Based on population of patients with relapses of pulmonary tuberculosis (344 Moscow residents, 18 years old and more) was definite the most dangerous period for relapses – the first two years after outcome “cured”, included 76% of relapses. The risk factors of pulmonary tuberculosis early relapses were evaluated in 66 patients with relapses, in comparison with 98 patients cured without relapses in three year-long follow-up. Eight risk factors for relapses were determined as significant: drug resistance of MBT, permanent disability, chronic alcoholism, the advanced post tuberculosis lesions, inadequate chemotherapy regimen, the absent of relapse-prevention treatment, concomitant diseases, no family or broken family. The simultaneous presence of two factors increase the relapse probability until 10–66%, three and more until 66–99%. The most unfavourable was the combination of drug resistance, permanent disability, chronic alcoholism, the advanced post tuberculosis lesions, inadequate chemotherapy regimen – in such cases the probability of the early relapse of pulmonary tuberculosis is 99,0%.

We carried out the investigation of genetic mutations connected with MBT drug resistance to isoniazid (H), rifampicin (R), fluoroquinolones (Fq) and aminoglycosides(Ag) detected by molecular-genetic methods in 85 isolates. The results were compared to microbiological drug susceptibility testing for that drugs performed in BACTEC™ MGIT™ 960 system. The agreement of the results of detection of MDR, MDR and Fq-resistance, MDR and Ag-resistance and XDR of MBT strains by molecular-genetic and microbiological
methods achieved 94,7, 93,3, 93,3 and 97,3%, consequently. The combination of mutations Ser531Leu in rpoB and Ser315Thr in katG genes was detected in 55,3% of MTB cultures. Asp516Tyr in rpoB, leading to the low resistance level was detected in 2 H-resistant MBT cultures. Among mutations in gyrA gene the substitutions in 94th (58,8%) and 90th (15,7%) codons were detected most frequently. Asp94Gly was found out in 60,0% of MTB cultures. Mutations only in gyrB gene were detected in 4,0% of MTB strains. 2% of MBT strains had the substitutions in the both gyrA and gyrB genes simultaneously. Detection of mutations in the promoter region of eis gene revealed 30 (62,5%) kanamycin and amikacin resistant MBT strains in addition to 18 (37,5%) MTB cultures with the substitutions in rrs gene. The rapid detection of the type of mutations in the MBT genes in combination with microbiologic detection of the resistance level for rifampicin, isoniazid, fluoroquinolones and aminoglycosides gives the best information about investigated MBT strains and helps the clinicians to monitor the development of drug resistance.

Determination of the critical concentrations (CC) of drugs, widely used in the treatment of tuberculosis, to evaluate the results of the drug susceptibility testing of M. tuberculosis isolates using Sensititre MycoTB test system.
We studied using Sensititre MycoTB test system the minimal inhibitory concentrations (MICs) of streptomycin, isoniazid, rifampicin, ethambutol, amikacin, kanamycin, moxifloxacin and ofloxacin on the panel of the conditionally sensitive and conditionally resistant MBT strains isolated from different diagnostic material obtained in patients with pulmonary tuberculosis who were treated at the Moscow research and Clinical Center for Tuberculosis Control.
As a result of the analysis of the obtained MICs values, we determined the critical concentrations of antituberculosis drugs by MycoTB test system as the lowest concentration which inhibits the growth of 95% of sensitive MBT strains and allows the growth of 95% resistant MBT strains. We determined the following values of CCs: streptomycin – 1,0, isoniazid – 0,25, rifampicin – 1,0, ethambutol – 4,0, ofloxacin – 2,0, moxifloxacin – 0,25, kanamycin – 2,5 and amikacin – 1,0 μg/ml.
We carried out the comparative analysis of the effectiveness of the drug susceptibility testing (DST) of M.tuberculosis performed by Sencsititre MycoTB test in comparison with the cultivation methods on Middlebrook in the BACTEC™ MGIT™ 960 system and on Löwenstein-Jensen solid medium.
The cultures of M.tuberculosis obtained from 137 patients were investigated. There was the high percentage of matches of data obtained by Sencsititre MycoTB test and other methods. The Sencsititre MycoTB test has some advantages such as the standardization of the process and the ability of simultaneous quantitative determination of the drug resistance level for 12 antituberculosis drugs in the short period (7-14 days). The method of the DST by Sencsititre MycoTB test is simpler then others. This Sencsititre MycoTB test-system was tested abroad and in Moscow TB Control Center, certified in Russia and can be used in clinical practice.

The treatment technologies, realized by bronchoscopy in tuberculosis patients, is considered based on 40-years (1974-2013) experience. 40% of performed 90 600 procedures include the treatment methods. In the least 20 years the average number of treatment procedures per one patient increased from 2 to 5,6. Were used the following methods: bronchial sanations with drugs insufflation per catheter, drugs injection in peribronchial cellular tissue by transbronchial puncture, the bronchus obturation by porolon obturator in acute and subacute pleural empyema, insufflations of nitric oxide (produced by apparatus named “Plason”) in cases of nonspecific endobronchitis and bronchial tuberculosis, the simultaneous using of two obturators – porolon and one-way valve for lung hemorrhages short-stop.
All these methods increase the treatment efficacy in tuberculosis patients with concomitant diseases, mycobacterial drug resistance and such complications as pleural empyema and lung hemorrhages

Background. The second-line drugs optionally combined with the WHO’s “fifth group” drugs (especially linezolid) are effective in MDR-TB patients. In some cases, the adequate chemotherapy (min 4 drugs) is unrealizable due to the extended drug-resistance (XDR) and/or treatment intolerance. The new drug – bedaquiline (Bdq) – is essential, but it is not yet thoroughly tested in regimens with traditional TB-drugs and new anti-mycobacterial agents.
Design and Methods. The prospective unblinded non-randomized onecentered study include 54 pulmonary TB patients, 18-73 years old, 68,5% male and 31,5% female, 20,4% (20 pts) new and 79,8% (31 pts) retreated. MDR was identified in 37,0% (20 pts) and XDR – in 57,4% (31 pts). Lung cavities were detected in 87,0% (47 pts), bilateral lesions – in 61,1% (33 pts). Bdq was included in regimens in all patients, the next some wеre, if possible (based on mycobacterial drug-resistance patterns and patients drug tolerances), linezolid (96,3% – 52 pts), cycloserine / terizidone (81,5% – 44 pts), fluoroquinolones (70,4% – 38 pts), capreomycin (46,8% – 25 pts), prothionamide (29,6% – 16 pts), PAS (27,8% – 15 pts), pyrazinamide (18,7% – 10 pts), ethambutol (13,0% – 7 pts). If the regimen didn’t include at least four drugs, we add macrolides (38,9% – 21 pts), meropenum (9,5% – 5 pts), amoxicillin / clavulanic acid (1 pt), isoniazid in high doses (2 pt). The evaluation was performed after 24 weeks of Bdq administration.
Results. The treatment with Bdq was completed in 87,0% (47 pts), in 4 pts (7,4%) treatment was interrupted (but they weren’t lost to follow-up) and in 3 pts (5,6%) Bdq was excluded due to the serious adverse events. The evident involution of symptoms were obtained in 85,1% (35/43 pts), the X-ray improvement – in 85,1% (40/47 pts). The sputum smear conversion totally score (on liquid media): 87,2% (30/36 pts) with Med = 4 wks (IQR 2,0-11,5). The time of conversion and conversion rate were similar in MDR- and XDRTB, but significantly (р < 0,05) depend on large cavities. 12 incidents of SAE III-IV were obtained in 11 pts (20,4%): toxic hepatitis (3), hypereosinophilia (19% and more – 3), QTс prolongation up to 520 ms (2, without arrhythmia), obstinate vomiting (2), hyperkalemia and azotemia (1) and anemia (Hb < 69 g/l) – in 1 pt. The bedaquilin administration was stopped in 3 pts (5,6 %) and interrupted in 3.
Conclusion. The regimens, based on Bdq, second-line TB-drugs and the “fifth group” drugs are well-tolerated and high effective in MDR- and XDRTB. We need to obtain data to argue the prolongation of Bdq course for 9–12 months’.