The activity of the antimetabolic drug Riamilovir (Triazavirin®) was studied on a model of SARS-CoV-2 infection on Syrian hamsters. Infectious process was caused by the intranasal administration of the virus accumulated in the Vero-B culture with a concentration of 4.25×104 TCID50, in a volume of 26 µl/hamster. The effects of the drug at a dose of 20 mg/kg intraperitoneally daily in the midst of the infectious process were traced to accelerate the clearance of the virus in the lungs, prevent body weight loss and the severity of pulmonary edema, as well as preserve the mass of the spleen. The protective effects of Riamilovir on the structure of the lungs and brain are shown, it is suggested that the drug has the ability to penetrate the blood-brain barrier. It was concluded that Riamilovir has antiviral activity against SARS-CoV-2.

Currently, the problem of antibiotic resistance of opportunistic and pathogenic microorganisms is extremely urgent. In order to find new effective natural antibiotics, it is necessary to intensify the search process. In the gradual selection of the most promising producers, we introduced the stage of determining the antibiotic activity of the culture fluid of the studied natural strains against the clinical isolates of hospital microorganisms with multiple resistance to medical antibiotics. Determining the species affiliation of potential producers allows to select those producers of a particular species that differ in the antimicrobial spectrum of activity from those described in the literature. Four strains of actinomycetes that showed activity against resistant clinical isolates of yeast Candida albicans, C.famata, C.parapsilosis and Cryptococcus neoformans were selected, namely: Nocardia soli INA 01217, Streptomyces bottropensis INA 01214, S.chromofuscus INA 01211 and S.netropsis INA 01190. The N.soli INA 01217 strain also shows antibiotic activity against the Gram-negative bacterium Escherichia coli ATCC 25922. These strains of actinobacterial producers were selected for subsequent chemical studies of the antimicrobial compounds formed by them.

Relevance: The two systems for determining the susceptibility of bacteria to antimicrobial drugs, CLSI and EUCAST, are recommended for use in the global system of epidemiological surveillance of antimicrobial resistance of the World Health Organization. However, they differ in the methodology of setting an antimicrobial susceptibility testing, threshold values of cut-off points, as well as interpretation of results. The true significance of methodological differences between these systems for global microbiological monitoring is unclear. The aim of the study was to evaluate the influence of differences in the cut-off points of CLSI and EUCAST on the interpretation of antimicrobial sensitivity of microorganisms to carbapenems in Saint Petersburg. Design: screening and comparative study. Materials and methods. Sensitivity to Meropenem was studied in Escherichia coli (n=2956), as well as Klebsiella pneumoniae (n=1189) for the period of 2011–2013 and 2016–2019, and interpreted according to the threshold values of the two guidelines (2020). Results. The weighted Kappa showed good agreement between the EUCAST vs CLSI standards for both E.coli (0.58; 95% CI 0.55–0.61) and K.pneumoniae (0.77; 0.73–0.81). Mcnemar's Chi-square test revealed differences between the two standards in assessing sensitivity to Meropenem of E.coli which were 5.31% (95% CI 5.06–5.31%, P<0.0001), and of K.pneumoniae — 3.95% (95% CI 3.36–3.95%, P<0.0001). Conclusion. The reliability of determining sensitivity bacteria to anti-microbial drugs has a significant impact on their rational use and the results of microbiological monitoring. The first priority is to develop national standards that take regional characteristics into account.

The wide spread of carbapenemases among gram-negative bacteria of the Enterobacterales order in hospitals around the world, including Russia, creates great difficulties in the effective use of antibiotics for these infections in the ICU. Ceftazidime-avibactam is the first antibiotic developed and studied for the treatment of infections caused by carbapenem-resistant enterobacteria. Ceftazidime-avibactam shows high activity against producers of class A and D serine carbapenemases (KPC and OXA-48). In combination with aztreonam it is effective in infections caused by producers of class B metallo-beta-lactamases (NDM and VIM). The review analyzes the results of 19 non-comparative and 10 comparative studies of ceftazidime-avibactam in infections caused by carbapenem-resistant Enterobacterales, as well as case reports. According to the data of non- comparative studies, the clinical efficacy of ceftazidime-avibactam ranged from 45.0 to 87.2%, on average 71.7±11.3%, and the eradication rate of KPC or OXA-48 carbapenemase producers ranged from 40.0 to 100%, on average 65.5±18.6%. The effectiveness of ceftazidime-avibactam in comparative studies was 67.9±17.3%, which was significantly higher compared to other antibiotics (44.3±14.4%, P=0.012). Treatment with ceftazidime-avibactam was accompanied by a significantly lower 30-day mortality in contrast to other antibiotics – 23.8±13.5% and 41.0±13.6%, respectively, P=0.001. The development of resistance in Enterobacterales species to ceftazidime-avibactam during therapy is rarely observed, on average 5.4±4.4%, which characterizes a rather low potential of the antibiotic in resistance selection. Early administration of ceftazidime-avibactam is accompanied by better treatment results as opposed to delayed therapy. Treatment of infections caused by carbapenem-resistant enterobacteria with ceftazidime-avibactam is associated with a significantly higher recovery rate and a lower mortality compared to other regimens of antibacterial therapy.

The review presents materials describing the seaweed-derived sulfated polysaccharides (SPS) as potential means for prevention and treatment of viral diseases of the respiratory tract, mainly influenza and COVID-19. The literature materials on the pathogenetic targets of influenza viruses and SARS-CoV-2, on the antiviral potential of SPS derived from red, brown and green algae, as well as on the mechanisms of antiviral action of these unique compounds are summarized. Seaweed SPS are characterized by high antiviral activity, good solubility, and almost complete absence of toxicity. Pathogens of respiratory infections do not form resistance under the SPS influence. The abovementioned facts allow us to consider these compounds as promising candidates for the creation of medicines, dietary supplements, and functional food products with antiviral and, above all, anti-influenza and anti-coronavirus activity on their basis in the future.

The article discusses the issues of drug interactions in the treatment of COVID-19 patients with concomitant cardiovascular diseases. It was revealed, that the most frequent comorbid background in patients with COVID-19 is cardiac pathology. Cardiac arrhythmias are observed in many cases, which can be aggravated by the proarrhythmogenic effect of drugs used to treat the novel coronavirus disease.

The article presents current data on the role of gut microbiota in the development of urinary tract infections. The main pathogenetic mechanisms contributing to the chronic recurrent course of the disease, the spread of antimicrobial resistance, as well as their connection to the disorders of gut microbiota are shown. It is known that most pathogens of urinary infections originate from the gut microbiota, where they exist for a long time, forming reservoirs. The normal composition and functions of the microbiota prevent colonization of the intestine by pathogenic bacteria and reduce the risk of developing this disease. Ways of correction through diet, probiotics, as well as fecal microbiota transplantation are considered. Modulation of gut microbiota may be a promising approach in the treatment and prevention of urinary tract infections. Meanwhile, a qualitative evidence base on the effectiveness of this strategy has not been formed. Further research in this direction is required.

Currently, the close attention of the medical and international community is still riveted on the novel coronavirus infection, which caused the pandemic in 2020. Understanding the underlying mechanisms of coronavirus disease-2019 (COVID-19) made it possible to move from the empirical selection of therapy, which was observed at the beginning of the pandemic, to the pathogenetically justified prescription of drugs, including glucocorticoids, anticoagulants, as well as some antirheumatic drugs. However, despite the huge amount of scientific and clinical material accumulated over 1.5 years, the interest in this problem does not wane both due to the existence of a number of unresolved issues, and due to the constant emergence of new (often contradictory) data.

One of the most used antimicrobial nitrofurans in Russian medical practice is nifuroxazide, which is distinguished by high therapeutic efficacy, drug safety, as well as economic availability in the treatment of acute bacterial diarrhea without deterioration of the general condition, fever, and intoxication. In the Russian Federation (RF), nifuroxazide preparations in general circulation are supplied by 19 domestic and foreign pharmaceutical organizations. The aim of this study was to analyze the nomenclature, as well as chemical and pharmaceutical characteristics of excipients (EXs) in the composition of nifuroxazide preparations, which received state registration in the RF. A comparative study of the chemical and pharmaceutical characteristics of EXs of 42 nifuroxazide preparations in the form of capsules, tablets, and suspension for oral administration was carried out. The pharmaco-economic status is noted and the demand prospects for all forms of nifuroxazide preparations in the RF are outlined. Quantitative and qualitative differences in the composition of the EXs of a number of nifuroxazide preparations in the form of capsules and suspensions has been shown.

The possibility of using methods for determining the oxidative status of an organism (enzymatic and non-enzymatic links of the cellular antioxidant system) to assess the antioxidant properties of peptides of the pituitary gland of the reindeer (Rangifer tarandus) were investigated in an experimental study conducted with a combined effect of factors of different nature on rats: a physical factor — prolonged light desynchronosis (different light modes) and a chemical factor - acute severe poisoning with depriving toxicant (sodium thiopental, LD50). The pharmacological correction of the oxidative status of cells in the animals of the experimental subgroups was carried out with the peptide product of the pituitary gland, intranasally injecting the surviving rats with the bioproduct at a dose of 100 µg/kg, once in the first half of the objective day for 14 days after poisoning with sodium thiopental. The surviving animals of the control groups were similarly injected with saline. The effectiveness of the correction of the disruptions of the cellular oxidative status with the peptide product of the pituitary gland was tested 30 days after the onset of the combined effect of stress factors on rats. It was found that the use of this bioactive peptide product in experimental animals exposed to different light modes and a chemical factor contributed to a decrease in the initially increased indicators of lipid peroxidation in rat erythrocytes and an increase in the initially reduced indicators of the enzymatic link of antioxidant protection. The activity of superoxide dismutase, glutathione peroxidase, glutathione transferase, as well as glucose-6-phosphate dehydrogenase increased after pharmacological correction. The concentration of reduced glutathione also increased in erythrocytes. The maximum changes were observed in the experimental subgroup of rats exposed to the combined effects of constant illumination and depriming toxicant. It was also found that the revealed positive changes in the indicators of the enzymatic link of antioxidant protection in animals of the experimental subgroups are associated with the maintenance of a sufficient concentration of reduced glutathione in red blood cells, which contributed to the maintenance of the cellular redox balance, when the conditions of the external lighting regime are violated.