pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2018-28-4-483-489pulmo-1035Research ArticleОБЗОРЫREVIEWАнтибактериальная ингаляционная терапия тиамфеникола глицинат ацетилцистеинатом в пульмонологической практикеAntibacterial inhalation therapy with thiamphenicol glycinate acetylcysteinate in pulmonologyКапустинаВ. А.KapustinaV. A.

к. м. н., доцент кафедры факультетской терапии № 1 лечебного факультета

тел.: (499) 245-23-02

119991, Москва, ул. Трубецкая, 8, стр. 2

Candidate of Medicine, Associate Professor, Department No.1 of General Internal Medicine, Medical Faculty

tel.: (499) 245-23-02

ul. Trubetskaya 8, build. 2, Moscow, 119991, Russia

kapustina.valentina.a@gmail.comОвчаренкоС. И.OvcharenkoS. I.

д. м. н., профессор кафедры факультетской терапии № 1 лечебного факультета

тел.: (499) 248-45-23

119991, Москва, ул. Трубецкая, 8, стр. 2

Doctor of Medicine, Professor, Department No.1 of General Internal Medicine, Medical Faculty

tel.: (499) 248-45-23

ul. Trubetskaya 8, build. 2, Moscow, 119991, Russia

svetftk@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М.Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский Университет)РоссияI.M.Sechenov Federal First Moscow State Medical University (Sechenov University), Healthcare Ministry of RussiaRussian Federation201818102018284483489Copyright © Капустина В.А., Овчаренко С.И., 20182018Капустина В.А., Овчаренко С.И.Kapustina V.A., Ovcharenko S.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/1035

Тиамфеникола глицинат ацетилцистеинат (ТГА) – комплексное лекарственное средство, содержащее антибактериальный препарат (АБП) широкого спектра действия тиамфеникол и  муколитический препарат N-ацетилцистеин. В обзоре представлены фармакологические,  микробиологические и клинические аспекты применения препарата. Ингаляционное  применение ТГА (Флуимуцил-антибиотик ИТ) может служить достойной альтернативной  пероральному приему ряда мукоактивных средств и АБП, используемых в лечении заболеваний верхних (острый и хронический риносинусит, средний отит, тонзиллит)  и нижних (острый бронхит, обострения хронического бронхита и хро ничес кой обструктивной болезни легких) дыхательных путей как у взрослых, так и у детей.

Thiamphenicol glycinate acetylcysteinate (TGA) is a combination of thiamphenicol, a broad-spectrum antibiotic, and mucolytic drug N-acetylcysteine. This article is a  review of pharmacological, microbiological, and clinical effects of this combined drug.  Inhaled TGA could be considered as a worthy alternative for oral mucolytics and oral  antibiotics in treatment of upper and lower airway diseases, such as acute and chronic  rhinosinusitis, otitis media, tonsillitis, acute bronchitis, and acute exacerbation of chronic bronchitis and chronic obstructive pulmonary disease, in children and adults.

тиамфеникола глицинат ацетилцистеинатN-ацетилцистеинтиамфениколзаболевания верхних дыхательных путейострый бронхитхронический бронхитхроническая обструктивная болезнь легкихобострениеthiamphenicol glycinate acetylcysteinateN-acetylcysteinethiamphenicolupper and lower airway diseasesacute bronchitischronic bronchitischronic obstructive pulmonary diseaseexacerbationReferencesАгеева Л.И., Александрова Г.А., Зайченко Н.М. и др. Здравоохранение в России. 2017: Статистический сборник. М.: Росстат; 2017. Доступно на: http://www.gks.ru/free_doc/doc_2017/zdrav17.pdfAgeeva L.I., Aleksandrova G.A., Zaychenko N.M. et al. Healthcare in Russia. 2017: Statistical compilation. Moscow: Rosstat; 2017. Available at: http://www.gks.ru/free_doc/doc_2017/zdrav17.pdf (in Russian).MacNee W., Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1999; 160 (5, Pt 2): S58–65. DOI: 10.1164/ajrccm.160.supplement_1.15.MacNee W., Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1999; 160 (5, Pt 2): S58–65. DOI: 10.1164/ajrccm.160.supplement_1.15.Rahman I., MacNee W. Role of oxidants/antioxidants in smoking induced lung diseases. Free Radic. Biol. Med. 1996; 21 (5): 669–681. DOI: 10.1016/0891-5849(96)00155-4.Rahman I., MacNee W. Role of oxidants/antioxidants in smoking induced lung diseases. Free Radic. Biol. Med. 1996; 21 (5): 669–681. DOI: 10.1016/0891-5849(96)00155-4.Barnes P.J. Chronic obstructive pulmonary disease. N. Engl. J. Med. 2000; 343 (4): 269–280. DOI: 10.1056/NEJM200007273430407.Barnes P.J. Chronic obstructive pulmonary disease. N. Engl. J. Med. 2000; 343 (4): 269–280. DOI: 10.1056/NEJM200007273430407.Costerton J.W., Geesey G.G., Cheng K.J. How bacteria stick. Sci. Am. 1978; 238 (1): 86–95.Costerton J.W., Geesey G.G., Cheng K.J. How bacteria stick. Sci. Am. 1978; 238 (1): 86–95.El-Azizi M., Rao S., Kanchanapoom T., Khardori N. In vitro activity of vancomycin, quinupristin/dalfopristin, and linezolid against intact and disrupted biofilms of staphylococci. Ann. Clin. Microbiol. Antimicrob. 2005; (4): 2. DOI: 10.1186/1476-0711-4-2.El-Azizi M., Rao S., Kanchanapoom T., Khardori N. In vitro activity of vancomycin, quinupristin/dalfopristin, and linezolid against intact and disrupted biofilms of staphylococci. Ann. Clin. Microbiol. Antimicrob. 2005; (4): 2. DOI: 10.1186/1476-0711-4-2.Sheffner A.L., Medler E.M., Jacobs L.W., Sarett H.P. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am. Rev. Respir. Dis. 1964; 90: 721–729.Sheffner A.L., Medler E.M., Jacobs L.W., Sarett H.P. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am. Rev. Respir. Dis. 1964; 90: 721–729.Iravani J., Melville G.N., Horstmann G. N-Acetylcysteine and mucociliary activity in mammalian airways. Arzneimittelforschung 1978; 28 (2): 250–254.Iravani J., Melville G.N., Horstmann G. N-Acetylcysteine and mucociliary activity in mammalian airways. Arzneimittelforschung 1978; 28 (2): 250–254.Olivieri D., Marsico S.A., Del Donno M. Improvement of mucociliary transport in smokers by mucolitics. Eur. J. Resp. Dis. Suppl. 1985; (139): 142–145.Olivieri D., Marsico S.A., Del Donno M. Improvement of mucociliary transport in smokers by mucolitics. Eur. J. Resp. Dis. Suppl. 1985; (139): 142–145.Aruoma O.I., Halliwell B., Hoey B.M., Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. J. Free Radic. Biol. Med. 1989; 6 (6): 593–597. DOI: 10.1016/0891-5849(89)90066-X.Aruoma O.I., Halliwell B., Hoey B.M., Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. J. Free Radic. Biol. Med. 1989; 6 (6): 593–597. DOI: 10.1016/0891-5849(89)90066-X.Rushworth G.F., Megson I.L. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol. Ther. 2014; (141): 150–159. DOI: 10.1016/j.pharmthera.2013.09.006.Rushworth G.F., Megson I.L. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol. Ther. 2014; (141): 150–159. DOI: 10.1016/j.pharmthera.2013.09.006.Айсанов З.Р., Авдеев С.Н., Архипов В.В. и др. Национальные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких: алгоритм принятия клинических решений. Пульмонология. 2017; 27 (1): 13–20. DOI: 10.18093/0869-0189-2017-27-1-13-20.Aisanov Z.R., Avdeev S.N., Arkhipov V.V. et al. National clinical guidelines on diagnosis and treatment of chronic obstructive pulmonary disease: a clinical decision-making algorithm. Pul’monologiya. 2017; 27 (1): 13–20. DOI: 10.18093/0869-0189-2017-27-1-13-20 (in Russian).Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. Reports 2018. Available at: https://goldcopd.org/gold-reports/Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. Reports 2018. Available at: https://goldcopd.org/gold-reports/Zheng J.P., Wen F.Q., Bai C.X. et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir. Med. 2014; 2 (3): 187–194. DOI: 10.1016/S2213-2600(13)70286-8.Zheng J.P., Wen F.Q., Bai C.X. et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir. Med. 2014; 2 (3): 187–194. DOI: 10.1016/S2213-2600(13)70286-8.Poole P., Chong J., Cates C.J. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; (7): CD001287. DOI: 10.1002/14651858.CD001287.pub5.Poole P., Chong J., Cates C.J. Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2015; (7): CD001287. DOI: 10.1002/14651858.CD001287.pub5.Cazzola M., Calzetta L., Page C. et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur. Respir. Rev. 2015; 24 (137): 451–461. DOI: 10.1183/16000617.00002215.Cazzola M., Calzetta L., Page C. et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur. Respir. Rev. 2015; 24 (137): 451–461. DOI: 10.1183/16000617.00002215.Чучалин А.Г., Синопальников А.И., Козлов Р.С. и др. Российское респираторное общество (РРО). Межрегиональная ассоциация по клинической микробиологии и антимикробной химиотерапии (МАКМАХ). Клинические рекомендации по диагностике, лечению и профилактике тяжелой внебольничной пневмонии у взрослых. Пульмонология. 2014; (4): 13–48. DOI: 10.18093/0869-0189-2014-0-4-13-48.Chuchalin A.G., Sinopal'nikov A.I., Kozlov R.S. et al. Russian Respiratory Society Interregional association on clinical microbiology and antimicrobial chemotherapy. Clinical guidelines on diagnosis, treatment and prevention of severe community acquired pneumonia in adults. Pul’monologiya. 2014; (4): 13–48. DOI: 10.18093/0869-0189-2014-0-4-13-48 (in Russian).Лопатин А.С., ред. Острыий риносинусит: клинические рекомендации. М.: Российское общество ринологов; 2017. Доступно на: http://rhinology.ru/2017/09/22/ostryj-rinosinusit-klinicheskie-rekomendacii-2017-ror/Lopatin A.S., ed. Acute Rinosinusitis: Clinical Guidelines. Moscow: Russian Society of Rinologists; 2017. Available at: http://rhinology.ru/2017/09/22/ostryj-rinosinusit-klinicheskie-rekomendacii-2017-ror/ (in Russian).Лопатин А.С., ред. Хроническиий риносинусит: патогенез, диагностика и принципы лечения. Российское общество ринологов. Клинические рекомендации. М.: Практическая медицина; 2014.Lopatin A.S., ed. Chronic Rinosinusitis: Pathogenesis, Diagnosis and Therapeutic Approaches. Russian Society of Rinologists. Clinical Guidelines. Moscow: Prakticheskaya meditsina; 2014. Available at: http://rhinology.ru/2014/07/14/klinicheskie-rekomendacii-xronicheskij-sinusit/ (in Russian).Albini E., Belluco G., Berton M. et al. In vitro antibacterial activity of thiamphenicol glycinate acetylcysteinate against respiratory pathogens. Arzneimittelforschung. 1999; 49 (6): 533–537. DOI: 10.1055/s-0031-1300456.Albini E., Belluco G., Berton M. et al. In vitro antibacterial activity of thiamphenicol glycinate acetylcysteinate against respiratory pathogens. Arzneimittelforschung. 1999; 49 (6): 533–537. DOI: 10.1055/s-0031-1300456.Rizzato G. Antibiotics for aerosol intake in respiratory infections: pole position for thiamfenicol. L’Internista J. 2001; (9): 120.Rizzato G. Antibiotics for aerosol intake in respiratory infections: pole position for thiamfenicol. L’Internista J. 2001; (9): 120.Lombardi A., Drago L., De Vecchi E. et al. Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae. Arzneimittelforschung. 2001; 51 (3): 264–267. DOI: 10.1055/s-0031-1300034.Lombardi A., Drago L., De Vecchi E. et al. Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae. Arzneimittelforschung. 2001; 51 (3): 264–267. DOI: 10.1055/s-0031-1300034.Drago L., Fassina M.C., Mombelli B. et al. Comparative effect of thiamphenicol glycinate, thiamphenicol glycinate N-acetylcysteinate, amoxicillin plus clavulanic acid, ceftriaxone and clarithromycin on pulmonary clearance of Haemophilus influenzae in an animal model. Chemotherapy. 2000; 46 (4): 275–281. DOI: 10.1159/000007299.Drago L., Fassina M.C., Mombelli B. et al. Comparative effect of thiamphenicol glycinate, thiamphenicol glycinate N-acetylcysteinate, amoxicillin plus clavulanic acid, ceftriaxone and clarithromycin on pulmonary clearance of Haemophilus influenzae in an animal model. Chemotherapy. 2000; 46 (4): 275–281. DOI: 10.1159/000007299.Raymond J., Boutros N., Bergeret M. [Role of thiamphenicol in the treatment of community-acquired lung infections]. Med. Trop. (Mars). 2004; 64 (1): 33–38 (in French).Raymond J., Boutros N., Bergeret M. [Role of thiamphenicol in the treatment of community-acquired lung infections]. Med. Trop. (Mars). 2004; 64 (1): 33–38 (in French).Melillo G., Chiummariello A., Scala G. [On the use of a new molecular combination of acetylcysteine with thiamphenicol glycinate in bronchopulmonary suppurations]. G. Ital. Chemioter. 1966; 13 (1): 156–160 (in Italian).Melillo G., Chiummariello A., Scala G. [On the use of a new molecular combination of acetylcysteine with thiamphenicol glycinate in bronchopulmonary suppurations]. G. Ital. Chemioter. 1966; 13 (1): 156–160 (in Italian).Bürgi H. Mucolytic and antibiotic effect of a new compound in chronic bronchitis. Chemotherapy. 1975; 21 (3–4): 167–174. DOI: 10.1159/000221857.Bürgi H. Mucolytic and antibiotic effect of a new compound in chronic bronchitis. Chemotherapy. 1975; 21 (3–4): 167–174. DOI: 10.1159/000221857.Mayaud C., Lentschner C., Bouchoucha S., Marsac J. [Thiamphenicol glycinate acetylcysteinate in the treatment of acute respiratory infections with mucostasis]. Eur. J. Respir. Dis. Suppl. 1980; (111): 70–73 (in French).Mayaud C., Lentschner C., Bouchoucha S., Marsac J. [Thiamphenicol glycinate acetylcysteinate in the treatment of acute respiratory infections with mucostasis]. Eur. J. Respir. Dis. Suppl. 1980; (111): 70–73 (in French).Grassi C., De Benedetto F. Recent clinical evidence of the efficacy and safety of thiamphenicol glycinate acetylcysteinate and thiamphenicol glycinate. J. Chemother. 2002; 14 (3): 279–284. DOI: 10.1179/joc.2002.14.3.279.Grassi C., De Benedetto F. Recent clinical evidence of the efficacy and safety of thiamphenicol glycinate acetylcysteinate and thiamphenicol glycinate. J. Chemother. 2002; 14 (3): 279–284. DOI: 10.1179/joc.2002.14.3.279.Vysotiuk L., Hromova A. [Fluimucyl-antibiotic IT: ability of antioxidant therapy for patients with acute attack of infectious chronic obstructive lung disease]. Lik. Sprava. 2006; (1–2): 65–81 (in Ukrainian).Vysotiuk L., Hromova A. [Fluimucyl-antibiotic IT: ability of antioxidant therapy for patients with acute attack of infectious chronic obstructive lung disease]. Lik. Sprava. 2006; (1–2): 65–81 (in Ukrainian).Овчаренко C.И., Морозова Н.В. Эффективность применения Флуимуцил-антибиотика ИТ в лечении обострений ХОБЛ. Атмосфера. Пульмонология и аллергология. 2003; (3): 26–28.Ovcharenko C.I., Morozova N.V. Effective treatment of Fluimucil-antibiotic IT in therapy of exacerbations of COPD. Atmosfera. Pul’monologiya i allergologiya. 2003; (3): 26-28 (in Russian).Овчаренко C.И., Капустина В.А., Сон Е.А. Успешное применение ингаляционной формы Флуимуцил-антибиотика ИТ в комплексной терапии инфекционно-воспалительных заболеваний органов дыхания. Фарматека. 2010; 11 (205): 42–45.Ovcharenko S.I., Kapustina V.A., Son E.A. Successful use of the inhaled form of Fluimucil-antibiotic IT in the complex therapy of infectious-inflammatory diseases of the respiratory system. Pharmateka. 2010; 11 (205): 42–45. (In Russian).Овчаренко С.И., Капустина В.А., Нерсесян З.Н., Морозова Н.В. Современные возможности комплексной небулайзерной терапии обострений хронической обструктивной болзени легких: клиническое наблюдение. Consilium medicum. 2012; (3): 64–66.Ovcharenko S.I., Kapustina V.A., Nersesyan Z.N., Morozova N.V. Modern possibilities of complex nebulizer therapy of exacerbations of chronic obstructive pulmonary disease: clinical observation. Consilium medicum. 2012; (3): 64–66 (in Russian).Овчаренко С.И., Капустина В.А. Эффективность и безопасность небулизироваанного тиамфеникола глицината ацетилцистеината в лечении хронических заболеваний органов дыхания. Практическая медицина. 2013; 5 (74): 102–105.Ovcharenko S.I., Kapustina V.A. Efficacy and safety of nebulized thiamphenicol glycinate acetylcysteinate in treatment of chronic respiratory diseases. Prakticheskaya meditsina. 2013; 5 (74): 102–105 (in Russian).Белевский А.С. Княжеская Н.П. Тиамфеникол глицинат ацетилцистеинат: некоторые аспекты применения при острых и хронических легочных заболеваниях. Практическая пульмонология. 2017; (3): 122–126.Belevskiy A.S. Knyazheskaya N.P. Thiamphenicol glycinate acetylcysteinate: some aspects of use in acute and chronic respiratory diseases. Prakticheskaya meditsina. 2017; (3): 122–126 (in Russian).Колосова Н.Г., Дронов И.А. Топическая ингаляционная антибактериальная терапия респираторных инфекций у детей. Русский медицинский журнал. 2017; (5): 319–321.Kolosova N.G., Dronov I.A. Topic inhaled antibacterial therapy of respiratory infections in children. Russkiy meditsinskiy zhurnal. 2017; (5): 319–321 (in Russian).Serra A., Schito G.C., Nicoletti G., Fadda G. A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route). Int. J. Immunopathol. Pharmacol. 2017; 20 (3): 607–617. DOI: 10.1177/039463200702000319.Serra A., Schito G.C., Nicoletti G., Fadda G. A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route). Int. J. Immunopathol. Pharmacol. 2017; 20 (3): 607–617. DOI: 10.1177/039463200702000319.Трушенко Н.В., Белевский А.С. Этиотропная терапия острого бронхита: дискуссия продолжается. Практическая пульмонология. 2017; (2): 37–47.Trushenko N.V., Belevskiy A.S. Etiotropic therapy of acute bronchitis: the discussion goes on. Prakticheskaya meditsina. 2017; (2): 37–47 (in Russian).Varricchio A., Capasso M., Di Gioacchino M., Ciprandi G. Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis. Int. J. Immunopathol. Pharmacol. 2008; 21 (3): 625–629. DOI: 10.1177/039463200802100316.Varricchio A., Capasso M., Di Gioacchino M., Ciprandi G. Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis. Int. J. Immunopathol. Pharmacol. 2008; 21 (3): 625–629. DOI: 10.1177/039463200802100316.Macchi A., Castelnuovo P. Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery. Int. J. Immunopathol. Pharmacol. 2009; 22 (2): 303–310. DOI: 10.1177/039463200902200207.Macchi A., Castelnuovo P. Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery. Int. J. Immunopathol. Pharmacol. 2009; 22 (2): 303–310. DOI: 10.1177/039463200902200207.Геппе Н.А., Дронов И.А., Колосова Н.Г. Эффективность применения тиамфеникола глицинат ацетилцистеината при острых бронхитах у детей. Русский медицинский журнал. 2016; (6): 386–390.Geppe N.A., Dronov I.A., Kolosova N.G. Efficacy of thiamphenicol glycinate acetylcysteinate in children with acute bronchitis. Russkiy meditsinskiy zhurnal. 2016; (6): 386–390 (in Russian).

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