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Antibiot Khimioter = Antibiotics and Chemotherapy

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Vol 68, No 11-12 (2023)
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EXPERIMENTAL STUDIES

4-9 256
Abstract

Polymer complexes of amikacin based on two sulfonic polymers, dextran sulfonic acid and poly-2-acrylamido-2-methylpropane sulfonic acid, containing 25 and 33 wt % of the antibiotic, respectively, have been synthesized. Molecular weights and limiting binding capacities were determined for carrier polymers. The formation of polymer complexes was confirmed by IR and UV spectroscopy, as well as by GPC. The kinetics of amikacin release from complexes was investigated in water at 37°С. The resulting complexes exhibited high antibacterial activity, close to control, and weak antiviral activity.

10-18 272
Abstract

This work presents ultraviolet (UV) spectra of various concentrations of polyene antibiotics. The spectra of Levorin and Amphotericin B differ in three main absorption maxima. The maximum absorption spectra of antibiotics vary in the range of 370–430 nm. UV absorption spectra reflect the characteristic spectrum of polyenes belonging to this class. Amphotericin B and Levorin in combination with cholesterol lower the maximum of the UV absorption spectra. Analysis of the obtained results shows that cholesterol molecules, combining with double-bond systems of Amphotericin B and Levorin, gradually reduce the maximum absorption of UV spectra, which creates opportunities for their more active use in various fields of biomedicine.

19-22 270
Abstract

Antibiotic resistance in pathogenic bacteria is a worldwide problem. In recent years, there has been increasing interest in the evaluation of plants and fungi with antibacterial activity against various infectious agents. The antibacterial activity of ethanol extract of Laricifomes officinalis (Vill.) Kotl. et Pouzar (Polyporaceae) fruiting body was studied. Activity was assessed using the disk diffusion method. L.officinalis ethanol extract showed high activity against Yersinia pseudotuberculosis, as well as moderate activity against Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, and Staphylococcus aureus. Listeria monocytogenes were not sensitive to ethanol extract of the fruiting body of L.officinalis.

23-29 795
Abstract

The sensitivity of field cultures of fungal microbe Aspergillus niger to new synthetic analogs of natural antifungal antibiotics of the isocoumarin class was determined in comparison with antimycotic activity of known drugs. The minimal mycocidal concentration (MMCC) and minimal mycostatic concentration (MMSC) of the drugs were documented. The inhibitory effect (IE) was expressed as the ratio of the average colony diameter of experimental samples to the average colony diameter of control samples. From the results presented in the present work, it follows that the investigated field cultures of Aspergillus niger are most sensitive to antimycotic drugs belonging to N-methylnaphthylmethylamine derivatives and polyene antimycotics — terbinafine (MMSC = 0–2 µg/cm3) and nystatin (MMSC = 4–8 µg/cm3, IE-1 = 1.69, IE-K2 = 1.51), which have a pronounced mycocidal effect. Other studied preparations, including synthesized analogues of natural isocoumarins, showed only mycostatic effect on cultures of fungal microbe Aspergillus niger: fluconazole — MMSC = more than 64 µg/cm3, IE-K1 = 3.38, IE-K2 = 2.52; griseofulvin — MMSC = more than 64 µg/cm3, IE-K1 = 1.79, IE-K2 = 1.53; 3-(3-oxobutyl)-isocoumarin — MMSC = more than 64 µg/cm3, IE-K1 = 1.27, IE-K2 = 1.07; 7-fluoro-3-(oxobutyl)-1-N-isochromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.28, IE-K2 = 1.03; (E)-3-(3-oxobutyl-1-en-1-yl)-1-N-isochromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.12, IE-K2 = 1.06; 3-(3,3-difluorobutyl)-1-N-iso-chromene-1-one — MMSC = greater than 64 µg/cm3, IE-K1 = 1.34, IE-K2 = 1.25.

GUIDELINES FOR PRACTITIONERS

30-37 365
Abstract

Topical use of antibacterial drugs as part of complex therapy for purulent-inflammatory infections of the skin and oropharynx can not only eliminate the symptoms but also influence the cause of the disease. Dioxidine® is a broad-spectrum antibacterial drug, active against both gram-positive and gram-negative bacteria. The aim of this study was to investigate the bioavailability, pharmacokinetic parameters, and safety profile of Dioxidine®, solution for topical and external use, 0.25 mg/ml, in cutaneous and topical application. Another dosage form of Dioxidine® — a solution for infusion and external use, 5 mg/ml — was used as a comparison drug. The study consisted of 4 stages reflecting different routes of drug administration: rinsing the oropharynx (path A), a single irrigation of the oropharynx using a spray nozzle (path B), back skin irrigation (path C), and intravenous administration (path D — for the reference drug). The results of the study made it possible to determine the absolute dose-normalized bioavailability of the study drug in the indicated routes of administration, as well as to evaluate its safety profile.

38-48 311
Abstract

The new AWaRe classification proposed by WHO for assessing the clinical practice of using antibiotics in adults in 2017 was adapted for children's hospitals in 2019, due to the update of the categorization of antimicrobials, and showed effec- tiveness for assessing the rationality of antimicrobials use in children's hospitals in WHO-participating countries in the observation protocol GARPEC. In this retrospective pharmacoepidemiological study, we assessed the rationality of antibiotic consumption in multidisciplinary hospitals in the subjects of the Russian Federation with a pediatric profile. An observational multicenter study of antibiotic consumption was carried out in the constituent entities of the Russian Federation (N=9). Consumption assessment was carried out using the AWaRe method, based on DDD analysis and the WHO list of essential antibiotics for children by groups: «Access» (green), «Watch» (yellow) and «Reserve»(red). The quantitative indicator «the number of days of therapy in the ATC group J01 Antibacterial drugs for systemic use» in the established standardized dose per 100 patient days in the pediatric profile in level III hospitals in 9 regions of Russia for 2021 was 214.93. On average, each of the hospitalized pediatric children received at least two antibiotics during the period of hospital treatment in 2021 in Russia. On average, in Russia, based on the results from 9 constituent entities of the Russian Federation, drugs in the «Admission» category were 44.24%, «Control» — 49.23%, «Reserve» — 0.88%. When categorizing according to WHO2019, negative characteristics were identified — either excessive use of cefazolin and amikacin in the «Access» category, or the predominance of drugs with antipseudomonas activity, ceftazidime and cefepime, in the «Watch» groups. A positive and more balanced version of the structure of antibiotic consumption in multidisciplinary children's hospitals was identified in Moscow («Access» — 37.3%, «Watch» — 59.29%, «Reserve» — 3.41%), in the Republic of Mari El («Access» — 30.28%, «Watch» — 69.42%, «Reserve» — 0.30%) and in the Republic of Khakassia («Access» — 30.95%, «Watch» — 67.39%, «Reserve» — 1.66%). Thus, «Access» (green), the main indicator of the assessment category of antibiotic consumption in children, did not reach 60% in 2021 in any of the multidisciplinary children's hospitals in Russia presented in this study, which was proposed as a target indicator for achieving rational consumption according to WHO. The results of this study showed the problems of irrational use of antibiotics: insufficient use of oral dosage forms in children, excessive use of aminoglycosides, unjustified switching to combination antimicrobial therapy with antibiotics of the «Reserve» group in multidisciplinary children's hospitals in Russia.

49-58 206
Abstract

Drug-drug interactions (DDIs) are a major cause of hospital admissions, accounting for 16.6% of ADRs and about 1% of all hospital admissions. Polypharmacy is on the rise, with a Swedish population-based study of people aged ;;;75 years showing that the prevalence of polypharmacy increased from 27% in 1988 to 54% in 2001 and to 65% in 2006. The aim of the study was to analyze the databases on DDI and to assess the possibility of their use in managing the risks of pharmacotherapy in the Russian Federation and the EAEU. Results. The main DDI databases are characterized. The degree of inconsistency in data on the number of DDI, severity and clinical recommendations was determined. The basic requirements for the completeness of information in databases are formulated. The necessity to harmonize approaches to providing information about DDI, as well as the need to create local databases for medical organizations were revealed. A computer program has been created to minimize the risks of DDI in clinical practice, for expert and scientific purposes. Conclusions. Databases and programs for DDI have different goals, a different set of data on DDI with varying degrees of evidence, differences in assessment of severity, likelihood of occurrence, clinical recommendations for treatment and correction of DDI. The variability of information is due to the lack of a unified system for assessing the severity and likelihood of potential negative consequences of DDI; different purposes for creation; difference in budgets at creation. This situation leads to warning redundancy and physician fatigue from insignificant or unproven DDIs. Based on the identified requirements for local databases, a computer program for modeling rational pharmacotherapy for lower respiratory tract infections was created and received a certificate of state registration. 

REVIEWS

59-66 387
Abstract

One of the central topics in bacteriophage research is the host specificity. It depends on the success of completing viral life cycle stages, including adsorption, penetration of the genetic material of the virus into the cell and its replication, assembly of phage particles and cell lysis. Laboratory assessments of the spectrum of lytic activity of phages are inextricably linked to significant methodological biases, and the often used spot test method can be associated with a large percentage of false-positive results. Along with the variety of types of phage specificity, there is temporal variability. The co-evolution of phages and bacteria leads to the acquisition of resistance to viruses by bacteria and the accumulation of mutations in the genomes of bacteriophages aimed at overcoming this resistance. At the same time, the adaptation of bacteriophages to bacteria that are evolutionarily distant from the isolation hosts is barely possible. This barrier is based on the peculiarities of metabolism, cell wall structures and mechanisms for the implementation of matrix processes. The spatial factor of phage specificity is manifested in the greater breadth of the spectra of lytic activity of bacteriophages on local samples of bacteria compared to the spectra assessed on samples of isolates from habitats geographically distant from the place of virus isolation.

67-74 301
Abstract

The review analyzes the research articles, guidelines, and clinical trial results on the effect of fluoroquinolones, bedaquiline, nitroimidazoles, and clofazimine on QTc prolongation. The importance of timely and regular monitoring of cardiotoxicity and the importance of continuing clinical trials for the discovery of anti-tuberculosis drugs with a satisfactory safety profile are presented.

75-90 232
Abstract

The article summarizes study results of the effect of polyphenols, polysaccharides, and lectins from terrestrial and marine biota on the hepatitis C virus and the course of HCV infection. The urgency of this problem is determined by the wide spread, the asymptomatic course of the acute form of the disease with the gradual development of adverse outcomes, limited access to effective etiotropic therapy due to high cost, as well as low public awareness of this disease. A wide range of physiological effects of natural biologically active substances with antiviral, immunomodulatory, anti-inflammatory, and antioxidant activity opens up the possibility of their use for the creation of pharmacological substances and drugs of a new generation for the prevention and adjuvant therapy of hepatitis C. The authors of the review draw attention to the difficulties associated with the development of such tools and some possible ways to overcome them.



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