A series of hybrid antibiotics on the basis of azithromycin and glycopeptides with the glycopeptide molecule attached via the aminoalkylcarbamoyl spacer to 11-position of the macrolide was synthesized. All the synthesized compounds demonstrated equal or superior to azithromycin and vancomycin antibacterial activity against 7 tested strains of grampositive bacteria. The new hybrid antibiotics were more active than azithromycin or vancomycin against S.pneumoniae ATCC 49619. Some of the compounds were active against E.faecium and E.faecalis strains resistant to vancomycin.

Different phosphocholine-cardlolipin-2'-deoxyuridine inclusion complexes were developed, that allowed to compose a water-soluble form of nucleoside analogues with previously defined antituberculosis activity. It was found that the resulting liposomes effectively penetrated to the cells. The increase of cytotoxicity was undoubtedly indicative of accumulation of the nucleoside in the cell culture. The result proved the ability of the liposomes for delivery of the low-soluble compounds to the cells for further investigation of their efficacy. It was shown that treatment of the bacterial cells with the liposomes of the modified nucleosides did not affect the bacterial growth.

The aim of the study was to evaluate antitumor and antioxidant properties of water-soluble polysaccharides from submerged mycelium of Flammulina velutipes grown under optimized conditions. The optimization of the nutrient medium composition allowed to increase the biomass yield by more than 2 times (up to 35 g/l) and to reduce the time of the cultivation process. The submerged mycelium of F.velutipes strain Fv-1 contained 14.8% of a water-soluble polysaccharides, 31.6% of proteins, 2.5% of total lipids, vitamins B (B₁, B₅, Bg). The polysaccharides contained glucose, galactose, fucose, mannose, xylose, rhamnose. The proteins contained all the essential amino acids except for tryptophan. Dry powder of the submerged mycelium, water extract of the mycelium and total fraction of the water-soluble polysaccharides demonstrated the antitumor activity against murine lymphocytic leukemia Р 388 in vivo. The antitumor activity of the substances was mainly due to the polysaccharides, since their purification increased the tumor growth inhibition. The maximum tumor growth inhibition by the water-soluble polysaccharides amounted to 94%. The total fraction of the water-soluble polysaccharides from F.velutipes strain Fv-1 demonstrated antioxidant activity. The antioxidant capacity (AOC) of the water-soluble fraction from F.velutipes was higher than that of the water-soluble polysaccharides from the submerged mycelium of Grifola frondosa, but inferior to the AOC of the water-soluble polysaccharides from the submerged mycelium of Ganoderma lucidum.

Bioinformatic analysis of the data on the genome sequencing of the isolates of the Streptococcus pneumoniae clonal complex SS320 from the Russian Federation, as well as the data on SS320 isolates from public sources in the penicillin resistant isolates resulted in detection of 139 missense mutations in 45 genes. In addition to the mutations in the genes of the main penicillin-binding proteins (PSB - PBP1A, PBP2B and PBP2X) there was detected high frequency of mutations in the genes of the (division and cell wall) dcw-cluster, as well as in RegR protein belonging to the transcription regulators of the LacI/GalR family. Development of resistance to beta-lactams in S.pneumoniae is defined not only by modification of the PSB, but also by adaptive changes in the metabolic pathways involved in the bacterial cell growth and division.

Carbapenemase-producing gramnegative bacteria, which hydrolyze most ofв-lactams, including carbapenems, is of global health care system threat. The number of the known carbapenemases is constantly increasing, however only four types are widely distributed: NDM-type, KPC-type, OXA-48-type and VIM-type. The frequency of carbapenemase-producing Klebsiella pneumoniae in hospitals of Saint Petersburg reached 9.2% (5.9% for NDM-type, 1.4% for ОХА-48-type, 1.9% for NDM-type + ОХА-48-type). Carbapenemase producers were also detected in hospitals of Moscow, Yekaterinburg, Vologda, Murmansk, Kurgan, Krasnoyarsk, Izhevsk, Krasnodar and Perm. In total 281 carbapenemase producers were recorded within 2011-2016, which were isolated from infected or colonized patients (K.pneumoniae - 247 isolates, Acinetobacter spp - 29 isolates, Enterobacter cloacae - 2 isolates, Serratia marcescens - 1 isolate, Escherichia coli - 1 isolate and Proteus mirabilis - 1 isolate). The carbapenemase-producing K.pneumoniae isolates were distinguished by considerable genetic diversity, the NDM-type carbapenemase-producers belonged to eight, КРС-type - to three and ОХА-48-type - to four different sequence-types (STs) respectively. The representatives of the globally dominant genetic line, Clonal Group 258 (CG258), and also a number of the less common lines (ST147, ST273, ST307 and ST377) were detected. The K.pneumoniae strains were distinguished by a high frequency of cross-resistance and the associated resistance to antibiotics of different groups. The frequency of resistance to cephalosporins and fluoroquinolones reached 100%. Among the NDM-type carbapenemase producers the frequency of resistance to aminoglycosides exceeded 90%, among the КРС-type carbapenemase producers the frequency of resistance corresponded to 66% for amikacin and 93% for gentamicin, among the ОХА-48 type carbapenemase producers the frequency of resistance was even lower (50% and 73% respectively). Approximately 80% of the NDM-type, 90% of the КРС-type and only 60% of the ОХА-48-type carbapenemase producers showed a high level of resistance to imipenem and meropenem. The frequency of resistance to tigecycline varied within 6.7% to 14.8% and the frequency of resistance to polymyxin was within 4.2% to 20%. The ОХА-40- and ОХА-23-types carbapenemase-producing Acinetobacter spp. remained susceptible only to polymyxin. It is obvious that the possibility of antibacterial therapy of infections caused by carbapenemases producers is limited.

Objective: to evaluate the incidence of bacterial aggravations and antibiotics administration with analysis of effectiveness of antiviral therapy in ambulatory patients with acute viral respiratory infection (ARVI) and influenza. Material and methods. International cohort open non-interventional study «Treatment of ARVI and influenza in routine clinical practice» was conducted. The data analysis covers treatment results of 18946 ambulatory patients aged 18-93 years with clinical diagnosis of ARVI or influenza in 262 centers in Russia, Moldova, Armenia and Georgia. One group of patients received treatment in accordance with approved and applicable in their country schemes of complex treatment of ARVI and influenza; other group included patients treated with the complex treatment including antiviral drug Kagocel® (Russia). On each of 3 visits were evaluated clinical symptoms (in scores), the presence of bacterial aggravations, and the effectiveness of drug treatment including antibacterial therapy. Results. Bacterial aggravations were recorded in 8.3% cases, and systemic antibiotics were prescribed by doctors in 9.3% cases. The incidence of bacterial aggravations and administration of systemic antibiotics increased proportionally to the age of patients, severity of disease, times of first visit to the doctor and the start of treatment. Prescription of Kagocel® in the complex treatment of ARVI and influenza contributes to reduction of number of bacterial aggravations in 1.65 times (p<0.01) and decreases necessity of systemic antibiotic therapy in 1.51 times (p<0.01), which leads to better disease outcome at various therapy start times. Maximum efficiency and fewer treatment aggravations were recorded for working age patients. Conclusions. Antiviral therapy has shown its effectiveness in the treatment of ARVI and influenza, its implementation leads to decrease of bacterial aggravations incidence.

In patients under artificial lung ventilation (ALV) there is often observed development of severe ventilator-associated pneumonia (VAP) due to polyresistant hospital pathogens. It should be noted that in the patient described here with the initial diagnosis of community-acquired pneumonia rapidly subjected to prolonged ALV the previous antibacterial therapy by broad spectrum drugs significantly increased the risk of contamination just by multiresistant nosocomial strains, which hampered the starting therapy of nosocomial pneumonia either when there were not available or sometimes there were available microbial cultures. When the treatment of severe pneumonias caused by multiresistant hospital flora resistant to carbapenems is actual, in the alternative therapy it could be used tigecycline, a tetracycline from the group of glycylcyclines. A case of successful treatment of nosocomial VAP by tigecycline based on the results of the bronchoalveolar lavage (BAL) culture is described. The case is of interest because tigecycline was used as off label.

Backgrounds Streptococcus pneumoniae cause serious disease including pneumonia, meningitis and bacteremia and mortality is seen most in developing countries. The aim of the study was to determine if the reduction in IPD and pneumonia rates were similar in developed and developing countries after the introduction of the pneumococcal conjugated vaccine and to determine changes in the disparities of these diseases rates in these countries. Methods. Literature searches were conducted by using the PubMed database and Google scholar. The main criterion for selection was that the studies compare incidence of IPD or pneumonia in children pre and post PCV7, PCV10, or PCV13 vaccine introduction. Only published articles that described the incidence rate of IPD or pneumonia with quantitative data were fully reviewed in detail. Results. A total of 22 articles were full-text original publications and one was a review article. Within 3 years of PCV introduction in the United States, all-cause IPD dropped from 98.7/100,000 to 20/100,000 children <5 years of age and similar such reductions were also documented in Europe, Canada, Australia and Israel. In South Africa, rate of IPD incidence among children younger than 2 years of age declined from 54.8 to 21.7 cases per 100,000 from the baseline to 2011 and the further decreased to 17.0 cases per 100,000 person in 2012 (total reduction of 69%. The incidence rates of pneumonia in children <5 years were estimated to be 0.29 episodes per child-year in developing and 0.05 episodes per child-year in developed countries. After PCV7 introduction the rates of pneumonia hospitalizations in <5 years old decreased in the US from 1,274/100,000 to 723/100,000 in UK, from 1,340/100,000 children to 1,079/per 100,000 children. In Nicaragua reduction of rate ration of 0.67 (95% CI: 0.59-0.75) among infants and 0.74 (95% CI: 0.67-0.81) among 1 year olds and Uruguay from 1,542/100,000 to 1,227/100,000 and in South Africa, from ~96/1,000 in 2008-2009 to 69.3/1,000 (27.8%). Conclusions. PCVs are effective in both industrialized and developing countries in reducing IPD and pneumonia. Although developing countries are behind in PCV introduction, there is hope that if PCV is introduced in national immunization programs, IPD can perhaps be reduced to that of levels in industrialized countries, also resulting in reduced levels of pneumonia incidences. More surveillance studies are needed in all countries, but especially in developing countries that have introduced PCV to more accurately determine IPD and pneumonia reduction as a result of vaccination.