Using of topical bacterial lysates in modern clinical practice

Acute and chronic infectious and inflammatory diseases of the upper respiratory tract occupy a leading position in the structure of the pathology of the world’s population and remain the most frequent reason for patients seeking medical care. The prevalence and frequency of this disease in this nosological group makes a decisive contribution to the structure of the causes of temporary disability, which entails significant negative social and economic consequences. In this aspect, the spread of resistance of pathogens to etiotropic drugs and the insufficient arsenal of pathogenetic drugs stimulate the medical community to search for alternative approaches to the treatment of patients with respiratory pathology. One of these therapeutic areas is the use of immunomodulators, the most commonly used group of which are bacterial lysates. In the modern literature, sufficiently convincing data have been accumulated on the effectiveness of the use of bacterial lysates of systemic action, as a result of which the immune cells of the gastrointestinal tract are activated, which in turn leads to the restoration of autoregulation of the immune response throughout the body, and a decrease in the frequency of infectious and allergic diseases. The latest developments of domestic pharmacologists are topical bacterial lysates, the principle of which is based on the local activation of mucosal immunity in the respiratory tract. The undoubted advantage is that bacterial lysates, with all their effectiveness, do not harm the human microbiome, practically do not cause side reactions, combine well with other drugs, and can also be used at any stage of the disease, including for prophylactic purposes.

1. Namazova L.S., Voznesenskaya N.I., Efendieva K.E., Torshkhoeva R.M. The use of Imudon in children with acute respiratory infection. Pediatricheskaya pharmacologiya = Pediatric Pharmacology. 2003;1(3):83–87. (In Russ.) Available at: https://elibrary.ru/item.asp?id=18838906.

2. Shakhnazarova M.D., Kolosova N.G. Bacterial lysates in the treatment and prevention of acute respiratory infections in children. Pediatriya (Pril. k zhurnalu Consilium Medicum) = Pediatrics (Suppl. Consilium Medicum). 2018;(3):40–44. (In Russ.) Available at: https://cyberleninka.ru/article/n/bakterialnye-lizaty-v-lechenii-i-profilaktike-ostryh-respiratornyh-infektsiyu-detey.

3. Cazzola M., Anapurapu S., Page C.P. Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: A meta-analysis. Pulm Pharmacol Ther. 2012;25(1):62–68. doi: 10.1016/j.pupt.2011.11.002.

4. Ljubin-Sternak S., Marijan T., Ivković-Jureković I., Čepin-Bogović J., Gagro A., Vraneš J. Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons. J Pathog. 2016;2168780. doi: 10.1155/2016/2168780.

5. Shestakova I.V., Malyshev N.A., Lebedev V.V., Sologub T.V. Acute respiratory viral infections in adults: clinical guidelines. Moscow; Natsional’noye nauchnoye obshchestvo infektsionistov; 2014. 69 p. (In Russ.) Available at: https://nnoi.ru/uploads/files/protokoly/ORVI_adult.pdf.

6. Cardinale F., Lombardi E., Rossi O., Bagnasco D., Bellocchi A., Menzella F. Epithelial dysfunction, respiratory infections and asthma: the importance of immunomodulation. A focus on OM-85. Expert Rev Respir Med. 2020;14(10):1019–1026. doi: 10.1080/17476348.2020.1793673.

7. Sukhovetskaya V.F., Dondurey E.A., Drinevskiy V.P., Sominina A.A., Mayorova V.G., Pisareva M.M. et al. Laboratory diagnostics acute respiratory virus infections under evolutionary variability influenza viruses. Zhurnal infektologii = Journal of Infectology. 2012;4(1):36–41. (In Russ.) Available at: https://journal.niidi.ru/jofin/article/view/83#.

8. Liskova E.V. Clinical picture of influenza at the present period. Meditsinskiy almanakh = Medical Almanac. 2011;(4):110–112. (In Russ.) Available at: https://elibrary.ru/item.asp?id=16376330.

9. Villa E., Garelli V., Braido F., Melioli G., Canonica G.W. May We Strengthen the Human Natural Defenses with Bacterial Lysates? World Allergy Organ J. 2010;3(2 Suppl.):S17-S23. doi: 10.1186/1939-4551-3-S2-S17.

10. McCarthy E.F. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154–158. Available at: https://ncbi.nlm.nih.gov/pmc/articles/PMC1888599.

11. Rozy A., Chorostowska-Wynimko J. Bacterial immunostimulants – Mechanism of action and clinical application in respiratory diseases. Pneumonol Alergol Pol. 2008;76:353–359. Available at: https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/27879/22693.

12. Kearney S.C., Dziekiewicz M., Feleszko W. Immunoregulatory and immunostimulatory responses of bacterial lysates in respiratory infections and asthma. Ann Allergy, Asthma Immunol 2015;114(5):364–369. doi: 10.1016/j.anai.2015.02.008.

13. Rychkova T.I., Borisova T.L. The use of imudon in children with bronchoobstructive syndrome. Voprosy sovremennoi pediatrii = Current Pediatrics. 2006;5(1):505a. (In Russ.) Available at: https://elibrary.ru/item.asp?id=12934553.

14. Yakovlev A.B., Savenkov V.V. Actinolizat in the treatment of the purulentinflamatory processes of the skin and subcutaneous tissues: history and prospects. Rossiyskiy zhurnal kozhnykh i venericheskikh bolezney = Russian Journal of Skin and Venereal Diseases. 2016;19(6):354–358. (In Russ.) doi: 10.18821/1560-9588-2016-19-6-354-358.

15. Marengo R., Ortega Martell J.A., Esposito S. Paediatric Recurrent Ear, Nose and Throat Infections and Complications: Can We Do More? Infect Dis Ther. 2020;9:275–290. doi: 10.1007/s40121-020-00289-3.

16. Gumerova M.I., Aznabaeva L.F., Arefieva N.A., Chemikosova T.S., Khusnarizanova R.F. Microbiological evaluation of the effectiveness of the use of bacterial lysates (Imudon) in the complex treatment of chronic generalized periodontitis. Problemy stomatologii = Actual Problems in Dentistry. 2008;(2):15–19. (In Russ.) Available at: https://elibrary.ru/item.asp?id=25918572.

17. Ahumada-Cota R.E., Hernandez-Chiñas U., Milián-Suazo F., ChávezBerrocal M.E., Navarro-Ocaña A., Martínez-Gómez D. et al. Effect and analysis of bacterial lysates for the treatment of recurrent urinary tract infections in adults. Pathogens. 2020;9(2):102. doi: 10.3390/pathogens9020102.

18. Jurkiewicz D., Zielnik-Jurkiewicz B. Bacterial lysates in the prevention of respiratory tract infections. Otolaryngol Pol. 2018;72(5):1–8. doi: 10.5604/01.3001.0012.7216.

19. Lau S. Bacterial lysates in food allergy prevention. Curr Opin Allergy Clin Immunol. 2013;13(3):293–295. doi: 10.1097/ACI.0b013e328360ede9.

20. Zaplatnikov A.L., Girina A.A., Lepiseva I.V., Svintsitskaya V.I. Topical bacterial lysates in pediatric practice. Farmateka. 2020;(9):31–37. (In Russ.) doi: 10.18565/pharmateca.2020.9.31-37.

21. Markova T.P., Yarilina L.G., Chuvirov D.G., Chuvirova A.G., Kim M.N. Bacterial lysates in pediatrics. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatria. Journal named after G.N. Speransky. 2016;95(5):91–98. (In Russ.) Available at: https://pediatriajournal.ru/files/upload/mags/354/2016_5_4728.pdf.

22. Cazzola M., Capuano A., Rogliani P., Matera M.G. Bacterial lysates as a potentially effective approach in preventing acute exacerbation of COPD. Curr Opin Pharmacol. 2012;12(3):300–308. doi: 10.1016/j.coph.2012.01.019.

23. D’Alò G.L., Zorzoli E., Loria A., Terracciano E., Zaratti L., Franco E. Bacterial lysates: history and availability. Ig Sanita Pubbl. 2017;73(4):381–396. (In Italian) Available at: https://pubmed.ncbi.nlm.nih.gov/29099828/.

24. Sydora B.C., Martin S.M., Lupicki M., Dieleman L.A., Doyle J., Walker J.W. et al. Bacterial antigens alone can influence intestinal barrier integrity, but live bacteria are required for initiation of intestinal inflammation and injury. Inflamm Bowel Dis. 2006;12(6):429–436. doi: 10.1097/00054725-200606000-00001.

25. Gubanova S.G., Pivneva N.D. Some aspects of the treatment of oropharyngeal diseases with topical immunomodulators. Voprosy sovremennoy pediatrii = Current Pediatrics. 2012;11(1):173–176. (In Russ.) doi: 10.15690/vsp.v11i1.152.

26. Parola C., Salogni L., Vaira X., Scutera S., Somma P., Salvi V. et al. Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway. PLoS ONE. 2013;8(12):e82867. doi: 10.1371/journal.pone.0082867.

27. Guaní-Guerra E., Negrete-García M.C., Montes-Vizuet R., Asbun-Bojalil J., Terán L.M. Human β-defensin-2 induction in nasal mucosa after administration of bacterial lysates. Arch Med Res. 2011;42(3):189–194. doi: 10.1016/j.arcmed.2011.04.003.

28. Liu C., Huang R., Yao R., Yang A. The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma. Lung. 2017;195:563–569. doi: 10.1007/s00408-017-0003-8.

29. Savenkova M., Afans’eva A., Minasyan V., Tyurkina S. Prophylaxis and treatment of respiratory diseases and frequently ailing children with topical bacterial lysates. Voprosy sovremennoy pediatrii = Current Pediatrics. 2009;8(6):92–96. (In Russ.) Available at: https://cyberleninka.ru/article/n/profilaktika-i-lechenie-respiratornyh-zabolevaniy-u-chasto-boleyuschihdetey-topicheskimi-bakterialnymi-lizatami.

30. Coviello S., Wimmenauer V., Polack F.P., Irusta P.M. Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4. Hum Vaccin Immunother. 2014;10(10):2896– 2902. doi: 10.4161/hv.29784.

31. Béné M.C., Kahl L., Perruchet A.M., Hermes H., Mösges M., Normier G. et al. Bacterial lysates and ribosomes as inducers of specific immune responses: a comparative study. Scand J Immunol. 1993;38(5):496–498. doi: 10.1111/j.1365-3083.1993.tb02594.x.

32. Liu Y.-W., Dong S.-H., Zhan G.-Y., Tan H.-Z., Peng Y.-Q., Wei F. Analysis of the effect of bacterial lysate and the immunologic mechanism in treating infant bronchiolitis. Eur Rev Med Pharmacol Sci. 2017;21:3332–3336. Available at: http://www.europeanreview.org/wp/wp-content/uploads/3332-3336-Effect-of-bacterial-lysate-and-the-immunologic-mechanism-in-treating-bronchiolitis.pdf.

33. Brunetti L., Francavilla R., Tesse R., Fiermonte P., Dambra P., Massagli M. et al. Effects of oral bacterial immunotherapy in children with atopic eczema/dermatitis syndrome: a pilot study. BioDrugs. 2005;19:393–399. doi: 10.2165/00063030-200519060-00006.

34. Luchikhin L.A., Malchenko O.V. The effectiveness of the drug Imudon in the treatment of patients with acute and chronic inflammatory diseases of the pharynx. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2001;(3):62–64. (In Russ.) Available at: https://medi.ru/info/8747/.

35. Kalyuzhin O.V. Topical bacterial lysates in the prevention and treatment of respiratory infections. Practicheskaya meditsina = Practical Medicine. 2016;(2-2):69–75. (In Russ.) Available at: http://pmarchive.ru/topicheskiebakterialnye-lizaty-v-profilaktike-i-lechenii-respiratornyx-infekcij/.

36. Suárez N., Ferrara F., Rial A., Dee V., Chabalgoity J.A. Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation. Front Bioeng Biotechnol. 2020;8:545. doi: 10.3389/fbioe.2020.00545.

37. Kryshen K.L., Kukharenko A.E., Vichare A.S., Gaidai E.A., Kryshen A.A., Gushchin Y.A. et al. Anti-inflammatory and immunomodulating effects of the bacterial lysate in the in vivo models of aseptic lymphadenitis and pneumococcal pneumonia. Meditsinskaya immunologiya = Medical Immunology (Russia). 2020;22(1):111–122. (In Russ.) doi: 10.15789/1563-0625-AAI-1758.

38. Shchubelko R.V., Zuikova I.N., Shuljenko A.E. Mucosal immunity of the upper respiratory tract. Immunologiya = Immunology. 2018;39(1):81–88. (In Russ.) Available at: https://elibrary.ru/item.asp?id=34902273.

39. Kladova O.V., Kornyushin M.A., Legkova T.P., Ryzhova E.A., Zemskova L.A., Butakova E.P. et al. Clinical efficacy of Imudon in patients with tonsillopharyngitis on the background of acute respiratory diseases. Detskie infektsii = Children Infections. 2005;4(1):53–57. (In Russ.) Available at: https://elibrary.ru/item.asp?id=12849639.

40. Garib F.Yu., Rizopulu A.P. Interactions of pathogenic bacteria with innate immune reactions of host. Infektsiya i immunitet = Russian Journal of Infection and Immunity. 2012;2(3):581–596. (In Russ.) doi: 10.15789/2220-7619-2012-3-581-596.

41. Akulich I.I., Lopatin A.S. Therapy of Imudon after tonsillectomy. Vestnik otorinolaringologii = Bulletin of Otorhinolaryngology. 2006;(6):57–58. (In Russ.).

42. Namazova-Baranova L., Privalova T., Shadrin S. Topical immunomodulators: from rhinitis treatment to collective prophylactics of acute and chronic pathology. Voprosy sovremennoy pediatrii = Current Pediatrics. 2011;10(5):32–38. (In Russ.) Available at: https://vsp.spr-journal.ru/jour/article/view/664.

43. Kladova O.V., Uchaikin V.F., Demina E.D., Legkova T.P., Kornyushin M.A. Local immunomodulator IRS-19 in the complex therapy of acute respiratory infections. Detskie infektsii = Children Infections. 2006;5(4):51–54. (In Russ.) Available at: https://elibrary.ru/item.asp?id=11790499.

44. Mora R., Salzano F.A., Mora E., Guastini L. Efficacy of a topical suspension of bacterial antigens for the management of chronic suppurative otitis media. Eur Arch Otorhinolaryngol. 2012;269:1593–1597. doi: 10.1007/s00405-011-1816-3.

45. Cao C., Wang J., Li Y., Li Y., Ma L., Abdelrahim M.E. A., Zhu Y. Efficacy and safety of OM-85 in paediatric recurrent respiratory tract infections which could have a possible protective effect on COVID-19 pandemic: A metaanalysis. Int J Clin Pract. 2021;e13981. doi: 10.1111/ijcp.13981.

46. De Boer G.M., Żółkiewicz J., Strzelec K.P., Ruszczyński M., Hendriks R.W., Braunstahl G.J. et al. Bacterial lysate therapy for the prevention of wheezing episodes and asthma exacerbations: A systematic review and metaanalysis. Eur Respir Rev. 2020;29:190175. doi: 10.1183/16000617.0175-2019.

47. Korovina N.A., Lepiseva I.V., Zaplatnikova L.V., Suzdalenkov A.V., Ivanov V.A. Efficiency of topical immunotherapy with bacterial lysates in frequently ill children. Pediatriya = Pediatria. 2009;88(5):104–109. (In Russ.) Available at: https://pediatriajournal.ru/archive?show=300§ion=2499.

48. Taranushenko T.E., Artemova S.Yu., Goncharuk Z.N. Preventive efficacy of topical application of the bacterial lysates mixture among the healthy children from organized collectives. Voprosy sovremennoy pediatrii = Current Pediatrics. 2007;6(5):61–64. (In Russ.) Available at: https://vsp.sprjournal.ru/jour/article/view/1282.

49. Artemova S., Taranushenko T., Goncharuk Z. Effectiveness of topical bacterial lysates in treatment of acute respiratory infections in younger schoolchildren in organized groups. Voprosy sovremennoy pediatrii = Current Pediatrics. 2008;7(6):118–121. (In Russ.) Available at: https://vsp.spr-journal.ru/jour/article/view/1490.

50. Tyurkina S.I., Minasyan V.S., Savenkova M.S., Kitaigorodsky A.P., Ovechkina N.V., Katz T.G., Lapshina T.A. Treatment and prevention of adenoiditis with bacterial lysates in sickly children. Detskie infektsii = Children Infections. 2013;12(1):26–30. (In Russ.) doi: 10.22627/2072-8107-2013-12-1-26-30.

51. Garashchenko T., Volodarskaya V. Bacterial lysates mixture for the topical administration in prophylaxis and treatment of chronic tonsillitis in children. Voprosy sovremennoy pediatrii = Current Pediatrics. 2009;8(6):109–112. (In Russ.) Available at: https://vsp.spr-journal.ru/jour/article/view/1203/0.