Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiology0372-93112686-7613Central Research Institute for Epidemiology17710.36233/0372-9311-2017-4-42-48IMMUNOLOGIC ASPECTS OF PHAGE THERAPY OF INFECTIONS RELATED TO MEDICAL CARE IN NEUROREANIMATIONBochkarevaS. S.noemail@neicon.ruAleshkinA. V.noemail@neicon.ruErshovaO. N.noemail@neicon.ruNovikovaL. I.noemail@neicon.ruAfanasievS. S.noemail@neicon.ruKiselevaI. A.noemail@neicon.ruZulkarneevE. R.noemail@neicon.ruRubalskyE. O.noemail@neicon.ruBorisovaO. Yu.noemail@neicon.ruKaraulovA. V.noemail@neicon.ruGabrichevsky Moscow Research Institute of Epidemiology and MicrobiologyBurdenko Research Institute of NeurosurgerySechenov First Moscow State Medical University28082017944424810042019Copyright © 2017, Bochkareva S.S., Aleshkin A.V., Ershova O.N., Novikova L.I., Afanasiev S.S., Kiseleva I.A., Zulkarneev E.R., Rubalsky E.O., Borisova O.Y., Karaulov A.V.2017Aim. Evaluate the effect of anti-phage humoral immune response on effectiveness of phage therapy of infections related to medical care (IRMC). Materials and methods. 42 patients on extended mechanical ventilation (MV) in neuroreanimation, 1 time in 2014, 4 times in 2015 and 1 time in 2016 had received bacteriophage cocktail per os - 20 ml including 6 patients - additionally 3-5 times. Effectiveness of phage therapy was evaluated by seeding of IRMC strains from samples of endotracheal aspirate, blood, urine and feces of patients before and after treatment. Results. 87.5% of samples from the patients initially had gram-negative pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa). Effective sanation for the first episodes of phage therapy was confirmed in 54 - 62.5% of cases. Pharmacokinetic studies have indicated a systemic mechanism of action for enteral forms of bacteriophages. Repeated courses of phage therapy did not result in significant eradication of pathogens. Antiphage immunity after a single administration of the cocktail of bacteriophages with a certain strain composition was detected using ELISA by the presence of specific IgG titers in a range from 1/16 to 1/4096 (in patients not receiving the cocktail antibodies were not detected). Conclusion. Reduction of sanation effect of bacteriophage could be due to formation of anti-phage antibodies after a repeated course in the same patient. Changes of strain composition of phage cocktail of bacteriophages is necessary to preserve results of phage therapy.bacteriophageIRMCantibiotics resistancehumoral immune responseanti-phage antibodiesбактериофагиИСМПантибиотикорезистентностьгуморальный иммунный ответантифаговые антитела[Алешкин А.В., Светоч Э.А., Воложанцев Н.В. и др. Инновационные направления использования бактериофагов в сфере санитарно-эпидемиологического благополучия, населения Российской Федерации. Бактериология. 2016, 1 (1): 22-31.][Борисова О.Ю., Рубальский Е.О., Алешкин А.В. и др. Применение молекулярногенетических технологий для индикации фагов в крови пациентов с инфекциями, связанными с оказанием медицинской помощи. В: Бактериофаги: теоретические и практические аспекты применения в медицине, ветеринарии и пищевой промышленности. 2016, с. 60-61.][Иммунологические методы. Подред. Г.Фримеля. М, Медицина, 1987.][Руководство по проведению доклинических исследований лекарственных средств (иммунобиологические лекарственные препараты). Часть 2. Под ред. А.Н.Миронова. М., Гриф и К, 2013.][AdamsMH. Methods ofstudy of bacterial viruses./я: Bacteriophages. New York, Interscience, 1959b: p. 443-522.][Aleshkin A., Ershova O., Volozhantsev N. et al. Phagebiotics in treatment and prophylaxis of healthcare-associated infections. In: Bacteriophages: An overview and synthesis of a reemerging field. Ed. Harrington D. New York, Nova Science Publishers Inc., 2016, ISBN: 978-1-63485-455-9, p. 105-122.][Aleshkin A.V., Ershova O.N., Volozhantsev N.V. et al. Phagebiotics in treatment and prophylaxis of healthcare-associated infections. Phagebiotics in treatment and prophylaxis of healthcare-associated infections. Bacteriophage. 2016, 6: el251379.][D^browska K., Miernikiewicza P, Piotrowicza A. et al. Immunogenicity studies of proteins forming the t4 phage head surface. J. Virol. 2014, 88 (21): 12551-12557.][Lusiak-Szelachowska M., Zaczek M., Weber-Dabrowska B. et al. Phage neutralization by sera of patients receiving phage therapy. Viral. Immunol. 2014, 27 (6): 295-304. doi: 10.1089/ vim.2013.0128.][Zaczek M., Lusiak-Szelachowska M., Jonczyk-Matysiak E. et al. Antibody production in response to staphylococcal ms-1 phage cocktail in patients undergoing phage therapy. Front. Microbiol. 2016, 7: 1681.]