Introduction. Due to the ability of the influenza virus to mutate, it is necessary to constantly search for new drugs with preventive and direct antiviral effects.The aim of the study is to investigate the protective antiviral properties of the drug Thymogen®, a dosed nasal spray, on a model of lethal influenza pneumonia in laboratory animals.Material and methods. White mature mice were selected for the experiment on the antiviral activity of the tested drug samples against H1N1 influenza virus; the mice were divided into the following groups (30 animals each): two negative control groups; two groups receiving Thymogen®, a dosed nasal spray (before and after infection); one group of animals received Tamiflu®, and one received Hexoral®. The mortality of animals with influenza pneumonia was assessed; histological and morphometric analyses were also carried out.Results and discussion. The morphological picture of the lungs of animals correlated with their protective activity when analyzing the survival of animals. The normalization of tissue structure was pronounced the most in the group of animals infected with the virus, pre-incubated with Thymogen®, a dosed nasal spray, and in the group receiving Tamiflu®. Moreover, the viral load in the lungs was lower by 1.5 and 1.2 orders of magnitude in the group receiving Thymogen®, dosed nasal spray, compared to the negative control group (the 3rd and the 6th days of the experiment, respectively), which corresponds to a decrease in the intensity of viral reproduction by 31.6 and 15.8 times

A significant increase in sales of antibacterial drugs in pharmacies and their purchases by medical institutions of the Russian Healthcare System was observed against the background of the past pandemic of a novel coronavirus infection in Russia. Microbiological monitoring that was carried out at City Clinical Hospital No. 67 named after. L. A. Vorokhobov (Moscow) in 2020–2021, revealed a pressing problem — primarily gram-negative bacteria, with a predominance of multidrug-resistant (MDR) strains, were isolated from patients with healthcare-associated infections (HAIs). As shown by pharmacoeconomic studies conducted by the authors, the cost of one course of targeted antibacterial therapy for HAI in this case could increase by 6–12 times compared to a similar course of therapy in the absence of both MDR strains and XDR strains of hospital pathogens. In order to achieve a reduction in the cost of antibacterial therapy developed and used by the authors, in addition to the development of effective antibacterial therapy regimens for HAIs caused by MDR/XDR pathogens, another study was carried out as a continuation of the work on creating and improving biotherapy regimens for HAIs, namely the development of personalized phage therapy regimens for patients with hospital-acquired pneumonia caused by MDR bacterial strains. Based on the data obtained, the concept of a personalized approach to phage therapy of various nosological forms of HAIs caused by hospital-acquired MDR pathogens in patients of a multidisciplinary hospital was proposed and tested. As a result of this approach, the effectiveness of phage therapy for various nosological forms of HAIs caused by MDR and XDR strains of hospital pathogens in City Clinical Hospital No. 67 named after. L. A. Vorokhobov increased by 30%, and the effectiveness of the initial antibiotic regimen was 70%. The economic effect of the combination of antibiotic therapy and phage therapy («booster therapy») amounted to 3,000,000 rubles, compared with the use of antibiotics alone in the treatment of patients with HAIs caused by MDR/XDR strains of hospital pathogens.

Background. The modern healthcare system is constantly improving and introducing new measures to protect the population from viral diseases, but the experience of the COVID-19 pandemic has shown that infections cannot always be controlled on global scale. In this regard, the development of new broad-spectrum antiviral drugs is more relevant than ever.The aim of the study was to investigate the antiviral activity and cytotoxicity of copolymers of sodium styrene sulfonate and vinyl monomers of various chemical structures, as well as to identify promising polymers for the development of new antiviral agents.Materials and methods. 14 copolymers of sodium styrene sulfonate (NaSS) with various functional comonomers were synthesized. Three viruses with different reproduction strategies and transmission methods — respiratory syncytial virus, influenza virus, and herpes virus — were selected for the assessment of antiviral activity.Results. The screening identified copolymers that showed high activity against all three viruses. It was found that the introduction of various functional groups into the structure of NaSS did not decrease antiviral activity, but significantly reduced cytotoxicity. The molecular weight has also shown a noticeable effect on the activity. Different sensitivity of viruses and cells to the studied polymers was revealed, likely due to the structural features of the virus shell and cell wall.Conclusions. The results demonstrate the potential of sodium styrene sulfonate copolymers as a model for developing a broad-spectrum antiviral drug.

Background. One of the main problems of antibiotic therapy is the development of resistance in microorganisms. In this regard, the search for new natural antibiotics, including those of plant origin, is relevant. The aim of the study was the determination of antibacterial action mechanisms of aqueous and alcoholic extracts of medicinal plants collected on the territory of the Republic of Bashkortostan. Methods. The bark, roots, stems, leaves, and inflorescences of medicinal plants were selected as objects of the study. The mechanisms of antibacterial action of plant preparations were determined via high throughput screening using the Dualrep2 double reporter system. Results. The mechanisms of the antibacterial action of certain plant extracts obtained from fresh and dried raw materials were established. It has been shown that the products of alcohol extraction of yarrow inflorescences inhibit protein synthesis, while the products of celandine roots and stems cause the activation of the SOS DNA repair system in Escherichia coli bacteria. Conclusion. The results obtained allow us to consider the studied extracts of medicinal plants as a basis for obtaining new antibacterial agents with a specific mechanism of action.

Antibiotic resistance is a global health problem. Its solution requires concerted efforts on the scale of global cooperation. Programs to prevent the development of antibiotic resistance, as well as to stimulate the development of new drugs with antimicrobial activity are implemented in a lot of countries. The use of antibacterial drugs, including inappropriate use, has increased during the COVID-19 pandemic, which may contribute to the growth of antibiotic resistance. The aim of this study is to assess the measures aimed at combating the growing antibiotic resistance in the world, analyze the market of antimicrobial drugs in the Russian Federation, as well as collect and process information on the antibiotic resistance of microorganisms that cause infectious diseases that develop against the backdrop of COVID-19. The analysis of the state register of the Russian Federation for antibacterial drugs was carried out. Mathematical and statistical processing of antibiotic resistance was performed according to the data of the European Surveillance Atlas of Infectious Diseases for Klebsiella pneumonia in relation to fluoroquinolones, aminoglycosides, third-generation cephalosporins, as well as combined resistance to these antibacterial drugs over the past sixteen years.

The paper presents the results of extended preclinical studies demonstrating the safety using the direct-acting antiviral drug Riamilovir in immature white rats. Riamilovir did not show any toxic effects on the growth of animals, their fertility, behavior, hematological and biochemical parameters, as well as morphology of visceral organs when used in a course. According to the results of the studies, Ramilovir can be recommended for multicenter clinical trials in adolescents and children of younger age groups.

Background. Antibiotic resistance of bacteria is a serious concern for modern medicine. The search for new compounds with a pronounced antibacterial effect is an urgent task of pharmaceutical chemistry. The aim of the study was to assess nfluence of the structure of benzimidazole and its derivatives the ability to inhibit the growth of gram-positive bacteria Bacillus subtilis. Materials and methods. Antibacterial activity of diazaheterocycles was evaluated by the method of serial dilutions. Сoncentrations from 0,06 to 1000 µg/l were used. Тhe minimum inhibitory concentration (MIC) of benzimidazole derivatives against Bacillus subtilis BKM B-407 was determined. The antibacterial effect of the studied halogen- and nitrobenzimidazoles was compared with the antimicrobial activity of benzimidazole. Results. The antimicrobial activity of the 12 benzimidazole derivatives was established. 2-trifluoromethylbenzimidazoles containing halogen atoms in the phenylene fragment had the most pronounced inhibitory effect. The dihalogenated derivatives exhibited greater antibacterial activity than the compounds with one halogen atom in the benzene ring. 5,6-dibromo-2-(trifluoromethyl)benzimidazole was the most active compound with an MIC of 0.49 µg/mL, comparable to the commercial antibiotic tetracycline. The antibacterial activity of erythromycin is a half that of this substance. Conclusions. Polyhalogen derivatives of benzimidazole are promising compounds for the development of new antimicrobial drugs against Gram-positive bacteria.

Background. The spread of extensive drug-resistance among gram-negative bacteria calls for the search for antimicrobics with new mechanisms of actions.The aim was to assess susceptibility of extensively drug-resistant K. pneumoniae strains to cefiderocol and other new inhibitor-protected β-lactams, and to determine genetic mechanisms of antibiotic resistance.Methods. This study included 30 extensively drug-resistant K. pneumoniae strains collected in 2016–2021 from 4 regions of Belarus. Carbapenemase genes were detected by real-time PCR. Minimum inhibitory concentrations (MICs) for cefiderocol and other new antibiotics were assessed by microdilution method using the Sensititre system. Whole genome sequencing was performed for 2 resistant and 3 cefiderocol-susceptible strains. Genome assemblies and annotation were performed using UGENE v. 37.0 software. Nucleotide sequences were translated using CLC Sequence Viewer v. 8.0 (QIAGEN) package. The PROVEAN software was used to assess amino asides substitutions and their influence on the functional activity of proteins.Results. KPC carbapenemase-producers were 4 strains, OXA-48 — 17, KPC+OXA-48 — 1, NDM — 7, OXA-48 + NDM — 1. All KPC-producers were susceptible to imipenem/relebactam and meropenem/vaborbactam. Resistance to ceftazidime-avibactam was noted in all NDM producers and OXA-48+NDM co-producer. The study has identified 9 cefiderocol-resistant strains. These were NDM and OXA-48-producers isolated from hospitalized patients with COVID-19 infection from 3 regions of Belarus. Resistant strains had functionally significant nonsynonymous substitutions in the genes of TonB-dependent receptors for catecholate siderophores FepA (F472V, P64S) and Fiu (T92S).Conclusion. The study has shown high efficacy of new inhibitor-protected carbapenems and cephalosporins against certain types of carbapenemase-producers. Strains with mutational resistance to cefiderocol, an antibiotic not previously used in Belarus, have been identified.

The basis for conducting bioequivalence studies is the determination of the bioavailability of the active substance of the drug at its place of action by establishing the concentration of the drug in biological fluids using sensitive analytical techniques. The bioanalytical technique used should provide reliable results which would lead to satisfactory level of interpretation. To investigate the bioequivalence of rivastigmine preparations, an 8 times more sensitive method (compared to the data in the available literature) for the quantitative determination of rivastigmine in human blood plasma by HPLC-MS/MS was developed. Rivastigmine is extracted from plasma by precipitation of plasma proteins with acetonitrile. Chromatographic separation of rivastigmine and the internal standard was carried out on a YMC Triart C18. 50×2.0 mm (1.9 µm) column in a gradient elution mode with a flow rate of 0.5 ml/min. A 0.1% solution of ammonium hydroxide and acetonitrile were used as mobile phases. The lower limit of the quantitative determination of the method was 25 pg/ml.

Over the past two years, the SARS-CoV-2 pandemic has dominated all aspects of health care around the world, often leaving other long-term public health problems in the background. Despite the fact that COVID-19 is a viral disease, the use of antibiotics in these patients was common practice, especially at the beginning of the pandemic. The use of antibiotics (ABs) in patients with the novel coronavirus infection (NCI) reaches over 70% cases. Suspected concomitant bacterial infection, lack of effective means of treating NCI, terminological problems associated with the definition of «pneumonia» may have been the motivating factor for such widespread use. The data of the conducted studies indicate that there is currently insufficient evidence for the widespread empirical use of antibiotics in the majority of hospitalized patients, as the total proportion of bacterial infections in COVID-19 is quite low. Thus, according to most researchers, combined bacterial infection is rare and is less than 10%. Unjustified prescription of ABs to patients with COVID-19 can lead to complications that could otherwise have been avoided, including increased bacterial resistance, Clostridioides difficile infection, kidney failure, and much more. The article provides information on the frequency of AB therapy at various stages of medical care. The analysis of data on the nature of antibiotics prescribed to inpatients and outpatients with COVID-19 in different countries was carried out. Recommendations from different countries on AB therapy in patients with COVID-19 are presented. Conclusion. The data reviewed confirm the discrepancy between the unjustified and excessive prescribing of antibiotics to patients with COVID-19 and the small number of evidence of associated bacterial infections.