pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2022-32-1-103-108pulmo-3519Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESЭффективность химиотерапии у больных туберкулезом с множественной лекарственной устойчивостью возбудителя с использованием бедаквилинаEffectiveness of chemotherapy of multidrug-resistant tuberculosis using bedaquilinehttps://orcid.org/0000-0001-6709-6789БаласанянцГ. С.BalasaniantcG. S.

Баласанянц Гоар Сисаковна – д. м. н., профессор, профессор кафедры фтизиатрии

194044, Санкт-Петербург, ул. Академика Лебедева, 6

тел.: (812) 514-14-08

Goar S. Balasaniantc, Doctor of Medicine, Professor, Professor of Phthysiology Department

ul. Academica Lebedeva 6, 194044, Saint Petersburg

tel.: (812) 514-14-08

balasanjanz@mail.ruФедеральное государственное бюджетное военное образовательное учреждение высшего образования «Военно-медицинская академия имени С.М.Кирова» Министерства обороны Российской ФедерацииРоссияFederal State Budgetary Military Educational Institution of higher education “Military Medical Academy named after S.M.Kirov” of the Ministry of Defense of the Russian FederationRussian Federation202221022022321103–108Copyright © Баласанянц Г.С., 20222022Баласанянц Г.С.Balasaniantc G.S.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/3519

Целью исследования явилась оценка эффективности лечения больных туберкулезом (ТБ) с множественной лекарственной устойчивостью (МЛУ) микобактерий туберкулеза (МБТ) с использованием бедаквилина в противотуберкулезных стационарах Санкт-Петербурга в 2017 г. Материалы и методы. Изучены результаты лечения больных (n = 56) с МЛУ МБТ, в схему терапии которых включен препарат бедаквилин. У всех пациентов установлено бактериовыделение (БВ). Широкая лекарственная устойчивость (ШЛУ) МБТ установлена у 43 (67,8 %), преширокая (пре-ШЛУ) – у 7 (12,5 %) пациентов, МЛУ отмечалась в 6 (10,7 %) случаях. Результаты. Полный курс бедаквилина получили 35 пациентов, неполный курс (от нескольких дней до 4 мес.) – 16; > 6 мес. получали бедаквилин 5 прооперированных больных с ШЛУ. Продолжительность приема бедаквилина в среднем составила 4,7 ± 0,3 мес. Из 27 (48,2 %) эффективно завершивших лечение пациентов ШЛУ выявлена у 22, пре-ШЛУ – у 3, МЛУ – у 2. Средний срок прекращения БВ в этой группе составил 4,00 ± 0,42 мес. Самостоятельно прекратили лечение 13 (23,2 %) пациентов, у 9 из них на момент прекращения терапии БВ не определялось. Эти пациенты получали бедаквилин в течение 1–14 мес. Неэффективность терапии зафиксирована в 12 (21,4 %) случаях, у всех сохранялось БВ после интенсивной фазы лечения. В течение интенсивной фазы лечения констатированы 4 (7,14 %) летальных исхода. В конце интенсивной фазы БВ прекратилось у пациентов, у которых зарегистрирован эффективный исход (n = 27), и лиц, эффективно завершивших интенсивную фазу лечения (n = 9), но прекративших лечение в фазе продолжения терапии. Заключение. При рутинном назначении бедаквилина по медицинским показаниям без отбора по принципу приверженности лечению повышается результативность интенсивной фазы (64,3 %) без существенного влияния на общую эффективность лечения (48,2 %). Серьезным препятствием на пути повышения эффективности лечения остается высокая частота самостоятельного прекращения терапии больными.

The aim of the study was to evaluate the effectiveness of MDR/XDR TB treatment with bedaquiline. Methods. The author analyzed the treatment results of 56 patients in Staint Petersburg in 2017 with MDR/XDR TB whose treatment regimen included bedaquiline. All patients were smear/ culture-positive: 43 (67.8%) cases with XDR MBT; 7 (12.5%) with pre-XDR MBT and only 6 (10.7 %) cases with MDR TB. Results. 35 (62.5%) patients received full bedaquiline course, 16 received the treatment for a few days to 4 months and did not complete the course, 5 patients with XDR tuberculosis who underwent surgery were treated for more than 6 months. The average duration of bedaquiline course was 4.7 ± 0.3 months. Among the 27 (48.2%) patients who completed the treatment effectively, 22 had XDR TB, 3 – pre-XDR TB, and 2 – MDR TB. The median sputum conversion period was 4.00 ± 0.42 months (CI: 3.14 – 4.86). 13 (23.2%) patients interrupted the treatment, but 9 of them had negative cultures for MBT at this time. These patients received bedaquiline for 1 to 14 months. Treatment failure was recorded in 12 (21.4%) patients, and 4 (7.14%) patients died during the intensive treatment phase. In general, 27 patients with a successful outcome had negative cultures at the end of the intensive phase and 9 patients who effectively completed the intensive phase but interrupted the treatment continuation phase. In total, 36 patients (64.3%) had a successful treatment outcome. Conclusion. The analysis showed that routine administration of the drug without consideration for treatment compliance increases the effectiveness of the intensive phase (64.3%) and does not significantly affect general effectiveness of the treatment (48.2%). The high frequency of treatment interruption remains a serious obstacle to improving the treatment effectiveness.

туберкулезмножественная лекарственная устойчивость микобактерий туберкулезабедаквилинрежим леченияэффективность леченияtuberculosismultidrug-resistant tuberculosisbedaquilinetreatment regimentreatment effectivenessReferencesВасильева И.А., Белиловский Е.М., Борисов С.Е., Стерликов С.А. Туберкулез с множественной лекарственной устойчивостью возбудителя в странах мира и в Российской Федерации. Туберкулез и болезни легких. 2017, 95 (11): 5–17. DOI: 10.21292/2075-1230-2017-95-11-5-17.Vasil’eva I.A., Belilovskij E.M., Borisov S.E., Sterlikov S.A. [Multi drug resistant tuberculosis in the world and Russian Federation]. Tuberkulez i bolezni legkih. 2017, 95 (11): 5–17. DOI: 10.21292/2075-1230-2017-95-11-5-17 (in Russian).Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2011. Available at: https://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_eng.pdf;jsessionid=15B51F3D928C3A3877156D07956EE7A0?sequence=1Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2011. Available at: https://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_eng.pdf;jsessionid=15B51F3D928C3A3877156D07956EE7A0?sequence=1Matteelli A., D’Ambrosio L., Centis R. et al. Compassionate and optimum use of new tuberculosis drugs. Lancet Infect. Dis. 2015; 15 (10): 1131–1132. DOI: 10.1016/S1473-3099(15)00296-0.Matteelli A., D’Ambrosio L., Centis R. et al. Compassionate and optimum use of new tuberculosis drugs. Lancet Infect. Dis. 2015; 15 (10): 1131–1132. DOI: 10.1016/S1473-3099(15)00296-0.Trauer J.M. TB, you’re a long time cured. Eur. Respir. J. 2019; 53 (3): 1900104. DOI: 10.1183/13993003.00104-2019.Trauer J.M. TB, you’re a long time cured. Eur. Respir. J. 2019; 53 (3): 1900104. DOI: 10.1183/13993003.00104-2019.Иванова Д.А., Борисов С.Е., Родина О.В. и др. Безопасность режимов лечения больных туберкулезом с множественной лекарственной устойчивостью возбудителя согласно новым рекомендациям ВОЗ 2019 г. Туберкулез и болезни легких. 2020; 98 (1): 5–15. DOI: 10.21292/2075-1230-2020-98-1-5-15.Ivanova D.A., Borisov S.E., Rodina O.V. et al. [Safety of treatment regimens in multiple drug resistant tuberculosis patients compiled as per the new WHO recommendations as of 2019]. Tuberkulez i bolezni legkikh. 2020; 98 (1): 5–15. DOI: 10.21292/2075-1230-2020-98-1-5-15 (in Russian).WHO consolidated guidelines on drug-resistant tuberculosis treatment. WHO/CDS/TB/2019.3. Geneva: World Health Organization; 2019. Available at: https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?sequence=1&isAllowed=yWHO consolidated guidelines on drug-resistant tuberculosis treatment. WHO/CDS/TB/2019.3. Geneva: World Health Organization; 2019. Available at: https://apps.who.int/iris/bitstream/handle/10665/311389/9789241550529-eng.pdf?sequence=1&isAllowed=yThe use of bedaquiline in the treatment of multidrug-resistant tuberculosis: interim policy guidance. Geneva: World Health Organization; 2013. Available at: https://www.ncbi.nlm.nih.gov/books/NBK154134/The use of bedaquiline in the treatment of multidrug-resistant tuberculosis: interim policy guidance. Geneva: World Health Organization; 2013. Available at: https://www.ncbi.nlm.nih.gov/books/NBK154134/Gandhi N.R., Brust J.C.M., Shah N.S. A new era for treatment of drug-resistant tuberculosis. Eur. Respir. J. 2018; 52 (4): 1801350 DOI: 10.1183/13993003.01350-2018.Gandhi N.R., Brust J.C.M., Shah N.S. A new era for treatment of drug-resistant tuberculosis. Eur. Respir. J. 2018; 52 (4): 1801350 DOI: 10.1183/13993003.01350-2018.Report of the Guideline Development Group Meeting on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis: a review of available evidence (2016). Geneva: World Health Organization; 2017. Available at: https://apps.who.int/iris/bitstream/handle/10665/254712/WHO-HTM-TB-2017.01-eng.pdf?sequence=1&isAllowed=yReport of the Guideline Development Group Meeting on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis: a review of available evidence (2016). Geneva: World Health Organization; 2017. Available at: https://apps.who.int/iris/bitstream/handle/10665/254712/WHO-HTM-TB-2017.01-eng.pdf?sequence=1&isAllowed=yPontali E., Raviglione M.C., Migliori G.B. et al. Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur. Respir. Rev. 2019; 28 (152): 190035. DOI: 10.1183/16000617.0035-2019.Pontali E., Raviglione M.C., Migliori G.B. et al. Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur. Respir. Rev. 2019; 28 (152): 190035. DOI: 10.1183/16000617.0035-2019.Dheda K., Chang K.C., Guglielmetti L. et al. Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis. Clin. Microbiol. Infect. 2017; 23 (3): 131–140. DOI: 10.1016/j.cmi.2016.10.008.Dheda K., Chang K.C., Guglielmetti L. et al. Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis. Clin. Microbiol. Infect. 2017; 23 (3): 131–140. DOI: 10.1016/j.cmi.2016.10.008.Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2014. Available at: https://apps.who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdfCompanion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization; 2014. Available at: https://apps.who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdfWHO treatment guidelines for drug-resistant tuberculosis. 2016 update. Geneva: World Health Organization; 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdfWHO treatment guidelines for drug-resistant tuberculosis. 2016 update. Geneva: World Health Organization; 2016. Available at: https://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdfDefinitions and reporting framework for tuberculosis – 2013 revision (updated December 2014 and January 2020). Geneva: World Health Organization 2013. Available at: https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdfDefinitions and reporting framework for tuberculosis – 2013 revision (updated December 2014 and January 2020). Geneva: World Health Organization 2013. Available at: https://apps.who.int/iris/bitstream/handle/10665/79199/9789241505345_eng.pdfGlobal Tuberculosis Report. Geneva: World Health Organization; 2018. Available at: https://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?sequence=1&isAllowed=yGlobal Tuberculosis Report. Geneva: World Health Organization; 2018. Available at: https://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdf?sequence=1&isAllowed=yHarari S. Randomised controlled trials and real-life studies: two answers for one question. Eur. Respir. Rev. 2018; 27 (149): 180080. DOI: 10.1183/16000617.0080-2018.Harari S. Randomised controlled trials and real-life studies: two answers for one question. Eur. Respir. Rev. 2018; 27 (149): 180080. DOI: 10.1183/16000617.0080-2018.Diacon A.H., Pym. A., Grobusch M.P. et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N. Engl. J. Med. 2014, 371 (8): 723–732. DOI: 10.1056/NEJMoa1313865.Diacon A.H., Pym. A., Grobusch M.P. et al. Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N. Engl. J. Med. 2014, 371 (8): 723–732. DOI: 10.1056/NEJMoa1313865.Olayanju O., Limberis J., Esmail A. et al. Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa. Eur. Respir. J. 2018; 51 (5): 1800544. DOI: 10.1183/13993003.00544-2018.Olayanju O., Limberis J., Esmail A. et al. Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa. Eur. Respir. J. 2018; 51 (5): 1800544. DOI: 10.1183/13993003.00544-2018.Mbuagbaw L., Guglielmetti L., Hewison C. et al. Outcomes of bedaquiline treatment in patients with multidrug-resistant tuberculosis. Emerg. Infect. Dis. 2019, 25 (5): 936–943. DOI: 10.3201/eid2505.181823.Mbuagbaw L., Guglielmetti L., Hewison C. et al. Outcomes of bedaquiline treatment in patients with multidrug-resistant tuberculosis. Emerg. Infect. Dis. 2019, 25 (5): 936–943. DOI: 10.3201/eid2505.181823.Министерство здравоохранения Российской Федерации. Туберкулез у взрослых: Клинические рекомендации. 2020. Доступно на: https://cr.minzdrav.gov.ru/schema/16_1Ministry of Health of the Russian Federation. [Tuberculosis in adults: Clinical guidelines]. 2020. Available at: https://cr.minzdrav.gov.ru/schema/16_1 (in Russian).

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