Long-term impact of fecal transplantation in healthy volunteers

Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes.Peer ReviewedPostprint (published version

Incidence of Common Herpesviruses in Colonic Mucosal Biopsies Following Hematopoietic Stem Cell Transplantation

Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5–6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients’ characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant

Опыт разработки и применения алгоритма клинико-организационного управления при туберкулезе на региональном уровне

Relevance. The high incidence, prevalence and mortality in tuberculosis determines the relevance of improving clinical and organizational processes in terms of algorithmization. The aim of the study was to develop and evaluate the effectiveness of the clinical and organizational management algorithm for tuberculosis medical care at the regional level. Materials and Methods. The object of the study (2007-2021) were the tuberculosis medical care system of the Sverdlovsk region, Russian Federation. The scientific and methodological bases were Department of Health Organization, Drug Supply, Medical Technologies and Hygiene of the Peoples’ Friendship University of Russia topic SRW № 214791-3-000. The development of the algorithm was carried out on the basis of a scientifically proven universal clinical management system. The epidemiological tuberculosis author data and of Rosstat in the Sverdlovsk region for 2007-2020 were used - general and structural morbidity, prevalence, mortality, as well as the number of 3, 4 and 6 groups of dispensary registration of patients. The efficiency of the algorithm was evaluated by the dynamics of the complex of epidemiological indicators of tuberculosis. Research methods were applied: content analysis, analytical, statistical, comparative, expert. Significance was assessed using the t-White test. Differences in the compared parameters were considered significant at p0.05. Results and Discussion. The effectiveness of the developed algorithm for managing regional tuberculosis medical care, including the components of needs analysis, systematization, automation and telecommunications, interdisciplinary integration, resource provision and performance evaluation, was confirmed by a significant decrease in the Sverdlovsk region for the period 2007-2020 general incidence by 2.05 times (from 119.9 to 51.7 per 100 thousand of the population), the incidence of children 0-14 years old by 1.48 times (from 18.7 to 12.6 per 100 thousand children of the corresponding age), prevalence in the population by 1.8 times (from 258.6 to 143 per 100 thousand of the population) and mortality from tuberculosis by 2.675 times (from 21.4 to 8.02 per 100 thousand of the population) (p0.001). The COVID-19 pandemic (2020-2021) did not worsen the epidemiological situation for tuberculosis in the region. In 2020, an active form of tuberculosis was detected in 2201 people, which is 16 % less than in 2019 (p0.05). The prevalence of epidemiologically dangerous bacillary forms of the disease for the period 2019-2020 decreased by 15.4 %, from 73.2 to 61.9 per 100 thousand population (p0.05). Conclusion. Clinical and organizational management of tuberculosis medical care based on the algorithmization of scientifically evidence processes increases the effectiveness of therapeutic and preventive measures and the social and epidemiological well-being of the population.Актуальность. Высокая заболеваемость, распространенность и смертность при туберкулезе определяет актуальность совершенствования клинико-организационных процессов управления методом алгоритмизации. Цель исследования - разработать, внедрить и оценить эффективность алгоритма клинико-организационного управления противотуберкулезной помощью на уровне региона. Материалы и методы. Объектом исследования (2007-2021 гг.) явилась система противотуберкулезной помощи Свердловской области, база и научно-методическое сопровождение осуществлялось кафедрой организации здравоохранения, лекарственного обеспечения, медицинских технологий и гигиены Российского университета дружбы народов в соответствии с темой НИР № 214791-3-000. Разработку алгоритма осуществляли на основании научно доказанной универсальной системы клинического управления. Использована авторская информация и данные по туберкулезу Росстата по Свердловской области 2007-2020 гг. - структура заболеваемости, распространенности, смертность, а также численность пациентов 3, 4 и 6 групп диспансерного учета. Оценку эффективности алгоритма проводили по динамике комплекса эпидемиологических показателей туберкулеза. Применены методы исследования: контент-анализ, аналитический, статистический, сравнительный, экспертный. Для оценки достоверности применялся критерий t-Уайта. Различия сравниваемых показателей считали достоверными при р < 0,05. Результаты и обсуждение. Эффективность разработанного алгоритма управления региональной противотуберкулезной помощью, включающего компоненты анализа потребности, систематизации, автоматизации и телекоммуникации, междисциплинарной интеграции, ресурсного обеспечения и оценки эффективности, подтверждена достоверным снижением в Свердловской области за период 2007-2020 гг. общей заболеваемости в 2,05 раза (с 119,9 до 51,7 на 100 тыс. населения), заболеваемости детей 0-14 лет в 1,48 раза (с 18,7 до 12,6 на 100 тыс. детей соответствующего возраста), распространенности в популяции в 1,8 раза (с 258,6 до 143 на 100 тыс. населения) и смертности от туберкулеза в 2,675 раза (с 21,4 до 8,02 на 100 тыс. населения) (p < 0,001). Пандемия COVID-19 (2020-2021 гг.) не ухудшила эпидемиологическую ситуацию по туберкулезу в регионе. В 2020 г. активная форма туберкулеза выявлена у 2201 человек, что на 16 % меньше, чем в 2019 г. (р < 0,05). Распространенность эпидемиологически опасных бациллярных форм заболевания за период 2019-2020 гг. снизилась на 15,4 %, с 73,2 до 61,9 на 100 тысяч населения (р < 0,05). Заключение. Клинико-организационное управление противотуберкулезной помощью на основе научно-доказанных процессов алгоритмизации повышает результативность лечебно-профилактических мероприятий и социально-эпидемиологическое благополучие населения

Time-Dependent Shifts in Intestinal Bacteriome, <i>Klebsiella</i> Colonization and Incidence of Antibiotic-Resistance Genes after Allogeneic Hematopoietic Stem Cell Transplantation

Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p p K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients

Isolation and Characterization of the First <i>Zobellviridae</i> Family Bacteriophage Infecting <i>Klebsiella pneumoniae</i>

In order to address the upcoming crisis in the treatment of Klebsiella pneumoniae infections, caused by an increasing proportion of resistant isolates, new approaches to antimicrobial therapy must be developed. One approach would be to use (bacterio)phages and/or phage derivatives for therapy. In this study, we present a description of the first K. pneumoniae phage from the Zobellviridae family. The vB_KpnP_Klyazma podovirus, which forms translucent halos around the plaques, was isolated from river water. The phage genome is composed of 82 open reading frames, which are divided into two clusters located on opposite strands. Phylogenetic analysis revealed that the phage belongs to the Zobellviridae family, although its identity with the closest member of this family was not higher than 5%. The bacteriophage demonstrated lytic activity against all (n = 11) K. pneumoniae strains with the KL20 capsule type, but only the host strain was lysed effectively. The receptor-binding protein of the phage was identified as a polysaccharide depolymerase with a pectate lyase domain. The recombinant depolymerase protein showed concentration-dependent activity against all strains with the KL20 capsule type. The ability of a recombinant depolymerase to cleave bacterial capsular polysaccharides regardless of a phage’s ability to successfully infect a particular strain holds promise for the possibility of using depolymerases in antimicrobial therapy, even though they only make bacteria sensitive to environmental factors, rather than killing them directly