Glycopeptides are the basis of the treatment of infections caused by MRSA (Methicillin-Resistant Staphylococcus aureus). Previously, it was demonstrated that antibiotic tolerant phenotypes are formed during selection of resistance under the influence of high concentrations of antibiotics. The present study uses a similar in vitro selection model with vancomycin. Clinical isolates of MRSA belonging to genetic lines ST8 and ST239, as well as the MSSA (ATCC29213) strain, were included in the experiment. Test isolates were incubated for five hours in a medium with a high concentration of vancomycin (50 μg/ml). Test cultures were grown on the medium without antibiotic for 18 hours after each exposure. A total of ten exposure cycles were performed. Vancomycin was characterized by bacteriostatic action; the proportion of surviving cells after exposure was 70–100%. After selection, there was a slight increase in the MIC to vancomycin (MIC 2 μg/ml), teicoplanin (MIC 1.5–3 μg/ml) and daptomycin (MIC 0.25–2 μg/ml). According to the results of PAP analysis, all strains showed an increase in the area under curve depending on the concentration of vancomycin after selection, while a heteroresistant phenotype (with PAP/AUC 0.9) was detected in three isolates. All isolates showed walK mutations (T188S, D235N, E261V, V380I, and G223D). Exposure to short-term shock concentrations of vancomycin promotes the formation of heteroresistance in both MRSA and MSSA. Formation of VISA phenotypes is possible during therapy with vancomycin.

Active search for new antiviral substances is currently underway. The purpose of this work is to identify the inhibitory activity of eprosartan medication in comparison with ribavirin in vitro and in vivo in relation to tick-borne encephalitis virus. The value of the half the maximum cytotoxic concentration (CC50) for eprosartan (8.8±1.2 mg/ml) and ribavirin (1.074±0.16 mg/ml) was established. To obtain a medium effective virus-inhibiting concentration (IC50) of the medications, EIA data were used. Using nonlinear regression analysis of the percentage of antigen positive samples, IC50 values of the studied substances were obtained, which for eprosartan was 0.64±0.23 mg/ml in the treatment regimen. The selective index (SI) or chemotherapeutic index (CTI) was 13.7. The IC50 of ribavirin was 0.0067±0.0015 mg/ml, SI or CTI was 160. The suppression of viral reproduction 2.0 log TCID50 occurred in PEK cell culture under the influence of eprosartan at concentrations of 1.2–3.0 mg/ml (treatment regimen), under the influence of ribavirin — 0.2 mg/ml (prophylactic regimen) and 0.2–0.0125 mg/ml (treatment regimen). Samples with eprosartan (1.5 and 0.6 mg/ml) showed an increase in survival of mice by 50% and 20% compared with the virus control group in the in vivo model and, accordingly, an increase in average life expectancy of 5.2 and 2.1 days. Samples with ribavirin (0.05 and 0.025 mg/ml) increased the survival of mice by 60% and 40% and, accordingly, increased the life expectancy by 7.3 and 4.8 days. The data obtained allow recommending eprosartan as an active agent against tick-borne encephalitis virus along with ribavirin.

Relevance. Indications for rifabutin use are constantly expanding. It is used in the treatment of extremely complex nosological forms of infectious diseases. However, side effects of the medication, such as gastrointestinal toxicity and myelosuppression, in many cases do not allow the completion of treatment and weaken the patient-s adherence to therapy. This determines the need to find means to reduce the toxic properties of rifabutin.

Objective. The aim of the study was to investigate the possibility of correction of gastrointestinal and hematological toxicity of rifabutin with ascorbigen.

Material and Methods. The study was performed in male Wistar rats. The drugs were administered per os at therapeutic doses (50 mg/kg daily for 15 days). Ascorbigen was administered 30 minutes before rifabutin. Body weight dynamics, hematological parameters, blood biochemical parameters, electrocardiography, and urinalysis were performed for all animals during the study. Five animals in each group were euthanized on the 1st and 30th days after the end of the treatment course. The internal organs were subjected to histological evaluation.

Results. It has been shown that combined treatment with rifabutin and ascorbigen leads to a weakening of the damaging effect of the antibiotic on the mucous membrane of the gastrointestinal tract and accelerates the processes of restoration of its structure. Clinically, this is expressed in the normalization of body weight gain of animals. The combined use of rifabutin with ascorbigen reduces the depth of cytopenia. The number of leukocytes in the peripheral blood of the rats was restored faster. There were no signs of atrophy of spleen-s lymphoid tissue. The administration of ascorbigen before rifabutin has a protective effect on the tissues of the kidneys and testes.

Conclusion. Oral administration of ascorbigen 30 minutes before rifabutin significantly reduces the gastrointestinal toxicity and hematotoxicity of rifabutin and prevents the development of spermatogenesis disorders. This allows us to recommend it for combined use in order to improve tolerance to anti-TB treatment.

One of the tasks of the hospital-s clinical pharmacologists service is to continuously monitor the consumption of antimicrobial drugs (DDD analysis) depending on the microbiological and epidemiological situation in the hospital. This is necessary for the implementation of various medical programs and technologies aimed at reducing the selection pressure of antimicrobial drugs and reducing the risk of the emergence, accumulation, and spread of bacteria strains with multiple and/or extreme drug resistance to these drugs in the hospital environment. To date, some medical institutions, especially in the various regions of the Russian Federation, do not have a proper team of clinical pharmacologists and a modern, well-equipped and computerized microbiological laboratory. This does not allow full implementation of the above-mentioned programs in such hospitals, e. g. Antimicrobial therapy monitoring system — SСAT and technologies, e. g. «carbapenem-preserving technologies» and «microbiological monitoring».

Immunological disorders were studied in 68 patients with herpesvirus infections (41 women and 27 men) aged 18 to 55 years. All patients were examined clinically, also laboratory tests were conducted during the period of exacerbation and clinical remission. Patients with herpesvirus infections showed a significant decrease in the relative number of CD3+, CD4+ T-lymphocytes and their subpopulations during exacerbation of herpes infection. A decrease in the content of CD 3+, CD4+ T-cells during exacerbation of the disease was associated with an increase in CD8+ T-lymphocytes. The immunoregulatory index also decreased. The relative number of CD19+ B cells significantly increased in the exacerbation stage. During the period of remission, the number of CD19+ lymphocytes decreased, remaining above the normal range in patients with severe disease. Studies have shown that patients with herpesvirus infections have immunopathological disorders both during the relapse period and during the remission period, which must be taken into account when treating these patients.

The aim of the study was to analyze the features of the organization of therapy for patients with HIV-associated tuberculosis (TB/HIV) and the effectiveness of pharmacotherapeutic approaches under the conditions of penitentiary institutions. Materials and methods: the data on the incidence and effectiveness of specialized medical care for TB/HIV patients were analyzed for a ten-year period in the population of penitentiary institutions of the Federal Penitentiary Service of one of the subjects of the Central Federal District of the Russian Federation. Therapy and examination of patients with TB/HIV was carried out in accordance with regulatory documents and using generally accepted diagnostic methods. The patients consulted the staff of the departments of the FSBEI HE KSMU to verify the diagnosis and correct treatment regimens. Results: the analysis showed that, despite the stabilization of the TB epidemic situation, the epidemiological indicators for comorbid TB/HIV are increasing in the penitentiary health sector, which is due to an increase in the number of HIV-infected patients. In order to intensify the treatment of patients with TB/HIV in the population of the penitentiary system, it is necessary to give priority to social and sanitary prevention, primarily in risk groups — HIV-infected and individuals with residual lung changes. The inclusion of Remaxol in the therapy regimens for TB/HIV patients promotes rapid relief of hepatotoxic reactions and, as a consequence, increases the effectiveness of the primary therapy, which is illustrated by clinical observation.

Nontyphoid Salmonella are gram-negative bacteria that induce Th1-mediated immunity. They rarely lead to a generalized infection, primarily developing in immunocompromised patients with cellular immunity defects. Septic pulmonary embolism is also a rare condition in which emboli contain microorganisms from extrapulmonary infective foci. The article presents a rare clinical case of a patient with pulmonary embolism and generalized nontyphoid salmonellosis due to the presence of Asp299Gly and Thr399Ile genetic polymorphisms in the TLR4 gene. Such a defect of cell-mediated immunity was a trigger for destructive changes in the lung parenchyma, prothrombotic state, and generalization of the infectious process.

The introduction of local programs for the rational use of antibiotics in a multidisciplinary hospital is aimed at reducing the level of antibiotic resistance and the frequency of healthcare associated infections (HAI). The aim of the study was to analyze the frequency of infectious complications caused by pathogens with multidrug resistance and the level of resistance at the B.V. Petrovsky National Research Center of Surgery based on the implementation of the SCAT program. Material and methods. A retrospective analysis of the SCAT program implementation results on the basis of the B.V. Petrovsky National Research Center of Surgery was carried out. 1850 case histories of the surgical profile for 2018 were analyzed (male —1095, average age 56.2±14.9 years; female — 755, average age 53.7±11.9 years) and 1502 case histories for the January–October period for 2019 (male — 1114, average age 58.3±12.1 years, and female — 388, average age 55.4±12.6 years). Results. The incidence of HAI in 2018 and 2019 was 354 and 159 cases, respectively. Of these, the incidence of nosocomial pneumonia (NP) was 64 cases (61.5%) and 40 cases (38.5%); skin and soft tissue infection (SSTI) — 93 cases (57.4%) and 69 cases (42.6%); surgical site infections (SSI) — 69 cases (82.1%) and 15 cases (17.9%) in 2018 and 2019, respectively. The drug resistance index (DRI) for the most clinically significant strains of the causative agents of HAI was: Klebsiella pneumoniae — 0.14, Acinetobacter baumannii — 0.22, Klebsiella spp. — 0.11, Enterobacter cloacae — 0.15, Enterococcus faecalis — 0.18, Enterococcus faecium — 0.21. Conclusion. The proposed measures for the implementation of the SCAT program at the level of a medical organization reduce the incidence of HAI and the local level of the drug resistance index.

Preclinical studies are one of the most important stages in the development of drugs for medical use, including cell therapy products (in accordance with the legislation of the Russian Federation — biomedical cell products). Regulatory authorities decide on the possibility of conducting clinical trials in order to bring the medications to the market on the basis of the results of the study of their specific activity and safety. Russian requirements for preclinical studies of cell therapy products generally correspond to foreign ones, the main difference is the need for an expanded program of their conduct. The article analyzes the aspects of preclinical studies (scope, justification of the reduced program, design, animal models used) of some cell therapy products approved for use in medical practice in the United States, the European Union, Japan, and South Korea.

Progredient growth of morbidity and mortality of patients with community-acquired pneumonia (CAP) requires optimization of treatment including antibacterial therapy. Implementation of molecular-genetic methods of diagnostics of viral and viral-bacterial infections in clinical practice has significantly augmented the conception of etiology of community-acquired pneumonia. Seasonal fluctuation of CAP prevalence corresponds with growth of morbidity of acute respiratory infections and influenza which contribute to the etiological structure of CAP by increasing the risk of infection caused by staphylococci. The synergy between influenza A virus and S.aureus has been shown; it is associated with an increase of virus replication in the presence of specific staphylococcal proteases and the ability of viruses to increase adhesion of S.aureusin the respiratory tract, to decrease phagocytosis of S.aureus by macrophages/neutrophils and production of antimicrobial peptides, as well as to increase the probability of secondary bacterial co-infection. Therefore, the most important requirement for the empiric therapy agents of CAP is high streptococcal and staphylococcal activity. According to the current guidelines on antimicrobial therapy of severe CAP, antipneumococcic cephalosporins, macrolides, and fluoroquinolones are the basic treatment agents, but none of them have the combined high antistaphylococcal and antipneumococcal activity inherent in ceftaroline. The advantages of ceftaroline over ceftriaxone and levofloxacin in terms of the probability of reaching target concentrations for clinically relevant pharmacokinetic/pharmacodynamic parameters are shown. Meta-analysis of randomized clinical trials showed the higher clinical efficacy of ceftaroline in comparison to ceftriaxone with similar adverse event rate. Summarized analysis of antibiotic susceptibility data, pharmacokinetic/pharmacodynamic and clinical data, as well as negative epidemiological trends confirms the necessity of optimization of antimicrobial therapy of CAP for implementation of ceftaroline advantages against pneumococci and staphylococci in comparison to other β-lactams. Therefore, empiric treatment with ceftaroline is the most rational option for the therapy of CAP in critically ill patients during the season of respiratory viral infection.