EFFECT OF THE ANTIVIRAL DRUG KAGOCEL® ON THE LEVELS OF MATRIX METALLOPROTEINASES MMP-8 AND MMP-9 AND THEIR TISSUE INHIBITORS TIMP-1 AND TIMP-2 IN INDUCED SPUTUM IN THE COMBINED TREATMENT OF COMMUNITY-ACQUIRED VIRAL-BACTERIAL PNEUMONIA


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Abstract

The effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum in the treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with a confirmed diagnosis of community-acquired pneumonia and viral-bacterial etiology were included in the follow-up research work. Materials and methods. All patients were randomly divided into 2 groups: 1 group (comparison group) included 30 patients receiving Ceftriaxone monotherapy; in the 2nd group (main) - 30 people who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in terms of gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 continued to be significantly higher than the reference values ​​in both groups, and in patients of the 2nd group there was a decrease compared to baseline values, and in patients in the 1st group at the same time. The activity of MMP-9 during hospitalization was also high in patients of both groups compared with the level of these enzymes in healthy people. By the 7th day of therapy various indicators' changes were recorded. The level of MMP-9 in patients of the 1st group increased, and in patients of the 2nd group - on the contrary - decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group - reached the reference values. The level of TIMP-2 decreased in both groups and reached the level of control values. Conclusion. Inclusion in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia of the antiviral drug Kagocel reduces the level of MMR-9 and reduces the severity of the imbalance in the MMP and TIMP system by 7 days of therapy, which leads to a faster clinical recovery of patients.

About the authors

A. F. Popov

FSBEI HE TSMU1, Ministry of Health of Russia, Far Eastern Federal University

Author for correspondence.
Email: doctor.popov@mail.ru
ORCID iD: 0000-0002-5166-5569

Doctor of Medical Sciences, Professor of the Department of Epidemiology and Military Epidemiology, FSBEI HE TSMU1, Ministry of Health of Russia, Far Eastern Federal University4.

Russian Federation

E. V. Markelova

FSBEI HE TSMU, Ministry of Health of Russia

Email: markev2010@mail.ru
ORCID iD: 0000-0002-5166-5569

Doctor of Medical Sciences, Professor, Head of the Department of Normal and Pathological Physiology, FSBEI HE TSMU, Ministry of Health of Russia

Russian Federation

I. A. Komarova

FSBEI HE TSMU, Ministry of Health of Russia

Email: mikhaira@yandex.ru
ORCID iD: 0000-0003-0483-7433

Assistant of the Department of Infectious Diseases, FSBEI HE TSMU, Ministry of Health of Russia

Russian Federation

A. V. Kosciuszko

FSBEI HE TSMU, Ministry of Health of Russia

Email: avkostyushko@gmail.com

candidate of medical sciences Sci., Associate Professor of the Department of Normal and Pathological Physiology, FSBEI HE TSMU, Ministry of Health of Russia

Russian Federation

M. Yu. Shchelkanov

G.P. Somov Institute of Epidemiology and Microbiology, Far Eastern Branch of Russian Academy of Sciences, the Far Eastern Federal University

Email: adorob@mail.ru
ORCID iD: 0000-0001-8610-7623

Director of G.P. Somov Institute of Epidemiology and Microbiology, Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Head of the Laboratory of Virology in Federal Scientific Center of the Eastern Asia Terrestrial Biodiversity, Far Eastern Branch of Russian Academy of Sciences, Head of the International Research and Educational Center of Biological Security in  the Far Eastern Federal University

Russian Federation

References

  1. Галимова Л.Ф., Пикуза О. И., Закирова А. М., Сулейманова З. Я. Особенности цитокинового профиля при внебольничной пневмонии у детей, вызванной атипичными возбудителями; Репродуктивное здоровье детей и подростков. 2017(2-3):73-74.
  2. Galimova L.F., Pikuza O. I., Zakirova A. M., Suleymanova Z. Ya. Features of the cytokine profile in community-acquired pneumonia in children caused by atypical pathogens; Reproductive health of children and adolescents;2017(2-3):73-74.
  3. Зайцев А.А. Внебольничная пневмония: диагностика, антимикробная терапия и вакцинопрофилактика; Инфекционные болезни: Новости. Мнения. Обучение. 2017(6): 62-71. doi: 10.24411/2305-3496-2017-00006.
  4. Zaytsev A.A. Community-acquired pneumonia: diagnosis, antimicrobial therapy and vaccine prevention; Infectious Diseases: News. Opinions. Training; 2017(6):23.
  5. Корецкая Наталия Александровна, Вавилова Т. П., Ткачев Г. А. Исследование количества проММП1, ТИМП1 и цистатина с в бронхоальвеолярном секрете пациентов с неспецифическими заболеваниями легких; Клиническая лабораторная диагностика; 2012(3), С.10-13.
  6. Koretskaya Nataliya Aleksandrovna, Vavilova T. P., Tkachev G. A. Study of the amount of proMMP1, TIMP1 and cystatin c in the bronchoalveolar secretion of patients with nonspecific lung diseases; Clinical laboratory diagnostics; 2012(3).
  7. Лоскутов О.А., Дружина А.Н., Колесников В.Г. Противовирусная и антибактериальная терапия в лечении внебольничных пневмоний. Медицина неотложных состояний. 2016. N 3. - С.28-34.
  8. Loskutov O.A., Druzhina A.N., Kolesnikov V.G. Antiviral and antibacterial therapy in the treatment of community-acquired pneumonia ; MNS; 2016(3):74.
  9. Мироманова Н.А., Мироманов А.М. Изменения в системе «матриксные металлопротеазы – ингибитор матриксных металлопротеаз» при гриппе у детей; Фундаментальные исследования; 2014(10-2):328-332;
  10. Miromanova N.A., Miromanov A.M.; Сhanges in the system "matrix metal proteases - inhibitor of matrix metal proteases" in children with influenza ; Fundamental research; 2014 (10-2):328-332.
  11. О состоянии санитарно-эпидемиологического благополучия населения в Российской Федерации в 2019 году: Государственный доклад.– М.: Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека, 2020.– 299 с.
  12. On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2019: State report. - Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Welfare, 2020. - 299 p.
  13. Пикуза О. И., Галимова Л. Ф., Агафонова Е. В. Использование индуцированной мокроты в диагностике внебольничной пневмонии у детей; Практическая пульмонология ; 2012(7):1 (77).
  14. Pikuza O. I., Galimova L. F., Agafonova E. V. The use of induced sputum in the diagnosis of community-acquired pneumonia in children; PM; 2012(7-1):63.
  15. Попов А.Ф., Маркелова Е.В., Комарова И.А., Костюшко А.В., Симакова А.И., Щелканов М.Ю. Влияние Кагоцела на уровень ИЛ-10 и ФНО-α при комбинированном лечении внебольничной вирусно-бактериальной пневмонии. Медицинский алфавит. 2020;2(21):63-68. doi: 10.33667/2078-5631-2019-2-27(402)-14-18.
  16. Popov A.F., Markelova E.V., Komarova I.A., Kostyushko A.V., Simakova A.I., Shchelkanov M.Yu. Influence of Kagocel on the level of IL-10 and TNF-α in the combined treatment of community-acquired viral-bacterial pneumonia. Medical alphabet. 2020; 2 (21): 63-68. Doi: 10.33667 / 2078-5631-2019-2-27 (402) -14-18
  17. Попов А.Ф., Симакова А.И., Комарова И.А. Эффективность применения противовирусного препарата Кагоцел® в комплексном лечении вирусно-бактериальных пневмоний в условиях стационара. Медицинский алфавит. 2019;2(27):14-18. doi: 10.33667/2078-5631-2019-2-27(402)-14-18.
  18. Popov A.F., Simakova A.I., Komarova I.A. The effectiveness of the use of the antiviral drug Kagocel® in the complex treatment of viral-bacterial pneumonia in a hospital setting. Medical alphabet. 2019; 2 (27): 14-18. Doi: 10.33667 / 2078-5631-2019-2-27 (402) -14-18
  19. Рачина С.А., Захаренков И.А., Дехнич Н.Н., и соавт.; Этиология тяжелой внебольничной пневмонии у взрослых в РФ: предварительные результаты многоцентрового исследования Sepia. Сборник трудов IX Всероссийской научно-практической конференции с международным участием “Молекулярная диагностика 2017”. Тамбов: ООО фирма “Юлис”, 2017, С. 256-257.
  20. Rachina S.A., Zakharenkov I.A., Dekhnich N.N., and etc.; Etiology of severe community-acquired pneumonia in adults in the Russian Federation: preliminary results of the Sepia multicenter study; Proceedings of the IX All-Russian Scientific and Practical Conference with International Participation "Molecular Diagnostics 2017"; Tambov: LLC firm “Yulis”; 2017: 256-257
  21. Рачина С.А., Козлов Р.С., Шаль Е.П., и соавт.; Структура бактериальных возбудителей внебольничной пневмонии в многопрофильных стационарах г. Смоленска; Пульмонология; 2011(1): 5-18. doi: 10.18093/0869-0189-2011-0-1-5-18.
  22. Rachina S.A., Kozlov R.S., Shal' E.P., and etc. The structure of bacterial pathogens of community-acquired pneumonia in multidisciplinary hospitals in Smolensk; Pulmonology; 2011( 1): 5-18. Doi: 10.18093 / 0869-0189-2011-0-1-5-18
  23. Рачина С.А., Синопальников А.И. Клинические рекомендации по внебольничной пневмонии у взрослых: что нас ждет в 2019 г; Практическая пульмонология; 2018(3):8-12.
  24. Rachina S.A., Sinopalnikov A.I. Clinical practice guidelines for community-acquired pneumonia in adults: what awaits us in 2019; Practical pulmonology; 2018 (3): 8-12.
  25. Сергеева И.В. Применение препарата Кагоцел в комплексной терапии гриппа // Современные проблемы науки и образования. – 2016. – № 5.;
  26. Sergeeva I.V. The use of the drug Kagocel in the complex therapy of influenza // Modern problems of science and education. - 2016. - No. 5 .;
  27. Сологуб Т.В. Грипп в современных условиях: противовирусная терапия прямого действия // МС. 2015. №4.
  28. Sologub T.V. Influenza in modern conditions: direct antiviral therapy // MS. 2015. No. 4.
  29. Сологуб Т.В., Цветков В.В. Кагоцел в терапии гриппа и острых респираторных вирусных инфекций: анализ и систематизация данных по результатам доклинических и клинических исследований // Терапевтический архив. 2017. №8.
  30. Sologub T.V., Tsvetkov V.V. Kagocel in the treatment of influenza and acute respiratory viral infections: analysis and systematization of data based on the results of preclinical and clinical studies // Therapeutic archive. 2017. No. 8.
  31. Турна Алия Абдурахмановна, Тогузов Руслан Тимофеевич, Турусина Т.А., Никонова Е.В.; Матриксные металлопротеиназы в диагностике пневмонии; Клиническая геронтология; 2009(6-7).
  32. Turna Aliya Abdurakhmanovna, Toguzov Ruslan Timofeevich, Turusina T.A., Nikonova E.V.; Matrix metalloproteinases in the diagnosis of pneumonia ; Clinical Gerontology; 2009(6-7).
  33. Чучалин А.Г., Синопальников А.И., Козлов Р.С., и соавт. Внебольничная пневмония у взрослых. Практические рекомендации по диагностике, лечению и профилактике (пособие для врачей). Клин микробиол антимикроб химиотер 2010; 12: 186-225.
  34. Chuchalin A.G., Sinopal'nikov A.I., Kozlov R.S., i soavt. Community-acquired pneumonia in adults. Practical recommendations for diagnosis, treatment and prevention (manual for doctors). Wedge microbiol antimicrobial chemother 2010; 12: 186-225.
  35. Чучалин А.Г., Респираторная медицина: в 3 т. Т. 1. [Электронный ресурс] : руководство / под ред. А. Г. Чучалина - М. : ГЭОТАР-Медиа, 2017. - 640 с. - ISBN 978-5-4235-0262-1
  36. Chuchalin A.G Respiratory medicine: in 3 volumes. V. 1. [Electronic resource]: manual / ed. A.G. Chuchalina - M.: GEOTAR-Media, 2017 .-- 640 p. - ISBN 978-5-4235-0262-1
  37. Adrian Rendon, Erick J. Rendon-Ramirez and Adrian G. Rosas. Relevant Cytokines in the Management of Community-Acquired Pneumonia. Curr Infect Dis Rep. 2016; 18(3): 10. doi: 10.1007/s11908-016-0516-y.
  38. -
  39. Bjarnason A., Westin J., Lindh M., et al. Incidence, Etiology, and Outcomes of CommunityAcquired Pneumonia: A Population-Based Study. Open Forum Infect Dis 2018;5(2):ofy010. doi: 10.1093/ofid/ofy010.
  40. -
  41. Choi S.H., Hong S.B., Ko G.B., et al. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med 2012;186: 325–332.
  42. -
  43. Chiang TY, Tsao SM, Yeh CB, Yang SF. Matrix metalloproteinases in pneumonia. Clin Chim Acta. 2014;433:272–277.
  44. -
  45. Christine M Hartog, Johanna A Wermelt, Carsten O Sommerfeld, Wolfgang Eichler, Klaus Dalhoff, Joerg Braun. Pulmonary matrix metalloproteinase excess in hospital-acquired pneumonia. Am J Respir Crit Care Med. 2003 Feb 15;167(4):593-8. doi: 10.1164/rccm.200203-258OC.
  46. -
  47. de Roux A., Ewig S., Garcia E., et al. Mixed community-acquired pneumonia in hospitalized patients. Eur Respir J 2006; 27: 795-800.
  48. -
  49. - https://ftiza.su/metod-indutsirovannoy-mokrotyi-dlya-issledovaniya-mokrotyi-na-mikobakterii-tuberkuleza/
  50. Ilumets, Helen et al. “Matrix metalloproteinases -8, -9 and -12 in smokers and patients with stage 0 COPD.” International journal of chronic obstructive pulmonary disease vol. 2,3 (2007): 369-79.
  51. -
  52. Johansson N., Kalin M., Tiveljung-Lindell A., et al. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Clin Infect Dis 2010;50:202–209.
  53. -
  54. Mikheev Aleksey Vladimirovich, Baskevich Maksim Arkad'evich The role of matrix metalloproteinases in the development of lung diseases // Science of the young - Eruditio Juvenium. 2015. No. 1.
  55. -
  56. Ng HH, Narasaraju T, Phoon MC, Sim MK, Seet JE, Chow VT. Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases. Exp Mol Pathol. 2012 Jun;92(3):287-95. doi: 10.1016/j.yexmp.2012.03.003.
  57. -
  58. Pavia A.T. What is the Role of Respiratory Viruses in Community-Acquired Pneumonia? What is the Best Therapy for Influenza and Other Viral Causes of Community-Acquired Pneumonia? Infect Dis Clin N Am 2013; 27: 157–175. -
  59. Ting-Yen Chiang 1, Yung-Luen Yu, Chiao-Wen Lin, Shih-Ming Tsao,
  60. Shun-Fa Yang, Chao-Bin Yeh. The circulating level of MMP-9 and its ratio to
  61. TIMP-1 as a predictor of severity in patients with community-acquired
  62. pneumonia. Clin Chim Acta. 2013 Sep 23;424:261-6. doi:
  63. 1016/j.cca.2013.06.013
  64. -
  65. Torres A., Blasi F., Peetermans W.E., et al. The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: a literature review. Eur J Clin Microbiol Infect Dis 2014;33(7):1065-79.
  66. -
  67. Welte T., Torres A., Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 2010. doi: 10.1136/thx.2009.129502.
  68. -
  69. Yia-Ting Li, Yao-Chen Wang, Hsiang-Lin Lee, Min-Chi Lu and Shun-Fa Yang.
  70. Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of
  71. Disease in Patients with Ventilator-Associated Pneumonia. Int. J. Med. Sci. 2016; 13(8):
  72. –645.
  73. -

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