Object of study: probiotic strains of microorganisms, reference, pathogenic and opportunistic bacteria, including multidrug-resistant isolates, cell structures, metabolic complexes, a combination of metabolic complex of saccharomycetes and lactobacilli. The purpose of the research: to substantiatе of a new strategy of development and application of native metabolic complexes on the basis of ultrasonic disintegrates L. rhamnosus GG ATCC 53103 and S. boulardii CNCM I-745 for overcoming severe inflammatory diseases, caused by antibiotic-resistant bacteria in planktonic and biofilm forms. Methods of research: bacteriological (cultivation of probiotic strains of L. rhamnosus GG, L. plantarum, E. faecium, S. boulardii, pathogenic and opportunistic bacteria, counting the number of viable cells of these microorganisms (CFU / ml), determining the sensitivity of bacteria to antibacterial drugs of different groups, study of antimicrobial properties of antibacterial drugs alone and in combination with native biologically active substances, microscopic, physical and physicochemical, biochemical, biological (study of antimicrobial properties of separate metabolic complexes and in combination with antibacterial drugs in the model of infected wounds in ants), toxicological (topical application, intragastric and intraperitoneal administration to mice, in the conjunctival test on guinea pigs), analytical and medical statistics. Equipment: electronic device Densi-La-Meter (PLIVA-Lachema, Czech Republic; ultrasonic devices G3-109; Centrifuge OPN-3 and CLS-3; analyser «Lisa Scanтм EM» (Erba Mannheim, Чеська Республіка); reader (Еlise microplate reader with PC software UTRAO SM 600, («Utrao», China)); Gel Chromatography Equipment of LKV (Sweden), Arthur Pfeiffer Wetzlar vacuum pump (Germany). The dissertation is devoted to substantiation of prospects of development and application of native metabolic complexes of L. rhamnosus GG ATCC 53103 and S. boulardii CNCM I-745 (as the main active ingredient) and in combination with antibiotics (as additional component) for overcoming severe inflammatory diseases, caused by antibiotic-resistant bacteria. For the first time it was proposed on the basis of ultrasonic disintegrates of probiotic microorganisms to obtain native highly active substances L. rhamnosus GG ATCC 53103 and S. boulardii CNCM I-745, which in low concentrations (from ≤ 0.02 mg / ml) have a bactericidal effect against planktonic and biofilm forms of pathogens of bacterial infections. For the first time, the possibility of using ultrasonic disintegrates to cultivate not only their own but also other producers of probiotic microorganisms, including fungi and bacteria, has been demonstrated. The expediency is substantiated and the technical stages are adapted of obtaining a combination of L. rhamnosus GG and S. boulardii to enhance the antimicrobial action of the final product against pathogenic bacteria, in 2,4 times, due to the joint cultivation of probiotic saccharomycetes and lactobacilli in ultrasonic disintegrates of probiotics. New data were obtained on the inhibition of hemolytic, lecithovitelase activities, accumulation of pigments (pyocyanin, pyoverdine, pyorubin) of pathogenic and opportunistic microorganisms by native biologically active substances. It is shown that the antimicrobial complex of S. boulardii CNCM I-745 and L. rhamnosus GG ATCC 53103, which contains cellular structures of lactobacilli and metabolites of saccharomycetes, has more pronounced anti-adhesive (S. aurues ATCC 6538 P) and antibiofilm (C. diphtheriae gravis tox + № 108, C. ulcerans tox + № 112, P. aeruginosa ATCC 27853) properties. The ability of native metabolites to increase the sensitivity of pathogenic and antibiotic-resistant opportunistic bacteria to antibacterial drugs in vitro was proved for the first time. For the first time, the suggested of sequential use of metabolic complexes of L. rhamnosus GG ATCC 53103 and S. boulardii CNCM I-745 with antibacterial drugs in vitro has been proposed. The advantage of this method in comparison with one test for antibiotics or their combined simultaneous effect is proved experimentally. The antimicrobial activity of the metabolic complex of L. rhamnosus GG ATCC 53103 was confirmed in vivo experiments on a model of wounds of guinea pigs infected with the antibiotic-resistant pathogen P. aeruginosa PR № 0924. New in vivo data were obtained on a model of skin wounds of guinea pigs, infected with the antibiotic-resistant strain of P. aeruginosa PR № 35, on the effectiveness of simultaneous and sequential use of the combination of L. rhamnosus GG ATCC 53103 and S. boulardii CNCM I-745 with amikacin, which promotes faster eradication of the pathogen, which can later be included in the treatment of purulent-inflammatory diseases. The degree of implementation: 2 patents, 8 acts of implementation. Sphere (industry) of use: health care (medicine: prevention and treatment of infectious diseases).
