Sergey Borisov

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: A multicentre study

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents. 428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92–280) days and exposed to bedaquiline for 168 (86–180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively). Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30–60) days and 60 (33–90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related. Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions. Bedaquiline is safe and effective in treating MDR- and XDR-TB patients http://ow.ly/6MWK30adHkw

Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery

OBJECTIVES No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. METHODS This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. RESULTS 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Treatment effectiveness of TB patients from different groups of population in Moscow

Introduction: Moscow has one of the lowest tuberculosis (TB) epidemiological rate in Russia. At the same time, the impacts of significant migration from CIS countries and Russian regions (MG), homeless (HML) and HIV are the major challenges of TB control in the megapolis. Differentiation of treatment outcomes evaluation for these groups of patients in depend on history of previous treatment are needed for targeted measures. Methods: Treatment outcomes for 2013 cohort (2803 not-MDR TB patients) were analyzed in the Moscow in the beginning of 2015. Cohorts of HIV-negative (HIVn) and HIV-positive (HIVp) residents (RS), as well as HML and MG were evaluated separately for new TB cases (NC), TB relapses (RLC) and retreatment TB cases (RTC). Results: Treatment success rate (TSR) of NC was highest in 1398 HIVn RS: 84.6% (95% CI: 82.6-86.5) in comparison with201 HIVp RS patients (54.7%, 47.6-61.7), 623 MG: (56.0%, 52.0-60.0) and 97 HML (48.5%, 38.2-58.8), p NC from HIVp RS had predictably the highest level of death rate: 27.9% (21.8-34.6) vs. 3.9%, 8.2% and 2.7% for NC from RS, HML and MG, accordingly (p TSR for 194 RLC from RS (69.1%, 59.7-73.1) was higher (p Both MG cohorts: 623 NC and 48 RLC, showed high level of “not evaluated” outcomes: 37.1% (33.3-41.0) and 50.0% (35.2-64.8), defined particularities of the moving population, in contrast of RS cohorts (1.5% -1.6%). 74 RTC patients from RS showed TSR: 39.2% (28.0-51.2). Conclusions: Evaluations of treatment effectiveness for patients from different strata of population allows define directions of purposeful activities to improvement of TB control in Moscow.

Trend of structure of TB death indicator in the Moscow city, Russia

Background: Moscow city has one of the lowest levels of TB mortality rate in the Russia (2.9 per 100K, 2014) which is decreasing annually. To further decrease of TB mortality, the Moscow TB program includes activities targeted to the various components of indicator, depend on mortality among TB patients with: 1) different status of inhabitancy before death, including permanent residents (PR), homeless (HL), arrived from other Russian regions (RF) and migrants (MG), and 2) different status of TB death registration, relatively to time of TB notification: postmortem detected TB (PM), died before 1 month (D1M) or later 1 month after TB notification. Method: Retrospective study of TB mortality components, defined by statuses of inhabitancy and TB registration, was conducted, based on data about 1928 and 1156 cases of death from TB, registered in Moscow in two comparable periods: A - 2007-2009 and B - 2012-2014, which characterized the time before and after certain management reforms in TB control in the city. Results: The B period, in comparison with A, were mainly characterized by: - increasing of proportion not-PR among TB death cases: RF - from 6.9% (95% CI 5.8-8.1) to 13.6% (11.7-15.7), MG - 2.7% (2.1-3.6) to 6.3% (5.0-7.9), p 0.05; - increasing of PM and D1M among PR from 26.3% (23.9-28.9) to 34.8% (31.2-38.6), p - decreasing of the proportion of TB deaths under 45 years both between PR and not PR cases: from 31.1% to 26.7% and from 56.8% to 50.4%, accordingly, p Conclusions: Activities for decrease of TB mortality have to be specified according to particularities of TB mortality components, and taking into account of possibilities of them control.

Bedaquiline-containing regimens for MDR TB treatment – Focus on the safety

Background. Bedaquiline (Bdq) is the new TB drug, high effective in MDR cases, but its safety isn9t tested enough in regimens with second- and third-line (e.g. moxifloxacin, linezolid etc.) TB-drugs, especially in patients with comorbidity and long term TB-history. Methods. The prospective unblinded non-randomized one-centered study included 70 MDR-TB pts (67.1% male, 32.9% female, 18-73 y. o.; 21.4% new and 78.6% re-treated cases), received Bdq in combinations with 4-6 TB-drugs. The group included 17 alcohol abusers (24.3%) and 11 intravenous drug-users (15.7%). Concomitant diseases (at least one, required the treatment) were diagnosed in 64 pts (91.4%), most frequent COPD (28 pts, 40.0%). The adverse events (AE) monitoring was based on the criteria of Division of Microbiology and Infectious Diseases (DMID). Results. AE were obtained in 60 pts (85.7%), in total – 149 episodes, 1-5 per patient (Med = 2.0).The seriously AE (III-IV DMID) were obtained in 14 pts (20.0%): hepatitis – 4, eosinophilia – 3, QTc prolongation up to 520 msec – 2, obstinate vomiting – 2, ototoxicity – 2, anemia – 1. SAE III-IV with treatment interruption were attributed to Bdq in 4 pts (5.7%): 3 had cardiac symptoms (in 1 case combined with severe anemia), and 1 – hypereosinophilia. Conclusion. The regimens, based on Bdq and other second- and third-line TB-drugs, are well-tolerated in MDR-TB with severe comorbidity and long term previous treatment. It is hoped that the prolongation of Bdq course and its combination with linezolid, essential for XDR TB, will be approved.

Characteristics of non-resident new TB cases in Moscow City, Russia

Background: About three thousand new TB cases (NC) are registered in Moscow per year, including 40% “Moscow non-residents” (NR), who has not a permanent inhabitance in the city. NR include: persons arrived from Russian regions (RR), migrants from former USSR countries (FU) or other countries (OC) and homeless (HM). There are differences in these groups in case-finding, contacts tracing, and access to medical care, so they need a different approaches to TB control activities. Methods: Data of all NC, notified in Moscow in 2012-2013 is used in the study. Characteristics of NR were analyzed for NR in comparison with residents (RD). Results: In 2012-2013 Moscow TB service notifies: 1504 NC arrived from 76 of 83 Russian regions (45.2% NR), 1132 FU (34.0%) and 170 OC (5.1%) cases from more than 30 countries, and 524 HM (15.7%). As compared with RD, NR TB cases had higher proportion of male: 66.3% vs. 62% (OR=1.15; 95% CI: 1.05-1.27). NR was younger 35 in 64.7% cases (45.8% for RD, OR=1.9, 1.7-2.1), which was observed in all NR groups except HM when 64.2% TB cases were older 35 (OR=1.4; 1.2-1.7). All NR groups had higher proportion of unemployment: 64.1% vs. 35.6% (OR=2.5; 2.2-2.8). NR had more extensive forms of pulmonary TB, which had cavity more often than RD patients: OR=1.3 (1.2-1.5). Smear positive rate was similar (43-44%) in all groups except FU (27%, p New TB cases from NR had comparable lower level of TB-HIV cases – 8.9% (8.0–10.0) vs. PR -17.1% (16.0-18.2), which was defined by medical control of foreign people, arriving to Russia. Conclusions: Knowledge of characteristics of different groups of non-resident TB cases can permit to develop effective TB control program for megapolis.