Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study:Epidemiologic Changes in a 15-Year Perspective

As part of a national surveillance programme initiated in 2004, fungal blood isolates from 2016–2018 underwent species identification and EUCAST susceptibility testing. The epidemiology was described and compared to data from previous years. In 2016–2018, 1454 unique isolates were included. The fungaemia rate was 8.13/100,000 inhabitants compared to 8.64, 9.03, and 8.38 in 2004–2007, 2008–2011, and 2012–2015, respectively. Half of the cases (52.8%) involved patients 60–79 years old and the incidence was highest in males ≥70 years old. Candida albicans accounted for 42.1% of all isolates and Candida glabrata for 32.1%. C. albicans was more frequent in males (p = 0.03) and C. glabrata in females (p = 0.03). During the four periods, the proportion of C. albicans decreased (p < 0.001), and C. glabrata increased (p < 0.001). Consequently, fluconazole susceptibility gradually decreased from 68.5% to 59.0% (p < 0.001). Acquired fluconazole resistance was found in 4.6% Candida isolates in 2016–2018. Acquired echinocandin resistance increased during the four periods 0.0%, 0.6%, 1.7% to 1.5% (p < 0.0001). Sixteen echinocandin-resistant isolates from 2016–2018 harboured well-known FKS resistance-mutations and one echinocandin-resistant C. albicans had an FKS mutation outside the hotspot (P1354P/S) of unknown importance. In C. glabrata specifically, echinocandin resistance was detected in 12/460 (2.6%) in 2016–2018 whereas multidrug-class resistance was rare (1/460 isolates (0.2%)). Since the increase in incidence during 2004–2011, the incidence has stabilised. In contrast, the species distribution has changed gradually over the 15 years, with increased C. glabrata at the expense of C. albicans. The consequent decreased fluconazole susceptibility and the emergence of acquired echinocandin resistance complicates the management of fungaemia and calls for antifungal drug development

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma.METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation.DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients.TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.</p

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20–365 from study allocation and (ii) days alive and without exacerbation within days 20–365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142. Registered on August 25, 2017. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06720-z

SPECTRAL ANALYSIS OF THE VARIOUS COMPONENTS OF AN AUTO CATALYST

This paper presents a study reaction comparison who was carried out in a glass continuous- flow reactor at atmospheric pressure. The inlet gas contained 8.1 vol. % CO in Ar (Messer MG Chimco Gas). The WGS reaction was carried out in the temperature range 270 − 400℃, space velocities (GHSV) from 2000 to 8000 ℎ^-1, H2O/CO ratio = 3 (vapour/gas = 0.27) and in the presence of 2 vol. % H2S. The converted mixture was controlled continuously by an Infralyt 200 spectral gas-analyser recording online CO and CO2 contents in vol. % (±1.5) at the reactor outlet. The research presented in this paper has obvious practical potential. The whole experiment was directed to the activity of low Ni- content catalyst and what is the effect of alkali addition when the reaction is performed at atmospheric pressure and higher H2S content in the reaction mixture. Improvement of engine characteristics both by reducing harmful quantities emitted and by increasing power were confirmed by analyzes made in a vehicle inspection station

Călătorind printr-o harpă – amenajarea unui portic

As far as today’s civilization development environment is concerned, man is living in an uninterrupted sound environment. Everywhere he is accompanied by a multitude of sounds and noises of varying intensity, having more or less violent effects on his hearing and his health. We can define noise as a representation of the sound vibration, not having a systematic attribute that is transmitted through various environments (air, water etc.) and that sensitizes the human ear negatively. In the Larousse dictionary, noise is a harmless sound system. Scientists with a specialization in physics characterize noise as a chaotic overlap with different frequencies and intensities, and physiologists appreciate the noise as any disturbing sound that causes an unpleasant sensation. It is proposed to revitalize the portico on street Ion Câmpineanu number 25, which hosts the entrance to a music shop. At present, it is a non-hostile and dark space dominated by massive pillars and shades of gray. Intervention involves the creation of a dynamic and interactive space in which the passageway is stimulated visually, tactile and auditory. With this solution, we want the public space in the studied area to develop a particular ambiance and vibration, allowing passers-by, hearing a harp melody, or even creating one’s own.</jats:p

ANALYSES OF RAILWAY BRIDGES

This paper discusses two models with load approaches to model the distribution is prescribed by the Eurocodes: in the first model, each axle load point is represented by three forces, with 50% of the axle load acting on the sleeper located underneath the axle and 25 % on the two adjacent sleepers. In the second model, the three point forces is distributed through further sleepers and the ballast with the height to width ratio of the 4: 1

Rezafungin <i>In Vitro</i> Activity against Contemporary Nordic Clinical <i>Candida</i> Isolates and <i>Candida auris</i> Determined by the EUCAST Reference Method

Rezafungin (formerly CD101) is a novel echinocandin in clinical development. EUCAST epidemiological cutoff values (ECOFFs) have not yet been established. We determined the in vitro activity of rezafungin and comparators against 1,293 Nordic yeast isolates and 122 Indian Candida auris isolates and established single-center wild-type upper limits (WT-UL). The isolates (19 Candida spp. and 13 other yeast species) were identified using Chromagar; matrix-assisted laser desorption ionization–time of flight (MALDI-TOF); and, when needed, internal transcribed spacer sequencing. </jats:p

Olorofim susceptibility testing of 1,423 danish mold isolates obtained in 2018-2019 confirms uniform and broad-spectrum activity

Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus. Here, we explored the MIC variability in more detail and prospectively investigated the susceptibility of contemporary clinical mold isolates, as population data are needed for future epidemiological cutoff (ECOFF) settings. Fifteen A. fumigatus isolates previously found with low/medium/high MICs (≤0.002 to 0.25 mg/liter) were tested repeatedly and EUCAST MICs read in a blinded fashion by three observers. pyrE, encoding the olorofim target enzyme dihydroorotate dehydrogenase (DHODH), was sequenced. A total of 1,423 mold isolates (10 Aspergillus species complexes [including 1,032 A. fumigatus isolates] and 105 other mold/dermatophyte isolates) were examined. Olorofim susceptibility (modal MIC, MIC(50), MIC(90), and wild-type upper limits [WT-ULs] [species complexes with ≥15 isolates]) was determined and compared to that of four comparators. MICs (mg/liter) were within two 2-fold dilutions (0.016 to 0.03) for 473/476 determinations. The MIC range spanned four dilutions (0.008 to 0.06). No significant pyrE mutations were found. Modal MIC/WT-UL(97.5) (mg/liter) values were 0.03/0.06 (A. terreus and A. flavus), 0.06/0.125 (A. fumigatus and Trichophyton rubrum), and 0.06/0.25 (A. niger and A. nidulans). The MIC range for Scedosporium spp. was 0.008 to 0.25. Olorofim susceptibility was similar for azole-resistant and -susceptible isolates of A. fumigatus but reduced for A. montevidensis and A. chevalieri (MICs of >1). With experience, olorofim susceptibility testing is robust. The testing of isolates from our center showed uniform and broad-spectrum activity. Single-center WT-ULs are suggested

Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity

Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus . Here, we explored the MIC variability in more detail and prospectively investigated the susceptibility of contemporary clinical mold isolates, as population data are needed for future epidemiological cutoff (ECOFF) settings. Fifteen A. fumigatus isolates previously found with low/medium/high MICs (≤0. </jats:p