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For the local health service, Elizabethkingia meningoseptica remains a relatively new and little-known pathogen, whereas in many countries of Europe, Asia and other continents it is considered as a potential causative agent of nosocomial infections, especially in premature infants and immunocompromised patients. An analysis of the literature data, as well as our results indicate that E. meningoseptica should be considered as a potential pathogen, which is characterized by a unique profile of susceptibility to antimicrobial agents (AMP) and disinfectants. This article presents the results of a study of susceptibility to AMP and disinfectants of three isolates of E. meningoseptica, isolated during an investigation of an outbreak in one of the perinatal centers of the Russian Federation, where three cases of sepsis with a fatal outcome in premature infants caused by co-infection with Acinetobacter baumannii and E. meningoseptica were recorded between January and February 2016.

The study is devoted to the study of the antimicrobial activity of the antioxidant dioxidin and the complex dioxin-containing preparation Nosolin-ultra, nasal drops against planktonic and biofilm cultures of pathogens of ENT infections, the dynamics of the formation of microbial resistance to dioxidine. 11 reference strains and 9 clinical strains of microorganisms were used in the study: Streptococcus spp., Staphylococcus spp., Micrococcus luteus, Haemophilus influenzae, Acinetobacter pittii, Klebsiella pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa. The antimicrobial activity of preparations against planktonic cultures was determined by serial dilution in broth and spot method on solid nutrient media, against biofilms by the applicator method. The dynamics of dioxidine resistance formation was studied by passaging cultures in a liquid nutrient medium with increasing concentrations of antiseptic. Based on the study, it was found that Dioxidin showed antimicrobial activity against plankton cells of all strains (MBC=0.08-5 mg/ml), except S. pyogenes SN345 (MBC>5 mg/ml), inhibited the growth of formed biofilms (MBC=0.08-2.5 mg/ml) of all strains except S. pyogenes SN345 (MBC>5 mg/ml). The drug «Nosolin-ultra, nasal drops» was highly active against plankton cells (MBC=0.04-0.63 mg/ml) and biofilms (MBC=0.02-0.31 mg/ml) of gram-negative bacteria, except A. pittii (MBC>2.5 mg/ml), less active against plankton cells (MBC=1.25-2.5 mg/ml) and biofilms (MBC=0.02-0.31 mg/ml) of gram-positive bacteria and C. albicans. One strain (S. aureus) formed a variant resistant to dioxidine at a concentration of 20 mg/ml, which exceeded the concentration of dioxidine in the complex preparation; other strains (P. aeruginosa, K. pneumoniae, C. albicans) did not form such variants. The data obtained indicate that the drug «Nosolin-ultra, nasal drops» can be effectively used against most pathogens of ENT infections. It is worth noting that with prolonged use of the drug for some types of ENT pathogens in the future, a slight decrease in effectiveness may be noted.

Antimicrobial resistance is a global public health problem. In recent years, increasing of multi-drug resistant bacteria has been noted, which are resistant to different antimicrobial groups simultaneously, including beta-lactams. The main mechanism of anti-beta-lactam resistance in gram-negative bacteria is synthesis of various beta-lactamases that hydrolyze the antibiotics. The review is devoted to the analysis of data on the expression of beta-lactamase genes by multi-drug resistant bacteria and molecular genetic methods for their determination in RNA transcripts. Key words: antibiotic resistance, transcriptome, molecular genetic methods, beta-lactamases

Shiga-toxin producing Escherichia coli (STEC) strains cause serious and life-threatening diseases, hemorrhagic colitis (HC) and associated hemolytic uremic syndrome (HUS). Antibacterial etiotropic therapy against these diseases are not recommended. There are no vaccines against human HA and HUS. The review provides materials on the design of various types of candidate vaccines against STEC strains and assessment of their immunogenic and protective properties in experiments on laboratory and farm animals. The prospects for the use of inactivated corpuscular and live (vector) vaccines, lipopolysaccharide vaccines, DNA vaccines and nanovaccines, vaccines based on bacterial cell membranes (ghost), as well as vaccines created by reverse vaccinology methods in practice are considered. Key words: STEC, hemorrhagic colitis, immunodominant antigens, shiga toxins, EspA, EspB, Tir, intimine, IgG, sIgA

Prevention and treatment of hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) caused by Shiga-toxin producing Escherichia coli (STEC) continues to be a public health concern. The main reason for the problem is the lack of vaccines and lack of evidence for using of antibacterial etiotropic drugs to treat this infection. A promising scientific approach to create specific agents against STEC infection is the development of subunit recombinant vaccines. The analysis of experimental studies presented in this review shows that effective subunit vaccines against STEC infection can be created on the basis of known immunogenic determinants of HC and HUS causative agents – EspA, EspB, and Tir proteins, intimin, as well as H7 antigen of E. coli O157:H7 and nontoxic proteins of Shiga toxins Stx1 and Stx2 A and B subunits. Using these epitopes, three types of subunit vaccines are designed: antibacterial vaccine, vaccine protecting the macroorganism from systemic intoxication caused by Shiga toxins, and vaccines that simultaneously induce the antibacterial and antitoxic immunity. Since the epitopes listed above are weak immunogenic, to increase their immunogenicity, complex chimeric antigenic structures containing protein inducers are constructed that significantly increase the immune response to target specific epitopes. Mineral adjuvants are also widely used to increase the immunogenicity of STEC epitopes. All three types of created candidate subunit vaccines, at subcutaneous, intramuscular and intranasal application induce production of specific IgG and secretory IgA antibodies in animals and protect them from the infection caused by the STEC strains. Key words: STEC, hemorrhagic colitis, immunodominant antigens, Shiga toxins, EspA, EspB, Tir, intimine, IgG, sIgA

The in vitro antibacterial activity of 11 commercial disinfectant preparations and 8 antiseptics against 10 strains of the bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloaceae and Providencia stuartii obtained from international collections and isolated from neuroresuscitation patients in Moscow in 2018 was studied. The sensitivity of planktonic cultures to the preparations was determined by the method of serial dilutions in broth and the spot method on solid nutrient media, the sensitivity of biofilms by the applicator method. A general pattern was revealed: the level of sensitivity to tested disinfectants in clinical strains was lower than in reference strains. It was found that the disinfectants «Mikrobak-Forte», «SAT-22», «Neobak-Oksi» at the concentrations recommended by the manufacturers were effective against bacteria of all test strains, both in the plankton state and in the form of biofilms. On the contrary, the disinfectant preparations «Biodez-Optima», «Biodez-Extra DVU», «Novodez-Aktiv», «Triosept-Oksi», «Tristel Fusion for Surfaces», «Effect-Forte Plus», «Lactic-Oxy» did not have sufficient effectiveness in the concentrations recommended by the manufacturers, therefore it is proposed to use these drugs in higher concentrations. It was found that the disinfectant «Biodez-Extra DVU» is able to inhibit the growth of biofilms of bacteria of the species K. pneumoniae. The ability to suppress the growth of bacterial biofilms of K. pneumoniae, A. baumannii, P. aeruginosa was revealed for the «Triestel Fusion for surfaces disinfectant». The bacteria of all used test strains in the planktonic state were sensitive to all tested antiseptic preparations. However, the biofilms of the clinical strains of P. aeruginosa and P. stuartii. possessed resistance to the antiseptics «Octenidol», «Octenisept», «Miramistin», «Hexoral». Our studies indicate the need for sensitivity analysis of antibacterial drugs in representatives of hospital pathogens, including the modeling of bacterial biofilms, which is a very relevant and important scientific direction, necessary to improve the control of nosocomial infections in the Russian Federation.

Aim to study antibacterial activity of benzydamine hydrochloride, against clinic isolated of bacteria, located in hospitals in Russia and compare this data to results of similar trail of Spanish isolates. Materials and method for this study were used clinical isolates of bacteria, which are counted as typical agents of infections in otorhinolaryngology and gynecology. Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, Staphylococcus spp. and Streptococcus spp., isolated from patients in Russians hospitals; reference strains Escherichia coli, Staphylococcus aureus and Streptococcus agalactiae, from ATCC collection; and also, Lactobacillus acidophilus strain, isolated from probiotic drug «Lactobacterin». Antibacterial activity of benzydamine hydrochloride was evaluated with serial dilution method in agar. For comparison of results we used data of Spanish study of benzydamine activity against clinical isolates and reference strains. The Spanish Study was completed in microbiological department of San-Pau hospital in Barcelona in 2001. Results . It was indicated that minimum inhibitory concentration (MIC) of benzydamine hydrochloride for clinical isolates of gram-negative and gram-positive bacteria, isolated from Russian and Spanish hospitals is about the same level: for E. coli it was 640 – 1280 mg/l, for K. pneumoniae – 512–1280 mg/l, for S. aureus – 256–1280 mg/l, for S. agalactiae – 320–1280 mg/l, for S. pyogenes – 256–640 mg/l, for E. faecalis – 512 mg/l, for E. faecium – 256 mg/l, for S. mitis – 640 mg/l, for S. epidermidis 320 – 1280 mg/l, for S. pneumoniae – 40 mg/l, for S. viridans – 40 mg/l. The same data was obtained by assessment of sensitivity to benzydamine hydrochloride reference-strains from ATCC collection: for E. coli MIC was 512 – 640 mg/l, for S. aureus – 512 – 640 mg/l, for S. agalactiae – 320 mg/l, for S. pneumoniae – 640 mg/l. Probiotic strain L. acidophilus was resistant to benzydamine hydrochloride activity with MIC = 20000 mg/l. Conclusion : It was indicated that antimicrobial activity of benzydamine hydrochloride against clinical strains, isolated from the patients of hospitals in Russia and Spain. Also, resistance of probiotic strain of lactobacteria was detected to this drug, which indicates the possibility of benzydamine hydrochloride application in clinical practice in otorhinolaryngology and gynecology without risk of negative influence on normal lactobacterial flora.

Rationale: Enterococci are the leading cause of a number of nosocomial and community-acquired human diseases. In the last decade, these pathogens are becoming resistant to antibacterials, including vancomycin. Multidrug-resistant enterococci have been also isolated from agricultural animals in many countries worldwide, which raises concern of scientists because of possible horizontal transfer of resistance genes. Aim : To assess antibacterial sensitivity of Enterococcus spp. isolates collected from the poultry in the Russian Federation from 2013 to 2016, and to identify vancomycin-resistance genes in their genomes. Materials and methods : Eighty-seven enterococci isolates belonging to E. faecalis (n = 47, 54%), E. faecium (n = 25, 28.7%) and other species (n = 15, 17.2%) were collected from clinical samples of 297 heads of poultry (liver, lungs, heart, spleen, contents of the nasal and sinus cavities) from 17 poultry farms of the Northwest, Central, Volga, Ural and Southern Federal districts of the Russian Federation. Sensitivity of enterococci to antibacterials was determined by disk-diffusion and broth microdilution methods. Vancomycin resistance genes van was detected by polymerase chain reaction with specific primers. Results : Most enterococci isolates were resistant to erythromycin (74/87, 85.1%), gentamicin (70/87, 80.5%), ceftriaxone (61/87, 70.1%), ciprofloxacin (56/87, 64.4%), tetracycline (57/87, 65.5%), and rifampicin (48/87, 55.2%), fewer ones to trimethoprim (38/87, 43.7%), ampicillin (28/87, 32.2%), linezolid (15/87, 17.2%) and chloramphenicol (5/87, 5.7%). The vanC type genes ( vanC1 and vanC2/3 ) were identified in 10 isolates. Vancomycin minimal inhibitory concentrations for these isolates were 2 to 8 mg/L. E. faecium with vanC1 gene was isolated from poultry probably for the first time ever. Conclusion : Commercial poultry in the Russian poultry farms is an important reservoir and source of antibiotic-resistant enterococci populations, including enterococci carrying vanC1 and vanC2/3 vancomycin resistance genes.

The results of the comparative tests of the «Agar Muller-Hinton II - Obolensk» nutrient medium developed in SRCAMB, Obolensk, and the control nutrient medium imported «Mueller Hinton II Agar» are presented in the study. The susceptibility of bacterial clinical strains to antimicrobial agents (AMP) was determined by the disc diffusion method and the method of gradient diffusion (E-test). The carbapenemase activity of the strains carrying the carbapenemase genes was determined by CIM-test. Total 173 characterized bacterial strains of species Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Proteus mirabilis, Serratia marcescens, Enterobacter aerogenes, Escherichia coli; Photorhabdus spp., Staphylococcus aureus, Enterococcus spp. were used in the study, including producers of OXA- and NDM-types carbapenemases for gram negative bacteria. A high degree of coincidence of the results obtained on both nutrient media was shown. The consistency index of the strain sensitivity categories to AMPs (S, I, and R) was 98.2% for the disc diffusion method, and 94.4-100% - for E-test and CIM-test methods. Thus, within the framework of the Import Substitution Program, the domestic nutrient medium «MHA II-Obolensk» has been successfully developed. The nutrient medium meets the requirements of GOST R ISO 20776-2-2010 «Clinical laboratory testing and in vitro diagnostic test systems - Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices».

The Central Asia Outbreak (CAO) clade is a growing public health problem for Central Asian countries. Members of the clade belong to the narrow branch of the Mycobacterium tuberculosis Beijing genotype and are characterized by multidrug resistance and increased transmissibility. The Rostov strain of M. tuberculosis isolated in Russia and attributed to the CAO clade based on PCR-assay and whole genome sequencing and the laboratory strain H37Rv were selected to evaluate the virulence on C57Bl/6 mice models by intravenous injection. All mice infected with the Rostov strain succumbed to death within a 48-day period, while more than half of the mice infected by the H37Rv strain survived within a 90-day period. Mice weight analysis revealed irreversible and severe depletion of animals infected with the Rostov strain compared to H37Rv. The histological investigation of lung and liver tissues of mice on the 30th day after injection of mycobacterial bacilli showed that the pattern of pathological changes generated by two strains were different. Moreover, bacterial load in the liver and lungs was higher for the Rostov strain infection. In conclusion, our data demonstrate that the drug-resistant Rostov strain exhibits a highly virulent phenotype which can be partly explained by the CAO-specific mutations.

We report here the genome sequences of 10 Klebsiella pneumoniae strains of capsular type K2 isolated in Russia from patients in an infectious clinical hospital and neurosurgical intensive care unit. The draft genome sizes range from 5.34 to 5.87 Mb and include 5,448 to 6,137 protein-coding sequences.