Identification of genetic determinants of bedaquiline resistance in Mycobacterium tuberculosis in Ural region, Russia.

Collecting data on rare Mycobacterium tuberculosis (Mtb) clinical isolates with resistance to the new anti-tuberculosis drug bedaquiline is an important task for improving antimicrobial susceptibility testing methods. Nanopore whole genome sequencing, the proportion method on Middlebrook 7H11 medium, and BACTEC MGIT 960 assays were used to analyze genotypic and phenotypic resistance to bedaquiline. We found four mutations: atpE I66M, atpE А63Р, Rv0678 А36Т, and Rv0678 S53P in five isolates with different levels of phenotypic bedaquiline resistance. IMPORTANCE: Bedaquiline (BDQ) is a new anti-tuberculosis drug. The phenotypic and genotypic data describing the mechanism of drug resistance are critical for the design of rapid and accurate diagnostic tests. We consider that our work, which describes genotypic and phenotypic resistance to BDQ, can contribute to the standardization of drug susceptibility testing.

Experimental Studies of the Liposomal Form of Lytic Mycobacteriophage D29 for the Treatment of Tuberculosis Infection.

We have studied the antimycobacterial efficacy of the liposomal preparation of mycobacteriophage D29 on models of tuberculous granuloma in vitro and in the experiment on laboratory mice of the relatively resistant strain C57BL/6, infected with the virulent strain of M. tuberculosis H37Rv. We have shown the preparation of liposomal preparation of the lytic mycobacteriophages and its characteristics. The experiments showed a significant lytic effect of the liposomal form of mycobacteriophage D29 both on the model of tuberculous granuloma formed by human blood mononuclear cells in vitro, which is formed in the presence of Mycobacterium tuberculosis and on the model of tuberculous infection in C57BL/6 mice. Keywords: mycobacteriophage D29, M. tuberculosis, liposomes, tuberculous granuloma in vitro, tuberculosis infection and its treatment.

Health-related quality of life and long-term mortality in young and middle-aged hemodialysis patients.

PURPOSE: The relationship of health-related quality of life (HRQoL) with mortality in young and middle-aged hemodialysis (HD) patients has scarcely been studied and remains unclear. The aim of the study was to examine whether physical and mental components of HRQoL are related to long-term risks of all-cause and cardiovascular (CV) death in this particular HD population. METHODS: A long-term observational prospective study included 238 prevalent HD patients aged 18-64 years. The median follow-up was 50 (22, 96) months (maximum 13.9 years). HRQoL variables of the Short Form 36 Health Survey (SF-36), clinical, and demographic data were assessed at the time of inclusion. Associations of baseline HRQoL scores with all-cause and CV mortality were assessed using Kaplan-Meier survival plots and Cox regression analysis adjusted for clinical and demographic confounders. RESULTS: The majority of HRQoL parameters were associated with outcomes in univariable analyses. In multivariable regression models adjusted for clinical and demographic confounders, Physical Functioning (PF) and Physical Component Summary Score (PCS) remained independently related to all-cause mortality [hazard ratio (HR) for a 1-point increase in PF and PCS were 0.981, 95% confidence interval (CI) 0.972-0.989 and 0.954, CI 0.929-0.980, respectively] and CV death (HR for a 1-point increase in PF and PCS were 0.975, CI 0.962-0.988 and 0.950, CI 0.915-0.985, respectively). CONCLUSION: PF and PCS assessment seems to be relevant for refining the prognosis and clinical decision-making in young and middle-aged HD patients.

Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study.

BACKGROUND: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. METHODS: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. FINDINGS: Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. INTERPRETATION: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies. FUNDING: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare.

Quality of life in chronic hemodialysis patients in Russia.

The aim of this cross-sectional study was to compare health-related quality of life (HRQOL) of Russian hemodialysis (HD) patients with the general population and international data, and to determine factors influencing HRQOL. One thousand forty-seven HD patients from 6 dialysis centers were studied (576 male, age 43.5 +/- 12.5 years, HD duration 55.0 +/- 47.2 months). Health-related quality of life was evaluated by SF-36. Self-appraisal Depression Scale (W. Zung), State-Trait Anxiety Inventory, and Level of Neurotic Asthenia Scale were used. Hemodialysis patients scored significantly lower than the general Russian population in the majority of SF-36 scales. The only exception was the Mental Health score, which was even better than the general population. The Mean physical component score (PCS) of HD patients was 36.9 +/- 9.7, and the mental component score was (MCS) 44.2 +/- 10.5. In multiple linear regression analysis, increasing age, HD duration, depression level and number of days of hospitalization in the past 6 months were significant independent predictors of low PCS along with a low level of serum albumin. Advancing age was also a predictive factor for low MCS along with increase of HD duration, depression level, trait anxiety, and level of asthenia. As far as we know, this is the first study to report on HRQOL of a large sample of Russian HD patients performed using SF-36. Compared with the general population, Russian HD patients had significantly lower scores on the majority of SF-36 scales, especially in the physical domain. The mean PCS and MCS were comparable with European data for HD patients. A number of demographic, clinical, and psychological variables affect HRQOL.