Glycopeptide antibiotics: structural and functional aspects, human medicinal use, and standardisation

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin

Determination of Vancomycin B and Vancomycin Impurities by Liquid Chromatography

The preferred test methods for control of product-related impurities in medicinal products are high-performance liquid chromatography (HPLC) with a fine sorbent, and ultra-performance liquid chromatography (UPLC), which allow for better chromatographic separation of active substances and related impurities, reduction of time costs, and saving of material resources. The aim of the study was to develop HPLC and UPLC test procedures and assess the chromatographic separation capacity and efficiency in order to improve determination of the main vancomycin component and related impurities. Materials and methods: vancomycin hydrochloride lyophilisate for oral solution and solution for injection, and vancomycin hydrochloride reference standard (USP RS) were used as test objects. Agilent 1290 Infinity liquid chromatography system, and Chromolith® Performance RP-18e, Kinetex C18, Nucleodur C18 Isis, Zorbax RRHD Eclipse Plus C18, and LiChrospher® RP-18 columns were used for the testing. Results: HPLC analysis using a Chromolith® column (100×4.6 mm) reduces the testing time by 10 minutes compared to the USP test procedure, and by 15 minutes compared to the British Pharmacopoeia procedure. The proposed test procedure requires less eluent and increases chromatographic separation efficiency. UPLC analysis using a Kinetex C18 column (50×4.6 mm, 2.6 μm) made it possible to reduce the testing time by two thirds compared to the British Pharmacopoeia procedure. The use of isocratic elution greatly simplified the testing. The testing time under the proposed chromatographic conditions was 10 minutes. Conclusions: the selected HPLC and UPLC test conditions made it possible to significantly reduce the time of testing, minimise the use of expensive reagents, and increase efficiency of chromatographic separation in the determination of vancomycin impurities and the main component Vancomycin B

Heterogeneity of population of microorganisms grown in presence of iron oxide maghemite nanoparticles

In this work γ-Fe2O3 MNPs were obtained by laser target evaporation and water based suspensions were prepared. Maximum permissive dose of iron in water (MPD) is 0.3 mg/L. It was found that 100 MPD dose of iron induces formation of non-typical colonies after 72 or 96 hours exposition: against a background of small black colonies large white colonies appeared due to a disruption in tyrosine synthesis. Multiple re-cloning of the white colonies grown with MNPs showed that they retained their properties both under standard conditions (temperature of 24 °C) and at the temperatures up to 37o C. E.nigrum grown with MNPs demonstrated very scant extension of small colonies at the cultivation temperature of 24o C, their growth was completely blocked at 37°C. Significant changes in the structure of the population were noted. First of all, large cells with pronounced aggregation were observed among the black colonies. These aggregates consisted of large cells connected to each other by matrix. In the white colonies the appearance of very long threadlike cells connecting different groups of the cells establishing an intercellular communication was evident. Fe2O3 MNPs induce an increase in the heterogeneity of the population, expressed as a change in morpho-physiological states. © 2018 The Authors, published by EDP Sciences.The work was supported by the Ministry of Education and Science of the Russian Federation (project No. 3.6121.210 )7 and R FFI №16-34-015 92 grant s. e tW hank R ndrA ade, Iu. Novoselova and I.V. Beketov for special support. Selected measurements were made at ISG KER services UPV/EHU

Ion-Pair Chromatography for the Determination of Capreomycin Sulfate Components and Related Substances

Chromatographic methods for the analysis of antibiotic degradation products are widely used to evaluate the quality of medicines. Natural multicomponent antibiotics, such as capreomycin, are the most challenging compounds in terms of developing analytical procedures for related substances. Capreomycin sulfate monographs of the leading pharmacopoeias do not contain specifications for related substances. The key requirement concerns the sum of the main components of capreomycin calculated by normalising the peak areas in the test solution chromatogram. Therefore, it is important to develop an analytical procedure for determining not only the main components but also related substances of capreomycin.The aim of the study was to develop an analytical procedure for determining both the main components (IA, IB, IIA, and IIB) and related substances of capreomycin by ion-pair ultra-high-performance liquid chromatography (UHPLC).Materials and methods. This study examined capreomycin sulfate powder, an active pharmaceutical ingredient (API). Capreomycin sulfate solutions were analysed after artificial degradation (alkaline or acid hydrolysis) to demonstrate the resolution, selectivity, and efficiency of the experimental chromatographic system. The authors used an Agilent 1100 liquid chromatography instrument (Agilent Technologies) and chromatographic columns: Kinetex C18, YMC-Triart С18, ACQUITY UPLC BEH C18, ACQUITY UPLC BEH C8, ACQUITY UPLC BEH Phenyl, and ACQUITY UPLC CSH C18 (experimental procedure) or Acclaim C18, Zorbax SB-C18, and XBridge BEH130 C18 (The International Pharmacopoeia procedure).Results. In contrast to pharmacopoeial procedures, which evaluate only the component composition, the experimental procedure under the selected chromatography conditions can determine both the component composition and related substances of capreomycin. This advantage results from substituting a column packed with 1.7 µm particles for a 5 µm column required for pharmacopoeial procedures. The experimental procedure remains suitable for liquid chromatography instruments with a pressure limit of no more than 400 bar in the gradient elution mode with two mobile phases. According to the efficiency and selectivity evaluation, ACQUITY UPLC BEH C18 columns (150 × 2.1 mm, 1.7 μm) provide optimal peak resolution for capreomycin isoforms and related substances after artificial degradation of capreomycin.Conclusions. This experimental procedure based on ion-pair UHPLC may be used in the production and stability testing of capreomycin medicines to evaluate the API quality by the content of its main components and related substances

Characterising the discharge cycle of CaCl 2 and LiNO 3 hydrated salts within a vermiculite composite scaffold for thermochemical storage

Transpired solar collectors (TSC) are an efficient means of building heating but due to the demand/use mismatch their capabilities are maximised when paired with a suitable storage technology. The Hydration and/dehydration of inorganic salts provides an appropriate energy storage medium which is compatible with the air temperature provided by a conventional TSC (<70 °C). The study reports on technical appraisal of materials which are compatible with building scale energy storage installations. Two salts (CaCl2, and LiNO3) were impregnated into porous vermiculite to form a salt in matrix (SIM). Their performance during the discharge portion of the cycle at high packing density was examined using a laboratory scale reactor. Reactor and exit temperature increases were considerably lower than those predicted from first principles. Peak reactor temperature rises of only 14 °C were observed with a reduction in temperature output from this initial peak over 60 hours. Poor salt utilization resulting from deliquescence near the reactor inlet was identified as being the source of the reduced performance. Changes in reactor size, orientation and cycling between input periods of moist and dry air did not improve reactor performance. The investigation has identified that moist air transit through the packed SIM reactor column is limited to approximately 100 mm from the air inlet. This has implications for reactor design and the operation of any practical building scale installation. Predictions of building scale energy storage capabilities based on simple scaling of laboratory test considerably under estimate the volume and complexity of equipment required

Changes in morphotype in the population of E.coli in the presence of metal containing nanoparticles

The level of variability of the E.coli morphotype under the influence of iron oxide nanoparticles (MNPs) depending on their concentration was studied as well as the adaptive capabilities of the microbial population under growth conditions was evaluated.The presence of γ-Fe2O3 nanoparticles in the cultivation fluid affects the cultural and morphological properties of the microbial population of E.coli in the process of its development. The appearance of new morphotypes of colonies and cells can be considered as a manifestation of an adaptive mechanism. A change in the morphology of the microbial cell with a high concentration of MNPs leads to abnormal growth and disruption of the division process. © Published under licence by IOP Publishing Ltd.MAT2017-83631-C3In part this research was supported by the Spanish Government under project MAT2017-83631-C3. We thank I.V. Beketov and O.M. Samatov for special support

Influence of metal containing nanocomposites on the kinetics of microbial population development

Magnetic nanoparticles are promising nanomaterials for biomedical applications. Studies have been conducted to study the effect of iron-containing nanoparticles at concentrations of 1.0 and 10.0 maximum tolerated dose for total iron on the growth and development of the microbial population of E.coli. On the basis of the obtained results, it was found that nanoparticles affect the growth characteristics of E.coli, related to human gram-negative prokaryotic microflora. The level of biological activity of nanoparticles depends on their concentration. © Published under licence by IOP Publishing Ltd.Russian Science Foundation, RSF: 18-19-00090In part this research was funded by the Russian Science Foundation, grant number 18-19-00090

Diffuse-Charge Dynamics in Electrochemical Systems

The response of a model micro-electrochemical system to a time-dependent applied voltage is analyzed. The article begins with a fresh historical review including electrochemistry, colloidal science, and microfluidics. The model problem consists of a symmetric binary electrolyte between parallel-plate, blocking electrodes which suddenly apply a voltage. Compact Stern layers on the electrodes are also taken into account. The Nernst-Planck-Poisson equations are first linearized and solved by Laplace transforms for small voltages, and numerical solutions are obtained for large voltages. The ``weakly nonlinear'' limit of thin double layers is then analyzed by matched asymptotic expansions in the small parameter $\epsilon = \lambda_D/L$, where $\lambda_D$ is the screening length and $L$ the electrode separation. At leading order, the system initially behaves like an RC circuit with a response time of $\lambda_D L / D$ (not $\lambda_D^2/D$), where $D$ is the ionic diffusivity, but nonlinearity violates this common picture and introduce multiple time scales. The charging process slows down, and neutral-salt adsorption by the diffuse part of the double layer couples to bulk diffusion at the time scale, $L^2/D$. In the ``strongly nonlinear'' regime (controlled by a dimensionless parameter resembling the Dukhin number), this effect produces bulk concentration gradients, and, at very large voltages, transient space charge. The article concludes with an overview of more general situations involving surface conduction, multi-component electrolytes, and Faradaic processes.Comment: 10 figs, 26 pages (double-column), 141 reference

Гликопептидные антибиотики: структурно-функциональные аспекты, применение в медицине и стандартизация

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin.В последние годы для лечения тяжелых бактериальных инфекций широко применяются гликопептидные антибиотики. Длительное использование в медицинской практике антибиотиков первого поколения этой группы соединений (ванкомицин и тейкопланин) способствовало появлению устойчивых к ним бактерий. Для решения проблемы резистентности были разработаны три новых гликопептидных антибиотика: далбаванцин, телаванцин и оритаванцин. Цель работы — анализ и обобщение данных литературы и действующих стандартов качества, касающихся антибиотиков гликопептидной природы. В работе приведены основные сведения об истории открытия антибиотиков-гликопептидов природного происхождения (ванкомицин, тейкопланин) и их производных (телаванцин, оритаванцин, далбаванцин). Охарактеризована структура гликопептидных антибиотиков, описаны их основные свойства, применение и распространение на фармацевтическом рынке. Приведена информация о спектре антибактериальной активности ванкомицина, тейкопланина и их полусинтетических производных. Рассмотрены подходы к стандартизации ванкомицина и тейкопланина, приведены основные требования ведущих фармакопей к качеству ванкомицина, тейкопланина и препаратов на их основе. Проведенное исследование показало, что гликопептидные антибиотики продолжают оставаться крайне востребованными благодаря высокой эффективности при лечении заболеваний, вызванных грамположительными бактериями. Однако на настоящий момент разработаны и введены в ведущие зарубежные фармакопеи стандарты качества только на два представителя этой группы антибиотиков: ванкомицин и тейкопланин. Обобщение данных литературных источников показало, что дальнейшая разработка модификаций гликопептидных антибиотиков направлена на создание соединений, характеризующихся пролонгированным действием и большей эффективностью действия против патогенных микроорганизмов. Таким образом, внимание исследователей должно быть направлено на дальнейшую стандартизацию новейших производных гликопептидных антибиотиков: телаванцин, оритаванцин и далбаванцин

Medical university students and facial masks usage. new aspects of safety in COVID-19 pandemic

Aspects of morphology, epidemiology and pathogen microorganism resistance of Covid-19 are presented in article. Data of the incidence and use of personal protective equipment are presented according to the survey of the student community of USMU. Current personal protective equipment requirements and standards are analyzed according with regulatory documents. Pharmacy and retail conditions of mask sales were discoveredВ статье рассмотрены вопросы морфологии, эпидемиологии и устойчивости во внешней среде вируса Covid-19. Представлены собственные данные по исследованию заболеваемости и использования средств индивидуальной защиты по данным анкетирования студенческого сообщества УГМУ. Проанализированы существующие требования и стандарты к средствам индивидуальной защиты в соответствии с нормативными документами. Проведены исследования условий реализации масок в различных аптечных и торговых сетях