Background. The current trend of growing antibiotic resistance among pathogenic microorganisms remains one of the urgent and significant problems of mankind. The constant spread of resistant strains of microorganisms requires the development of innovative methods and the search for medicinal compounds with a highly effective mechanism of action. One of these multi-resistant pathogens that are difficult to eradicate is the causative agent of tuberculosis — Mycobacterium tuberculosis. The aim is to study the effect of newly synthesized pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, as well as on the structural changes in cells.

Material and methods. In order to assess the effect of a number of pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, 6 samples of 5-(arylmethylene) hexahydropyrimidine-2,4,6-triones (TAG1 — TAG6), 7 samples of 5-hetarylmethylidene-2,4,6-triones (TAG7 — TAG13), and 2 new samples of 3-(2-Benzyloxy-2-oxoethyl)quinazoline-4(3H)-one and 3-[2-(1-Naphthyl)-2-oxoethyl]quinazoline-4(3H)-one were screened under the laboratory ciphers VMA-13-03 and VMA-13-04 in the course of the study. M.tuberculosis H37RV strain was used as a test culture; it was provided by the bacteriological laboratory of the Regional Infectious Clinical Hospital named after A. M. Nichoga. A 4-week culture of M.tuberculosis, synchronized by cold (+4°C) for 72 hours, was used to prepare a suspension of mycobacteria. The number of mycobacteria in the suspension was determined using the McFarland 0.5 turbidity standard. 0.2 ml of M.tuberculosis working suspension was added to each tube of a series of successive dilutions of the studied substances, including the control. The study was carried out in 4 series of replicates. The minimum bactericidal concentration of the compounds, at which no colony growth was detected, as well as the minimum inhibitory concentration, at which mycobacterium growth was delayed by 50% compared to the control, were determined. Smears were prepared from the sediment for staining using the

Ziehl-Neelsen method to determine the presence of acid-resistant and non-acid-resistant forms of mycobacteria, as well as to study the effect of pyrimidines and a comparison drug on structural changes in M.tuberculosis cells.

Results. In the course of the study, the TAG4, TAG6, and TAG8 compounds were found to have the closest antibacterial activity to the comparison drug isoniazid, according to the indicator of mycobacteria growth retardation. The greatest bactericidal activity against M.tuberculosis was observed in TAG4, TAG7, and VMA–13–04. The remaining compounds have shown minimal inhibitory effect on the growth of M.tuberculosis. Microscopic studies have shown that under the influence of TAG3, TAG4, TAG7, TAG12, VMA-13-03, and VMA-13-04, the main structural components of M.tuberculosis cells undergo fragmentation and morphological changes compared to mycobacterium cells without exposure.

Conclusion. As a result, it was found that all the studied compounds possess antimycobacterial activity. Compounds under the laboratory ciphers TAG1, TAG4, TAG7, and TAG13 were comparable to isoniazid by the nature of the inhibitory effect on the growth of M.tuberculosis, and the TAG3 compound even slightly exceeded the effect of the comparison drug. Compounds under the laboratory codes VMA-13-03, and VMA-13-04 had the least pronounced anti-tuberculosis effect. Compounds under the laboratory codes TAG5, TAG6, TAG11, and TAG12 showed the least antimycobacterial activity.

Background. The effect on the activity of the multidrug resistance protein P-glycoprotein (P-gp, MDR1 gene) in pro-inflammatory (M1) human macrophages is considered one of the promising strategies for increasing the effectiveness of the treatment in patients with pulmonary tuberculosis: P-gp activity is considered a factor that reduces intracellular accumulation of rifampicin (RIF), a substrate for P-gp. The aim of this work was to reveal the effect of the therapeutic concentration of RIF on the activity of P-gp in M1 human macrophages. The objectives were as follows: to determine the expression levels of the MDR1 gene, P-gp protein, as well as its functional activity at different periods of cell differentiation and under the influence of RIF.

Material and methods. The following cell lines were used in the work: suspension cells of promonocytic leukemia THP-1 and THP-1 macrophages induced by phorbol ether according to the pro-inflammatory phenotype. Suspension cells of myeloid leukemia K562/IS-9 transfected with the MDR1 gene were used as a comparison group. An important factor is the choice of the experimental concentration of RIF: the average concentration of the drug in patients with pulmonary tuberculosis was 10 µg/ml. The methods of RT-PCR, immunocytochemistry, and flow cytometry were used in the work.

Results and discussion. The induction of MDR1 gene expression in M1 macrophages under short-term exposure to a therapeutic concentration of RIF was revealed. This effect is typical only for THP-1 macrophages, in which a significant functional activity of P-gp is registered. This induction does not occur in the cells with no detectable P-gp activity (THP-1 suspension cells). This indicates the presence of different mechanisms of RIF influence on MDR1, which can be used to develop a strategy for P-gp inhibition in inflammatory macrophages.

Conclusion. Given the key role of macrophages in tuberculosis, further evaluation of MDR1/P-gp in the surgical material of patients with pulmonary tuberculosis is necessary, which makes it possible to draw a conclusion that it is necessary to develop and apply drug strategies aimed at blocking the functional activity of P-gp and choosing more effective anti-tuberculosis therapy regimens.

Currently, the diversity of resistant strains with a certain set of resistance mechanisms is growing, and the frequency of their distribution is increasing. One of the options for finding optimal ways to treat severe infections, including orthopedic infections caused by Klebsiella pneumoniae and Pseudomonas aeruginosa, is the use of new drugs with possible activity against resistant strains.
The aim of the study is comparative evaluation of biapenem antibacterial activity against meropenem-resistant K.pneumoniae and P.aeruginosa.
Materials and Methods. A total of 14 K.pneumoniae and 18 P.aeruginosa isolates were included in the study. The determination of sensitivity to biapenem and meropenem was carried out via determining the minimum inhibitory concentrations (MIC) for each microorganism by the method of serial dilutions in accordance with ISO 20776-1-2010. Carbapenemases genes (MBL:VIM-, IMP- and NDM-types; OXA-48; KPC) were detected by commercially available real-time PCR.
Results. The highest MIC value of meropenem was registered in the carbapenemase-producing K.pneumoniae strain (NDM and OXA-48) and amounted to 512 mg/l, while the MIC value of biapenem in this isolate was 256 mg/l. The MIC50 of meropenem was determined to be 16 mg/l, while in case of biapenem it was 4 mg/l. MIC90 of meropenem against P.aeruginosa was 512 mg/l, of biapenem — 256 mg/l. Among all meropenem-resistant strains included in this study, 28.6% K.pneumoniae and 22.2% P.aeruginosa isolates showed sensitivity to biapenem, the rest were resistant to this drug or sensitive at increased exposure.
Conclusion. Comparative analysis of the antibacterial activity against meropenem-resistant K.pneumoniae and P.aeruginosa showed that MIC50/90 of biapenem is several times lower than that of meropenem. Sensitivity to this drug was recorded in 25% of the studied isolates resistant to meropenem (4 — K.pneumoniae and 4 — P.aeruginosa), which increases the possibility of using this drug in the treatment of patients with orthopedic infections.

The aim of this work was to evaluate the antibacterial activity of the aqueous and ethanolic extracts of Betula pendula (silver birch) bark against various microorganisms causing urinary tract infections.

Material and methods. Aqueous and ethanol extracts of biologically active compounds from Betula pendula bark were tested against ten clinical uropathogenic strains (gram-positive bacteria — Kocuria rhizophila 1542, Staphylococcus simulans 5882, Enterococcus avium 1669, Enterococcus faecalis 5960, and Corynebacterium spp. 1638; gram-negative bacteria — Enterococcus cloacae, Morganella morganii 6392, Escherichia coli 1449, Seratia mansescens 6441, and Achromobacter xylosoxidans 4892). Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 25922 were used as reference standards for Gram-positive and Gram-negative microorganisms. The sensitivity of the experimental strains to the antibiotic was evaluated by the Kirby–Bauer disk diffusion method, while the antibacterial activity of the obtained extracts was evaluated using the agar diffusion method. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were also determined via the serial dilution method.

Results. The bark of B.pendula contained 78.85% of dry matter. The volume yield of the aqueous (AE) and ethanol extract (EE) was 74.66% and 86.66% (v/v), respectively, while their mass yields were 6.59% and 10.65% (w/w). K.rizophilia 1542 and Corynebacterium spp. 1638 were the most resistant bacteria with a multidrug resistance index of 0.45. AE and EE were active against all microorganisms tested. MIC of AE ranged from 8 to 32 mg/ml, while MIC of EE ranged from 2 to 16 mg/ml.

Conclusion. An aqueous extract of Betula pendula bark exhibits weak antimicrobial activity, while the ethanol extract exhibits a more pronounced antimicrobial activity, but has a bacteriostatic effect.

The aim of the study was to evaluate the effectiveness of including remaxol in the medical rehabilitation of elderly and senior patients with COVID-19-associated pneumonia and changes in liver enzyme activity.

Material and methods: 116 patients (56 men and 60 women) were examined. All patients underwent a complex of medical rehabilitation on an outpatient basis on the 10–12th day after discharge from the hospital and in the presence of 2 negative results of PCR tests for SARS-CoV-2, which included, in addition to the recommended measures (drug therapy and exercise therapy), vacuum labile massage according to the author's methodology and a course of hepatoprotective drugs. Depending on the latter, the patients were divided into two groups: I — the main group (n=60) — received remaxol in the drug treatment regimen: 400 ml, intravenously, drip, in a course of 10 days, II – comparison (n=56) — ademetionine: 400 ml, intravenously, drip, in 0.9% saline, in a course 10 days. Before rehabilitation and at its end, the following tests were carried out: Stange and Genchi tests; quality of life was assessed using the SF-36 questionnaire. Laboratory studies included determination of the following indicators levels: ALT, AST, their ratio, alkaline phosphatase, GGT, total and direct bilirubin, LDH, albumin and total protein levels.

Results. The inclusion of hepatoprotectors in the medical rehabilitation of the patients of this group contributes to a decrease in cytolytic and cholestatic syndromes, which is more pronounced in patients who received remaxol: (a decrease in AST by 1.5 times (from 35.4±1.4 to 23.5±l), and ALT — by 1.8 times (from 38.7±1.3 to 21.5±0.4 IU/l), as well as normalization of bilirubin metabolism: a decrease of total bilirubin by 2.1 times (from 32.1± 0.6 to 14.8±0.9 µmol/l) and of direct — by 2.5 times (from 7.1±0.6 to 2.8±0.1 µmol/l). A pronounced increase in resistance to hypoxia was noted during the therapy with the drug (according to Stange and Genche), which contributed to an improvement in psychophysiological indicators of patients’ quality of life (according to the SF-36 questionnaire). The obtained results, along with the safety of the drug, allow us to recommend its use in patients with this pathology.

A study which included 97 children who had COVID-19 during the period from September 2021 to January 2022 was conducted. This article discusses the symptoms occurring after COVID-19 infection. The analysis of the results showed that the largest proportion among sick children was in patients with reduced cognitive functions, an increased level of neuroticism, depressed state and emotional instability. The most common comorbidities were the diseases of the gastrointestinal tract, respiratory and cardiovascular systems.

Background. Drug-drug interactions can seriously affect the safety profile of a drug and are an important problem worldwide. Due to the aging of the population, the increasing frequency of polypharmacy, as well as the spread of self-medication, adverse events that are difficult to identify may occur. It is hard to establish a causal relationship between the administration of a certain drug and the occurrence of an adverse event; it may also lead to the conversion of the adverse event into an adverse drug reaction. The risk of drug-drug interactions increases with combination therapy, as a result of misuse of a drug (off-label use), as well as in the absence of full disclosure from physician and patient about potential drug-drug interactions.

One of the ways to detect an adverse reaction to a drug is a method of «spontaneous messages», when notification cards issued according to the regulated form are sent from subjects of drug circulation to the national centers for pharmacovigilance, then to the global database of the World Health Organization VigiBase.

The aim of the work was a comprehensive analysis of the content compliance of the information presented in the instructions for the medical use of antibacterial drugs on potential drug-drug interactions with validated signals from the WHO global VigiBase database.

Material and Methods. The study used information and analytical comparative non-quantitative, graphical, logical methods of analysis, as well as regression analysis. Objects of the study: instructions for medical use for international generic drugs ampicillin, amoxicillin, azithromycin, clarithromycin.

Results. The contents of the instructions for use concerning possible interactions of ampicillin, amoxicillin, azithromycin, clarithromycin upon administration with other drugs were studied. Subsequently, a comparative analysis of the obtained data on drug-drug interactions of antibiotics with other drugs was carried out with signals of drug-drug interactions were validated by VigiBase.

Conclusion. The study showed that a detailed description of the risks of potential drug-drug interactions in the instructions for medical use with the aim of informing doctors, patients, and caregivers helps to prevent the use of undesirable combinations, thereby reducing the risk of adverse reactions when drugs are used together. The study found that most of the identified information on the safe use of drugs was missing in the instructions for medical use.

The search and creation of etiotropic drugs is one of the most important tasks of modern virology. This review examines the antiviral influence of certain natural substances (sulfated polysaccharides and lectins from marine hydrobionts) on the causative agents of hemorrhagic fevers. Such compounds can be used as an alternative to synthetic drugs due to their low toxicity, rare side effects, and the absence of virus resistance. In addition to a strong antiviral effect, polysaccharides and lectins possess anti-inflammatory, immunomodulatory, antioxidant, and antitoxic properties, which are important for the relief of numerous disorders caused by the pathogens of viral hemorrhagic fevers. The prospects of using these compounds as the basis for the creation of new drugs and biologically active food additives are considered in the final part of the review.

Background. The issues of vaccination against the herpesvirus infection are still important in rheumatological practice.

This infection often develops in patients receiving immunosuppressive treatment, especially Janus kinase inhibitors (a class-specific adverse reaction) and genetically engineered biologics.

The aim of this review is to highlight the current state of the issue of vaccination against Herpes zoster (HZ).

Materials and Methods. 37 publications (4 domestic, 33 foreign) were analyzed, in which the mechanisms of pathogenesis

and clinical features of herpesvirus infection in patients with immunodeficiency, both with and without immunoinflammatory rheumatic diseases (IIRD), the frequency and variety of post-vaccination reactions, complications and exacerbations of the course of IIRD were considered.

Results. There is currently a trend towards reassessment of the rheumatological community's opinion about HZ vaccination, including live vaccine. Literature data allow us to express optimism regarding the effective prevention of herpes zoster in patients who plan to take drugs, primarily from the group of Janus kinase inhibitors. The advantages of the adjuvant recombinant subunit vaccine (Shingrix®) include the possibility of its use against the background of treatment with antirheumatic drugs without significant restrictions, as well as no need to postpone the initiation of the necessary therapy.

Conclusions. Publications on the issues of HZ vaccination are few. It is necessary to conduct carefully controlled studies on the efficacy and safety of antiherpetic vaccines with an emphasis on the post-vaccination course of IIRD in patients with rheumatological profile, including in the Russian Federation.

Human brucellosis is a particularly dangerous socially significant infection that still poses a serious threat to public health due to a wide range of clinical manifestations, severe course, and the development of serious complications of infection that may lead to disability, which, in turn, causes significant damage to the economy. Treatment issues remain debatable, since the pathogen's ability to cause intracellular parasitism complicates effective antibiotic therapy. The review presents the data on in vitro activity and effic acy when using tetracyclines, rifampicin, fluoroquinolones, aminoglycosides, carbapenems, macrolides, cephalosporins, chloramphenicol, and trimethoprim/sulfamethoxazole as monotherapy agents. The data on the effectiveness of the use of antibacterial drugs in various combinations, and the inclusion of immunomodulators in the treatment regimen are presented. Information concerning promising modern developments that facilitate better penetration of antibacterial drugs into phagocytic cells is considered. Some results of searching for sources of new means of antibacterial therapy of brucellosis are presented.

In 1942, G. F. Gause and M. G. Brazhnikova created one of the first antibiotics in the Soviet Union — gramicidin C. In the same year, its successful use started in front-line hospitals in the treatment of complications of wound infections. Thanks to it, the lives of hundreds of thousands of soldiers and officers were saved. Gramicidin C has passed the test of time, and today this antibiotic is effectively used in the treatment of infectious and inflammatory diseases, as well as purulent wounds. In this regard, the 80th anniversary is a good reason to recall the history of the creation of this peptide antibiotic possessing bactericidal action based on the presence of the D-isomer of the amino acid phenylalanine in the producing bacteria. However, the study of ways to overcome the spreading antibiotic resistance in bacteria, as well as the search for alternative antimicrobial strategies are currently on the agenda. For this reason, it is appropriate to recall that the study of the molecular structure of gramicidin C gave impetus not only to the discovery of a whole family of cyclic peptide antibiotics, but also to the discovery of the ability of various organisms to nonribosomal synthesis of biologically active peptides containing D-amino acids with a pronounced antimicrobial effect. Their development is already a vital task today, and the use of peptides is considered a real and promising alternative to traditional antibiotics. Thus, gramicidin C, obtained at the dawn of the era of antibiotics, became a harbinger of the birth of a fundamentally new and promising antimicrobial strategy.