Methods for the synthesis of hybrid molecules that combine the structure of a highly active antimicrobial compounds - tris(1-alkylindol-3-yl)methylium as well as 3-(indol-1-yl)maleimides that previously showed activity against some protein kinases have been developed. The main purpose of this study was to investigate the influence of substituents on the activity of compounds against different test microorganisms, as well as their toxicity on human cells. For example, with the introduction of a fragment of maleimide, it was possible to reduce cytotoxicity by almost 40 times compared to the original prototype in some cases. At the same time, antimicrobial activity of the new substance remained approximately at the same level.

The problem of formation and spread of S.aureus isolates with reduced sensitivity to vancomycin (Vancomycin intermediate S.aureus, VISA) limits the use of this antibiotic for the treatment of infections caused by MRSA. The formation of such a phenotype is complex and is associated with the accumulation of mutations in the genes involved in the biosynthesis of the cell wall. Genomic sequencing of seven isolates with different sensitivity to vancomycin and belonging to the same genetic line was carried out in the study: ST8 - t008 - SCCmec IVc. PAP analysis of isolates with reduced sensitivity to vancomycin did not reveal hVISA/VISA phenotypes, while PAP/AUC was 0.53-0.7. Comparison of 83% of the core parts of isolates’ genomes with MIC = 1 mg/ml and 2 mg/ml, as well as control genomes (NCBI GenBank) with known sensitivity, revealed different clustering, the isolates with MIC=2 mg/ml were localized in one cluster. Comparison of the nucleotide concatenate composed of 44 genes involved in the assembly of the cell wall also showed that the isolates were assembled into one cluster. Unique mutations were identified for isolates with MIC=2 mg/ml in murZ (T353A), rpoB (Y946C), and fdh2 (G446S). Thus, isolates with reduced sensitivity to vancomycin did not have the hVISA or VISA phenotype. However, the identified mutations in the «key» genes of peptidoglycan biosynthesis may indicate the initial stage of selection of resistance to vancomycin with the formation of pre-hVISA.

The objective of the study was to investigate the influence of the NO donor nitroglycerin (NG) on the antitumour effect of doxorubicin (Dox) in rats with the intracranially implanted 101.8 glioblastoma. Materials and methods. Male Wistar rats with the implanted 101.8 glioblastoma were treated with the following formulations (n=15-19): doxorubicin (Dox, 1.5 mg/kg, i.v.), nitroglycerin (NG, 5 mg/kg, oil solution, topical), and a combination of doxorubicin and nitroglycerin (Dox+NG: 1.5 mg/kg and 5 mg/kg, respectively) on 2^nd, 5^th, and 8^th day after tumor implantation. The tumor size was measured on the histological sections of the brain on the 14^th day (n=6-9). The remaining animals were followed up for survival for 100 days. Untreated animals were used as control (n=22). Results. The antitumor effect was evaluated by the increase in life expectancy (ILE, %) and tumor growth inhibition (TGI, %) relative to untreated animals in control group. The increased life expectancy was observed in all groups. The maximal effect was achieved in the Dox+NG group: ILE 176%, TGI 89%. In the Dox group, the ILE was 130% and TGI was 75%. Nitroglycerin alone produced the ILE of 130%. Conclusion. Nitric oxide donor nitroglycerin considerably potentiated the antitumor activity of doxorubicin against the intracranial glioblastoma in rats. This phenomenon is most probably explained by the increased penetration of doxorubicin into the tumor due to the enhanced permeability of the cerebral endothelium produced by NO generated by nitroglycerin.

Confirmed evidence of sufficient effectiveness of monotherapy of zoonotic cutaneous leishmaniasis with meglumine antimonate and doxycycline in combination with interferon alpha 2b human recombinant (reaferon) has been obtained. Leishmania in the lesion was completely absent on day 60 of treatment with doxycycline. According to in vivo data, the combined therapy of experimental zoonotic cutaneous leishmaniasis in golden hamsters increased the effectiveness of meglumine antimonate and doxycycline by all parameters due to the addition of recombinant human interferon alpha 2b in comparison with monotherapy with the same drugs.

The spread of Vibrio cholerae strains with multiple antibiotic resistances makes it necessary to search for alternative antibiotics that are effective against the cholera pathogen. The aim of the study was to investigate the lytic activity of cholera phages from the collection of the bacteriophage laboratory in vitro and in vivo with respect to antibiotic-resistant genovariants of V.cholerae El Tor. As a result of the in vitro study, it was possible to identify the promising phages for phagotherapy of experimental cholera. Comparative evaluation of the effectiveness of the phage mixture in relation to the antibiotic-resistant El Tor 19243 strain of V.cholerae in vivo on a model of a generalized infection in white mice showed high effectiveness of its preventive and therapeutic use (more than 70% of surviving animals).

Coagulase-negative staphylococci (CNS), in particular Staphylococcus haemolyticus, play an important role in the etiology of nosocomial infections. Most CNS are resistant to beta-lactam antibiotics, which is realized through the production of the second penicillin-binding protein. This protein is encoded by the mecA gene and, together with the genes of recombinases (ccr), is part of the mobile element of staphylococci - the staphylococcal cassette chromosome. During the study, the mecA and ccr genes were analyzed using a collection of 142 genomes of S.haemolyticus. The mecA gene was detected in 117 genomes (82.4%) and had a pronounced conservation. Based on the analysis of recombinase gene sequences, it was established that 118 samples (83%) contain ccr, and 22 different combinations of the mecA and recombinase genes presence are described. The combination of ccrA4B4 was the most common for S.haemolyticus (25%). Type-specific primers were proposed, to assess the variability of recombinase genes, their performance was validated on 54 clinical isolates.

The ability of clinical isolates Escherichia coli (16), Klebsiella pneumoniae (20), Pseudomonas aeruginosa (12) to survive under the influence of high bactericidal concentrations of meropenem was studied. After 2 and 4 hours of exposure to the antibiotic, the authors have identified antibiotic-tolerant populations of bacteria (persisters) represented by ordinary sized colonies and SCV type (small variant colony). The number of colonies that have grown after the antibiotic attack of each isolate of above-mentioned species of bacteria positively correlated (P<0.05) with the growth time of the same bacterial cultures from the beginning of the lagphase to the moment of doubling of the optical density in the medium without the antibiotic, while SCV number and the aforementioned time interval were not interdependent (P>0.05). Thus, it has been shown that kinetic parameters of bacterial growth in a medium can designate their level of persisters formation in the same medium after the addition of an antibiotic.

An open comparative observational study of the clinical efficacy and safety of riamilovir (Triazavirin™) in patients over age 18 with influenza and acute respiratory viral infections (ARVIs) was conducted during the epidemic seasons of2016-2017 and 2017-2018. Clinical efficacy and safety of riamilovir (Triazavirin™) in groups of patients with influenza and ARVI was demonstrated. The use of riamilovir (Triazavirin™) allowed to achieve rapid positive dynamics in the management of febrile-intoxication and catarrhal-respiratory syndromes; it was equally effective in patients who did not immediately seek professional help.

The last few decades are characterized by the appearance of phenotypes of allergic rhinitis, the inflammatory cascade of which is realized in a complex process of interaction of infectious and allergic components. The infectious component in people with allergopathology is a herpes-viral infection, which often changes the clinical picture in such patients, the volume of pharmacotherapy, and the prognosis of the disease. The presence of chronic herpes-viral infection in immunocompromised patients presents this problem with particular urgency, since any viral infection is dangerous for the state of human health with allergies. Cycloferon is an effective and promising low-molecular inducer of interferon. The mechanism of action of cycloferon is an important link in the selection of immunomodulatory therapy for the treatment of herpesvirus infection. The article presents a scheme of using cycloferon in immunocompromised patients with allergic rhinitis. The combined use of local immunotherapy and allergen-specific sublingual immunotherapy (SLIT) in these patients is a highly effective method.

One of the reasons of the failure of educational activities in the field of rational antimicrobial therapy is, most likely, the discrepancy between the level of initial training of students and the complexity of the presented material. The aim of this study was to assess the baseline knowledge of physicians in the field of microbiology, clinical pharmacology of antimicrobial agents and the level of antibiotic resistance in health facilities to develop an effective training program. Materials and methods. The study was conducted in the framework of implementation of the first phase of the antimicrobial stewardship program - SCAT program (Strategy for the Control of Antimicrobial Therapy). An anonymous survey of physicians of different specialties was carried out. Clinical pharmacologists composed the questionnaire, which included questions of different levels of complexity, divided into thematic blocks. The results of the survey were evaluated and compared depending on specialty and experience. The expected and real level of knowledge was analyzed. Results. 110 doctors of different specialties have participated in the survey. The respondents showed a low level of knowledge in the scope of the inquiry (50% correct answers on average), survey results significantly depended on specialty. The correlation between results and experience was also revealed - the knowledge was accumulated in the first 15 years of experience, while the number of correct answers among specialists with more extensive professional experience had a tendency to decrease. The complexity of the questions predicted by the experts did not correspond with the actual one in 66% of the cases. In 96% of inconsistencies, the real complexity was higher than the predicted one. Conclusion. The results of the study revealed that experts should assess the baseline level of knowledge of specialists more objectively. The training course should be as understandable and interesting for the audience as possible. It may also be advisable to develop various training programs for doctors of different specialties. The main emphasis should be placed on the training of young doctors, unobtrusively involving doctors with greater clinical experience in the process, if possible. The small group of respondents and only one center that participated in the survey do not allow making generalizing conclusions.

The article covers microbiological methods that help assess the biological activity of antibiotics, which is fundamental for determination of clinical efficacy of antimicrobial drugs. The authors chose gentamicin, an aminoglycoside antibiotic, to illustrate the development and validation of the turbidimetric assay, which is based on antibiotic's inhibitory effect on the growth of Staphylococcus aureus ATCC 6538Р test strain in liquid medium. The obtained data were assessed with ANOVA and were recognized as linear (r=0.9921) in the concentration range of 0.64-1.56 mg/ml. The results of gentamicin assay validation studies demonstrate great potential and applicability of the turbidimetric method for standardization and ensuing quality control of aminoglycoside antibiotics.

The review presents the main directions of biomedical research on exopolysaccharides (EPS) obtained from various species of marine bacteria. EPS are high molecular weight polymers consisting of sugar residues; they are characterized by a large variety of structures, which causes unique biological properties. Numerous data on antioxidant, immunomodulatory, and antitumor activity of EPS are presented. Particular attention is drawn to the antiviral, antibacterial, and inhibitory effect of EPS on the formation of biofilms. Taking into account the wide spectrum of pharmacological activity and low toxicity, these compounds have attracted attention as a potential source of medicinal substances.

The present review contains data on microtubular protein ß_III-tubulin (TUBB3): its structure, functions, role in tumor progression, expression in normal cells and in neural and epithelial tumors of different origins. Basic working principles of microtubular system and links between TUBB3 and related β-tubulins are also briefly reviewed. We analyzed the clinical potential of TUBB3 as prognostic marker of tumor aggressiveness and drug-resistance and suggested that locally disseminated tumor cells might be found by comparison of TUBB3 expression in normal and tumor tissue of each patient. Finally, we conclude that screening for TUBB3 and other tumor markers in morphologically normal tissue adjacent to the tumor is essential for accurate diagnostics.