epidemiologyЭпидемиология и ВакцинопрофилактикаEpidemiology and Vaccinal Prevention2073-30462619-0494«Numicom» LLC10.31631/2073-3046-2023-22-3-64-69epidemiology-1826Research ArticleПРАКТИЧЕСКИЕ АСПЕКТЫ ЭПИДЕМИОЛОГИИ И ВАКЦИНОПРОФИЛАКТИКИPRACTICAL ASPECTS OF EPIDEMIOLOGY AND VACCINE PREVENTIONЛекарственная чувствительность к бедаквилину штаммов М. kansasii, выделенных в противотуберкулезных учреждениях МосквыDrug Sensitivity to Bedaquiline of M. kansasii Strains Isolated in Antituberculous Institutions of the City of Moscowhttps://orcid.org/0000-0002-2686-0952МакароваМ. В.MakarovaM. V.

Макарова Марина Витальевна, д. б. н., главный научный сотрудник отдела проблем лабораторной диагностики туберкулеза и патоморфологии

107014, Москва, ул. Стромынка, д.10

+7 (495) 603-30-33, факс: +7 (499) 785-20-82

Makarova Marina V., Dr. Sci. (Biol.), Chief Researcher of the Department of Problems of Laboratory Diagnosis of Tuberculosis and Pathomorphology

10 Stromynka Street, Moscow, 107114, Russia

+7 (495) 603-30-33, fax: +7 (499) 785-20-82

makarova75@yandex.ruhttps://orcid.org/0000-0001-6849-0702МихайловаЮ. Д.MikhajlovaYu. D.

Юлия Дмитриевна Михайлова – к. б. н., ведущий научный сотрудник отдела проблем лабораторной диагностики туберкулеза и патоморфологии

107014, Москва, ул. Стромынка, д. 10

+7 (495) 603-30-33, факс: +7 (499) 785-20-82

Yulia D. Mikhajlova – Cand. Sci. (Biol.), Leading Researcher of the Department of Problems of Laboratory Diagnosis of Tuberculosis and Pathomorphology

10 Stromynka Street, Moscow, 107114, Russia

+7 (495) 603-30-33, fax: +7 (499) 785-20-82

juliaisaeva81@rambler.ruhttps://orcid.org/0000-0002-9125-5038ХачатурьянцЕ. Н.KhachaturiantsE. N.

Елена Николаевна Хачатурьянц – к. б. н., врач-бактериолог Централизованной бактериологической лаборатории

107014, Москва, ул. Стромынка, д.10

+7 (499) 268-70-33, факс: +7 (499) 785-20-82

Elena N. Khachturiants – Cand. Sci. (Biol.), Bacteriologist of the Centralized Bacteriological Laboratory

10 Stromynka Street, Moscow, 107114, Russia

+7 (499) 268-70-33, fax: +7 (499) 785-20-82

hen65b@mail.ruhttps://orcid.org/0000-0002-5335-7690ЛитвиновВ. И.LitvinovV. I.

Виталий Ильич Литвинов – д. м. н., профессор, академик РАН, научный руководитель

107014, Москва, ул. Стромынка, д.10

+7 (499) 268-04-15, факс: +7 (499) 785-20-82

Vitaly I. Litvinov – Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, Scientific Supervisor

Moscow, 107114, Russia. +7 (499) 268-04-15

fax: +7 (499) 785-20-82

mnpcbtlv@yandex.ruГБУЗ Московский городской научно-практический центр борьбы с туберкулёзом Департамента здравоохранения города МосквыРоссияMoscow City Scientific and Practical Center for the Control of Tuberculosis of the Moscow City Health DepartmentRussian Federation2023010720232236469Copyright © Макарова М.В., Михайлова Ю.Д., Хачатурьянц Е.Н., Литвинов В.И., 20232023Макарова М.В., Михайлова Ю.Д., Хачатурьянц Е.Н., Литвинов В.И.Makarova M.V., Mikhajlova Y.D., Khachaturiants E.N., Litvinov V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epidemvac.ru/jour/article/view/1826Актуальность

Актуальность. M. kansasii в большинстве стран Европы (в т.ч. России) являются одними из основных нетуберкулезных микобактерий – возбудителей микобактериозов. Важная проблема лечения микобактериозов – устойчивость их возбудителей к антибактериальным препаратам (АБП). Бедаквилин (Bdq) является одним из новых АБП, эффективность которого показана, в частности, при наиболее распространенном микобактериозе – туберкулёзе.

Цель

Цель. Охарактеризовать особенности лекарственной чувствительности M. kansasii, выделенных из респираторного биоматериала пациентов Московского научно-практического центра борьбы с туберкулёзом (МНПЦБТ). 

Материалы и методы

Материалы и методы. Изучено 76 культур M. kansasii. Определялся спектр МИК Bdq в отношении M. kansasii, MИK50, МИК90 (минимальные концентрации препарата, подавляющие рост 50% и 90% культур соответственно). Оценили также лекарственную чувствительность M. kansasii к основным АБП, применяющимся в широкой практике для лечения соответствующих микобактериозов. 

Результаты и обсуждение

Результаты и обсуждение. Было установлено, что МИК Bdq в отношении M. kansasii распределились в диапазоне 0,003–2,0 (мкг/мл), рост большинства штаммов (73,7%) подавляла концентрация Bdq 0,015 мкг/мл. Среди всех исследованных штаммов M. kansasii выделено 2 резистентных к Bdq изолята (2,6%). 

Заключение

Заключение. Результаты проведенного исследования, как и данные литературы, свидетельствуют о том, что M. kansasii на сегодняшний день, как правило, чувствительны к Bdq. Однако в отдельных случаях резистентность к этому препарату уже развивается.

Relevance

Relevance. M. kansasii are one of the main nontuberculous bacteria pathogens causing mycobacterial infections in most European countries (including Russia). An important problem in the treatment of mycobacteriosis is the resistance of their pathogens to antibacterial drugs (ABDs). Bedaquiline (Bdq) is one of the new ABDs, the effectiveness of which is shown, in particular, in the most common mycobacteriosis – tuberculosis.

Aim

Aim. To characterize the features of drug sensitivity of M. kansasii isolated from respiratory material at the Moscow Scientific and Practical Center for Tuberculosis Control (MNPC BT).

Materials and methods

Materials and methods. A total of 76 M. kansasii cultures have been studied. The MIC spectrum of Bdq was determined for M. kansasii, MIC50, MIC90 (the concentrations of Bdq providing inhibition of the growth of 50% and 90% mycobacterial strains, respectively) and ECOFF (epidemiological cut-off value) – the MIC value characterizing the upper limit for the «wild» population type, which was determined using the ECOFFinder statistical calculator – EUCAST. The drug sensitivity of M. kansasii to the main ABDs used in general practice for the treatment of the corresponding mycobacterioses was also evaluated.

Results

Results. It was found that the MIC of Bdq in relation to M. kansasii were distributed in the range of 0.003-2.0 (mcg/ml), the growth of most strains (73.7%) was be inhibited by the concentration of Bdq0.015 mcg/ml. Among all studied strains of M. kansasii, the number of isolates resistant to Bdq were 2 (2.6%). The data obtained are generally consistent with the data of other authors and show that Bdq can currently be an effective drug for the treatment of mycobacterial infections caused by M. kansasii.

Conclusion

Conclusion. The results of the study, as well as literature data, indicate that M. kansasii is currently usually sensitive to Bdq. However, in some cases, resistance to this drug is already developing.

нетуберкулёзные микобактерииM. kansasiiбедаквилинлекарственная чувствительностьрезистентностьминимальные ингибирующие концентрацииnon-tuberculosis mycobacteriaM. kansasiibedaquilinedrug sensitivityresistanceminimal inhibitory concentrationsReferencesGriffith D., Aksamit T., Brown-Elliott B., et al. ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367–416. doi: 10.1164/rccm.200604-571ST.Griffith D., Aksamit T., Brown-Elliott B., et al. ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367–416. doi: 10.1164/rccm.200604-571ST.Prevots D., Marras T. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015 Mar;36(1):13–34. doi: 10.1016/j.ccm.2014.10.002.Prevots D., Marras T. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015 Mar;36(1):13–34. doi: 10.1016/j.ccm.2014.10.002.Проблемы лекарственной устойчивости микобактерий. Богородская Е. М., Кудлай Д. А., Литвинов В. И.,ред. М.: МНПЦБТ. 2021:504.Problemy` lekarstvennoj ustojchivosti mikobakterij. Ed.: Bogorodskaya E.M., Kudlay D.A., Litvinov V.I. M.: MNPCzBT. 2021:504.Kumar K., Loebinger M. Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis: The Nontuberculous Mycobacterial Series.Chest. 2022 Mar;161(3):637–646. doi: 10.1016/j.chest.2021.10.003.Kumar K., Loebinger M. Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis: The Nontuberculous Mycobacterial Series.Chest. 2022 Mar;161(3):637–646. doi: 10.1016/j.chest.2021.10.003.Нетуберкулезные микобактерии, микобактериозы.Литвинов В. И., Богородская Е. М., Борисов С. Е., ред. М.: МНПЦБТ. 2014:256.Netuberkulezny`e mikobakterii, mikobakteriozy. Ed.: Litvinov V.I., Bogorodskaya E.M., Borisov S.E.M.: MNPCzBT. 2014:256.Bakuła Z., Kościuch J., Safianowska A., et al. Clinical, radiological and molecular features of Mycobacterium kansasii pulmonary disease. Respir Med. 2018 Jun;139:91–100. doi: 10.1016/ j.rmed.2018.05.007.Bakuła Z., Kościuch J., Safianowska A., et al. Clinical, radiological and molecular features of Mycobacterium kansasii pulmonary disease. Respir Med. 2018 Jun;139:91–100. doi: 10.1016/ j.rmed.2018.05.007.Brown-Elliott B., Nash K., Wallace R. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012 Jul;25(3):545–82. doi: 10.1128/CMR. 05030-11.Brown-Elliott B., Nash K., Wallace R. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012 Jul;25(3):545–82. doi: 10.1128/CMR. 05030-11.van Ingen J., Kuijper E. Drug susceptibility testing of nontuberculous mycobacteria.Future Microbiol. 2014;9(9):1095–110. doi: 10.2217/fmb.14.60.van Ingen J., Kuijper E. Drug susceptibility testing of nontuberculous mycobacteria.Future Microbiol. 2014;9(9):1095–110. doi: 10.2217/fmb.14.60.Litvinov V., Makarova M., Galkina K., et al. Drug susceptibility testing of slowly growing non-tuberculous mycobacteria using slomyco test-system. PLoS One. 2018 Sep 17;13(9):e0203108. doi: 10.1371/journal.pone.0203108.Litvinov V., Makarova M., Galkina K., et al. Drug susceptibility testing of slowly growing non-tuberculous mycobacteria using slomyco test-system. PLoS One. 2018 Sep 17;13(9):e0203108. doi: 10.1371/journal.pone.0203108.DeStefano M., Shoen C., Cynamon M. Therapy for Mycobacterium kansasii Infection: Beyond 2018. Front Microbiol. 2018 Sep 24;9:2271. doi: 10.3389/fmicb.2018.02271.DeStefano M., Shoen C., Cynamon M. Therapy for Mycobacterium kansasii Infection: Beyond 2018. Front Microbiol. 2018 Sep 24;9:2271. doi: 10.3389/fmicb.2018.02271.Huang H., Lu P., Lee C., Chong I. Treatment of pulmonary disease caused by Mycobacterium kansasii. J Formos Med Assoc. 2020 Jun;119 Suppl 1:S51–S57. doi: 10.1016/j.jfma.2020.05.018.Huang H., Lu P., Lee C., Chong I. Treatment of pulmonary disease caused by Mycobacterium kansasii. J Formos Med Assoc. 2020 Jun;119 Suppl 1:S51–S57. doi: 10.1016/j.jfma.2020.05.018.Huitric E., Verhasselt P., Koul A., et al. Rates and mechanisms of resistance development in Mycobacterium tuberculosis to a novel diarylquinoline ATP synthase inhibitor. Antimicrob Agents Chemother. 2010 Mar;54(3):1022–8. doi: 10.1128/AAC.01611-09.Huitric E., Verhasselt P., Koul A., et al. Rates and mechanisms of resistance development in Mycobacterium tuberculosis to a novel diarylquinoline ATP synthase inhibitor. Antimicrob Agents Chemother. 2010 Mar;54(3):1022–8. doi: 10.1128/AAC.01611-09.Борисов С. Е., Филиппов А. В., Иванова Д. А., и др. Эффективность и безопасность основанных на использовании бедаквилина режимов химиотерапии у больных туберкулезом органов дыхания: непосредственные и окончательные результаты.Туберкулез и болезни легких. 2019;97(5):28–42.Borisov S.E., Filippov A.V., Ivanova D.A. et al. E`ffektivnost` i bezopasnost` osnovanny`x na ispol`zovanii bedakvilina rezhimov ximioterapii u bol`ny`x tuberkulezom organov dy`xaniya: neposredstvenny`e i okonchatel`ny`e rezul`taty`. Tuberkulez i bolezni legkix. 2019;97(5):28–42.WHO. The Use of Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis: Interim Policy Guidance. Geneva: World Health Organization; 2013.WHO. The Use of Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis: Interim Policy Guidance. Geneva: World Health Organization; 2013.Philley J., Griffith D. Medical Management of Pulmonary Nontuberculous Mycobacterial Disease.Thorac Surg Clin. 2019 Feb;29(1):65–76. doi: 10.1016/j.thorsurg.2018.09.001.Philley J., Griffith D. Medical Management of Pulmonary Nontuberculous Mycobacterial Disease.Thorac Surg Clin. 2019 Feb;29(1):65–76. doi: 10.1016/j.thorsurg.2018.09.001.Daley C., Iaccarino J., Lange C., et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Eur Respir J. 2020 Jul 7;56(1):2000535. doi: 10.1183/13993003.00535-2020.Daley C., Iaccarino J., Lange C., et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Eur Respir J. 2020 Jul 7;56(1):2000535. doi: 10.1183/13993003.00535-2020.Ruth M., Sangen J., Remmers K., et al. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria.J Antimicrob Chemother. 2019 Apr 1;74(4):935–943. doi: 10.1093/jac/dky526.Ruth M., Sangen J., Remmers K., et al. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria.J Antimicrob Chemother. 2019 Apr 1;74(4):935–943. doi: 10.1093/jac/dky526.Andries K., Villellas C., Coeck N., et al. Acquired resistance of Mycobacterium tuberculosis to bedaquiline.PLoS One. 2014 Jul 10;9(7):e102135. doi: 10.1371/journal.pone.0102135.Andries K., Villellas C., Coeck N., et al. Acquired resistance of Mycobacterium tuberculosis to bedaquiline.PLoS One. 2014 Jul 10;9(7):e102135. doi: 10.1371/journal.pone.0102135.Peretokina I., Krylova L., Antonova O., et al. Reduced susceptibility and resistance to bedaquiline in clinical M. tuberculosis isolates // J Infect. 2020 May;80(5):527–535. doi:0.1016/j.jinf.2020.01.007.Peretokina I., Krylova L., Antonova O., et al. Reduced susceptibility and resistance to bedaquiline in clinical M. tuberculosis isolates // J Infect. 2020 May;80(5):527–535. doi:0.1016/j.jinf.2020.01.007.Pang Y., Zheng H., Tan Y., et al. In Vitro Activity of Bedaquiline against Nontuberculous Mycobacteria in China.Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02627–16. doi: 10.1128/AAC.02627-16.Pang Y., Zheng H., Tan Y., et al. In Vitro Activity of Bedaquiline against Nontuberculous Mycobacteria in China.Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02627–16. doi: 10.1128/AAC.02627-16.Yu X., Gao X., Li C., et al. In Vitro Activities of Bedaquiline and Delamanid against Nontuberculous Mycobacteria Isolated in Beijing, China. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00031–19. doi: 10.1128/AAC.00031-19.Yu X., Gao X., Li C., et al. In Vitro Activities of Bedaquiline and Delamanid against Nontuberculous Mycobacteria Isolated in Beijing, China. Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00031–19. doi: 10.1128/AAC.00031-19.Brown-Elliott B., Wallace R. In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium abscessus complex.Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01919–18. doi: 10.1128/AAC.01919-18.Brown-Elliott B., Wallace R. In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium abscessus complex.Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01919–18. doi: 10.1128/AAC.01919-18.Brown-Elliott B., Philley J., Griffith D., et al. In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium avium complex.Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01798–16. doi: 10.1128/AAC. 01798-16.Brown-Elliott B., Philley J., Griffith D., et al. In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium avium complex.Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01798–16. doi: 10.1128/AAC. 01798-16.Kim D., Jhun B., Moon S., et al. In Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates.Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00665–19. doi: 10.1128/AAC.00665–19.Kim D., Jhun B., Moon S., et al. In Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical Isolates.Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00665–19. doi: 10.1128/AAC.00665–19.Martin A., Godino I., Aguilar-Ayala D., et al. In vitro activity of bedaquiline against slow-growing nontuberculous mycobacteria // J Med Microbiol. 2019 Aug;68(8):1137–1139. doi:10.1099/jmm. 0.001025.Martin A., Godino I., Aguilar-Ayala D., et al. In vitro activity of bedaquiline against slow-growing nontuberculous mycobacteria // J Med Microbiol. 2019 Aug;68(8):1137–1139. doi:10.1099/jmm. 0.001025.Litvinov V., Makarova M., Kudlay D., et al. In vitro activity of bedaquiline against Mycobacterium avium complex. J Med Microbiol. 2021 Oct;70(10). doi: 10.1099/jmm.0.001439.Litvinov V., Makarova M., Kudlay D., et al. In vitro activity of bedaquiline against Mycobacterium avium complex. J Med Microbiol. 2021 Oct;70(10). doi: 10.1099/jmm.0.001439.Clinical and Laboratory Standards Institute (CLSI). Susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes. (3rd ed.), CLSI, Wayne, PA (2018).Clinical and Laboratory Standards Institute (CLSI). Susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes. (3rd ed.), CLSI, Wayne, PA (2018).European Committee on Antimicrobial Susceptibility Testing. EUCAST subcommittee on MIC distributions and epidemiological cut-off values (ECOFFs). 2014. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Consultation/2017/MIC_and_ECOFF/EUCAST_MIC_and_ECOFF_discussion_document_version_3_20170309.pdf.European Committee on Antimicrobial Susceptibility Testing. EUCAST subcommittee on MIC distributions and epidemiological cut-off values (ECOFFs). 2014. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Consultation/2017/MIC_and_ECOFF/EUCAST_MIC_and_ECOFF_discussion_document_version_3_20170309.pdf.

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