The growth of antibiotic resistance necessitates studying the processes of acquisition and loss of genetic elements responsible for resistance. The aim of the study was to investigate the effect of temperature, biofilm formation, and antibiotics on the efficiency of integrative conjugative element (ICE) transfer in Vibrio cholerae O1 El Tor strains. Material and methods. Conjugative transfer of the ICE element from V. cholerae O1 El Tor strains to Escherichia сoli QD 5003 Rifr and V. cholera O1 El Tor 5879 Nalr cells was carried out in plankton and in biofilms on plastic and chitin at 25–37°C. The presence of ICE was determined by the integrase gene (int). Transconjugants were tested for antibiotic sensitivity and for the presence of resistance genes to tetracyclines (tetR), fluoroquinolones (qnrVC1), trimethoprim (dfrA1), and chloramphenicol (floR). Conjugation was induced by subinhibitory concentrations of ciprofloxacin, doxycycline, trimethoprim/sulfamethoxazole, and streptomycin. Results. Conjugation efficiency was higher in biofilms than in plankton, and lover with decreasing temperature. Streptomycin and trimethoprim/sulfamethoxazole stimulated conjugation in chitinous biofilms. Doxycycline and ciprofloxacin increased conjugation frequency in plankton. Conclusion. Temperature and biofilm formation affect the transfer of antibiotic resistance genes in V. cholerae. In complex biofilm conditions, compared to the planktonic form, there is an increase in the efficiency of conjugation between V. cholerae and other representatives of the Enterobacteriaceae family, which is more pronounced on the biotic substrate (chitin) and at 37°C. Subinhibitory concentrations of antibiotics can both stimulate and suppress the conjugation process in biofilms. It is necessary to solve environmental problems associated with environmental pollution by plastic waste and antibiotics, and to observe dosages when prescribing etiotropic therapy, as well as to search for substances that suppress the transfer of antibiotic resistance genes or promote the elimination of existing mobile genetic elements responsible for antibiotic resistance.

Relevance. The problem of prevention and treatment of influenza remains relevant due to the consistently high incidence rate of the disease in the population of all age groups, especially children and the elderly. Antiviral drugs have become the most important tools in the fight against influenza viruses. The main problem is the search and development of new antiviral drugs that do not have side effects. The aim of the present study is to investigate the effect of a new synthetic drug candidate based on adamantane (NMG 1110) and its combination with ribavirin on the reproduction of influenza A virus in MDCK cell culture. The aim of the present study is to investigate the effects of drugs and their combinations on the reproduction of influenza A virus in MDCK cell culture. Materials and methods. Determination of cytotoxicity and antiviral activity of drugs on MDCK cell line for influenza A(H3N2)/Aichi/1/68 virus at different schemes of drug introduction into cells: immediately after infection, 2 hours after infection, 4 hours after virus infection of cells. Results. It was found that the drugs were low-toxic for MDCK cell culture at the studied concentrations. Using the influenza A(H3N2)/Aichi/1/68 virus model, it was shown that the time of application of the studied samples did not affect the reproduction of the virus in cell culture. The NMG1110 preparation exhibits high antiviral activity at a concentration of 9.7 µg/ml with the chemotherapeutic index of 16.0. At the same time, ribavirin showed a lower effect with a chemotherapeutic index of 8.0. There is a significant suppression of virus reproduction with the combined use of the preparations. A pronounced antiviral effect of the additive nature is observed in the combination of ribavirin and the drug candidate NMG 1110.

Background. The precise identification of microorganism species that cause infectious complications in hospitalized patients is beyond doubt relevant in modern healthcare. The aim of this study was to determine the possibility of using Sanger sequencing in routine microbiological examination of patients in an Internal Medicine Clinic to improve the quality of etiological diagnosis of bacterial complications. Material and methods. Clinical isolates of microorganisms isolated from patients of a multidisciplinary medical center were studied. The study used classical microbiological methods of seeding and identification of cultures, as well as Sanger sequencing. Results. Sanger identification using the MicroSeq system (Applied Biosystems, USA) ensured identification of all 231 studied bacterial isolates – causative agents of nosocomial infections. For differential diagnostics of streptococci and coagulase-negative staphylococci, in some cases, when the known sequences of the first 500 nucleotides of the 16S rRNA gene of two species differed by 1–2 nucleotides, increasing the discrimination level of species identification to 100% allowed valid determination of the species affiliation of the studied microorganism. Phenotypic methods failed to identify a significant proportion of species (25.9%) of nosocomial infection pathogens, and only 8 (13.8%) of them were reliably identified in all cases. The use of Sanger sequencing to identify bacteria led to a long-term effect associated with improved qualifications of laboratory doctors, and enhanced discriminatory capabilities of visual assessment of the macromorphology of bacterial cultures, which is important for identifying all types of microorganisms present in biosubstrates. Conclusion. The Sanger sequencing method is highly efficient and quite cost effective, compared to the biochemical test panels widely used in clinical practice — the «gold standard» method in the etiological diagnosis of bacterial complications in the clinic of internal diseases.

The effectiveness and safety of favipiravir may be determined by polymorphisms of genes encoding enzymes involved in the biotransformation of the drug — AOX1 and CYP1A2. The aim of the study was to analyze the distribution frequency of allelic variants of genes encoding enzymes involved in the biotransformation of favipiravir AOX1 (rs55754655 and rs10931910) and CYP1A2*F1 (rs762551) among ethnic groups of the Volga region and the Far East. Material and methods. The study involved 497 volunteers from five ethnic groups: Russians, Mari, Mordvins, Nanai, and Buryats. The definition of belonging to an ethnic group was determined by double self-identification. Biomarker carriage was determined by the RT-PCR method. Results. Statistically significant differences between ethnic groups were observed in relation to the studied single nucleotide polymorphisms. The frequency of occurrence of the mutant allele C rs10931910 AOX1 among the Nanai differs from all ethnic groups except the Buryats, and the minor allele C rs55754655 AOX1 was significantly different among the Mari. A difference was found in the distribution of the A allele of rs762551 CYP1A2*F1 between the Buryat and Russian groups. Distribution patterns corresponded to frequencies in the larger populations from which the studied subpopulations originated. The frequencies of occurrence of the C allele of rs55754655 AOX1 were 10% in Russians, 5% in Mari, 3% in Buryats, 7.5% in Mordvins, 3.5% in Nanai. Allele C rs10931910 AOX1 was detected in 48%, 42%, 86%, 36%, and 77.5%, respectively, polymorphism of the CYP1A2*F1 gene rs762551 (mutant allele — A) — 65%, 55%, 68%, 70%, and 74%, respectively. Conclusion. There is heterogeneity in the distribution of polymorphisms of genes and enzymes that metabolize drugs, including favipiravir, which may be important when personalizing therapy for patients representing certain ethnic groups of the Russian Federation.

The multicenter prospective randomized trial of clinical and microbiological efficacy of cefepime in combination with fluorothiazinone or placebo was conducted to expand the possibilities of empirical therapy for patients with complicated urinary tract infections. The primary endpoint of the study in the MITT population was the clinical cure and pathogen eradication on the 21st day after the conclusion of antibacterial therapy: this indicator was 75.6% in cefepim/fluorothiazinone group and 50.8% in cefepim/placebo group; 97.5% one-sided confidential interval (14.7%) exceeded the hypothesis of equal efficacy (0%), allowing an alternative hypothesis of the superiority of cefepime/fluorothiazinone over cefetime/placebo to be accepted. There was a significant (P=0.012) decrease in relapses occurrences of infection at follow-up (90 days after the start of treatment) after the use of cefepime/fluorothiazinone compared with cefepime/placebo, 3/178 (1.7%; 95% CI: 0.3–4.8) and 14/175 (8.0%; 95% CI: 4.4–13.1), respectively. Adverse events were detected in 37 (20.6%; 13.4–25.3) patients in group cefepim/fluorothiazinone and in 27 (15.2%; 8.0–18.2) patients in group cefepim/placebo; their number did not significantly differ, they were not severe and did not require drug discontinuation. The results of the study showed the clinical and microbiological advantages of cefepime/fluorothiazinone combination compared with cefepime/placebo with an equal safety profile, which makes it possible to expand the effectiveness of empirical therapy for complicated urinary tract infections.

The aim of the study was to analyze epidemiological data on tuberculosis in the Kursk region, taking into account the changing socio-economic situation in the region, as well as to study the possibilities of using remaxol in the regimens of accompanying therapy for hepatotoxic reactions in patients with tuberculosis. During the analysis of the data array, it was noted that the dynamics of infectious processes were similar to the other regions of the Russian Federation: a decrease against the background of COVID-19 and a gradual increase in morbidity in the post-pandemic period. A third of the patients included in the study were diagnosed with comorbid forms of tuberculosis, characterized by greater severity of the disease and lower effectiveness of therapy: recovery (with deregistration) was recorded in half (49.8%) of patients with monoinfection, while in patients with a comorbid course of the disease, this figure was 35%. At the same time, clinical recovery was diagnosed in 38.2% of patients with monoinfection and in 47% of patients with comorbid tuberculosis (P<0.5). The inclusion of remaxol (intravenous drip, 400 ml/day, every other day — course No. 5, then 1 time per week No. 4) in the treatment regimens for hepatotoxic reactions during the main course of treatment in patients with tuberculosis, in both monoinfection and comorbid forms, contributed to a more rapid relief of deviations in clinical and laboratory parameters and an increase in the effectiveness of treatment: 84.2% in patients with tuberculosis and 85.7% with a comorbid form of tuberculosis versus 81.9% and 83.7% in patients in the comparison group (P≤0.05).

Favipiravir is an antiviral drug that has become widely used for the etiotropic treatment of COVID-19. According to a number of studies, the incidence of adverse reactions during favipiravir therapy reaches 93%, and the most common adverse reaction is an increase in the level of liver enzymes in the blood. The aim was to study the influence of gender-age, clinical-anamnestic and pharmacogenetic factors on the development of drug-induced liver injury during favipiravir therapy in hospitalized patients with COVID-19. Material and methods. The study included 150 hospitalized patients with COVID-19 receiving favipiravir therapy. Patients were divided into 2 groups: group 1 — 31 patients who developed an increase in alanine transaminase levels multiple of two upper limits of normal or more against the background of favipiravir therapy; group 2 (control) — 119 patients who did not develop this adverse reaction. A retrospective analysis of case histories was performed in patients of both groups, and a pharmacogenetic study was performed in 14 patients of group 1 and 71 patients of group 2. Based on the data obtained, the association of clinical, laboratory, pharmacological, and pharmacogenetic parameters with the development of drug-induced liver injury during favipiravir therapy was studied. Results. There were significantly more younger individuals in the group of patients who developed drug-induced liver injury than in the control group (60.48±15.93 and 66.38±14.23 years respectively, P=0.047), with a lower level of lymphocytes in the blood (1.103±0.644 and 1.537±1.866 109/l respectively, P=0.022) and a higher level of interleukin-6 (288.019±344.794 and 152.490±274.67 pg/ml respectively, P=0.045), as well as those receiving cephalosporin therapy (OR=4.891, CI=1.610–14.862, 2χ =9.047, P=0.003), beta-blockers (OR=0.416, CI=0.177–0.978, χ²=4.190, P=0.041), diuretics (OR=0.328, CI=0.107–1.006, P=0.043), interleukin inhibitors (OR=4.891, CI=1.610–14.862, χ²=9.047, P=0.003) and those who underwent repeated administration of interleukin inhibitors (OR=6.884, CI=2.609–18.168, χ²=18.048, P=0.000). Conclusions. Younger age, lower lymphocyte counts, and higher interleukin-6 levels in the blood, as well as concomitant therapy with cephalosporins, betablockers, diuretics, and interleukin inhibitors, including repeated administration of interleukin inhibitors, increase the likelihood of developing drug-induced liver injury during favipiravir therapy. Therefore, it is necessary to take these factors into account when prescribing favipiravir therapy, conduct more careful monitoring of clinical and laboratory indicators of liver damage, and develop personalized approaches to the treatment of patients with COVID-19.

The article describes a case of congenital combined immunodeficiency with severe atopy – deficiency of the cytogenesis regulator (DOCK8) The article examines modern ideas about the role of DOCK8 protein in ensuring the basic functions of the immune system, the consequences of loss of function of DOCK8 protein, epidemiology, clinical manifestations, modern principles of diagnosis and treatment of DOCK8 deficiency.

Globally, infectious diseases continue to be one of the leading causes of death, even in the face of substantial advancements in basic biological and medical sciences. Diagnostics of life-threatening conditions, including bacteremia, sepsis, meningitis, and encephalitis, is frequently constrained by the low sensitivity associated with culture methods. The application of PCR and various serological methods is constrained by a defined set of specific primers, DNA probes, antibodies, and antigens that are restricted to a limited range of potential pathogens. The accuracy and timeliness of laboratory diagnostics for infectious diseases are critical. In the past decade, a new discipline has emerged — clinical metagenomics, representing a novel approach in medical microbiology. Because clinical metagenomics can identify potentially any pathogen, regardless of its biological nature, it is a hypothesis-free diagnostic approach. The benefits and efficiency of using metagenomic methods of sequencing to identify bacterial, viral, fungal, and parasitic pathogens of infectious diseases in humans are discussed in this review.

In recent decades, bacteriocins have been actively studied as antimicrobial compounds. Bacteriocins have been primarily used to preserve food, but they are currently of increasing interest as potential clinical antimicrobial agents and possible immunomodulatory agents. Infections caused by antibiotic-resistant bacteria have been declared a global public health threat. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. In particular, despite their role as natural alternatives to chemical preservation in ensuring food safety, nisin remains the only bacteriocin approved by regulatory authorities for food preservation. The article highlights data on the safety of bacteriocins and their possible toxicity, which may become a barrier to their wider use in medicine and industry. The article describes the latest trends in the development of bacteriocin-based drugs, their effectiveness, spectrum of antimicrobial activity, and mechanisms of action on microorganisms.

Recently, an active increase in the incidence of non-tuberculous mycobacteriosis has been registered, which is determined not only by the improvement of methods for detecting non-tuberculous mycobacteria, but also by a fairly high level of awareness of medical personnel. The choice of the most accurate identification method is extremely important in determining the treatment tactics, since mycobacteria with different growth rates have pronounced differences in resistance to antimicrobial drugs. The emergence of molecular genetic research methods makes it possible to identify and type most of the currently known non-tuberculous mycobacteria, as well as determine their drug sensitivity. The prevalence of mycobacteriosis, which today represents a serious problem for both clinicians and laboratory specialists, requires the development of a new strategy for its microbiological diagnostics.

An analysis of the literature for 2022 was carried out in order to study the latest data on the cardiotoxicity of antitumor drugs. The abundance of data on the pathogenesis of cardiotoxicity of even a single chemotherapeutic agent indicates the multifactorial effect and the characteristics of the individual sensitivity of each patient to a particular drug. Due to the multifactorial nature of the pathogenesis of cardiotoxicity, the clinical manifestations of this complication are also numerous. It should be taken into account that oncological patients could have suffered from various cardiovascular diseases even before tumor development, and that cancer progression even without therapeutic intervention, or before it, can cause cardiac side effects. To identify such processes, it is necessary to monitor cardio-oncological patients in dynamics. When conducting conservative cancer treatment and in the event of the development of side effects, the complete cancellation of treatment is impossible, as it is necessary to continue the therapy, as well as repeat its courses, often throughout the patient's life. In this regard, methods are needed to reduce the severity of the cardiotoxic effect, as well as suppress the adverse effects of anticancer drugs on the myocardium, and the search and development of effective methods for the prevention and treatment of cardiotoxicity of chemotherapy drugs are still relevant. Timely detection, and hence, prevention, as well as reduction of the degree of damaging effects of the beginning cardiotoxic effect when using cancer chemotherapy agents is possible only with close cooperation between oncologists and cardiologists.

Antimicrobial resistance is a major global threat to public health and development. The problem of antibiotic resistance arose as a result of widespread and uncontrolled use of antimicrobial drugs in medicine and agriculture. Antimicrobials, including antibiotics, are widely used in modern agriculture to treat animals, birds, and other domestic animals, as well as in the food industry. A decrease in the sensitivity of bacteria to certain classes of antibiotics was discovered as early as the very beginning of the antibiotic discovery era, which subsequently, in some cases, transformed into multidrug resistance. The resistance of microorganisms depends on the structure of the antibiotic and is associated with the mechanism of its antibacterial activity. The review examines the properties of various groups of antibiotics that are critically important in terms of the resistance problem, intended for the treatment, prevention, and growth stimulation of farm animals. The possibilities of using methods alternative to antibiotic therapy in veterinary medicine were also discussed.