Background. Intensive research is currently underway to find new drugs to treat COVID-19, including the search for alternative antiviral treatments. Marine bacteria polysaccharides (PSs) are safe, biodegradable, and biocompatible polymers with a wide range of biological activity, including the ability to exert antiviral and immunomodulatory effects. In this regard, PSs attract the close attention of scientists as a promising source of antiviral medicinal substances.

The aim of the work is to evaluate the effect of PSs from 3 different species of marine bacteria on the expression of surface activation markers of innate immunity cells and to study their antiviral activity against the SARS-CoV-2 virus.

Methods. The effect of PSs on the expression of surface activation markers of innate immunity cells was studied by flow cytofluorometry. The study of the anti-SARS-CoV-2 activity of the PSs at the early stages of the virus life cycle was evaluated by inhibiting the cytopathogenic effect of the virus (in the MTT assay) and by real-time reverse transcription polymerase chain reaction (RT-PCR-RV).

Results. It was found that the studied PSs, differing in chemical structure, induced activation of innate immunity cells (monocytes, neutrophils, NK cells) in vitro. The results obtained both in the test of inhibition of the cytopathogenic effect of the virus and in reducing the level of RNA of the SARS-CoV-2 virus demonstrated the anti-SARS-CoV-2 activity of the PSs. PS1 showed the greatest activity, effectively inhibiting the early stages of SARS-CoV-2 interaction with the cell. Conclusion. The studied PSs can be considered a promising source of antiviral medicinal substances.

The absence of contamination is an important condition for the reliability of the results obtained when conducting experiments on cell cultures. At the same time, long-term cultivation significantly increases the risk of contamination of the cellular material, and therefore it is necessary to maintain cellular purity and remove contaminants in the event of contamination. The most common contaminants are bacteria, yeast and fungi, and, in rare cases, viruses and protozoa. Accordingly, to combat biological contamination, it is necessary to use drugs of different mechanisms depending on the nature of the contaminant. The article examines the effect of the most common antibiotic and antimycotic drugs in laboratory practice on the vital activity of continuous adherent human cell cultures. It was shown that different cell cultures have different sensitivity to the drugs used for decontamination, which indicates the need to develop individual treatment regimens for a specific cell line. Safe ranges of drug concentrations were established for lung adenocarcinoma, osteosarcoma, colorectal carcinoma, and human embryonic kidney cells. Taking into account the obtained data, spontaneous contamination was treated in a long-cultivated strain of the H1299 line. Artificial infection of the studied cell lines with the identified contaminant followed by treatment according to a similar scheme confirmed the adequacy of using ciprofloxacin for decontamination of various adherent cultures in laboratory practice.

Background. Respiratory syncytial virus is widespread in the population and poses a serious danger to people at risk. Among them are infants, the elderly, and people with weakened immune systems. Despite the fact that respiratory syncytial virus vaccines have recently been approved for pregnant women and the elderly, there is still no universally approved drug for effective etiotropic therapy.

The aim of the study was to evaluate the antiviral activity of three polymer electrolyte derivatives, which showed effectiveness against a wide range of viruses at previous stages of work, upon encapsulation in calcium carbonate microparticles.

Methods. The encapsulation of polymer electrolytes was carried out by the absorption method and the coprecipitation method. The encapsulation efficiency was evaluated by spectrometry. A transmission electron microscope was used to study the size and morphology of the obtained carriers and encapsulated preparations of polymer electrolytes. The dynamic light scattering method was used to study the colloidal stability of the obtained carriers and encapsulated specimens of polymer electrolytes. The cytotoxicity of the compounds was evaluated on HEp-2 cell culture using an MTT assay. Virus detection when measuring the antiviral activity of compounds was carried out using enzyme immunoassay (cell-ELISA).

Results. The results of spectrophotometry led to the conclusion that the method of coprecipitation is the most effective way to incorporate compounds into carriers. When polymer compounds are added to CaCO₃ microparticles, the carriers retain their original size and structure. The study of the antiviral activity of the compounds showed that encapsulation can help reduce their cytotoxicity while maintaining antiviral properties.

Conclusion. Thus, further studies of this group of substances and their delivery methods are promising for the creation of an effective and safe broad-spectrum antiviral drug.

Background. Combinations of carbapenems with new-generation carbapenemase inhibitors are successfully used to combat infections caused by carbapenemase-producing Klebsiella pneumoniae strains. However, K. pneumoniae resistance to such combinations is already described. Therefore, the search for new antibiotic/inhibitor combinations is important. In this regard, meropenem/avibactam combination seems promising, with its effectiveness becoming the subject of the current study.

The aim of this study was to evaluate the effectiveness of the combination of meropenem with the new carbapenemase inhibitor avibactam against carbapenemase-producing K. pneumoniae strains in an in vitro dynamic model.

Methods. Two carbapenemase-producing strains, KPC (K. pneumoniae 28) and OXA-48 (K. pneumoniae 145), were exposed to meropenem or its combination with avibactam in the hollow fiber infection model that simulated the pharmacokinetic profiles of drugs in the human lung epithelial fluid. The following dosage regimens were simulated: 2000 mg of meropenem and 500 mg of avibactam as a 2-hour infusion every 8 hours during 5 days. The effect of the drugs on the total and resistant subpopulations of K. pneumoniae was evaluated by plating samples on agar media without and with meropenem at different MIC-fold concentrations.

Results. Meropenem alone did not reduce the numbers of the total population and did not suppress the growth of resistant subpopulations of both strains, while combining meropenem with avibactam significantly reduced the total bacterial numbers and completely prevented the growth of resistant cells.

Conclusion. The combination of meropenem/avibactam seems promising, due to the fact that it was characterized by high efficacy and a lack of development of resistance to meropenem throughout the entire simulated course of therapy.

Cough is one of the most common reasons for initial visits to healthcare providers, affecting 40–50% of patients with viral respiratory tract infections. Treatment options for cough include medications that block signal transmission at the central or peripheral level of the reflex arc, as well as mucolytic and expectorant agents. Valenta Pharm JSC has developed an innovative drug, Eladis® (film-coated tablets, 20 mg and 40 mg), intended for the treatment of cough in patients with acute respiratory infections. The aim of the present study was to assess the safety profile and toxicokinetic parameters of the drug after repeated administrations. In the study conducted on mature rabbits, the drug was administered orally at doses of 1, 3, or 6 tablets/animal over 28 days, corresponding to 13.3, 40, and 80 mg/kg, respectively. No signs of intoxication were observed in any of the experimental groups. To evaluate toxicokinetic parameters, blood samples were collected from the marginal ear vein after the 1st and 28th days of administration. Both single and multiple (28-day) administrations of the drug showed a statistically significant increase in Cmax and AUC0–24 with increasing doses. No drug accumulation was observed following repeated administration on day 28. In a separate study on juvenile rats, Eladis® was administered intragastrically for 30 days at doses of 11.8, 118, and 236 mg/kg. The results indicated no significant effects of the drug on body weight gain, animal behavior in a battery of functional tests, as well as the estimated physiological, biochemical, and hematological parameters. The drug demonstrated no local irritant or immunotoxic effects and had no impact on spermatogenesis.

Introduction. The viral disease COVID-19 has caused a global emergency. The rapid and widespread spread of COVID-19 and the urgent need for etiotropic drugs have sparked interest in repositioning existing drugs. SARS-CoV proteases (Mpro) and papain protease (PLpro) have been identified as attractive targets for the development of antiviral agents.

The aim of this work was to evaluate the antiviral efficacy of indole chloropyridinyl ethers against the SARS-CoV-2 virus in vitro, as well as against the experimental form of COVID-19 in Syrian golden hamsters.

Material and methods. The experiments were carried out on a permanent culture of African green monkey kidney cells — Vero Cl008. The effectiveness of the drugs was assessed by suppressing the reproduction of the virus in vitro. Biological activity was assessed by titration of the viruscontaining suspension in Vero Cl008 cell culture by the formation of negative colonies. Syrian golden hamsters orally infected with the SARS-CoV-2 virus, variant B, were used. The effectiveness of the drug was assessed by the coefficient of therapeutic action.

Results. The antiviral efficacy of indole chloropyridinyl ethers against the new pandemic virus SARSCoV-2 was studied in vitro during experiments in Vero C1008 cell culture. The results of the study revealed that the drugs effectively suppress the reproduction of the virus when applied after infection. In the concentration range of 12.5–50.0 µg/ml, the drugs almost completely suppress the reproduction of the SARS-CoV-2 virus. According to the complex of clinical, virological, biochemical, and hematological indicators, the disease severity indех (DSI) and the therapeutic action coefficient (TAC) were calculated. For AMND-1X — the DSI was 0.635; the TAC was 36.5%; for AMND-1OL-3 — the DSI was 0.115; the TAC was 88.5%. Conclusion. Of the studied compounds, the drug AMND-1OL-3 showed the highest antiviral activity.

Background. Superinfection caused by Klebsiella pneumoniae occupies a leading position in the structure of bacterial complications in COVID-19 patients. The intensive circulation of Klebsiella in specialised hospitals has contributed to the consolidation of the most clinically and epidemiologically important strains of this pathogen, in particular, representatives of hypervirulent and carbapenem-resistant clonal lines, which have not lost their relevance even in the post-pandemic period. The use of bacteriophages as therapeutic and anti-epidemic agents seems justified given the widespread use of multidrugresistant strains of K. pneumoniae.

Aim of the study. To evaluate the susceptibility of K. pneumoniae strains associated with nosocomial infections in patients with COVID-19 to polyvalent bacteriophage medications.

Materials and methods. The study included 96 non-repeating K. pneumoniae strains isolated from clinical material of patients admitted to a major hospital in St. Petersburg with severe and moderate forms of COVID-19 from May 2020 to January 2021. The susceptibility of clinical strains to bacteriophages was assessed using the spot test analysis. Commercially available bacteriophage preparations used for testing included the following: purified polyvalent pyobacteriophage, sextaphage, and purified polyvalent Klebsiella pyobacteriophage. In order to identify the probable mechanisms of resistance of hospital strains of K. pneumoniae, the nucleotide sequences of the genomes of 6 strains of this pathogen belonging to the dominant hospital genetic lines ST3, ST39, ST307, ST395, ST874 were studied.

Results. Negative results of spot tests were observed in 32.29% (95% CI=23.8–42.2) of cases; in general, the proportion of patients eligible for treatment with phage therapy was 49% (95% CI=39.2–58.8). Loci of class 1 subtypes IV-A3 and I-E, potentially associated with resistance to CRISPR-Cas, were identified in the genome structure of the studied strains, as well as a number of prophage sequences potentially associated with resistance to bacteriophages.

Conclusion. The study demonstrated low activity of polyvalent bacteriophage medications against K. pneumoniae strains causing nosocomial infections in patients with COVID-19. Increasing the diversity of bacteriophage strains active against epidemiologically relevant K. pneumoniae clones can expand the possibilities of phage therapy for Klebsiella infections. The rational use of medications containing these bacteriophages is possible within the paradigm of personalised phage therapy.

Growing concern about the emergence of resistance in clinically significant pathogens has led to the establishment of a number of surveillance programs to monitor the actual level of resistance at local, regional, and national levels. The aim of the study is to analyze the antibiotic susceptibility of Staphylococcus aureus in infections of various localizations in pediatric practice. Material and methods. The study was conducted using biological material from patients (blood, urine, sputum, pharynx, etc.) received by the bacteriological laboratory of the Republican Scientific and Practical Medical Center of Pediatrics (P4) from different departments, for the period from January 2020 to December 2022. Nutrient media and discs with antimicrobial drugs manufactured by Himedia (India) were used. Results. The analysis of the sensitivity of Staphylococcus aureus strains showed that in the pilot institution of the Republican Specialized Scientific Practice Medical Center, the local antibiotic profile of the Staphylococcus aureus strains has the following picture: 98.3% are resistant to penicillin, 62.5% are resistant to erythromycin, 52.6% are resistant to clindamycin, 48.7% are resistant to cefoxitin, which indicates resistance to all β-lactam antimicrobial drugs, 16.2% are resistant to ciprofloxacin, 15.4% are resistant to levofloxacin, 7.7% are resistant to linezolid, and 5.3% are resistant to amikacin. Conclusion. In the general structure of microorganisms of the hospital, Staphylococcus aureus strains prevailed (50%). A high level of sensitivity to amikacin (94.7%), and rifampicin (94.3%), as well as high resistance to penicillin (98.3%) and cefoxitin (48.7%), was noted when studying the sensitivity of Staphylococcus aureus strains isolated from patients with various diseases from various biological materials.

The article presents a clinical observation of an elderly polymorbid patient with a complicated course of the underlying disease, which led to an expanded scope of surgical intervention. The effectiveness of inclusion in the complex treatment regimens of negative pressure wound therapy (NPWT systems in the mode of 120–160 mm Hg, 7-day course) and 1.5% reamberin infusions (400.0, intravenous drip, daily, general course No. 6) is shown. It manifested in the acceleration of reparative processes and a decrease in the area of the wound surface and contributed to the stabilization of the general condition of the patient: a decrease in the severity of clinical symptoms and vascular disorders. The obtained results can serve as a basis for a more in-depth study in this direction.

Urolithiasis (UL) occupies a leading place in the structure of urologic diseases and is characterized by an increase in morbidity, accompanied by serious complications leading to disability and mortality among the working-age population. In order to establish a comprehensive solution to the problem, it is necessary to study the aspects of UL epidemiology in each region for early diagnosis and timely treatment. Based on the study of statistical materials, the specifics of UL spread in the Kabardino-Balkarian Republic are shown.

Isolated bacteria, their morphological, biochemical, and genetic properties are, to this day, the main object of research since the isolation of a pure culture of the pathogen by R. Koch and his formulation of the postulates reflecting the role of the microorganism in the development of infectious diseases. The pharmacokinetic and pharmacodynamic properties of compounds with potential antibacterial activity are also studied in relation to planktonic, free cells. In recent years, as knowledge accumulates and new infections and conditions involving specially organized microbial communities — biofilms — are discovered, the approach to the diagnosis and treatment of infectious diseases, especially those with a chronic course, is changing. In this regard, the improvement and development of new representative models of microbial consortia both in vitro and in vivo are extremely relevant. Along with modern research methods, this will allow us to deepen our knowledge of the patterns of formation, construction, and functioning of the microbial world in a specific ecological niche, to develop innovative approaches to the treatment of biofilm infections, and to discover new target points for the action of antimicrobial drugs, directed at a multifaceted microbial consortium instead of individual bacteria. The review presents the main approaches to reproducing biofilm infections in vitro and in vivo experiments, highlighting their advantages, disadvantages, and possible prospects for increasing the relevance and validity of the models.

Gram-negative non-fermenting bacteria Acinetobacter baumannii are a common cause of severe complications (pneumonia, bacteremia, sepsis) in the clinic of internal diseases, especially in patients with weakened immune system: 3,2% of bacteremia and sepsis cases are associated with A. baumannii, with mortality rate 26–91%. A. baumannii has the ability to rapidly acquire antimicrobial resistance. In recent decades, strains with multiple resistance to antimicrobial drugs have emerged, including beta-lactams, including carbapenems, aminoglycosides, and fluoroquinolones, which are the drugs of choice in the treatment of severe hospital infections caused by Gram-negative microorganisms. Globally, about 45% of A. baumannii isolates are multidrug-resistant, with multidrug resistance reaching 90% in the Middle East, Southern Europe, and North Africa, and 60% in China. The prevalence of polyresistant strains of A. baumannii in patients with nosocomial pneumonia associated with mechanical ventilation is estimated at 80%. The main mechanisms of antimicrobial resistance of the pathogen are impaired permeability of the cell wall to antibiotics as a result of modification of porin proteins, activation of efflux pump systems, production of enzymes that destroy antibacterial drugs, and biofilm formation. The review examines the molecular basis of the formation of resistance to antibacterial drugs in A. baumannii.

The spread of antibiotic resistance in pathogenic microorganisms is one of the main problems of modern medicine. Given the unique metabolic properties of extremophilic microorganisms, the search for producers of new antimicrobial compounds among extremophilic actinomycetes is reasonably justified. The review examines acidophilic and acidotolerant actinomycetes, which are an integral part of the microbiomes of acidic soils and, as studies show, have high antimicrobial potential.

During the last decades, the number of cases of invasive mycoses has risen dramatically, and one of the reasons for that is the rise in the number of immunocompromised patients. The main causative agents of invasive mycoses are the pathogenic fungi from Candida and Aspergillus genera. The cases of invasive mycoses caused by the fungi from Mucorales order, Fusarium genus (sometimes from other taxa) also became more frequent. In 2022, WHO published for the first time a ranked list of fungal pathogens dangerous to human health, including the ones causing invasive mycoses. The most cases of invasive mycoses in intensive care units are caused by the causative agents from the Candida genus. The frequency of detection of Candida albicans as a causative agent has decreased from 70–80% in the end of 20th century to 40–60% in recent years. In contrast, the number of candidiasis caused by Nakaseomyces glabratus and Candida parapsilosis is growing. A limited number of drugs for systemic use from the polyenes, azoles, echinocandins, and flucytosine groups are used for treatment of invasive mycoses. The number of cultures resistant to antimycotics is increasing worldwide. The main factors of resistance to antimycotics among fungi are the general resistance of the species and long-term usage of such medications. Resistant or low-sensitive isolates of pathogenic fungi and the mechanisms of resistance have been identified for all used antimycotics. The strategy to overcome the problem of increasing cases of invasive mycoses should include the optimisation of treatment protocols for the invasive mycoses, the fundamental research of the mechanisms of resistance of pathogenic fungi, and the development of ways to overcome the resistance, including the search for the new antimycotics.

Antibiotic resistance remains one of the most significant barriers to successful treatment of bacterial diseases. The microorganisms present in biofilms develop antimicrobial resistance much faster and more powerfully than planktonic forms. With the help of «quorum sensing», bacteria in biofilms exchange information with each other to maximize their pathogenicity. This review examines the main mechanisms of antibiotic resistance, the structure and vital activity of biofilms, the mechanisms of the «sense of quorum», as well as possible ways to overcome antibiotic-resistant bacterial resistance due to the effect of suppressing the «sense of quorum».

Comorbid infections (CI) in immuno-inflammatory rheumatic diseases (IIRDs) are associated with significant morbidity and mortality and, in addition, involve significant costs in the health care system due to the need for additional treatment and hospitalization. The development of CI requires the temporary cancellation of ongoing immunosuppressive therapy, which can lead to an exacerbation of IIRD. High activity of rheumatic disease and treatment with immunosuppressive drugs may increase the risk of CI. Of particular interest is the study of the frequency, structure and risk factors in patients with spondyloarthritis (SpA) — ankylosing spondylitis (AS) and psoriatic arthritis (PsA), especially in the aspect of the increasing use of biologics or targeted (b/tsDMARD) modifying disease agents and contradictory literature data.