BackgroundThe spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis compromises effective control of tuberculosis (TB) in Siberia. Early identification of drug-resistant isolates is, therefore, crucial for effective treatment of this disease. The aim of this study was to conduct drug susceptibility testing and identify mutations in drug resistance genes in clinical isolates of M. tuberculosis from some TB patients presenting for treatment in Siberia.MethodsThirty randomly selected clinical isolates of M. tuberculosis were obtained from the Novosibirsk Research Institute of Tuberculosis, Russia. Isolates were screened for drug resistance and characterized by variable number of tandem repeats (VNTR)-typing using 15 standard and four additional loci. Deligotyping on multiple large sequences was performed using 10 loci.ResultsTwenty-nine of the isolates were assigned XDR status. Twenty-eight isolates belonged to the M. tuberculosis Beijing family, from which 11 isolates were considered the M11 type (39%), two the M2 type (7%), and one the M33 type (3%). Seventeen isolates (60.7%) from this family exhibited unique genetic patterns. The remaining two isolates belonged to the Latino-American Mediterranean family. Gene sequences (rpoB, katG, rrs, rpsL, tlyA, gidB, gyrA, gyrB) were analyzed to identify mutations that confer resistance to rifampicin, isoniazid, amikacin, kanamycin, capreomycin, and ofloxacin. The most common mutations among the XDR isolates were S531L in RpoB, S315T in KatG, various codon 94 mutations in gyrA, A90V in GyrA, K43R in RpsL, and 1401 A → G in rrs; these confer resistance to rifampicin, isoniazid, ofloxacin, streptomycin and kanamycin/capreomycin, respectively. There was high congruence between the two typing methods (VNTR typing and deligotyping) and RD105, RD149, RD152, RD181, and RD207 regions of difference were absent from the 28 Beijing family isolates.ConclusionsDeligotyping can be used for rapid and reliable screening of M. tuberculosis isolates, followed by more in-depth genotyping. Identification of Beijing family isolates with extensive drug resistance confirms that such strains have epidemiological importance in Siberia. Rapid detection of mutations that lead to drug resistance should facilitate selection of effective drug therapies, and the development of early prevention strategies to combat this infection.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-478) contains supplementary material, which is available to authorized users.

Цель исследования: оценить эффективность и безопасность лечения больных туберкулезом с преширокой лекарственной устойчивостью и с широкой лекарственной устойчивостью возбудителя (ШЛУ-ТБ) по V режиму химиотерапии (РХТ) с применением новых противотуберкулезных препаратов (ПТП), в том числе с длительным применением бедаквилина. Материалы и методы. Изучены эффективность и безопасность лечения 39 больных по V РХТ. Из них с фиброзно-кавернозным туберкулезом-17 (43,6%), с ШЛУ-ТБ-31 (79,5%), с ВИЧ-инфекцией-9 (23,1). Результаты исследования. Эффективность лечения: излечены 32 (82,0%), неудача-1 (2,6%), умерли не от туберкулеза-4 (10,2%), самостоятельно прекратили лечение-2 (5,1%). Принимали бедаквилин в течение всего курса химиотерапии 23 (69,7%) пациента (средний срок-19,3 мес.). Из них 22 (95,6%) излечены, неудача лечения-1 (4,4%). Отмечена хорошая переносимость препарата. Нежелательные эффекты, потребовавшие отмены некоторых ПТП, зафиксированы у 9 (23,1%) пациентов. После абациллирования 30 (76,9%) пациентов лечились в стационарозамещающих условиях, в том числе у 10 из них использовался видеоконтроль приема препаратов. Постлечебное наблюдение осуществляется у 28 из 32 (2 сменили место жительства, 2 умерли не от туберкулеза) излеченных пациентов, средний срок 11,7 ± 6,3 мес., рецидива туберкулеза у них нет.

1 ФГБУ «Новосибирский научно-исследовательский институт туберкулеза» МЗ РФ, г. Новосибирск, РФ 2 ФГАОУ ВО «Новосибирский национальный исследовательский государственный университет (НГУ)», г. Новосибирск, РФ 3 ГБУЗ НСО «Государственная областная Новосибирская клиническая туберкулезная больница», г. Новосибирск, РФ 4 Научно-исследовательский институт клинической и экспериментальной лимфологии -филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», г. Новосибирск, РФ Цель: исследование противотуберкулезных эффектов лазерной фотодинамической инактивации (ФДИ) M. tuberculosis H 37 Rv in vitro метиленовым синим (МС) в минимальной концентрации (1 мкг/мл) при лазерном излучении длиной волны 662 нм. Материалы и методы. Проведен сравнительный анализ интенсивности роста Mycobacterium tuberculosis H 37 Rv после лазерного облучения и лазерной ФДИ МС при различных дозах световой энергии. Результаты. Обнаружено, что лазерное излучение длиной волны 662 нм оказывает ингибирующее действие на ростовые свойства M. tuberculosis H 37 Rv. Впервые зарегистрирована ФДИ микобактерий туберкулеза в присутствии минимальной концентрации МС (1 мкг/мл), при которой реализуется подавление роста колоний на 97 и 93% при их обработке излучением длиной волны 662 нм с наименьшими значениями плотности доз световой энергии (46,9 и 93,75 Дж/см 2 ). Ключевые слова: антимикробная фотодинамическая терапия, туберкулез, Mycobacterium tuberculosis H 37 Rv, метиленовый синий Для цитирования: Бредихин Д. А., Никонов С. Д., Чередниченко А. Г., Петренко Т. И., Корбут А. И. Фотодинамическая инактивация Mycobacterium tuberculosis метиленовым синим in vitro // Туберкулёз и болезни лёгких. -2019. -Т. 97, № 7. -С. 28-33. http://doi.The objective: to investigate the anti-tuberculosis effect of laser photodynamic inactivation (PDI) of M. tuberculosis H 37 Rv in vitro by methylene blue (MB) in the minimum concentration (1 μg/ml) with laser radiation of 662 nm. Subjects and methods.A comparative analysis of the intensity of growth of Mycobacterium tuberculosis H 37 Rv after laser irradiation and laser FDI by MB with different doses of light energy was carried out.Results. Laser radiation with a wavelength of 662 nm was found to have an inhibitory effect on the growth of M. tuberculosis H 37 Rv. FDI of Mycobacterium tuberculosis was first registered in the presence of a minimum concentration of MB (1 µg/ml) which suppressed colony growth by 97 and 93% when they were processed by radiation with a wavelength of 662 nm with the lowest density of doses of light energy (46.9 and 93.75 J/cm 2 ).

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ObjectiveTo analyse the epidemiological trends of tuberculosis in the Siberian and Far Eastern federal districts, the areas with the highest disease burden in the Russian Federation.MethodsWe applied principal coordinate analysis to study a total of 68 relevant variables on tuberculosis epidemiology, prevention and control. Data on these variables were collected over 2003–2016 in all 21 regions of the Siberian federal district and Far Eastern federal district (total population: 25.5 million) through the federal and departmental reporting system. We identified the regions with a favourable or unfavourable tuberculosis epidemiological profile and ranked them as low or high priority for specific interventions.FindingsThe median number of tuberculosis notifications in the regions was 123.3 per 100 000 population (range: 54.5–265.7) in 2003, decreasing to 82.3 per 100 000 (range: 52.9–178.3) in 2016. We found large variations in the tuberculosis epidemiological profile across different regions. The principal coordinate analysis revealed that three aggregated indicators accounted for 55% of the variation. The first coordinate corresponded to tuberculosis prevalence and case notifications in the regions; the second to the severity of the disease among patients; and the third to the percentage of multidrug-resistant tuberculosis among tuberculosis patients. The regions where intervention was most urgently needed were Chukotka Autonomous Okrug, Jewish Autonomous Oblast and Tyva Republic.ConclusionThe variability in tuberculosis epidemiology across regions was likely due to differences in the quality of antituberculosis services. Precision in defining necessary interventions, as determined through the principal coordinate analysis approach, can guide focused tuberculosis control efforts.