Применение фаготерапии в лечении ожоговых больных (обзор)

После выхода больного из состояния ожогового шока ведущей проблемой, замедляющей процессы выздоровления и являющейся основной причиной летального исхода, по праву считаются местные инфекционные осложнения. После нарушения целостности кожного покрова микроорганизмы беспрепятственно проникают во внутреннюю среду макроорганизма, вызывая развитие септического состояния с полиорганной недостаточностью. Широкое и зачастую бесконтрольное применение антибактериальных препаратов в лечебной практике приводит к появлению у микроорганизмов множественной лекарственной устойчивости (multiple drug resistance — MDR).

В последнее время все большее значение приобретает введение в практическую деятельность препаратов, изготовленных на основе бактериофагов. Это подтверждается ростом интереса к данной области фармакологии, разработкой специальных программ, направленных на изучение процессов взаимодействия фага с бактериальной клеткой.

В обзоре представлены основные виды бактерий, отнесенных к группе MDR-патогенов, факторы риска заражения пациентов. Демонстрируются механизмы избирательного действия частиц фага на бактериальную клетку, возможности применения фаготерапии в лечении ожоговой травмы (экспериментальные и клинические данные), раскрываются новые положительные свойства фагов, связанные с изменениями в иммунном статусе макроорганизма при взаимодействии с частицами бактериофагов.

1. Saaiq M., Zaib S., Ahmad S. Early excision and grafting versus delayed excision and grafting of deep thermal burns up to 40% total body surface area: a comparisonofoutcome. Ann Burns Fire Disasters 2012; 25(3): 143–147.
2. Сахаров С.П., Иванов В.В., Шень Н.П., Сучков Д.В. Летальные исходы ожоговой болезни у детей: 189 летний опыт работы. Скорая медицинская помощь 2011; 12(3): 52–57.
3. Boissin C., Wallis L.A., Kleintjes W., Laflamme L. Admission factors associated with the in-hospital mortality of burns patients in resource-constrained settings: a two-year retrospective investigation in a South African adult burns centre. Burns 2019; 45(6): 1462–1470, https://doi.org/10.1016/j.burns.2019.03.005.
4. Brusselaers N., Monstrey S., Snoeij T., Vandijck D., Lizy C., Hoste E., Lauwaert S., Colpaert K., Vandekerckhove L., Vogelaers D., Blot S. Morbidity and mortality of bloodstream infections in patients with severe burn injury. Am J CritCare 2010; 19(6): e81-e87, https://doi.org/10.4037/ajcc2010341.
5. Wang T.H., Yeh Y.Н., Pu C. Excess mortality reduction given a “reduce patient mortality at all costs” scenario for mass burn casualties. Burns 2019; 45(6): 1477–1482, https://doi.org/10.1016/j.burns.2019.04.009.
6. Tan Chor Lip H., Tan J.H., Thomas M., Imran F.H., Azmah Tuan Mat T.N. Survival analysis and mortality predictors of hospitalized severe burn victims in a Malaysian burns intensive care unit. Burns Trauma 2019; 7: 3, https://doi.org/10.1186/s41038-018-0140-1.
7. Rex S. Burn injuries. Curr Opin Crit Care 2012; 18(6): 671–676, https://doi.org/10.1097/mcc.0b013e328359fd6e.
8. Manning J. Sepsis in the burn patient. Crit Care Nurs Clin North Am 2018; 30(3): 423–430, https://doi.org/10.1016/j.cnc.2018.05.010.
9. Tridente A. Sepsis 3 and the burns patient: do we need Sepsis 3.1? Scars Burn Heal 2018; 4: 2059513118790658, https://doi.org/10.1177/2059513118790658.
10. Safiri S., Ashrafi-Asgarabad A. Platelet count: a predictor of sepsis and mortality in severe burns; methodological issues. Burns 2018; 44(3): 728–729, https://doi.org/10.1016/j.burns.2017.10.027.
11. The bacterial challenge: time to react. ECDC/EMEA joint technical report. 2009. URL: https://www.ecdc.europaeu/sites/portal/files/ media/en/publications/Publications/0909_TER_ The_Bacterial_Challenge_Time_to_React.pdf.
12. Zhang W.L., Huang J., Wu S.Y., Liu Y., Long F., Xiao Y.L., Xie Y., He C., Kang M. Antibiotic resistance and risk factors for mortality of blood stream infections (BSIs) with Escherichia coli in patients with hematological malignancies. Sichuan Da Xue Xue Bao Yi Xue Ban 2018; 49(1): 133–135.
13. Weintrob A.C., Murray C.K., Xu J., Krauss M., Bradley W., Warkentien T.E., Lloyd B.A., Tribble D.R. Early infections complicating the care of combat casualties from Iraq and Afghanistan. Surg Infect (Larchmt) 2018; 19(3): 286–297, https://doi.org/10.1089/sur.2017.240.
14. van Langeveld I., Gagnon R.C., Conrad P.F., Gamelli R.L., Martin B., Choudhry M.A., Mosier M.J. Multiple-drug resistance in burn patients: a retrospective study on the impact of antibiotic resistance on survival and length of stay. J Burn Care Res 2017; 38(2): 99–105, https://doi.org/10.1097/bcr.0000000000000479.
15. 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, https://doi.org/10.1016/j.ijpharm.2019.118779.
16. Machowska A., Stålsby Lundborg C. Drivers of irrational use of antibiotics in Europe. Int J Environ Res Public Health 2018; 16(1): 27, https://doi.org/10.3390/ijerph16010027.
17. Munier A.L., Biard L., Rousseau C., Legrand M., Lafaurie M., Lomont A., Molina J.M. Incidence, risk factors, and outcome of multidrug-resistant Acinetobacter baumannii acquisition during an outbreak in a burns unit. J Hosp Infect 2017; 97(3): 226–233, https://doi.org/10.1016/j.jhin.2017.07.020.
18. Van Boeckel T.P., Brower C., Gilbert M., Grenfell B.T., Levin S.A., Robinson T.P., Teillant A., Laxminarayan R. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci U S A 2015; 112(18): 5649–5654, https://doi.org/10.1073/pnas.1503141112.
19. Alumran A., Hou X.Y., Hurst C.J. Validity and reliability of instruments designed to measure factors influencing the overuse of antibiotics. J Infect Public Health 2012; 5(3): 221–232, https://doi.org/10.1016/j.jiph.2012.03.003.
20. Chen Y., Hammer E.E., Richards V.P. Phylogenetic signature of lateral exchange of genes for antibiotic production and resistance among bacteria highlights a pattern of global transmission of pathogens between humans and livestock. Mol Phylogenet Evol 2018; 125: 255–264, https://doi.org/10.1016/j.ympev.2018.03.034.
21. The human microbiome project consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486(7402): 207–214, https://doi.org/10.1038/nature11234.
22. Ani C., Farshidpanah S., Bellinghausen Stewart A., Nguyen H.B. Variations in organism-specific severe sepsis mortality in the United States: 1999–2008. Crit Care Med 2015; 43(1): 65–77, https://doi.org/10.1097/ccm.0000000000000555.
23. Chen K., Lin S., Li P., Song Q., Luo D., Liu T., Lingbing Z., Zhang W. Characterization of Staphylococcus aureus isolated from patients with burns in a regional burn center, southeastern China. BMC Infectious Diseases 2018; 18(1): 51, https://doi.org/10.1186/s12879-018-2955-6.
24. Almyroudis N.G., Fuller A., Jakubowski A., Sepkowitz K., Jaffe D., Small T.N., Kiehn T.E., Pamer E., Papanicolaou G.A. Pre- and post- engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2005; 7(1): 11–17, https://doi.org/10.1111/j.1399-3062.2005.00088.x.
25. Gravante G., Delogu D., Sconocchia G. “Systemic apoptotic response” after thermal burns. Apoptosis 2007; 12(2): 259–270, https://doi.org/10.1007/s10495-006-0621-8.
26. Herruzo Cabrera R., García Torres V., Martínez Ratero S., Denia Lafuente R., Rey Calero J. Risk factors for local infection in burns. Multivariate study. Med Clin (Barc) 1996; 106(3): 91–94.
27. Faunce D.E., Gamelli R.L., Choudhry M.A., Kovacs E.J. A role for CD1d-restricted NKT cells in injury-associated T cell suppression. J Leukoc Bio 2003; 73(6): 747–755, https://doi.org/10.1189/jlb.1102540.
28. Kim E.Y., Oldham W.M. Innate T cells in the intensive care unit. Mol Immunol 2019; 105: 213–223, https://doi.org/10.1016/j.molimm.2018.09.026.
29. Barret J.P., Herndon D.N. Effects of burn wound excision on bacterial colonization and invasion. Plast Reconstr Surg 2003; 111(2): 744–750, https://doi.org/10.1097/01.prs.0000041445.76730.23.
30. Xie Y.J., Zhu L.H., Sun D., Lyu G.Z. Multi-disciplinary cooperative treatment and management experience of 35 patients with extremely severe burns involved in August 2nd Kunshan factory aluminum dust explosion accident. Zhonghua Shao Shang Za Zhi 2019; 35(4): 316–318.
31. Krezalek M.A., Skowron K.B., Guyton K.L., Shakhsheer B., Hyoju S., Alverdy J.C. The intestinal microbiome and surgical disease. Curr Probl Surg 2016; 53(6): 257–293, https://doi.org/10.1067/j.cpsurg.2016.06.001.
32. Ferreira R.L., da Silva B.C., Rezende G.S., Nakamura-Silva R., Pitondo-Silva A., Campanini E.B., Brito M.C.A., da Silva E.M.L., Freire C.C.M., da Cunha A.F., Pranchevicius M.D.S. High prevalence of multidrug-resistant Klebsiella pneumoniae harboring several virulence and β-lactamase encoding genes in a Brazilian intensive care unit. Front Microbiol 2019; 9: 3198, https://doi.org/10.3389/fmicb.2018.03198.
33. Hwang W., Yoon S.S. Virulence characteristics and an action mode of antibiotic resistance in multidrug-resistant Pseudomonas aeruginosa. Sci Rep 2019; 9(1): 487, https://doi.org/10.1038/s41598-018-37422-9.
34. Bahemia I.A., Muganza A., Moore R., Sahid F., Menezes C.N. Microbiology and antibiotic resistance in severe burns patients: a 5 year review in an adult burns unit. Burns 2015; 41(7): 1536–1542, https://doi.org/10.1016/j.burns.2015.05.007.
35. Ojo S.K., Sargin B.O., Esumeh F.I. Plasmid curing analysis of antibiotic resistance in beta-lactamase producing Staphylococci from wounds and burns patients. Pak J Biol Sci 2014; 17(1): 130–133, https://doi.org/10.3923/pjbs.2014.130.133.
36. Plichta J.K., Holmes C.J., Gamelli R.L., Radek K.A. Local burn injury promotes defects in the epidermal lipid and antimicrobial peptide barriers in human autograft skin and burn margin: implications for burn wound healing and graft survival. J Burn Care Res 2017; 38(1): e212–e226, https://doi.org/10.1097/bcr.0000000000000357.
37. Abesamis G.M.M., Cruz J.J.V. Bacteriologic profile of burn wounds at a tertiary government hospital in the Philippines — UP-PGH ATR Burn Center. J Burn Care Res 2019; 40(5): 658–668, https://doi.org/10.1093/jbcr/irz060.
38. Honari S. Topical therapies and antimicrobials in the management of burn wounds. Crit Care Nurs Clin North Am 2004; 16(1): 1–11, https://doi.org/10.1016/j.ccell.2003.09.008.
39. Glasser J.S., Guymon C.H., Mende K., Wolf S.E., Hospenthal D.R., Murray C.K. Activity of topical antimicrobial agents against multidrug-resistant bacteria recovered from burn patients. Burns 2010; 36(8): 1172–1184, https://doi.org/10.1016/j.burns.2010.05.013.
40. Theodorou P., Thamm O.C., Perbix W., Phan V.T. Pseudomonas aeruginosa bacteremia after burn injury: the impact of multiple-drug resistance. J Burn Care Res 2013; 34(6): 649–658, https://doi.org/10.1097/bcr.0b013e318280e2c7.
41. Yali G., Jing C., Chunjiang L., Cheng Z., Xiaoqiang L., Yizhi P. Comparison of pathogens and antibiotic resistance of burn patients in the burn ICU or in the common burn ward. Burns 2014; 40(3): 402–407, https://doi.org/10.1016/j.burns.2013.07.010.
42. Decraene V., Ghebrehewet S., Dardamissis E., Huyton R., Mortimer K., Wilkinson D., Shokrollahi K., Singleton S., Patel B., Turton J., Hoffman P., Puleston R. An outbreak of multidrug-resistant Pseudomonas aeruginosa in a burns service in the North of England: challenges of infection prevention and control in a complex setting. J Hosp Infect 2018; 100(4): 239–245, https://doi.org/10.1016/j.jhin.2018.07.012.
43. Gong Y.L., Yang Z.C., Yin S.P., Liu M.X., Zhang C., Luo X.Q., Peng Y.Z. Analysis of the pathogenic characteristics of 162 severely burned patients with bloodstream infection. Zhonghua Shao Shang Za Zhi 2016; 32(9): 529–535.
44. Dou Y., Zhang Q. Analysis of distribution and drug resistance of pathogens of burn patients during 9 years. Zhonghua Shao Shang Za Zhi 2018; 34(3): 153–159.
45. Mahmoudi H., Pourhajibagher M., Chiniforush N., Soltanian A.R., Alikhani M.Y., Bahador A. Biofilm formation and antibiotic resistance in meticillin-resistant and meticillin-sensitive Staphylococcus aureus isolated from burns. J Wound Care 2019 28(2): 66–73, https://doi.org/10.12968/jowc.2019.28.2.66.
46. Church D., Elsayed S., Reid O., Winston B., Lindsay R. Burn wound infections. Clin Microbiol Rev 2006; 19(2): 403–434, https://doi.org/10.1128/cmr.19.2.403-434.2006.
47. Altoparlak U., Erol S., Akcay M.N., Celebi F., Kadanali A. The time-related changes of antimicrobial resistance patterns and predominant bacterial profiles of burn wounds and body flora of burned patients. Burns 2004; 30(7): 660–664, https://doi.org/10.1016/j.burns.2004.03.005.
48. Hsueh P.R., Teng L.J., Yang P.C., Chen Y.C., Ho S.W., Luh K.T. Persistence of a multidrug-resistant Pseudomonas aeruginosa clone in an intensive care burn unit. J Clin Microbiol 1998; 36(5): 1347–1355.
49. Pirnay J.P., De Vos D., Cochez C., Bilocq F., Pirson J., Struelens M., Duinslaeger L., Cornelis P., Zizi M., Vanderkelen A. Molecular epidemiology of Pseudomonas aeruginosa colonization in a burn unit: persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol 2003; 41(3): 1192–1202, https://doi.org/10.1128/jcm.41.3.1192-1202.2003.
50. Panghal M., Singh K., Kadyan S., Chaudary U., Yadav J.P. The analysis of distribution of multidrug resistant Pseudomonas and Bacillus species from burn patients and burn ward environment. Burns 2015; 41(4): 812–819, https://doi.org/10.1016/j.burns.2014.10.014.
51. Rostami S., Farajzadeh Sheikh A., Shoja S., Farahani A., Tabatabaiefar M.A., Jolodar A., Sheikhi R. Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients. J Chin Med Assoc 2018; 81(2): 127–132, https://doi.org/10.1016/j.jcma.2017.08.016.
52. Adebayo O.S., Gabriel Ajobiewe R.A.O., Taiwo M.O., Kayode J.S. Phage therapy: a potential alternative in the treatment of multidrugresistant bacterial infections. J Microbiol Exp 2017; 5(5): 00173, https://doi.org/10.15406/jmen.2017.05.00173.
53. Sevgi M., Toklu A., Vecchio D., Hamblin M.R. Topical antimicrobials for burn infections — an update. Recent Pat Antiinfect Drug Discov 2013; 8(3): 161–197, https://doi.org/10.2174/1574891x08666131112143447.
54. Dedrick R.M., Guerrero-Bustamante C.A., Garlena R.A., Russell D.A., Ford K., Harris K., Gilmour K.C., Soothill J., Jacobs-Sera D., Schooley R.T., Hatfull G.F., Spencer H. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med 2019; 25(5): 730–733, https://doi.org/10.1038/s41591-019-0437-z.
55. Manohar P., Tamhankar A.J., Lundborg C.S., Nachimuthu R. Therapeutic characterization and efficacy of bacteriophage cocktails infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter species. Front Microbiol 2019; 10: 574, https://doi.org/10.3389/fmicb.2019.00574.
56. Patey O., McCallin S., Mazure H., Liddle M., Smithyman A., Dublanchet A. Clinical indications and compassionate use of phage therapy: personal experience and literature review with a focus on osteoarticular infections. Viruses 2018; 11(1): E18, https://doi.org/10.3390/v11010018.
57. 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, https://doi.org/10.1093/jhmas/jry024.
58. Асланов Б.И., Зуева Л.П., Долгий А.А., Люби­мо­ва А.В., Хорошилов В.Ю. Перспективы фаготерапии госпитальных инфекций в условиях формирования антибиотикорезистентности. Инфекция и иммунитет 2012; 2(1–2): 471.
59. Додова Е.Г., Горбунова Е.А., Аполихина И.А. Пост­антибиотиковая эра: бактериофаги как лечебная стратегия. Медицинский совет 2015; 11: 49–53.
60. Есипов А.В., Алехнович А.В., Кисленко А.М., Мар­ке­вич П.С., Зайцев А.Е., Мишина Л.В. Бактериофаги в условиях поглощающей антибиотикорезистентности. Госпи­тальная медицина: наука и практика 2018; 1(2): 39–42.
61. Тапальский Д.В., Козлова А.И. Чувствительность к препаратам бактериофагов клинических изолятов Klebsiella pneumoniae с различными уровнями антибиотикорезистентности. Проблемы здоровья и экологии 2018; 55(1): 56–62.
62. Назаров П.А. Альтернативы антибиотикам: литические ферменты бактериофагов и фаговая терапия. Вестник РГМУ 2018; 1: 5–15.
63. Rehman S., Ali Z., Khan M., Bostan N., Naseem S. The dawn of phage therapy. Rev Med Virol 2019; 29(4): e2041, https://doi.org/10.1002/rmv.2041.
64. Desgranges F., Bochud P.Y., Resch G. Customised infectiology — phage therapy: from theory to clinical evidence. Rev Med Suisse 2019; 15(646): 771–775.
65. Pelfrene E., Willebrand E., Cavaleiro Sanches A., Sebris Z., Cavaleri M. Bacteriophage therapy: a regulatory perspective. J Antimicrob Chemother 2016; 71(8): 2071–2074, https://doi.org/10.1093/jac/dkw083.
66. Cooper I.R. A review of current methods using bacteriophages in live animals, food and animal products intended for human consumption. J Microbiol Methods 2016; 130: 38–47, https://doi.org/10.1016/j.mimet.2016.07.027.
67. Villarreal L.P. Overall issues of virus and host evolution. In: Viruses and the evolution of life. Washington DC: ASM Press; 2005.
68. Górski A., Międzybrodzki R., Weber-Dąbrowska B., Fortuna W., Letkiewicz S., Rogóż P., Jończyk-Matysiak E., Dąbrowska K., Majewska J., Borysowski J. Phage therapy: combating infections with potential for evolving from merely a treatment for complications to targeting diseases. Front Microbiol 2016; 7: 1515, https://doi.org/10.3389/fmicb.2016.01515.
69. Pirnay J.P., Verbeken G., Ceyssens P.J., Huys I., De Vos D., Ameloot C., Fauconnier A. The magistarl phage. Viruses 2018; 10(2): E64, https://doi.org/10.3390/v10020064.
70. Pirnay J.P., Verbeken G., Rose T., Jennes S., Zizi M., Huys I., Lavigne R., Merabishvili M., Vaneechoutte M., Buckling A., De Vos D. Introducing yesterday’s phage therapy in today’s medicine. Future Virol 2012; 7(4): 379–390.
71. Abul-Hassan H.S., El-Tahan k Massoud B., Gomaa R. Bacteriophage therapy of Pseudomonas burn wound sepsis. Annals of the MBC 1990; 3(4): 262–266.
72. Weber-Dabrowska B., Mulczyk M., Górski A. Bacteriophage therapy of bacterial infections: an update of our institute’s experience. Arch Immunol Ther Exp (Warsz) 2000; 48(6): 547–551.
73. Jikia D., Chkhaidze N., Imedashvili E., Mgaloblishvili I., Tsitlanadze G., Katsarava R., Glenn Morris J. Jr., Sulakvelidze A. The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin Exp Dermatol 2005; 30(1): 23–26, https://doi.org/10.1111/j.1365-2230.2004.01600.x.
74. Markoishvili K., Tsitlanadze G., Katsarava R., Morris J.G. Jr., Sulakvelidze A. A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int J Dermatol 2002; 41(7): 453–458, https://doi.org/10.1046/j.1365-4362.2002.01451.x.
75. 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, https://doi.org/10.1016/j.burns.2006.02.012.
76. Rose T., Verbeken G., Vos D.D., Merabishvili M., Vaneechoutte M., Lavigne R., Jennes S., Zizi M., Pirnay J.P. Experimental phage therapy of burn wound infection: difficult first steps. Int J Burns Trauma 2014; 4(2): 66–73.
77. Nationales Forum Phagen. URL: https://nationales-forum-phagen.uni-hohenheim.de/.
78. Huber I., Potapova K., Kuhn A., Schmidt H., Hinrichs J., Rohde C., Beyer W. 1-st German phage symposium — conference report. Viruses 2018; 10(4): E158, https://doi.org/10.3390/v10040158.
79. McVay C.S., Velásquez M., Fralick J.A. Phage therapy of Pseudomonas aeruginosa infection in a mouse burn wound model. Antimicrob Agents Chemother 2007; 51(6): 1934–1938, https://doi.org/10.1128/aac.01028-06.
80. Kumari S., Harjai K., Chhibber S. Efficacy of bacteriophage treatment in murine burn wound infection induced by klebsiella pneumoniae. J Microbiol Biotechnol 2009; 19(6): 622–628.
81. Soothill J.S. Bacteriophage prevents destruction of skin grafts by Pseudomonas aeruginosa. Burns 1994; 20(3): 209–211, https://doi.org/10.1016/0305-4179(94)90184-8.
82. Kumari S., Harjai K., Chhibber S. Bacteriophage versus antimicrobial agents for the treatment of murine burn wound infection caused by Klebsiella pneumoniae B5055. J Med Microbiol 2011; 60(Pt 2): 205–210, https://doi.org/10.1099/jmm.0.018580-0.
83. Golkar Z., Bagasra O., Jamil N. Experimental phage therapy on multiple drug resistant Pseudomonas aeruginosa infection in mice. J Antivir Antiretrovir 2013; S10, https://doi.org/10.4172/jaa.s10-005.
84. Holguín A.V., Rangel G., Clavijo V., Prada C., Mantilla M., Gomez M.C., Kutter E., Taylor C., Fineran P.C., Barrios A.F., Vives M.J. Phage ΦPan70, a putative temperate phage, controls Pseudomonas aeruginosa in planktonic, biofilm and burn mouse model assays. Viruses 2015; 7(8): 4602–4623, https://doi.org/10.3390/v7082835.
85. Hoff-Lenczewska D., Kawecki M., Glik J., Klama-Baryla A., Nowak M. The potential of bacteriophages in the treatment of burn wounds. Pol Przegl Chir 2013; 85(10): 615–618, https://doi.org/10.2478/pjs-2013-0092.
86. Лазарева Е.Б., Смирнов С.В., Хватов В.Б., Спи­ридонова Т.Г., Биткова Е.Е., Дарбеева О.С., Майская Л.М., Парфенюк Р.Л., Меньшиков Д.Д. Эффективность применения бактериофагов в комплексном лечении больных с ожоговой травмой. Антибиотики и химиотерапия 2001; 46(1): 10–14.
87. Chadha P., Katare O.P., Chhibber S. In vivo efficacy of single phage versus phage cocktail in resolving burn wound infection in BALB/c mice. Microb Pathog 2016; 99: 68–77, https://doi.org/10.1016/j.micpath.2016.08.001.
88. Międzybrodzki R., Borysowski J., Weber-Dąbrowska B., Fortuna W., Letkiewicz S., Szufnarowski K., Pawełczyk Z., Rogóż P., Kłak M., Wojtasik E., Górski A. Clinical aspects of phage therapy. Adv Virus Res 2012; 83: 73–121, https://doi.org/10.1016/b978-0-12-394438-2.00003-7.
89. Zimecki M., Artym J., Kocieba M., Weber-Dąbrowska B., Borysowski J., Górski A. Effects of prophylactic administration of bacteriophages to immunosuppressed mice infected with Staphylococcus aureus. BMC Microbiol 2009; 9: 169, https://doi.org/10.1186/1471-2180-9-169.
90. Przerwa A., Zimecki M., Switała-Jeleń K., Dabrowska K., Krawczyk E., Łuczak M., Weber-Dąbrowska B., Syper D., Miedzybrodzki R., Górski A. Effects of bacteriophages on free radical production and phagocytic functions. Med Microbiol Immunol 2006; 195(3): 143–150, https://doi.org/10.1007/s00430-006-0011-4.
91. Górski A., Jończyk-Matysiak E., Łusiak-Szelachowska M., Weber-Dąbrowska B., Międzybrodzki R., Borysowski J. Therapeutic potential of phages in autoimmune liver diseases. Clin Exp Immunol 2018; 192(1): 1–6, https://doi.org/10.1111/cei.13092.
92. Górski A., Jończyk-Matysiak E., Łusiak-Szelachowska M., Międzybrodzki R., Weber-Dąbrowska B., Borysowski J. Phage therapy in allergic disorders? Exp Biol Med (Maywood) 2018; 243(6): 534-537, https://doi.org/10.1177/1535370218755658.
93. Górski A., Dąbrowska K., Międzybrodzki R., Weber-Dąbrowska B., Łusiak-Szelachowska M., Jończyk-Matysiak E., Borysowski J. Phages and immunomodulation. Future Microbiol 2017; 12: 905–914, https://doi.org/10.2217/fmb-2017-0049.
94. Górski A., Jończyk-Matysiak E., Łusiak-Szelachowska M., Międzybrodzki R., Weber-Dąbrowska B., Borysowski J. The potential of phage therapy in sepsis. Front Immunol 2017; 8: 1783, https://doi.org/10.3389/fimmu.2017.01783.
95. Pires D.P., Melo L., Vilas Boas D., Sillankorva S., Azeredo J. Phage therapy as an alternative or complementary strategy to prevent and control biofilm-related infections. Curr Opin Microbiol 2017; 39: 48–56, https://doi.org/10.1016/j.mib.2017.09.004.
96. Sarhan W.A., Azzazy H.M. Apitherapeutics and phage-loaded nanofibers as wound dressings with enhanced wound healing and antibacterial activity. Nanomedicine (Lond) 2017; 12(17): 2055–2067, https://doi.org/10.2217/nnm-2017-0151.
97. Gündoğdu A., Kılıç H., UluKılıç A., Kutateladze M. Susceptibilities of multidrug-resistant pathogens responsible for complicated skin and soft tissue infections to standard bacteriophage cocktails. Mikrobiyol Bul 2016; 50(2): 215–223, https://doi.org/10.5578/mb.24165.
98. Gorski A., Nowaczyk M., Weber-Dabrowska B., Kniotek M., Boratynski J., Ahmed A., Dabrowska K., Wierzbicki P., Switala-Jelen K., Opolski A. New insights into the possible role of bacteriophages in transplantation. Transplant Proс 2003; 35(6): 2372–2373, https://doi.org/10.1016/s0041-1345(03)00811-x.
99. Kutateladze M., Adamia R. Bacteriophages as potential new therapeutics to replace or supplement antibiotics. Trends Biotechnol 2010; 28(12): 591–595, https://doi.org/10.1016/j.tibtech.2010.08.001.
100. Jault P., Leclerc T., Jennes S., Pirnay J.P., Que Y.A., Resch G., Rousseau A.F., Ravat F., Carsin H., Le Floch R., Schaal J.V., Soler C., Fevre C., Arnaud I., Bretaudeau L., Gabard J. 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, https://doi.org/10.1016/s1473-3099(18)30482-1.

Leontyev А.E., Pavlenko I.V., Kovalishena О.V., Saperkin N.V., Tulupov А.А., Beschastnov V.V. Application of Phagotherapy in the Treatment of Burn Patients (Review). Sovremennye tehnologii v medicine 2020; 12(3): 95, https://doi.org/10.17691/stm2020.12.3.12