Formation of metallic magnetic clusters in a Kondo-lattice metal: Evidence from an optical study

Magnetic materials are usually divided into two classes: those with localised magnetic moments, and those with itinerant charge carriers. We present a comprehensive experimental (spectroscopic ellipsomerty) and theoretical study to demonstrate that these two types of magnetism do not only coexist but complement each other in the Kondo-lattice metal, Tb2PdSi3. In this material the itinerant charge carriers interact with large localised magnetic moments of Tb(4f) states, forming complex magnetic lattices at low temperatures, which we associate with self-organisation of magnetic clusters. The formation of magnetic clusters results in low-energy optical spectral weight shifts, which correspond to opening of the pseudogap in the conduction band of the itinerant charge carriers and development of the low- and high-spin intersite electronic transitions. This phenomenon, driven by self-trapping of electrons by magnetic fluctuations, could be common in correlated metals, including besides Kondo-lattice metals, Fe-based and cuprate superconductors.Comment: 30 pages, 6 Figure

Evaluation of the antibacterial activity of the preparation benzydamine hydrochloride

Introduction. With an increase in the level of acquired antibiotic resistance of pathogens, treatment becomes more complicated and slows down, especially in infections associated with biofilms. There is a growing need for the development and use of new antibacterial drugs with specific antimicrobial activity.Aim. To study the antimicrobial action and the dynamics of the formation of resistance to benzydamine hydrochloride from a various infection agents. Materials and methods. To obtain biofilms, microorganisms were cultivated in flat-bottomed culture plates. Planktonic cells were obtained by suspending and reseeding single colonies of the daily culture into flat-bottomed culture plates. To determine the antimicrobial activity of the studied preparations, two-fold dilutions were prepared and added to the wells of the plate with a bacterial culture. The dynamics of the formation of resistance to benzydamine hydrochloride was studied by passaging the cultures in a liquid nutrient medium with increasing concentrations of the antiseptic by a twofold step. After 2–3 days of incubation from a test tube with the maximum concentration of the drug, in which bacterial growth was observed, the bacteria were transferred to new ones with higher concentrations of the drug.Results. It was shown that benzydamine hydrochloride showed a high level of activity against bacteria M. catarrhalis and yeast-like fungi C. albicans. A slightly lower activity of the drug was noted for bacteria of the species S. aureus and E. coli, however, within the limits of the therapeutic concentration of the drug in finished dosage forms. Benzydamine hydrochloride had a significantly higher level of antibacterial activity against pre-formed biofilms compared to drugs such as chlorhexidine and hexetidine. An analysis of the dynamics of the formation of resistance to the drug benzydamine hydrochloride in microorganisms of various species showed that the possibility of developing resistance to benzydamine hydrochloride is extremely small. The process of adaptation was observed only in E. coli. The studied strains of the species S. aureus, C. albicans, and M. catarrhalis did not acquire resistance to the test drug.Conclusion. Benzydamine hydrochloride can be effectively used against a wide range of pathogens of ENT infections, as it has been shown to have a significantly higher level of antibacterial activity against pre-formed biofilms, various types of bacteria and yeast-like fungi and an extremely low level of resistance compared to other antiseptic drugs

Кандидемия у онкологических больных: фенотипические и молекулярно-генетические характеристики резистентности к противогрибковым лекарственным средствам, гены факторов патогенности Candida spp.

Relevance. The global trend of rapid increase in resistance to antifungal drugs due to multiple factors, dictates the need for continuous monitoring of taxonomic structure and susceptibility of nosocomial pathogens, causing invasive fungal infections, for permanent correction of the optimal prevention and treatment strategies.Purpose: to determine antifungal susceptibility of the main yeast pathogens in candidemia in cancer patients, as well as to determine resistance genes and pathogenic factor genes.Material and Methods. Eighty-two strains of Candida spp. isolated from blood of cancer patients from 2015 to 2021 were analyzed. Minimum inhibitory concentrations of fuconazole, voriconazole, posaconazole, anidulafungin and micafungin were determined by a gradient method (E-test, BioMerieux, France). The EUCAST and CLSI criteria were used for MIC value assessment. The genes, associated with pathogenicity factors, and resistance to antifungal drugs were identifed.Results. Our study results based on EUCAST 2020, v.10.0 criteria showed that triazoles, especially fuconazole, were the least effective drugs in empirical therapy for invasive candidiasis (including candidemia). Resistance of Candida spp. fuconazole was superior to that of voriconazole (47.2 % vs 23.2 %, respectively, p<0.01) and posaconazole (47.2 % vs 30.4 %, respectively, p><0.05). The highest in vitro activity was observed in echinocandins, and anidulafungin was 2 times more active than micafungin (4.1 % of resistant strains vs 11.4 %, respectively), with no statistically signifcant difference (p>0.05). The ERG11 and FKS1 genes associated with resistance to antifungal drugs were detected in 28.6 % of Candida spp. strains. The ERG11 gene was detected in 8.6 % of cases, exclusively in Candida albicans strains. The FKS1 gene was identifed in 20.0 % of strains (85.7 % of them were C. parapsilosis, 7.1 % each were C. tropicalis and C. glabrata). Pathogenic factor genes were identifed in 78.6 % of C. albicans and in 79.1 % of C. parapsilosis strains.Conclusion. Molecular genetic methods for the detection of Candida spp strains carrying resistance genes to antifungal drugs, and the determination of pathogenicity factors are promising trends in searching for biomarkers. They facilitate interpretation of results of microbiological study to assess the ability of Candida spp. strains to develop invasive mycoses.Актуальность. Мировая тенденция стремительного увеличения уровня резистентности к противогрибковым препаратам, которая связана со многими факторами, диктует необходимость постоянного мониторинга таксономической структуры нозокомиальных возбудителей инвазивных грибковых инфекций и их чувствительности к антифунгальным лекарственным средствам с целью постоянной коррекции наиболее оптимальной тактики профилактики и лечения инвазивных грибковых инфекций.Цель исследования – определение чувствительности к антифунгальным препаратам основных возбудителей при кандидемии у онкологических больных, а также определение генов резистентности и факторов патогенности.Материал и методы. Проанализировано 82 штамма Candida spp., выделенных из крови онкологических больных в течение 2015–21 гг. Определение минимальных ингибирующих концентраций флуконазола, вориконазола, позаконазола, анидулафунгина и микафунгина выполняли градиентным методом (Е-тест, BioMerieux, France). Для оценки значений МИК использовали критерии EUCAST и CLSI. Определены гены, ассоциированные с факторами патогенности и резистентности к противогрибковым лекарственным средствам.Результаты. По результатам нашего исследования (критерии EUCAST) в качестве эмпирической терапии инвазивного кандидоза (в т. ч. кандидемии) наименее эффективными препаратами являются триазолы, особенно флуконазол, к которому статистически значимо чаще штаммы Candida spp. резистентны по сравнению с вориконазолом (47,2 % против 23,2 %, p<0,01) и позаконазолом (47,2 % против 30,4 %, p><0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis. Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности –><  0,01) и позаконазолом (47,2 % против 30,4 %, p<0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis. Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности –>< 0,05). Наибольшая активность in vitro отмечается у препаратов группы эхинокандинов, причем анидулафунгин в 2 раза активнее микафунгина (4,1 % резистентных штаммов против 11,4 %), но статистически значимой разницы при этом не выявлено. Гены ERG11 и FKS1, ассоциированные с резистентностью к противогрибковым препаратам, были выявлены у 28,6 % штаммов Candida spp.. Ген ERG11 детектирован в 8,6 % случаев, причем только у штаммов Candida albicans. Ген FKS1 определен у 20,0 % штаммов (85,7 % – C. parapsilosis, по 7,1 % – C. tropicalis и C. glabrata). Гены факторов патогенности определены у 78,6 % штаммов C. albicans и у 79,1 % изолятов C. parapsilosis.Заключение. Молекулярно-генетические методы выявления штаммов Candida spp., несущих гены резистентности к антифунгальным препаратам, определение факторов патогенности – это перспективные направления для поиска биомаркеров, облегчающих сложную задачу трактовки результатов микробиологического исследования по оценке способности штаммов Candida spp. к развитию инвазивных микозов

Antibacterial Activity of Benzydamine Hydrochloride against Clinical Isolates of Bacteria, isolated from people in Russia and Spain

Aim to study antibacterial activity of benzydamine hydrochloride, against clinic isolated of bacteria, located in hospitals in Russia and compare this data to results of similar trail of Spanish isolates.Materials  and  method  for this study were used clinical isolates  of bacteria,  which are counted as typical agents  of infections in otorhinolaryngology and gynecology. Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, Staphylococcus spp. and Streptococcus  spp.,  isolated from patients  in Russians  hospitals;  reference  strains  Escherichia coli, Staphylococcus  aureus and Streptococcus agalactiae, from ATCC collection; and also, Lactobacillus acidophilus strain, isolated from probiotic drug «Lactobacterin». Antibacterial activity of benzydamine hydrochloride was evaluated with serial dilution method in agar. For comparison of results we used data of Spanish study of benzydamine activity against clinical isolates and reference strains. The Spanish Study was completed in microbiological department of San-Pau hospital in Barcelona in 2001.Results.  It was indicated that minimum inhibitory concentration (MIC) of benzydamine hydrochloride for clinical isolates of gram-negative and gram-positive  bacteria, isolated from Russian and Spanish hospitals is about the same level: for E. coli it was 640 – 1280  mg/l, for K. pneumoniae  – 512–1280  mg/l, for S. aureus  – 256–1280  mg/l, for S. agalactiae  – 320–1280  mg/l, for S. pyogenes – 256–640 mg/l, for E. faecalis – 512 mg/l, for E. faecium – 256 mg/l, for S. mitis – 640 mg/l, for S. epidermidis 320 – 1280 mg/l, for S. pneumoniae  –  40 mg/l, for S. viridans  –  40 mg/l. The same data was obtained by assessment of sensitivity to benzydamine hydrochloride reference-strains from ATCC collection: for E. coli MIC was 512 – 640 mg/l, for S. aureus – 512 – 640 mg/l, for S. agalactiae – 320 mg/l, for S. pneumoniae – 640 mg/l. Probiotic strain L. acidophilus was resistant to benzydamine hydrochloride activity with MIC = 20000 mg/l. Conclusion: It was indicated that antimicrobial activity of benzydamine hydrochloride against clinical strains, isolated from the patients of hospitals in Russia and Spain. Also, resistance of probiotic strain of lactobacteria was detected to this drug, which indicates the possibility of benzydamine hydrochloride application in clinical practice in otorhinolaryngology  and gynecology without risk of negative influence on normal lactobacterial flora

Early Response of Antimicrobial Resistance and Virulence Genes Expression in Classical, Hypervirulent, and Hybrid hvKp-MDR Klebsiella pneumoniae on Antimicrobial Stress

Klebsiella pneumoniae is an increasingly important hospital pathogen. Classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) are two distinct evolutionary genetic lines. The recently ongoing evolution of K. pneumoniae resulted in the generation of hybrid hvKP-MDR strains. K. pneumoniae distinct isolates (n = 70) belonged to 20 sequence types with the prevalence of ST395 (27.1%), ST23 (18.6%), ST147 (15.7%), and ST86 (7.1%), and 17 capsular types with the predominance of K2 (31.4%), K57 (18.6%), K64 (10.0%), K1 (5.7%) were isolated from patients of the Moscow neurosurgery ICU in 2014–2019. The rate of multi-drug resistant (MDR) and carbapenem-resistant phenotypes were 84.3% and 45.7%, respectively. Whole-genome sequencing of five selected strains belonging to cKp (ST395K47 and ST147K64), hvKp (ST86K2), and hvKp-MDR (ST23K1 and ST23K57) revealed blaSHV, blaTEM, blaCTX, blaOXA-48, and blaNDM beta-lactamase genes; acr, oqx, kpn, kde, and kex efflux genes; and K. pneumoniae virulence genes. Selective pressure of 100 mg/L ampicillin or 10 mg/L ceftriaxone induced changes of expression levels for named genes in the strains belonging to cKp, hvKp, and hybrid hvKp-MDR. Obtained results seem to be important for epidemiologists and clinicians for enhancing knowledge about hospital pathogens