Background. To date, there is little data on the clinical characteristics of Bacillus bacteria found in clean rooms and aseptic facilities.

The aim of the study was to identify and determine the resistance of Bacillus strains isolated from the International Space Station and medical laboratory to clinically significant antibiotics.

Methods. Isolates were identified using 16S rRNA gene analysis, MALDI-TOF, and whole-genome sequencing. Antibiotic sensitivity was assessed using the disk diffusion method.

Results. Seven Bacillus strains out of 13 showed resistance to imipenem, and each of B. cereus LR2HG21, HSA01, HSA03, and HSA12 showed resistance to imipenem, ciprofloxacin, levofloxacin, and norfloxacin. Whole-genome sequencing of B. cereus LR2HG21, HSA01, HSA03, HSA12 and B. safensis SE192, resistant to imipenem and meropenem, showed that resistance to them is provided by the TEM-116 gene. In addition to TEM-116, the resistance of B. cereus LR2HG21 to imipenem and meropenem, and B. cereus HSA01 and HSA03 to imipenem, is provided by the BcI and/or BcII genes. Resistance to erythromycin in B. subtilis SE15 and B. subtilis SE171 is encoded by the mphK gene.

Conclusion. Resistance to a particular antibiotic in different Bacillus strains can be achieved by one or more mechanisms simultaneously.

Background. Annual studies of West Nile virus (WNV) circulating in endemic areas are necessary to characterize its properties and track them over time. Given the lack of specific antiviral therapy for West Nile fever (WNF), it is of interest to study sensitivity to drugs widely used in modern practice.

The aim of the study is to study the sensitivity of West Nile virus strains circulating in the Russian Federation in 2018–2021 to drugs used to treat viral infections.

Material and methods. The sensitivity of WNV strains to ribavirin, riamilovir, and umifenovir was determined using Vero cell culture.

Results and discussion. A study of the sensitivity of WNV strains circulating in the Russian Federation in 2018–2021 to therapeutic drugs used to treat viral infections showed their heterogeneity in this regard. Thus, 5 strains (WNV_Volgograd_601/18, Volgograd_723/18, Volgograd_830/18, Voronezh_794/21, Astrachan_962/21) out of 10 studied were characterized by some differences in resistance to ribavirin and riamilovir. No statistically significant differences were revealed when comparing drug resistance indicators of the group of WNV strains of the «old» genovariant with those of the «new» group.

Conclusion. Further analysis of the genome of the studied WNV strains will allow us to establish genetic characteristics, which may contribute to the establishment of molecular mechanisms of resistance to ribavirin, riamilovir, and umifenovir.

Background. The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, originated in Wuhan, China, has claimed millions of lives around the world. In this regard, the search for effective drugs, including the repurposing of existing ones, has become an urgent task. A promising treatment strategy appears to be drug disruption of viral reproduction. RNA-dependent RNA polymerase (RdRp) is the central subunit of the RNA synthesis process for all positive-strand RNA viruses and is therefore an attractive target for antiviral inhibitors.

The aim of this work is an experimental study of the antiviral activity of various drugs based on 6-fluoro-3-hydroxy-2-pyrazinecarboxamide (Favipiravir) in vitro and in vivo against the SARS-CoV-2 coronavirus (COVID-19).

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 virus-containing 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 in the study. The effectiveness of the drug was assessed by the coefficient of therapeutic action.

Results. The results of the study revealed that the compounds FP-1 and Avifavir in the concentration range of 100–400 µg/ml almost completely suppress the reproduction of the SARS-CoV-2 virus; the CTI index for the drug FP-1 was 4, for Avifavir it was 2. The ED₅₀ value for FP-1 was 26 µg/ml, for Avifavir it was 36 µg/ml. Preparations T-705 and Coronavir revealed antiviral activity only at extremely high concentrations. The CTI was 1. During the study on Syrian golden hamsters orally infected with the SARS-CoV-2 virus, variant B, at a dose of 5×10⁵ PFU, it was shown that the use of Avifavir and FP-1 has a high protective efficacy, while Coronavir and T-705 cause a moderate suppression of virus reproduction in the target organ. According to the complex of clinical-virological, biochemical, and hematological indicators, the disease severity index (DSI) and the therapeutic index (TI) were calculated. For the drug Avifavir, the DSI was 0.269; the TI was 71.3% with a probability of 99.9%.

Conclusion. Of the studied compounds, Avifavir and FP-1 showed the highest antiviral activity.

Introduction. Rotavirus infection causes more than 250 million episodes of acute gastroenteritis annually, of which approximately 130,000 cases in children under 5 years of age are fatal. In this regard, the search for drugs for the treatment of rotavirus infection seems extremely relevant.

The aim of the research was to evaluate the antiviral activity of Cytovir^®-3 against human rotavirus on a cellular infection model.

Material and methods. The objects of the study were a mixture of active ingredients and individual components, identical in composition and ratio, contained in Cytovir^®-3. The study was carried out using a monkey kidney cell culture MA-104 and a laboratory strain of human group A rotavirus — 568, genotype G3P. Cultural, virological, molecular biological and statistical methods were used during the study.

Results and discussion. Analysis of the survival of MA-104 cells in the presence of Cytovir^®-3 showed that in the concentration range from 100 to 200 µg/ml, the drug reproducibly exhibited antiviral activity, which was expressed in increased cell survival compared to the viral control. Cytovir^®-3 in a non-toxic concentration of 150 µg/ml suppressed the reproduction of rotavirus by 1.0-2.0 lg СC₅₀/ml with various schemes of introduction into cell culture at all periods of observation, which was accompanied by a significant decrease in the concentration of viral RNA and a cytoprotective effect. 

Background. The minimum inhibitory concentration (MIC) does not predict the risk of antibacterial resistance development due to a small sample of tested bacteria. Minimum inhibitory concentration at an increased inoculum (MIC_HI) may become a suitable parameter for this purpose as a sample of tested bacteria is larger while the method of determination remains easy.

The aim of the study was to evaluate the potential of using MIC_HI as a parameter for predicting the resistance development in Klebsiella pneumoniae to aztreonam.

Methods. Aztreonam MIC and MIC_HI values were assessed against two strains of K. pneumoniae using the microdilution method (0.2 ml volume; inoculum of 5×10⁵ and 5×10⁷ CFU/ml, respectively) and compared the results with the effect of aztreonam in a dynamic in vitro model, in which  aztreonam regimen of 2 grams every 8 hours as a 2-hour infusion for 5 days was simulated.

Results. The efficacy of aztreonam against K. pneumoniae observed in the dynamic model was consistent with the MIC_HIs values assessed based on bacterial viability. During the visual assessment, the MIC_HIs values were greatly overestimated due to excessive turbidity caused by the formation of filamentous forms of bacteria exposed to aztreonam.

Conclusions. The MIC_HI parameter can be used to predict the development of resistance in K. pneumoniae to aztreonam when assessing the values of this parameter by the number of viable cells, but not by the visual boundary of bacterial growth.

The article describes a case of a rare primary immunodeficiency with immune dysregulation — CD25 deficiency with manifestation in the neonatal period in the form of severe chronic diarrhea, susceptibility to viral, bacterial, and fungal infections, autoimmune manifestations, malabsorption syndrome, hypotrophy, skin lesions, confirmed by a homozygous mutation in the IL2-RA gene detected by DNA analysis. The article discusses the role of IL2-RA in the maturation and differentiation of T-lymphocytes, modern approaches to the classification of primary immunodeficiencies with immune dysregulation, principles of diagnosis and treatment of CD25 deficiency, as well as analyzes and compares other cases of CD25 deficiency described in the literature.

A study of interleukin-1β, interleukin-10, and CD40 ligand (CD40L) parameters in patients with arterial hypertension (AH), coronary heart disease (CHD), including cardiac arrhythmias (CA), was carried out. The study included 90 patients, divided into 3 groups (AH, CHD, CHD + CA). The results of the study demonstrated the possible involvement of an inflammatory cytokine, interleukin-1, in the development of AH, the level of which in our study significantly increased with the addition of such cardiovascular complications as heart failure (HF), CHD, including CHD with CA. 

The most important direction of modern pharmacology is the study of systems used for controlled and targeted delivery of medications, which is carried out by creating nanoencapsulated forms of different nature and chemical structure. Nanoencapsulation is a promising method for creating innovative dosage forms with prolonged action, which allows expanding the range of medications, as well as changing approaches to various diseases that require long-term therapy. This review provides information highlighting the most promising classes of nanosized drug carriers, describes the processes of their use based on lipids, polymers, and biodegradable mineral substances, as well as provides examples of their use in modern pharmaceutical practice.

Influenza is an acute respiratory viral infection, known for its epidemics and pandemics, claiming millions of lives everywhere. Influenza A virus (Orthomyxoviridae family), whose genome consists of 8 RNA segments of negative polarity, is widespread due to its patterns of variability, which determine the development of resistance, for example, to antiviral drugs. Reassortment mechanisms and point mutations in the influenza A virus genome can lead to a great variety of different variants of this pathogen. The considered life cycle of the influenza A virus with a detailed description of the molecular genetic features of its structures allows us to highlight the advantages and disadvantages of the etiotropic therapy used, affecting different stages of virus replication from the point of view of evidence-based medicine in aspects related to its resistance.

According to the currently available data from large cohort studies, patients with immuno-inflammatory rheumatic diseases (IIRDs) are at increased risk of infectious complications, including influenza, compared to the general population. Vaccinations are a critical component of their care. However, data on the immunogenicity, efficacy, and safety of influenza vaccines in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) receiving modern anti-rheumatic drugs are limited.

The aim of the study was to investigate the immunogenicity, efficacy, and safety of the trivalent inactivated influenza split vaccine in patients with RA, AS and PsA, observed at the V. A. Nasonova Research Institute.

Materials and methods. The open prospective comparative study included 247 patients: 74 patients with RA, 62 patients with AS, 14 patients with PsA, as well as 97 people without IIRDs who comprised the control group (СG). The patients were selected over six epidemic seasons: 2016–2017, 2017–2018, 2018–2019, 2020–2021, 2021–2022, and 2022–2023. The majority of patients (78,7%) received immunosuppressive therapy at the time of inclusion in the study. The trivalent inactivated influenza split vaccine was administered in an amount of 1 dose (0,5 ml) intramuscularly against the background of anti-rheumatic therapy, regardless of the activity of the main IIRD. The level of class G antibodies to hemagglutinin (HA) of influenza A (H1N1), A (H3N2), and B viruses was determined in optical density units (OD units) using an enzyme-linked immunosorbent assay (PPDP LLC, St. Petersburg) before vaccination, 1–3 and 6 months after vaccination. The clinical efficacy and safety of the trivalent inactivated influenza split vaccine were also evaluated, including the effect on the course of RA, AS, and PsA according to the dynamics of disease activity indices.

Results. After vaccination, a significant increase in the level of antibodies was observed in patients with RA, AS, and PsA. At the second visit after vaccination the level of antibodies, determined in units of optical density, to HA of influenza A (H1N1), A (H3N2) and B was significantly higher compared to baseline values. By the third visit (6 months after vaccination), there was a slight decrease in the immune response, but the level of antibodies remained significantly higher than the initial level for all strains of influenza virus, with the exception of influenza B in the group of patients with RA. During follow-up, influenza or influenza-like illness was absent in 98,6% of patients who completed the study. No negative effect of vaccination on the activity of the underlying IIRD was noted. The frequency of post-vaccination reactions in patients with IIRDs and in the СG was comparable.

Conclusions. The results obtained in the study indicate sufficient immunogenicity, clinical efficacy, and safety of the trivalent inactivated influenza split vaccine in patients with RA, AS, and PsA.