Medicinal probiotic Sporobacterin is based on the Bacillus subtilis 534 strain, which has been shown to have antimicrobial activity against many bacteria, both the collection strains and the antibiotic-resistant forms of clinical isolates of pathogenic bacteria and fungi. Considering this strain as an antibiotic producer, a step-by-step mutagenic treatment was carried out in order to obtain a variant that consistently exhibits a certain high-level antibiotic activity. A mutant variant was obtained during the three stages of mutagenic treatment and selection; it effectively suppresses the growth of pathogenic staphylococci, including methicillin-resistant staphylococcus (MRSA).

Background. It is known that bacteria develop resistance to antibiotics in response to their presence and tend to maintain it for a long time. In addition, microbes can remain viable by passing into an uncultivated state that is not detected by microbiological methods. This state of the population is characterized by cell resistance to various stresses, including the effects of antibiotics.
Aim. To study the parameters of transition into an uncultivated state in E.coli M-17 cells resistant to an antibiotic.
Material and methods. Resistant E.coli M-17 cells were obtained by culturing the initial population in media with increasing concentrations of ampicillin (up to 50 µg/mL). Seed cultures were prepared from sensitive and resistant substrains, from which the cells were transferred to a hyperosmotic, «starvation» medium — artificial sea water. The resulting populations were incubated for a long time, samples were periodically taken to conduct the assessment of viability parameters.
Results. The experiments on long-term incubation of sensitive and resistant populations of E.coli M-17 showed that ampicillin-resistant substrain of the studied culture transitioned into an uncultivated state significantly faster and quantitatively higher than its sensitive variant. The presence of the antibiotic in the inoculum increased the time for the transition of resistant R2 bacteria to a viable uncultivated state to a level of >90% compared to R1. The R1 population at the beginning of the stress exposure massively (up to 77.7%) transitioned into viable but non-culturable cells (VBNCs) in the medium without an antibiotic in a similar seed culture. Periods of cell death were noted during the observation, with those cells becoming a substrate for the living part of the population and could lead to secondary growth of bacteria or partial restoration of dormant cells.
Conclusion. Cells resistant to the antibiotic quickly transitioned into the non-culturable state compared to sensitive cells of the studied strain. The addition of an antibiotic to the medium for obtaining a seed culture slowed down the transition of cells to an uncultivated state.

Lipoglycopeptide antibiotics are semi-synthetic derivatives of glycopeptides and are characterized by a pronounced bactericidal activity against gram-positive pathogens. The aim of the study was comparative assessment of the sensitivity of gram-positive clinical isolates to lipoglycopeptide antibiotics (telavancin, dalbavancin, oritavancin). The following isolates were included in the work: methicillin-resistant Staphylococcus aureus (MRSA, n=780), methicillin-resistant coagulase-negative Staphylococcus spp. (MRCoNS, n=163), and vancomycin-resistant Enterococcus faecium (VREf, n=93). Serial dilutions were used to assess sensitivity with the addition of 0.002% polysorbate 80 to the medium. Lipoglycopeptides showed more pronounced antibacterial activity against MRSA compared to vancomycin, teicoplanin, and daptomycin, and had a MIC₅₀/MIC₉₀ (µg/ml): for telavancin — 0.06 /0.125, for dalbavancin — 0.016/0.06, and for oritavancin — 0.06/0.125. A trend towards an increase in the MIC of lipoglycopeptides and daptomycin was established in MRSA with the MIC of 2 µg/ml for vancomycin, the proportion of which was 13%. For MRCoNS, MIC₅₀ and MIC₉₀ of lipoglycopeptides did not exceed 0.06 µg/ml and 0.125 µg/ml, respectively. Oritavancin showed strong activity against VREf at MIC range of 0.03 µg/ml to 0.5 µg/ml, and at MIC₉₀ of 0.25 µg/ml. Thus, lipoglycopeptide antibiotics are a plausible alternative to vancomycin and daptomycin; they are characterized by pronounced activity and can be used to treat severe forms of staphylococcal infections.

Creation of synergistic combinations of antifungal and antiseptic agents can be considered as one of the promising strategies for reducing the spread of drug resistance in pathogenic fungi.
Aim. The aim of this work was to study the synergistic antifungal activity of amphotericin B (AMB) and antiseptic miramistin (MST) in their combined use to fight against drug-resistant Candida isolates.
Material and methods. One AMB-resistant C.albicans strain (MIC 3.1 µg/ml), sensitive to MST, two isolates of C.albicans with different level of resistance to MST and AMB (MIC 1.6–6.3 µg/ml), and one MST-resistant C.lusitaniae isolate susceptible to AMB (MIC 0.4 µg/ml) were studied. Isolates’ susceptibility to AMB and MST alone was determined by broth microdilution method and time–kill assay, respectively. Individual anti-candida activity of test combinations of 0.001% MST with AMB in 10 or 50 µg/ml concentrations was studied using quantitative time–kill assay.
Results. A significant decrease in the growth of all the isolates treated with both test combinations of MST and AMB in comparison with individual medication treatment was observed at each time interval studied (15–60 minutes). As part of the combination, MST exhibited significant synergy with AMB in sublethal concentration of 10 µg/ml against all the isolates. Treatment of the fungi with a combination of MST with AMB in 50 µg/ml concentration caused complete inactivation of all the isolates after 30 minutes. Under these conditions, AMB exhibited separate antifungal activity.
Conclusion. These findings suggest the possible effective use of miramistin in combination with amphotericin B against multi-drug resistant isolates of the genus Candida.

Interferons (IFN) have antiviral activity against many viruses, including SARS-CoV-2. A combination of IFN-a2b and the antioxidant taurine is widely used in the Russian Federation, and its antiviral activity has not been studied before. The aim of this study was to determine the antiviral activity of interferon drugs, in combination with taurine and without it. The study included cytotoxicity and antiviral activity assays of IFN-a2b preparations, when stored according to the instructions at 2–8°C, and after 1 month storage at the temperature of 20–26°C in a pre-opened state. The combination of IFN alpha-2b with taurine has a higher antiviral activity compared to IFN alpha-2b mono-preparation by more than 25% at a «low» and 85% at a «high» multiplicity of infection. Selectivity index for combinations of IFN-a2b (50,000 IU/dose) + taurine (1 mg/ml) and IFN-a2b (10,000 IU/ml) + taurine (0.8 mg/ml) was more than 600 units, whereas for the IFN-a2b (10,000 IU/ml) it was 200 units. Antiviral activity does not change after one month at room temperature. The combination of interferon with taurine at high concentrations was less toxic than interferon. The results obtained demonstrate practicability of interferon alpha-2b and taurine combination use for treatment and prevention of COVID-19.

Interferon inducers are of interest as the first line of defense against viral infections, including influenza. Double-stranded ribonucleic acid (dsRNA) for intranasal administration has been developed, the excipients and drug components were selected at the Institute of Medical Biotechnology, a branch of the State Research Center of Virology and Biotechnology «Vector». This work presents the results of the study on antiviral activity and pharmacological safety of a new form of dsRNA. The antiviral activity of the preparation was studied in BALB/c mice infected with influenza A/Aichi/2/68 (H3N2) or Bishkek/01/2009 (H1N1pdm09) viruses. A safety study was performed with a single administration of intranasal dsRNA into white outbred ICR mice. The study showed that the administration of therapeutic and prophylactic regimen of intranasal dsRNA at a dose of 2.5 mg/kg increases the survival and average life expectancy of mice infected with the mentioned strains of influenza virus. The protective effect of the preparation in mice infected with a lethal dose of Bishkek/01/2009 virus was comparable to the effect of Tamiflu. The absence of toxic effects of intranasal dsRNA at a pharmacological dose in laboratory mice, the functional state of their physiological systems, as well as main types of metabolism, established in the experiments, lead to a conclusion concerning pharmacological safety of the preparation and the prospects for further work to complete pharmaceutical development of a new antiviral drug.

The COVID-19 virus has caused a global emergency and has attracted the attention of healthcare professionals and the public around the world. The significant increase in the number of new cases of infection with this virus demonstrates the relevance of the search for drugs that are effective against this pathogen. The aim of this work was to evaluate the antiviral efficacy of Mefloquin® against COVID-19. The antiviral efficacy of Mefloquin® against the new pandemic virus SARS-CoV-2 was studied in in vitro experiments in Vero C1008 cell culture and in vivo on Syrian golden hamsters. The results of the study revealed that the drug Mefloquine® at a concentration of 2.0 µg ml-1, when applied after infection of cells, suppresses the reproduction of the SARS-CoV-2 virus by 1.7–1.9 lg, the inhibition rate is about 99%. When using Mefloquine, pathological changes in the lung tissue were less pronounced than in the control group. 6 days after infection, it was shown that when using Mefloquine, there was a statistically significant decrease in viral load in the lungs of infected Syrian golden hamsters, with an inhibition rate of 95.5%.

Despite the fact that the incidence of community-acquired pneumonia (CAP) among young people is significantly lower than among older patients, the frequency of hospitalizations for severe CAP among people under 45 years of age remains high. The effectiveness and duration of treatment directly depend on the rationally selected initial empirical antibacterial therapy (ABT).
The aim of the study is to analyze the factors influencing the effectiveness of initial empiric antibacterial therapy for CAP in young people in multidisciplinary medical institutions.
Materials and methods. The study was designed as a retrospective observational study; it analyzes 105 medical records of young patients with CAP admitted to one of the multidisciplinary hospitals in Moscow from 2017 to 2019.
Results. The empiric ceftriaxone + azithromycin ABT regimen (70% of all prescriptions) was ineffective in 13.7% of cases; monotherapy with ceftriaxone (13% of all prescriptions) was ineffective in 57% cases. Severe CAP, acute respiratory failure, systemic inflammatory response syndrome, and exudative pleurisy were diagnosed with significantly higher frequency in the group of patients with ineffective initial empirical ABT. There was no predominance of any comorbid pathology and Charlson Comorbidity Index in groups where the initial ABT was changed and in groups without a change in initial ABT. The microbiological spectrum of CAP pathogens did not significantly differ in young patients between groups with a changed initial empirical ABT and a group without changing initial ABT.
Conclusion. The reasons for the ineffectiveness of the initial empirical ABT could be such factors as: underestimation of the risk of the presence of multidrug-resistant pathogens; underestimation of the risk of viral genesis of CAP; underestimation of the severity of CAP, as well as the severity of CAP complications.

The problem of antimicrobial therapy (AMT) for the new coronavirus infection has been the cornerstone of practical healthcare since its emergence to the present day. The article summarizes a number of problems concerning the unjustified prescription of AMT based on the data of foreign and domestic studies, as well as actual clinical practice. On the one hand, viral damage to the lung tissue during COVID-19 is difficult to distinguish from community-acquired or secondary bacterial pneumonia; it prompts clinicians to prevent possible bacterial complications in the lungs by prescribing broad-spectrum antibiotics starting from the first day. On the other hand, the presence of clear clinical and biological markers of bacterial pneumonia; and COVID-19 makes it possible not to use antibiotics in routine practice, at least in the early stages of treatment. The introduction of procalcitonin as a biomarker of bacterial infection in COVID-19 into everyday clinical practice has a reasonable, methodical, and scientific approach to prescribing antibiotics.

Diseases caused by Streptococcus pneumoniae are a serious medical and social problem for healthcare systems of all leading countries around the globe. In this regard, the relevance of their laboratory diagnostics increases, as the effectiveness of therapeutic, preventive, and anti-epidemic measures depends on it. Currently, there is no universal method of intraspecific identification of S.pneumoniae, which simultaneously possess high specificity, sensitivity, and reproducibility. For this purpose, new alternative strategies aimed at improving the quality of research are being developed. The review presents data from domestic and foreign publications (electronic search databases eLibrary.Ru, ScienceDirect, Scopus, PubMed, Springerlink) on serotyping and genotyping of S.pneumoniae; the advantages and disadvantages of the methods are analyzed. Epidemiologically significant serotypes and widespread clonal complexes of S.pneumoniae circulating on the territory of the Russian Federation have been identified. The necessity of improving new methods of intraspecific typing of the pathogen is recognized.

The incidence of pneumocystis pneumonia (PCP) in patients with rheumatic diseases (RD) continues to increase. This is facilitated by the increasing use of genetically engineered biological agents in addition to the use of cytostatics and glucocorticoids. Mortality due to PCP among patients with RD is extremely high, so the issues of its prevention are relevant. European and American scientists focus on the frequency of detection of PCP and the determination of the proportionality of certain risk factors, while the recommendations for prevention are formulated cautiously. Asian medical communities are unanimous in their opinion about the need to prevent PCP, only the dosage of drugs and the duration of the course of treatment are discussed.