ririРаны и раневые инфекции. Журнал имени проф. Б.М. КостючёнкаWounds and wound infections. The prof. B.M. Kostyuchenok journal2408-96132500-0594Regional non-governmental organization “Surgical society - Wounds and wound infections”10.25199/2408-9613-2022-9-1-6-11riri-269Research ArticleОБЗОРЫ, ЛЕКЦИИ, ИСТОРИЯ РАН И РАНЕВЫХ ИНФЕКЦИЙREVIEWS, LECTURES, HISTORY OF WOUNDS AND WOUND INFECTIONSФаготерапия при лечении боевой травмыPhage therapy in the treatment of combat traumaБесчастновВ. В.BeschastnovV. V.

Владимир Викторович Бесчастнов

603005, Нижний Новгород, пл. Минина, д. 10/1

10/1 Minina Sq., Nizhny Novgorod, 603005

vvb748@mail.ruУниверситетская клиника ФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РоссииРоссияUniversity Clinic of the Privolzhsky Research Medical University of the Ministry of Health of RussiaRussian Federation20222306202291611Copyright © Бесчастнов В.В., 20222022Бесчастнов В.В.Beschastnov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.riri.su/jour/article/view/269

Высокая устойчивость бактериальной флоры к существующим антибактериальным препаратам заставляет искать новые подходы в тактике лечения инфекционных раневых осложнений. Фаготерапия является одним из альтернативных способов решения данной проблемы. Зарубежные военно-медицинские организации совместно с частными фармацевтическими компаниями при финансовой поддержке государств активно разрабатывают всевозможные пути использования бактериофагов в различных направлениях борьбы с бактериальными инфекционными агентами. В статье обозначены основные научно-исследовательские программы, направленные на изучение возможностей фаготерапии при боевой и ожоговой травме, разрабатываемые в странах Западной Европы (Франции, Польши, Бельгии, Австрии, Швейцарии), США, Китае, Израиле.

The high resistance of the bacterial flora to existing antibacterial drugs makes it necessary to look for new approaches in the tactics of treating infectious wound complications. Phage therapy is one of the alternative ways to solve this problem. Foreign military medical organizations, together with private pharmaceutical companies, with the financial support of states, are actively developing all kinds of ways to use bacteriophages in various areas of combating bacterial infectious agents. The article outlines main research programs aimed at studying the possibilities of phage therapy in combat and burn injuries, which are being developed in Western Europe (France, Poland, Belgium, Austria, Switzerland), the USA, China, and Israel.

бактериофагифаготерапияинфекционные осложненияустойчивая микрофлорапрограммы разработки фаготерапиизарубежные военно-медицинские исследованияbacteriophagesphage therapyinfectious complicationsresistant microfloraphage therapy development programsforeign military medical researchReferencesMurray C. K, Wilkins K. , Molter N. C., et al. Infections complicating the care of combat casualties during operations Iraqi Freedom and Enduring Freedom. J Trauma. 2011; 71 (1 Suppl): S62–73.Murray C. K, Wilkins K. , Molter N. C., et al. Infections complicating the care of combat casualties during operations Iraqi Freedom and Enduring Freedom. J Trauma. 2011; 71 (1 Suppl): S62–73.Petersen K., Riddle M. S., Danko J.R., et al. Trauma-related infections in battlefield casualties from Iraq. Ann Surg. 2007; 245 (5): 803–811.Petersen K., Riddle M. S., Danko J.R., et al. Trauma-related infections in battlefield casualties from Iraq. Ann Surg. 2007; 245 (5): 803–811.Krueger C. A., Wenke J. C., Ficke J. R. Ten years at war: comprehensive analysis of amputation trends. J Trauma Acute Care Surg. 2012; 73 (6 Suppl 5): S438–S444.Krueger C. A., Wenke J. C., Ficke J. R. Ten years at war: comprehensive analysis of amputation trends. J Trauma Acute Care Surg. 2012; 73 (6 Suppl 5): S438–S444.Weintrob A. C., Murray C. K., Xu J., et al. Early Infections Complicating the Care of Combat Casualties from Iraq and Afghanistan. Surg Infect (Larchmt). 2018; 19 (3): 286–297.Weintrob A. C., Murray C. K., Xu J., et al. Early Infections Complicating the Care of Combat Casualties from Iraq and Afghanistan. Surg Infect (Larchmt). 2018; 19 (3): 286–297.McDonald J. R., Liang S. Y., Li P., et al. Infectious Complications After Deployment Trauma: Following Wounded US Military Personnel Into Veterans Affairs Care. Clin Infect Dis. 2018; 67 (8): 1205–1212.McDonald J. R., Liang S. Y., Li P., et al. Infectious Complications After Deployment Trauma: Following Wounded US Military Personnel Into Veterans Affairs Care. Clin Infect Dis. 2018; 67 (8): 1205–1212.Rostami S., Farajzadeh Sheikh A., Shoja S., et al. Investigating of four main carbapenem-resistance mechanisms in highlevel carbapenem resistant Pseudomonas aeruginosa isolated from burn patients. J Chin Med Assoc. 2018; 81 (2): 127–132.Rostami S., Farajzadeh Sheikh A., Shoja S., et al. Investigating of four main carbapenem-resistance mechanisms in highlevel carbapenem resistant Pseudomonas aeruginosa isolated from burn patients. J Chin Med Assoc. 2018; 81 (2): 127–132.Кокин Г. А. Применение бактериофагов в хирургии. Советская медицина. 1941; 9: 15–18.Kokin G. A. Application of bacteriophages in surgery = Kokin G. A. Primeneniye bakteriofagov v khirurgii. Sovetskaya meditsina. 1941; 9: 15–18. (In Russ.)Крестовникова В.А. Фаготерапия и фагопрофилактика и их обоснование в работах советских исследователей. Журнал микробиологии, эпидемиологии и иммунологии. 1947; 11: 56–65.Krestovnikova V. A. Phage therapy and phage prophylaxis and their substantiation in the works of Soviet researchers = Krestovnikova V. A. Fagoterapiya i fagoprofilaktika i ikh obosnovaniye v rabotakh sovetskikh issledovateley. Zhurnal mikrobiologii, epidemiologii i immunologii. 1947; 11: 56–65. (In Russ.)Покровская М. П. Каганова Л. С., Морозенко М. А. и др. Лечение ран бактериофагами. М.: Медгиз, 1941. 51 с.Pokrovskaya M. P. Kaganova L. S., Morozenko M. A., et al. Treatment of wounds with bacteriophages = Pokrovskaya M. P., Kaganova L. S., Morozenko M. A. i dr. Lecheniye ran bakteriofagami. M.: Medgiz, 1941. 51 s. (In Russ.)Häusler T. Virus vs. Superbug: A solution to the antibiotic crisis? New York, N.Y: Macmillan, 2006. 294 p.Häusler T. Virus vs. Superbug: A solution to the antibiotic crisis? New York, N.Y: Macmillan, 2006. 294 p.Kwiatek M., Parasion S., Nakonieczna A. Therapeutic bacteriophages as a rescue treatment for drug-resistant infections – an in vivo studies overview. J Appl Microbiol. 2020; 128 (4): 985–1002.Kwiatek M., Parasion S., Nakonieczna A. Therapeutic bacteriophages as a rescue treatment for drug-resistant infections – an in vivo studies overview. J Appl Microbiol. 2020; 128 (4): 985–1002.Mirski T., Lidia M., Nakonieczna A., Gryko R. Bacteriophages, phage endolysins and antimicrobial peptides – the possibilities for their common use to combat infections and in the design of new drugs. Ann Agric Environ Med. 2019; 26 (2): 203–209.Mirski T., Lidia M., Nakonieczna A., Gryko R. Bacteriophages, phage endolysins and antimicrobial peptides – the possibilities for their common use to combat infections and in the design of new drugs. Ann Agric Environ Med. 2019; 26 (2): 203–209.Zimecki M., Artym J., Kocieba M., et al. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus. BMC Microbiol. 2009; 9: 169.Zimecki M., Artym J., Kocieba M., et al. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus. BMC Microbiol. 2009; 9: 169.Przerwa A., Zimecki M., Switała-Jeleń K., et al. Effects of bacteriophages on free radical production and phagocytic functions. Med Microbiol Immunol. 2006; 195: 143–150.Przerwa A., Zimecki M., Switała-Jeleń K., et al. Effects of bacteriophages on free radical production and phagocytic functions. Med Microbiol Immunol. 2006; 195: 143–150.Górski A., Jończyk-Matysiak E., Łusiak- Szelachowska M., et al. Phage therapy in allergic disorders? Exp Biol Med (Maywood). 2018; 243 (6): 534–537.Górski A., Jończyk-Matysiak E., Łusiak- Szelachowska M., et al. Phage therapy in allergic disorders? Exp Biol Med (Maywood). 2018; 243 (6): 534–537.Górski A., Dąbrowska K., Międzybrodzki R., et al. Phages and immunomodulation. Future Microbiol. 2017; 12: 905–914.Górski A., Dąbrowska K., Międzybrodzki R., et al. Phages and immunomodulation. Future Microbiol. 2017; 12: 905–914.Górski A., Jończyk-Matysiak E., Łusiak- Szelachowska M., et al. The Potential of Phage Therapy in Sepsis. Front Immunol. 2017; 8: 1783.Górski A., Jończyk-Matysiak E., Łusiak- Szelachowska M., et al. The Potential of Phage Therapy in Sepsis. Front Immunol. 2017; 8: 1783.Chang R. Y. K., Morales S., Okamoto Y., Chan H. K. Topical application of bacteriophages for treatment of wound infections. Transl Res. 2020; 220: 153–166.Chang R. Y. K., Morales S., Okamoto Y., Chan H. K. Topical application of bacteriophages for treatment of wound infections. Transl Res. 2020; 220: 153–166.Myelnikov D. An Alternative Cure: The Adoption and Survival of Bacteriophage Therapy in the USSR, 1922–1955. J Hist Med Allied Sci. 2018; 73 (4): 385–411.Myelnikov D. An Alternative Cure: The Adoption and Survival of Bacteriophage Therapy in the USSR, 1922–1955. J Hist Med Allied Sci. 2018; 73 (4): 385–411.Chanishvili N. Bacteriophages as Therapeutic and Prophylactic Means: Summary of the Soviet and Post Soviet Experiences. Curr Drug Deliv. 2016; 13 (3): 309–323.Chanishvili N. Bacteriophages as Therapeutic and Prophylactic Means: Summary of the Soviet and Post Soviet Experiences. Curr Drug Deliv. 2016; 13 (3): 309–323.Verbeken G., Huys I., Pirnay J. P., et al. Taking bacteriophage therapy seriously: a moral argument. Biomed Res Int. 2014; 2014: 621316.Verbeken G., Huys I., Pirnay J. P., et al. Taking bacteriophage therapy seriously: a moral argument. Biomed Res Int. 2014; 2014: 621316.FDA разрешило применение бактериофагов у больных COVID-19. Phagex. Фагопрепараты и фаготерапия.FDA разрешило применение бактериофагов у больных COVID-19. Phagex. Фагопрепараты и фаготерапия.Pirnay J. P., Verbeken G., Ceyssens P. J., et al. The Magistral Phage. Viruses. 2018; 10: 64.FDA allows phage therapy for COVID19 patients = FDA razreshilo primeneniye bakteriofagov u bol’nykh COVID-19. Phagex. Fagopreparaty i fagoterapiya. (In Russ.) https://bacteriophages.info/ru/news/fda-razreshiloprimenenie-bakteriofagov-u-bolnyh-covid-19.Schooley R. T., Biswas B., Gill J. J., et al. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection Antimicrob Agents Chemother. 2017; 61 (10): e00954–e00917.Pirnay J. P., Verbeken G., Ceyssens P. J., et al. The Magistral Phage. Viruses. 2018; 10: 64.Duplessis C., Biswas B., Hanisch B., et al. Refractory Pseudomonas Bacteremia in a 2-Year-Old Sterilized by Bacteriophage Therapy. J Pediatric Infect Dis Soc. 2018; 7 (3): 253–256.Schooley R. T., Biswas B., Gill J. J., et al. Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection Antimicrob Agents Chemother. 2017; 61 (10): e00954–e00917.Vogt D., Sperling S., Tkhilaishvili T., et al. Beyond antibiotic therapy – Future antiinfective strategies – Update 2017. Unfallchirurg. 2017; 120 (7): 573–584.Duplessis C., Biswas B., Hanisch B., et al. Refractory Pseudomonas Bacteremia in a 2-Year-Old Sterilized by Bacteriophage Therapy. J Pediatric Infect Dis Soc. 2018; 7 (3): 253–256.Oechslin F., Piccardi P., Mancini S., et al. Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence. J Infect Dis. 2017; 215: 703–712.Vogt D., Sperling S., Tkhilaishvili T., et al. Beyond antibiotic therapy – Future antiinfective strategies – Update 2017. Unfallchirurg. 2017; 120 (7): 573–584.Valério N., Oliveira C., Jesus V., et al. Effects of single and combined use of bacteriophages and antibiotics to inactivate Escherichia coli. Virus Res. 2017; 240: 8–17.Oechslin F., Piccardi P., Mancini S., et al. Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence. J Infect Dis. 2017; 215: 703–712.Ryan E. M., Alkawareek M. Y., Donnelly R. F., Gilmore B. F. Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro. FEMS Immunol Med Microbiol. 2012; 65: 395–398.Valério N., Oliveira C., Jesus V., et al. Effects of single and combined use of bacteriophages and antibiotics to inactivate Escherichia coli. Virus Res. 2017; 240: 8–17.Chaudhry W. N., Concepción-Acevedo J., Park T., et al. Synergy and order effects of antibiotics and phages in killing Pseudomonas aeruginosa biofilms. PLoS ONE. 2017; 12: e0168615.Ryan E. M., Alkawareek M. Y., Donnelly R. F., Gilmore B. F. Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro. FEMS Immunol Med Microbiol. 2012; 65: 395–398.Marza J. A., Soothill J. S., Boydell P., Collyns T. A. Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns. 2006; 32 (5): 644–646.Chaudhry W. N., Concepción-Acevedo J., Park T., et al. Synergy and order effects of antibiotics and phages in killing Pseudomonas aeruginosa biofilms. PLoS ONE. 2017; 12: e0168615.Melo L. D. R., Oliveira H., Pires D. P., et al. Phage therapy efficacy: a review of the last 10 years of preclinical studies. Crit Rev Microbiol. 2020; 46 (1): 78–99.Marza J. A., Soothill J. S., Boydell P., Collyns T. A. Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns. 2006; 32 (5): 644–646.Freyberger H. R., He Y., Roth A. L., et al. Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro. Viruses. 2018; 10(11): 617.Melo L. D. R., Oliveira H., Pires D. P., et al. Phage therapy efficacy: a review of the last 10 years of preclinical studies. Crit Rev Microbiol. 2020; 46 (1): 78–99.Regeimbal J. M., Jacobs A. C., Corey B. W., et al. Personalized Therapeutic Cocktail of Wild Environmental Phages Rescues Mice from Acinetobacter baumannii Wound Infections. Antimicrob Agents Chemother. 2016; 60 (10): 5806–5816.Freyberger H. R., He Y., Roth A. L., et al. Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro. Viruses. 2018; 10(11): 617.Jault P., Leclerc T., Jennes S., et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis. 2019; 19 (1): 35–45.Regeimbal J. M., Jacobs A. C., Corey B. W., et al. Personalized Therapeutic Cocktail of Wild Environmental Phages Rescues Mice from Acinetobacter baumannii Wound Infections. Antimicrob Agents Chemother. 2016; 60 (10): 5806–5816.Kaur P., Gondil V. S., Chhibber S. A novel wound dressing consisting of PVA-SA hybrid hydrogel membrane for topical delivery of bacteriophages and antibiotics. Int J Pharm. 2019; 572: 118779.Jault P., Leclerc T., Jennes S., et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect Dis. 2019; 19 (1): 35–45.Dąbrowska K., Abedon S.T. Pharmacologically Aware Phage Therapy: Pharmacodynamic and Pharmacokinetic Obstacles to Phage Antibacterial Action in Animal and Human Bodies. Microbiol Mol Biol Rev. 2019; 83 (4): e00012–e00019.Kaur P., Gondil V. S., Chhibber S. A novel wound dressing consisting of PVA-SA hybrid hydrogel membrane for topical delivery of bacteriophages and antibiotics. Int J Pharm. 2019; 572: 118779.Pinto A. M., Cerqueira M. A., Bañobre-Lópes M., et al. Bacteriophages for Chronic Wound Treatment: from Traditional to Novel Delivery Systems. Viruses. 2020; 12 (2): 235.Dąbrowska K., Abedon S.T. Pharmacologically Aware Phage Therapy: Pharmacodynamic and Pharmacokinetic Obstacles to Phage Antibacterial Action in Animal and Human Bodies. Microbiol Mol Biol Rev. 2019; 83 (4): e00012–e00019.Lin P., Pu Q., Shen G., et al. CdpR Inhibits CRISPR-Cas Adaptive Immunity to Lower Anti-viral Defense while Avoiding Self-Reactivity. iScience. 2019; 13: 55–68.Pinto A. M., Cerqueira M. A., Bañobre-Lópes M., et al. Bacteriophages for Chronic Wound Treatment: from Traditional to Novel Delivery Systems. Viruses. 2020; 12 (2): 235.Yin S., Huang G., Zhang Y., et al. Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii. Cell Physiol Biochem. 2017; 44 (6): 2337–2345.Lin P., Pu Q., Shen G., et al. CdpR Inhibits CRISPR-Cas Adaptive Immunity to Lower Anti-viral Defense while Avoiding Self-Reactivity. iScience. 2019; 13: 55–68.Wang R., Xing S., Zhao F., et al. Characterization and genome analysis of novel phage vB_EfaP_IME195 infecting Enterococcus faecalis. Virus Genes. 2018; 54 (6): 804–811.Yin S., Huang G., Zhang Y., et al. Phage Abp1 Rescues Human Cells and Mice from Infection by Pan-Drug Resistant Acinetobacter Baumannii. Cell Physiol Biochem. 2017; 44 (6): 2337–2345.Deng L. Y., Yang Z. C., Gong Y.L., et al. Therapeutic effect of phages on extensively drug-resistant Acinetobacter baumannii-induced sepsis in mice. Zhonghua Shao Shang Za Zhi. 2016; 32 (9): 523–528.Wang R., Xing S., Zhao F., et al. Characterization and genome analysis of novel phage vB_EfaP_IME195 infecting Enterococcus faecalis. Virus Genes. 2018; 54 (6): 804–811.Yang Z. C., Deng L. Y., Gong Y. L., et al. Inventory building of phages against extensively drug-resistant Acinetobacter baumannii isolated from wounds of patients with severe burn and related characteristic analysis. Zhonghua Shao Shang Za Zhi. 2016; 32 (9): 517–522.Deng L. Y., Yang Z. C., Gong Y.L., et al. Therapeutic effect of phages on extensively drug-resistant Acinetobacter baumannii-induced sepsis in mice. Zhonghua Shao Shang Za Zhi. 2016; 32 (9): 523–528.Gelman D., Eisenkraft A., Chanishvili N., et al. The history and promising future of phage therapy in the military service. J Trauma Acute Care Surg. 2018; 85 (1S Suppl 2): S18–S26.Yang Z. C., Deng L. Y., Gong Y. L., et al. Inventory building of phages against extensively drug-resistant Acinetobacter baumannii isolated from wounds of patients with severe burn and related characteristic analysis. Zhonghua Shao Shang Za Zhi. 2016; 32 (9): 517–522.Gelman D., Eisenkraft A., Chanishvili N., et al. The history and promising future of phage therapy in the military service. J Trauma Acute Care Surg. 2018; 85 (1S Suppl 2): S18–S26.Gelman D., Eisenkraft A., Chanishvili N., et al. The history and promising future of phage therapy in the military service. J Trauma Acute Care Surg. 2018; 85 (1S Suppl 2): S18–S26.

The authors declare that there are no conflicts of interest present.