In order to predict the biological activity of the new derivatives of 4,4a-dihydroxanthone, the PASS (Prediction ofActivity Spectra for Substances) computer program was used. It allows predicting the biological activity spectrum of chemical compounds based on the analysis of structure-activity interrelation. Derivatives of 4,4a-dihydroxanthone were synthesized at the Department of Organic Chemistry of the Saint Petersburg State Chemical Pharmaceutical University. As a result of the screening, it was found that 4,4a-dihydroxanthones can exhibit antibacterial, antifungal, antitumor, and antiviral effects. Antimicrobial activity of the obtained compounds was studied against Gram-positive and Gram-negative bacteria, as well as fungi. Dihydroxanthones were shown to have an inhibitory effect on Gram-positive bacteria. Relationship between the structure of derivatives and their antimicrobial activity is established. The presence of electron-withdrawing substituents led to an increase in activity, and electron-donating substituents reduced the antibacterial effect of the compounds. The most active compound, 5-bromo-7-chloro-4,4a-dihydrox-anthone, was found to be active against certain clinical strains of staphylococci.

The acquisition of resistance to the antibiotics and antibacterial agents used by microorganisms sets the task of finding new active disinfectants. It is known that compounds of the oligoguanidine class possess pronounced antibacterial properties, low toxicity, and can exhibit a prolonged biocidal effect, causing destruction of biofilms formed by pathogenic microflora. One of these compounds is branched oligohexamethylene guanidine hydrosuccinate (OHMG succ). The specified compound can be used as an active component in the development of a drug that acts on microbial dehydrogenases for the prevention and treatment of conjunctivitis of an infectious nature. In this regard, the purpose of this work is to study and visualize the mechanism of action of OHMG succ in relation to microbial dehydrogenases of Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa by colorimetric methods, to study its effect on the formation of biofilms and mature biofilms of E.coli, on its cell wall by scanning electron microscopy, as well as experimental evidence of the influence of OHMG succ on the morphology of several types of bacteria, yeasts, and molds that cause conjunctivitis, by atomic force microscopy. In addition, it was necessary to identify the dependence of cell segregation disturbance on the increasing concentration of OHMG succ. Thus, it was proved that OHMG succ affects not only the microbial dehydrogenases of certain Gram-negative bacteria, the mature biofilm of E.coli, but also its cell wall. The effect of OHMG succ on the morphology of several types of bacteria, yeast and mold fungi was also revealed. The indicated information shows that the creation of an antimicrobial drug based on OHMG succ is of interest, and this work may serve as the basis for the development of an innovative pharmacological drug for the treatment of conjunctivitis of an infectious nature.

The aim of this study was to examine the immunocorrective and antiviral activity of extracellular polysaccharide (EPS) from the marine bacteria Pseudoalteromonas nigrifaciens against tick-borne encephalitis virus (TBEV). Materials and Methods. The cytotoxicity of EPS was determined in pig embryo kidney (PK) cells using the MTT test. Antiviral activity of EPS against virus TBE was evaluated in cell cultures of PK cells and human peripheral blood mononuclear cells using the methods of inhibiting the cytopathogenic effect of the virus, indirect immunofluorescence, and real-time PCR. The immunocorrective activity of EPS was investigated in whole-blood samples (from 10 healthy donors) infected with TBEV, using flow cytometry assay and enzyme immunoassay. Results. It was found that EPS is non-toxic, inhibits the TBEV replication in PK cells and mononuclear cells, significantly reduces the number of virus-infected cells and levels of viral RNA, exhibits pronounced virucidal effects (selectivity index of polysaccharide is more than 40). EPS treatment of TBEV-infected whole blood samples restored the virus-induced decline of CD69, HLA-DR and CD107a expression levels on the surface of monocytes, NK and CD8⁺T-cells and the pro-inflammatory cytokine production (IL-1/3, IFN-a, TNF- a, IFN-y, IL-6) by immunocompetent cells. Conclusion. The results obtained allow considering extracellular polysaccharide from marine bacteria Pseudoalteromonas nigrifaciens as a promising antiviral and immunocorrective agent against TBE infection.

The phenotypic sensitivity of the influenza virus strain A/Anhui/1/2013 (H7N9) to antiviral drugs with different mechanisms of action in the MDCK cell culture and in outbred ICR mice experiments was observed. The A/Anhui/1/2013 (H7N9) strain of influenza virus showed the highest sensitivity to Tamiflu in in vitro experiments, whereas the sensitivity of this influenza virus strain to Rimantadine and Ingavirin was less pronounced. The A/Anhui/1/2013 (H7N9) strain exhibited absolute sensitivity only to Tamiflu in in vivo studies of such factors as virus titers in the lungs, the protection factor, and the average life expectancy of the animals. The sensitivity of this strain of influenza virus to Ingavirin was not detected in dose and administration regimen used in vivo. Rimantadine sensitivity of this strain in vivo was significantly weaker than to Tamiflu, and manifested only in reducing viral titers in the lungs 3 days after the mice were infected.

Studies have been carried out on the effectiveness of the high molecular weight interferon inducer Ridostin® in relation to the experimental form of severe acute respiratory syndrome in Syrian hamsters. It is shown that Ridostin® is effective when used according to the prophylaxis regimen and post-exposure prophylaxis regimen. The coefficient of therapeutic effect was 47.5 and 55.0%, respectively. At the same time, there was a statistically high level of significant differences in the severity of the disease in animals treated with the medication according to the post-exposure prophylaxis regimen and control animals (P<0.05).

The article discusses the issues of nosocomial infections in a general hospital. As a result of studies, it was found that Pseudomonas aeruginosa and Proteus vulgaris were more often found in the spectrum of microorganisms isolated from patients being treated in the intensive care units of various profiles. A leading place in the microbial contamination of environmental objects also belongs to P.aeruginosa. The differences in the spectrum of identified pathogens in the intensive care units and surgical and neurological intensive care units were revealed.

An increase in the frequency of antibiotic consumption, especially their irrational use as empirical therapy, led to an increase in the resistance of microorganisms and caused a significant decrease in the effectiveness of antibiotic treatment. In the course of the study, a retrospective pharmacoepidemiologic analysis of the consumption of antimicrobial agents and microbiological monitoring were conducted in obstetric departments of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov for the 2014-2018. A comparative analysis of antibiotic consumption indicators was carried out before and after the implementation of Risk Stratification Approach (patients with infection are stratified according to the risk of poly-resistant pathogens). Standardized ATC/DDD methodology was used to assess the dynamics of antibiotic consumption. Antibiotic levels were assessed by the rate of DDD/100 bed days, with total DDD accepted by WHO. As a result of pharma-coepidemiologic analysis and microbiological monitoring, the main vectors of empirical antibiotic therapy in an obstetric hospital of level 3 federal significance were determined. The widespread use of protected aminopenicillins and the tendency to increase their consumption can lead to a decrease in the sensitivity of enterobacteria - the main opportunistic pathogens in obstetrics and gynecology - to them. The study showed that the sensitivity of E.coli to beta-lactam antibiotics remains quite high. Nevertheless, increasing consumption of cephalosporins can provoke «parallel damage» and, as a result, increase the level of antibiotic resistance in medical institutions. The sensitivity of Enterobacterial strains to fluoroquinolones remains at a high level, so these drugs should be classified as second-line antibiotics and used in case if the initial treatment of postpartum infectious complications proves to be ineffective. Nevertheless, it is advisable to use protected aminopenicillins for the purpose of perioperative prophylaxis and initial therapy. The study also demonstrated that the introduction of stratification of hospitalized patients with infection reduced the consumption of antibiotics, taking into account the risk of multiresistant pathogens release in the Center. Using the DDD methodology, the authors were able to determine the rational volumes of antibiotic consumption in obstetric departments: not exceeding 810 DDD/100 bed days for Department of Physiology and not more than 15-20 DDD/100 bed days for Department of Pregnancy Pathology. Reliable data on antimicrobial consumption and microbiological monitoring should form a basis for national and local policies devised to reduce the resistance of microorganisms to antibiotics.

The authors conducted a retrospective analysis of Russian database of spontaneous reports (SRs) for the period from 01.01.2012 to 01.08.2014. They analyzed 3608 SRs concerning adverse drug reactions associated with beta-lactam antibiotics to identify medication errors (MEs). MEs were detected in 1043 (28.9%) SRs, total amount of MEs was 1214. Medication error-related terms were indicated by reporters in 29 (0.8%) SRs. The most common types of identified MEs were inappropriate indication for the antibiotic - 32.5% MEs, deviations from the recommended dosing scheme - 29.7% MEs, and the use of contraindicated drug - 17.3% MEs. The use of antibiotics for viral infections and errors associated with a patient with documented hypersensitivity to administered drug pose a special problem. The highest number of SRs with MEs was associated with the use of cefazolin (50.8% SRs), amoxicillin (40.9% SRs), amoxicillin/clavulanate (40.0% SRs). The study shows the need to develop measures for prevention of MEs associated with the use of beta-lactam antibiotics in clinical practice.

The review contains recent materials on the effects of extracts, polysaccharides, and polyphenols from brown algae in type 2 diabetes mellitus, which are a potential basis for creating effective antihyperglycemic agents. These biologically active substances are polyvalent biomodulators that have a multi-component effect in diabetes. These biopolymers reduce blood glucose levels, increase insulin production, decrease insulin resistance, inhibit α-amylase and α-glucosidase production, have antioxidant and anti-inflammatory activity, protect pancreatic, liver, and kidney tissues from high glucose concentrations. Algae are promising candidates for creating new generation drugs with associated activity, functional foods and dietary supplements for use in type 2 diabetes mellitus.

One of the fundamental features of tuberculosis pathomorphism in modern conditions is secondary immune deficiency, which manifests itself at the initial stage of the infection process and aggravates as the disease progresses. This review presents analysis results of cumulative clinical and laboratory data, confirming high efficiency of cycloferon as a support drug in the treatment of newly diagnosed tuberculosis forms and in patients with advanced forms, which allows recommending its inclusion in the treatment regimens of these disease forms. The effectiveness of the drug in treatment of comorbid tuberculosis and features of its non-specific prophylaxis require further research.

The article provides a review of the literature on the mechanisms of entry and action of antibiotics of various classes on the cellular systems of the human body. The non-antibacterial effects of antimicrobials widely used in clinical practice are considered. The results of authors' own studies of the biophysical mechanisms of antibiotics interaction with eukaryotic cells are presented on the example of the «antibiotic-erythrocyte» model system. A certain affinity of antibiotics for human erythrocyte cells was revealed using biophysical methods (recording osmotic and acid erythrograms, scanning electron microscopy, absorption spectrophotometry, protolithometric titration). It was shown that when the studied antibiotics penetrate into the cells, they induce heterogeneous changes in erythrocyte populations, affecting their polymorphism and the number of biconcave discocytes. A dose-dependent effect of structural modifications of cells, determined by the time of interaction with antibiotics and their chemical structure, was revealed. Antibiotics induce a change in the structural and functional properties of intraerythrocyte hemoglobin, which is reflected, inter alia, in a decrease in the concentration of the hemoproteid met-forms. The presented review of the results of authors' own studies, as well as the literature data, allows authors to consider antibiotics as modifying agents, causing a typical reaction of the erythron of the peripheral unit to the pathogenetic effect.