Escherichia coli strains carrying genes coding for several carbapenemases or ESBLs was performed and pharmacodynamic interactions were quantified by modelling and simulations.

Towards REPO nanocrystal-doped optical fibers for distributed sensing applications.

Rayleigh scattering enhanced nanoparticle-doped optical fibers, for distributed sensing applications, is a new technology that offers unique advantages to optical fiber community. However, the existing fabrication technology, based on in situ grown alkaline earth nanoparticles, is restricted to few compositions and exhibit a great dependence on many experimental conditions. Moreover, there is still several uncertainties about the effect of drawing process on the nanoparticle characteristics and its influence on the scattering enhancement and the induced optical loss.

Unveiling Structural Insights into Nanocrystal-Doped Optical Fibers via Confocal Raman Microscopy.

An in-depth characterization of nanoparticle-doped optical fibers is crucial to understand the potential new functionalities of the engineered glass and thus their applicability fields. The high temperatures of the manufacturing process strongly affect the nanoparticle features, and therefore, their analysis is necessary after fiber drawing. However, the difficulties associated with the use of atomic resolution microscopies to analyze the nanoparticle features in the fiber core, mainly related to sample preparation and expensive costs, usually prevent their study.

Demonstration of laser cooling in a novel all oxide GAYY silica glass.

We demonstrate laser induced cooling in ytterbium doped silica (SiO) glass with alumina, yttria co-doping (GAYY-Aluminum: Yttrium: Ytterbium Glass) fabricated using the modified chemical vapour deposition (MCVD) technique. A maximum temperature reduction by - 0.9 K from room temperature (296 K) at atmospheric pressure was achieved using only 6.

Enantioselective activity and toxicity of chiral acaricide cyflumetofen toward target and non-target organisms.

Cyflumetofen (CYF), a novel chiral acaricide, exert enantiomer-specific effects on target organisms by binding to glutathione S-transferase. However, there is limited knowledge regarding the response of non-target organisms to CYF, including enantioselective toxicity. In this study, we investigated the effects of racemic CYF (rac-CYF) and its two enantiomers (+)-CYF and (-)-CYF on MCF-7 cells and non-target (honeybees) and target (bee mites and red spider mites) organisms.

"How we do it": A qualitative study of strategies for adopting an exercise routine while living with type 1 diabetes.

Introduction: For people living with type 1 diabetes (T1D) the challenge of increasing daily physical activity (PA) is compounded by the increased risks of hypoglycemia and glucose variability. Little information exists on the lived experience of overcoming these barriers and adopting and maintaining an active lifestyle while living with T1D.

Research Design And Methods: We conducted a patient-led qualitative study consisting of semi-structured interviews or focus groups with 22 individuals at least 16 years old living with T1D.

Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study.

Background: Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice.

Methods: A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose.

A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients.

Understanding antibiotic concentration-time profiles in the central nervous system (CNS) is crucial to treat severe life-threatening CNS infections, such as nosocomial ventriculitis or meningitis. Yet CNS distribution is likely to be altered in patients with brain damage and infection/inflammation. Our objective was to develop a physiologically based pharmacokinetic (PBPK) model to predict brain concentration-time profiles of antibiotics and to simulate the impact of pathophysiological changes on CNS profiles.

Coaxial Mach-Zehnder Digital Strain Sensor Made from a Tapered Depressed Cladding Fiber.

An in-line digital optical sensor was proposed. It was built from a tapered depressed-cladding single-mode fiber and modeled as a coaxial Mach-Zehnder interferometer. The principle of operation of the optical digital sensor is based on the computation of the number of optical power transfer turning points (PTTP) from the transmission data of the component.

Optimized Rhombic Experimental Dynamic Checkerboard Designs to Elucidate Pharmacodynamic Drug Interactions of Antibiotics.

Purpose: Quantification of pharmacodynamic interactions is key in combination therapies, yet conventional checkerboard experiments with up to 10 by 10 combinations are labor-intensive. Therefore, this study provides optimized experimental rhombic checkerboard designs to enable an efficient interaction screening with significantly reduced experimental workload.

Methods: Based on the general pharmacodynamic interaction (GPDI) model implemented in Bliss Independence, a novel rhombic 'dynamic' checkerboard design with quantification of bacteria instead of turbidity as endpoint was developed.

Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance.

Objectives: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients.

A physiologically based pharmacokinetic (PBPK) model exploring the blood-milk barrier in lactating species - A case study with oxytetracycline administered to dairy cows and goats.

Antibiotic excretion into milk depends on several factors such as the compound's physicochemical properties, the animal physiology, and the milk composition. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model describing the passage of drugs into the milk of lactating species. The udder is described as a permeability limited compartment, divided into vascular, extracellular water (EW), intracellular water (IW) and milk, which was stored in alveolar and cistern compartments.

Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for sensitive pathogens were assigned to either the II (2 g every 8 h over 0.

Lipid Nanoparticles Loaded with Farnesol or Geraniol to Enhance the Susceptibility of MCR-1 to Colistin.

Resistance to colistin, one of the antibiotics of last resort against multidrug-resistant Gram-negative bacteria, is increasingly reported. Notably, MCR plasmids discovered in 2015 have now been reported worldwide in humans. To keep this antibiotic of last resort efficient, a way to tackle this mechanism seems essential.

A liquid chromatography coupled to tandem mass spectrometry method for the quantification of spiramycin and its active metabolite neospiramycin in milk of major and minor species: Validation using the accuracy profile.

A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of residues of spiramycin, a macrolide antibiotic, and its active metabolite neospiramycin in cow's milk as well as in minor species 'milk, goat and ewe. Spiramycin-d3 was used as internal standard for quantification of both analytes. This analytical method was validated using a global accuracy profile as a graphical decision tool built according to the trueness and the precision of the method.

Functionalization of Mono- and Bimetallic MIL-100(Al,Fe) MOFs by Ethylenediamine: Postfunctionalization, Brønsted Acido-Basicity, and Unusual CO Sorption Behavior.

The metal sites of MIL-100(Fe), MIL-100(Fe,Al), and MIL-100(Al) metal-organic frameworks (MOFs) were decorated with ethylenediamine (EN). Interestingly, the Al-containing MOFs presented hierarchized porosity, and their structural integrity was maintained upon functionalization. Solution and solid-state NMR confirmed the grafting efficiency in the case of MIL-100(Al) and the presence of a free amine group.